The Anxious Bipolar Phenotype: Clinical Complexity and Treatment Resistance

The Anxious Bipolar Phenotype: Clinical Complexity and Treatment Resistance | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Anxious Bipolar Phenotype: Clinical Complexity and Treatment Resistance Balwinder Singh, Ada Man-Choi Ho, Brandon Coombes, Francisco Romo-Nava, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8503080/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Feb, 2026 Read the published version in International Journal of Bipolar Disorders → Version 1 posted 11 You are reading this latest preprint version Abstract Background Anxiety disorders (ANX) affect 30–60% of individuals with bipolar disorder (BD), yet limited research has systematically examined clinical characteristics and treatment patterns in this comorbid population. This study investigated demographic, clinical, and pharmacotherapeutic differences between individuals with BD with and without comorbid ANX. Methods Cross-sectional data from 2,225 adults with BD enrolled in the Mayo Clinic Bipolar Disorder Biobank were analyzed. Participants were assessed for comorbid ANX, demographics, clinical characteristics, medication use, and treatment response using the Alda-A scale. Results Overall, 61% (n = 1,366) had comorbid ANX. Individuals with BD + ANX were younger (40.4 vs. 43.6 years, p < 0.001), more likely female (66.6% vs. 54.8%, p < 0.001), and exhibited higher rates of rapid cycling (64.2% vs. 45.2%, p < 0.001), suicide attempts (40.4% vs. 24.8%, p < 0.001), substance use disorders (63.5% vs. 54.8%, p < 0.001), and somatic comorbidities (MCIRS: 6.68 vs. 5.42, p < 0.001). Pharmacotherapeutically, BD + ANX individuals were less likely to receive lithium (37.1% vs. 47.8%, p = 0.005) and valproic acid (21.7% vs. 29.6%, p = 0.047), but more likely to receive antidepressants (53.8% vs. 39.5%, p < 0.001), benzodiazepines (39.9% vs. 26.6%, p < 0.001), and gabapentinoids (8.5% vs. 4.5%, p < 0.001). Notably, 17.3% of BD + ANX individuals received antidepressants without mood stabilizer coverage. Treatment response (Alda-A) scores were significantly lower in BD + ANX for lithium (4.91 vs. 6.05, p < 0.001), mood-stabilizing anticonvulsants (5.09 vs. 6.22, p < 0.001), and second-generation antipsychotics (4.67 vs. 5.73, p < 0.001). Similar patterns were observed in both BD-I and BD-II subtypes. Conclusions Individuals with BD + ANX represent a more severely affected subgroup with distinct prescribing patterns favoring antidepressants over mood stabilizers and attenuated mood stabilizers response. These findings highlight the need for anxiety-informed treatment algorithms recognizing anxiety comorbidity as a negative prognostic factor. Bipolar disorder anxiety disorders comorbidity pharmacotherapy treatment response mood stabilizers antidepressants Figures Figure 1 Figure 2 INTRODUCTION A significant challenge in effectively managing bipolar disorder (BD) is the high prevalence of comorbidities, particularly anxiety disorders (ANX) (Pavlova et al., 2015 ; Singh et al., 2024 ), with clinical estimates up to 60% (Kinrys et al., 2019 ; McIntyre et al., 2006 ; Pavlova et al., 2015 ; Singh et al., 2025b ). Those with ANX are at increased risk for developing substance use disorders (SUD) and frequently self-medicate with alcohol (Smith and Book, 2008 ). Previous research has indicated that BD with comorbid ANX (BD + ANX) correlates with substantial functional impairment, risk for suicidality, and poor quality of life (Burdick et al., 2022 ; Simon et al., 2004 ). A recent systematic review reported the current prevalence of ANX in BD at approximately 38%, with generalized anxiety disorder (GAD) being the most common subtype (Yapici Eser et al., 2018 ). Although some studies suggest the lifetime risk of ANX may be as high as 60–85% (Merikangas et al., 2007 ; Mitchell et al., 2013 ), there remains a lack of consistent data on prevalence rates across bipolar I and bipolar II subtypes, as well as on associated clinical outcomes (Cullen et al., 2021 ; Galimberti et al., 2020 ; Kauer-Sant'Anna et al., 2009 ; Keck et al., 2006 ; Kinrys et al., 2019 ; Schaffer et al., 2012 ; Vazquez et al., 2014 ). There is a paucity of recent data examining pharmacotherapeutic approaches and treatment response differences among bipolar individuals with (BD + ANX) and without lifetime anxiety (BD + NoANX). A critical discussion within the field of BD concerns the prescription rates of monoaminergic antidepressants (Elmosalamy et al., 2025 ; Park et al., 2022 ), which may vary between 30–70%, depending on the region and study populations (Singh et al., 2024 ; Yocum and Singh, 2025 ). Evidence suggests that individuals with ANX are frequently prescribed monoaminergic antidepressants (Yatham et al., 2018 ), which may increase the risk of affective switching in BD. This raises the question of whether pharmacotherapy patterns differ between individuals with BD + ANX and BD + NoANX, with the former typically receiving higher rates of antidepressant prescriptions (Keck et al., 2006 ). Understanding these prescribing trends can inform clinical practices and contribute to strategies aimed at enhancing treatment outcomes in future research. Recent data from the Global Bipolar Cohort Collaboration showed prevalence rates of comorbid ANX as high as 60% in the North American cohorts compared to 30% in the European cohorts (Singh et al., 2024 ). We also observed regional variations in prescription patterns; however, data regarding the BD + ANX phenotype were not available. Leveraging data from the Mayo Clinic Bipolar Disorder Bank, this study examined the differences in clinical and demographic characteristics as well as pharmacotherapeutic prescription patterns among individuals with BD + ANX and BD + NoANX. Furthermore, we analyzed prescription patterns among individuals with bipolar I (BD-I) and bipolar II disorder (BD-II) with and without ANX, as those with BD-II tend to be prescribed more monoaminergic antidepressants (Singh et al., 2024 ). METHODS Detailed information about the Mayo Clinic Bipolar Disorder Biobank has been previously published (Frye et al., 2015 ). In summary, cross-sectional data was collected from study participants at enrollment (Gardea-Resendez et al., 2022 ; Pahwa et al., 2021b). Participants were recruited from five sites: Mayo Clinic, Rochester, Minnesota; Lindner Center of HOPE/University of Cincinnati College of Medicine, Cincinnati, Ohio; University of Minnesota, Minneapolis, Minnesota; Universidad Autónoma de Nuevo León, Mexico; and Universidad de los Andes, Chile. The inclusion criteria consisted of adults aged 18–80 with BD who spoke English at the U.S. sites and Spanish at Mexico and Chile sites, provided informed consent, and met DSM-IV-TR criteria for BD-I/BD-II or schizoaffective BD. Participants exhibiting active psychosis or suicidal ideation were excluded. At the time of study enrollment, data were collected on demographics, family history, psychiatric conditions (including adult and childhood attention deficit hyperactivity disorder [ADHD], anorexia nervosa, bulimia nervosa, binge eating disorder (BED), GAD, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD), medications, and somatic comorbidities. For this study, GAD, panic disorder, SAD, and phobias were categorized under the ANX category. Since most ANX persist as psychiatric diagnoses throughout an individual's life, our study concentrated on lifetime ANX diagnoses. The overall burden of medical illness was measured using the Modified Cumulative Illness Rating Scale (MCIRS) (Salvi et al., 2008 ), with psychiatric comorbidity data excluded. Data for additional somatic comorbidities were extracted using structured surveys. We collected data on current and lifetime prescriptions for second-generation antipsychotics (SGAs) and mood stabilizers, including lithium and mood-stabilizing anticonvulsants (MSACs) such as valproate, carbamazepine, and lamotrigine. Additional data were obtained for first-generation antipsychotics (FGAs), monoaminergic antidepressants—including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs)—as well as benzodiazepines, gabapentinoids (gabapentin or pregabalin), stimulants, wakefulness-promoting agents, and dopamine agonists. We examined patterns of polypharmacotherapy, defined as the concurrent use of two or more SGAs or mood stabilizers, and assessed the frequency of monoaminergic antidepressant prescriptions without a concurrent mood stabilizer. Treatment response to lithium, SGAs, and MSACs was assessed using the Alda-A score from the Alda Scale (Grof et al., 2002 ). The Alda-A score measures clinical improvement in illness severity during the treatment, rated from 0 (no improvement or worsening) to 10 (full recovery or absence of symptoms). Although initially developed to retrospectively measure response to lithium, it has been modified to assess response to other mood stabilizers in previous studies (Cuellar-Barboza et al., 2020 ; Ho et al., 2020 ; Joseph et al., 2023 ; Pahwa et al., 2021a ; Singh et al., 2025a ). Statistical analysis Clinical and demographic characteristics were compared between participants with and without a lifetime anxiety diagnosis (BD + ANX and BD + NoANX, respectively) using the arsenal package in R. The modelsum function was applied to perform multiple univariate tests, using linear models for continuous variables and logistic models for categorical variables. All models were adjusted for age, sex, and recruitment site (Mayo Clinic, Lindner Center of HOPE, University of Minnesota, Chile, or Mexico). Given the large number of comparisons, a threshold of p < 0.001 was used to define statistical significance. Analyses were conducted using R version 4.2.2. RESULTS The study cohort consisted of 2,225 adults with BD (1,451 BD-I, 723 BD-II, 51 schizoaffective disorder BD). The mean age was 41.6 years; 62.1% were female, 84.0% White, and 12.4% Hispanic ( Table-1 ). Rapid cycling was prevalent in 57.1% of individuals, with a history of psychosis in 39.6%, and 38.1% had early onset of BD. Ninety percent of ANX data came from the US, with the rest from Mexico and Chile. Overall, 61.4% (n = 1366) had ANX, with similar rates in BD-I (66.7%) and BD-II (64.3%). Among individuals with BD-I and BD-II, the most common ANX was GAD (50%), followed by panic disorder (30.3%), SAD (21.8%), and phobias (9.6%). There is a trend toward a higher prevalence of GAD in BD-II compared to BD-I (54.0% vs. 47.7%, p = 0.021), while rates of other ANX disorders were similar across BD subtypes ( Figure-1 ). Comparison of individuals with BD + ANX (n = 1366) and BD + NoANX (n = 859) Table 1 shows the comparisons of demographic and clinical characteristics between individuals with BD + ANX and BD + NoANX, adjusted for age, sex, and recruitment site. Individuals with BD + ANX were younger (mean age 40.4 vs. 43.6 years, p < 0.001) and more likely female (66.6% vs. 54.8%, p < 0.001) compared to those with BD + NoANX. They exhibited higher rates of rapid cycling (64.2% vs. 45.2%, p < 0.001), BED (12.3% vs. 7.5%, p < 0.001), PTSD (34.6% vs. 12.6%, p < 0.001), OCD (21.3% vs. 8.5%, p < 0.001), and SUDs (63.5% vs. 54.8%, p < 0.001). Suicidal attempts (40.4% vs. 24.8%, p < 0.001), tobacco use disorder (43.1% vs. 35.1%, p < 0.001), cocaine use disorder (16.6% vs. 10.6%, p < 0.001), alcohol use disorder (42.3% vs. 36.0%, p = 0.002), cannabis use disorder (33.3% vs. 24.4%, p < 0.001), methamphetamine use disorder (10.4% vs. 7.0%, p = 0.002), and opioid use disorder (12.8% vs. 6.9%, p < 0.001) were more prevalent in individuals with BD + ANX. A family history of BD (51.5% vs. 40.3%, p < 0.001), anxiety (68.5% vs. 49.7%, p < 0.001), depression (84.8% vs. 72.6%, p < 0.001), and alcohol use disorder (54.0% vs. 40.8%, p < 0.001) was also more common. Individuals with BD + ANX had higher MCIRS scores (6.68 vs. 5.42, p < 0.001), more migraines (36.8% vs. 18.9%, p < 0.001), and more current (2.86 vs. 2.50, p < 0.001) and lifetime use of psychotropics (7.27 vs. 5.74, p < 0.001). Table 1 Comparisons of demographic and clinical characteristics between individuals with BD, with and without ANX, adjusted for age, sex, and recruitment site. Total ( N = 2225) No ANX ( N = 859) ANX ( N = 1366) p -value Site of recruitment , n 2225 859 1336 Mayo, n (%) 1154 (51.9%) 495 (57.6%) 659 (48.2%) < 0.001* Lindner, n (%) 770 (34.6%) 219 (25.5%) 551 (40.3%) University of Minnesota, n (%) 75 (3.4%) 29 (3.4%) 46 (3.4%) Chile, n (%) 75 (3.4%) 51 (5.9%) 24 (1.8%) Mexico, n (%) 151 (6.8%) 65 (7.6%) 86 (6.3%) Age , n 2219 856 1363 Mean (SD) 41.6 (15.0) 43.6 (15.9) 40.4 (14.3) < 0.001* Sex , n 2225 859 1366 Male, n (%) 844 (37.9%) 388 (45.2%) 456 (33.4%) < 0.001* Female, n (%) 1381 (62.1%) 471 (54.8%) 910 (66.6%) Race , n 2191 840 1351 White, n (%) 1840 (84.0%) 705 (83.9%) 1135 (84.0%) 0.005* Black, n (%) 62 (2.8%) 18 (2.1%) 44 (3.3%) Asian, n (%) 22 (1.0%) 15 (1.8%) 7 (0.5%) Other, n (%) 170 (7.8%) 73 (8.7%) 97 (7.2%) Multiracial, n (%) 97 (4.4%) 29 (3.5%) 68 (5.0%) Hispanic , n 2179 833 1346 Yes, n (%) 271 (12.4%) 124 (14.9%) 147 (10.9%) 0.223 Body mass index , n 2118 818 1300 Mean (SD) 29.9 (7.4) 29.4 (6.8) 30.2 (7.7) 0.094 Currently married , n 2201 848 1353 Yes, n (%) 997 (45.3%) 403 (47.5%) 594 (43.9%) 0.821 Employment , n 2106 809 1297 Full-time, n (%) 544 (25.8%) 226 (27.9%) 318 (24.5%) 0.012 Part-time, n (%) 401 (19.0%) 170 (21.0%) 231 (17.8%) Not working for pay at present, n (%) 1161 (55.1%) 413 (51.1%) 748 (57.7%) Education , n 2134 814 1320 High school or less, n (%) 61 (2.9%) 26 (3.2%) 35 (2.7%) 0.271 High school graduated, n (%) 284 (13.3%) 97 (11.9%) 187 (14.2%) Beyond high school graduation, n (%) 1789 (83.8%) 691 (84.9%) 1098 (83.2%) Bipolar Disorder Characteristics Bipolar type , n 2225 859 1366 Bipolar I, n (%) 1451 (65.2%) 573 (66.7%) 878 (64.3%) 0.234 Bipolar II, n (%) 723 (32.5%) 263 (30.6%) 460 (33.7%) Schizoaffective, n (%) 51 (2.3%) 23 (2.7%) 28 (2.0%) Rapid cycling , n 2083 783 1300 Yes, n (%) 1189 (57.1%) 354 (45.2%) 835 (64.2%) < 0.001 History of psychosis , n 2207 852 1355 Yes, n (%) 874 (39.6%) 352 (41.3%) 522 (38.5%) 0.302 Manic psychosis , n 2207 852 1355 Yes, n (%) 693 (31.4%) 301 (35.3%) 392 (28.9%) 0.012 Early onset (≤ 19 years old) , n 2094 791 1303 Yes, n (%) 797 (38.1%) 275 (34.8%) 522 (40.1%) 0.016 Suicide attempt , n 2211 854 1357 Yes, n (%) 760 (34.4%) 212 (24.8%) 548 (40.4%) < 0.001 Suicide attempt (≤ 19 years old) , n 571 156 415 Yes, n (%) 256 (44.8%) 66 (42.3%) 190 (45.8%) 0.457 Lifetime Psychiatric Illness History Child ADHD , n 2185 853 1332 Yes, n (%) 347 (15.9%) 110 (12.9%) 237 (17.8%) 0.015 Anorexia or bulimia , n 2200 857 1343 Yes, n (%) 194 (8.8%) 50 (5.8%) 144 (10.7%) 0.005 Binge eating disorder , n 2202 855 1347 Yes, n (%) 270 (12.3%) 64 (7.5%) 206 (15.3%) < 0.001 Post-traumatic stress disorder , n 2202 855 1347 Yes, n (%) 574 (26.1%) 108 (12.6%) 466 (34.6%) < 0.001 Obsessive compulsive disorder , n 2196 857 1339 Yes, n (%) 358 (16.3%) 73 (8.5%) 285 (21.3%) < 0.001 Lifetime Substance Use Disorder Substance use disorder , n 2135 836 1299 Yes, n (%) 1283 (60.1%) 458 (54.8%) 825 (63.5%) < 0.001 Tobacco use disorder , n 2200 854 1346 Yes, n (%) 880 (40.0%) 300 (35.1%) 580 (43.1%) < 0.001 Alcohol use disorder , n 2207 856 1351 Yes, n (%) 879 (39.8%) 308 (36.0%) 571 (42.3%) 0.002 Cocaine use disorder , n 2193 852 1341 Yes, n (%) 313 (14.3%) 90 (10.6%) 223 (16.6%) < 0.001 Cannabis use disorder , n 2205 855 1350 Yes, n (%) 658 (29.8%) 209 (24.4%) 449 (33.3%) < 0.001 Methamphetamine use disorder , n 2200 855 1345 Yes, n (%) 200 (9.1%) 60 (7.0%) 140 (10.4%) 0.002 Opioid use disorder , n 2189 854 1335 Yes, n (%) 230 (10.5%) 59 (6.9%) 171 (12.8%) < 0.001 Family History (First-degree Relatives) Bipolar disorder , n 1692 648 1044 Yes, n (%) 799 (47.2%) 261 (40.3%) 538 (51.5%) < 0.001 Anxiety , n 722 296 426 Yes, n (%) 439 (60.8%) 147 (49.7%) 292 (68.5%) < 0.001 Depression , n 1877 707 1170 Yes, n (%) 1505 (80.2%) 513 (72.6%) 992 (84.8%) < 0.001 Alcohol use disorder , n 1894 721 1173 Yes, n (%) 928 (49.0%) 294 (40.8%) 634 (54.0%) < 0.001 Suicide , n 1873 721 1152 Yes, n (%) 167 (8.9%) 55 (7.6%) 112 (9.7%) 0.124 MCIRS , mean (SD) 6.191 (6.570) 5.421 (6.207) 6.676 (6.746) < 0.001 Medical comorbidities , n 758 312 446 Hypertension, n (%) 130 (17.2%) 52 (16.7%) 78 (17.5%) 0.522 Musculoskeletal, integumentary, n (%) 6 (0.8%) 2 (0.6%) 4 (0.9%) 0.707 Eczema, n (%) 69 (9.1%) 27 (8.7%) 42 (9.4%) 0.275 Psoriasis, n (%) 24 (3.2%) 10 (3.2%) 14 (3.1%) 0.721 Vitiligo, n (%) 4 (0.5%) 2 (0.6%) 2 (0.4%) 0.390 Diabetes, n (%) 58 (7.7%) 21 (6.7%) 37 (8.3%) 0.193 PCOS, n (%) 40 (5.3%) 11 (3.5%) 29 (6.5%) 0.172 Thyroid, n (%) 135 (17.8%) 61 (19.6%) 74 (16.6%) 0.734 Rheum arthritis, n (%) 14 (1.8%) 5 (1.6%) 9 (2.0%) 0.529 Fibromyalgia, n (%) 44 (5.8%) 11 (3.5%) 33 (7.4%) 0.068 Stroke, n (%) 4 (0.5%) 1 (0.3%) 3 (0.7%) 0.882 Epilepsy, n (%) 50 (6.6%) 11 (3.5%) 39 (8.7%) 0.038 Obstructive sleep apnea, n (%) 82 (10.8%) 32 (10.3%) 50 (11.2%) 0.666 Migraines, n (%) 223 (29.4%) 59 (18.9%) 164 (36.8%) < 0.001 Osteoporosis, n ( %) 31 (4.1%) 7 (2.2%) 24 (5.4%) 0.010 Osteoarthritis, n (%) 94 (12.4%) 28 (9.0%) 66 (14.8%) 0.098 COPD, n (%) 23 (3.0%) 8 (2.6%) 15 (3.4%) 0.345 Obese , n 2118 818 1300 Yes, n (%) 888 (41.9%) 317 (38.8%) 571 (43.9%) 0.140 Current psychotropics , n 2216 854 1362 Mean (SD) 2.723 (1.581) 2.502 (1.469) 2.861 (1.632) < 0.001 Lifetime psychotropics , n 2216 854 1362 Mean (SD) 6.681 (5.456) 5.737 (4.765) 7.273 (5.772) < 0.001 Antidepressant-induced mania , n 1848 672 1176 0.207 Mean (SD) 384 (20.8%) 118 (17.6%) 266 (22.6%) Tardive dyskinesia , n 729 293 436 Yes, n (%) 67 (9.2%) 25 (8.5%) 42 (9.6%) 0.391 *Not adjusted for age, sex, and site of recruitment. Pharmacotherapeutic differences among individuals with BD + ANX (n = 1366) and BD + NoANX (n = 859) Individuals with BD + ANX ( n = 1366) differed significantly from those with BD + NoANX ( n = 859) across multiple pharmacotherapeutic variables (Table 2 , Fig. 2 ). Individuals with BD + ANX were less likely to be currently prescribed lithium (37.1% vs. 47.8%, p = 0.005) and showed a trend towards lower valproic acid use (21.7% vs. 29.6%, p = 0.047), but more likely to receive gabapentinoids (8.5% vs. 4.5%, p < 0.001) and benzodiazepines (39.9% vs. 26.6%, p < 0.001). They were also significantly more likely to receive antidepressant treatment (53.8% vs. 39.5%, p < 0.001), including two or more concurrent antidepressants (13.0% vs. 6.9%, p < 0.001), particularly SSRIs (28.8% vs. 16.8%, p < 0.001), and to be prescribed antidepressants without a concomitant mood stabilizer (17.3% vs. 9.7%, p < 0.001). Olanzapine prescriptions were lower among BD + ANX individuals (8.0% vs. 14.0%, p = 0.008), while there was a trend toward slightly higher lamotrigine use (39.7% vs. 35.8%, p = 0.027). No significant differences were observed for carbamazepine, quetiapine, FGAs, thyroid hormones, stimulants, or dopamine agonists. Table 2 Differences in pharmacotherapeutic prescriptions among individuals with bipolar disorder, with and without comorbid anxiety (ANX). Total ( N = 2225) No ANX ( N = 859) ANX ( N = 1366) p -value* Current Prescriptions Lithium , n 1516 579 937 0.005 Yes, n (%) 625 (41.2%) 277 (47.8%) 348 (37.1%) Lamotrigine , n 1700 628 1072 0.027 Yes, n (%) 651 (38.3%) 225 (35.8%) 426 (39.7%) Valproic acid , n 1638 631 1007 0.047 Yes, n (%) 406 (24.8%) 187 (29.6%) 219 (21.7%) Carbamazepine , n 1543 578 965 0.807 Yes, n (%) 43 (2.8%) 15 (2.6%) 28 (2.9%) Gabapentinoids , n 2198 848 1350 < 0.001 Yes, n (%) 153 (7.0%) 38 (4.5%) 115 (8.5%) Benzodiazepines , n 1985 743 1242 < 0.001 Yes, n (%) 693 (34.9%) 198 (26.6%) 495 (39.9%) Non-BZD sedatives , n 1974 740 1234 0.387 Yes, n (%) 154 (7.8%) 52 (7.0%) 102 (8.3%) SGA , n 2092 801 1291 0.635 Yes, n (%) 1110 (53.1%) 418 (52.2%) 692 (53.6%) Olanzapine , n 1544 601 943 0.008 Yes, n (%) 159 (10.3%) 84 (14.0%) 75 (8.0%) Clozapine , n 1514 585 929 0.740 Yes, n (%) 23 (1.5%) 9 (1.5%) 14 (1.5%) Quetiapine , n 1625 620 1005 0.141 Yes, n (%) 461 (28.4%) 171 (27.6%) 290 (28.9%) Aripiprazole , n 1566 599 967 0.353 Yes, n (%) 250 (16.0%) 84 (14.0%) 166 (17.2%) Risperidone , n 1551 597 954 0.735 Yes, n (%) 128 (8.3%) 48 (8.0%) 80 (8.4%) FGA , n 1583 602 981 0.388 Yes, n (%) 25 (1.6%) 12 (2.0%) 13 (1.3%) Any antidepressants , n 2102 783 1319 < 0.001 Yes, n (%) 1018 (48.4%) 309 (39.5%) 709 (53.8%) Two or more antidepressants , n 2102 783 1319 <0.001 Yes, n (%) 226 (10.8%) 54 (6.9%) 172 (13.0%) SSRI , n 2078 772 1306 < 0.001 Yes, n (%) 506 (24.4%) 130 (16.8%) 376 (28.8%) SNRI , n 1764 656 1108 0.254 Yes, n (%) 228 (12.9%) 77 (11.7%) 151 (13.6%) TCA , n 1894 684 1210 0.140 Yes, n (%) 83 (4.4%) 26 (3.8%) 57 (4.7%) Antidepressant without MS , n 2160 828 1332 < 0.001 Yes, n (%) 311 (14.4%) 80 (9.7%) 231 (17.3%) Thyroid hormone , n 1185 431 754 0.067 Yes, n (%) 262 (22.1%) 113 (26.2%) 149 (19.8%) Stimulants/wakefulness agents , n 1675 610 1065 0.939 Yes, n (%) 199 (11.9%) 67 (11.0%) 132 (12.4%) Dopamine agonist , n 1684 618 1066 0.769 Yes, n (%) 24 (1.4%) 9 (1.5%) 15 (1.4%) Two or more SGA , n 2092 801 1291 0.430 Yes, n (%) 91 (4.3%) 39 (4.9%) 52 (4.0%) One or more MS , n 2165 833 1332 0.060 Yes, n (%) 1503 (69.4%) 617 (74.1%) 886 (66.5%) Two or more MSs , n 2165 833 1332 0.597 Yes, n (%) 220 (10.2%) 87 (10.4%) 133 (10.0%) Three or more MSs , n 2165 833 1332 0.957 Yes, n (%) 2 (0.1%) 0 (0.0%) 2 (0.2%) No MS , n 2165 833 1332 0.060 Yes, n (%) 662 (30.6%) 216 (25.9%) 446 (33.5%) No medications , n 2216 854 1362 0.762 Yes, n (%) 183 (8.3%) 62 (7.3%) 121 (8.9%) Lifetime Prescriptions Lithium ever, n 1876 717 1159 0.030 Yes, n (%) 1009 (53.8%) 415 (57.9%) 594 (51.3%) Lamotrigine ever, n 2063 781 1282 0.150 Yes, n (%) 880 (42.7%) 310 (39.7%) 570 (44.5%) Valproate ever, n 2071 783 1288 0.013 Yes, n (%) 769 (37.1%) 323 (41.3%) 446 (34.6%) Gabapentinoids ever, n 2198 848 1350 < 0.001 Yes, n (%) 286 (13.0%) 75 (8.8%) 211 (15.6%) Benzodiazepines ever, n 1985 743 1242 < 0.001 Yes, n (%) 1060 (53.4%) 330 (44.4%) 730 (58.8%) FGA ever, n 1583 602 981 0.897 n (%) 163 (10.3%) 66 (11.0%) 97 (9.9%) SGA ever, n 2092 801 1291 0.172 n (%) 1457 (69.6%) 534 (66.7%) 923 (71.5%) Olanzapine ever, n 2043 788 1255 0.034 Yes, n (%) 374 (18.3%) 171 (21.7%) 203 (16.2%) Quetiapine ever, n 2050 788 1262 0.010 Yes, n (%) 787 (38.4%) 274 (34.8%) 513 (40.6%) Aripiprazole ever, n 2042 785 1257 0.386 n (%) 543 (26.6%) 178 (22.7%) 365 (29.0%) Risperidone ever, n 2045 789 1256 0.773 n (%) 419 (20.5%) 153 (19.4%) 266 (21.2%) Any antidepressant ever, n 2102 783 1319 < 0.001 n (%) 1710 (81.4%) 590 (75.4%) 1120 (84.9%) SSRI ever, n 2078 772 1306 < 0.001 Yes, n (%) 1373 (66.1%) 452 (58.5%) 921 (70.6%) SNRI ever, n 1764 656 1108 0.002 Yes, n (%) 644 (36.5%) 200 (30.5%) 444 (40.1%) TCA ever, n 1894 684 1210 0.012 Yes, n (%) 350 (18.5%) 105 (15.4%) 245 (20.2%) Antidepressant without MS ever, n 2164 831 1333 < 0.001 n (%) 267 (12.3%) 72 (8.7%) 195 (14.6%) Thyroid hormone ever, n 1185 431 754 0.300 n (%) 120 (10.1%) 51 (11.8%) 69 (9.2%) Stimulants/wakefulness agents ever, n 1675 610 1065 0.060 n (%) 432 (25.8%) 129 (21.1%) 303 (28.5%) Dopamine agonist ever, n 1684 618 1066 0.736 n (%) 44 (2.6%) 17 (2.8%) 27 (2.5%) Two or more SGAs ever, n 2092 801 1291 0.866 n (%) 640 (30.6%) 229 (28.6%) 411 (31.8%) One or more MS ever, n 2165 833 1332 0.043 n (%) 1799 (83.1%) 714 (85.7%) 1085 (81.5%) Two or more MSs ever, n 2165 833 1332 0.873 n (%) 721 (33.3%) 279 (33.5%) 442 (33.2%) Three or more MSs ever, n 2165 833 1332 0.415 n (%) 249 (11.5%) 101 (12.1%) 148 (11.1%) No MS ever, n 2165 833 1332 0.043 n (%) 366 (16.9%) 119 (14.3%) 247 (18.5%) No medications ever, n 2216 854 1362 0.827 n (%) 36 (1.6%) 15 (1.8%) 21 (1.5%) *Models adjusted for age, sex, and recruitment site. ANX: anxiety disorders; BZD: benzodiazepines; FGA: first-generation antipsychotics; MS: mood stabilizer (includes valproate, lamotrigine, carbamazepine, and lithium); SGA: second-generation antipsychotic; SNRI: serotonin-norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant. Lifetime treatment patterns mirrored these trends: individuals with BD + ANX show a trend toward lower use of lithium (51.3% vs. 57.9%, p = 0.030) and valproate (34.6% vs. 41.3%, p = 0.013) but were more likely to have received gabapentinoids (15.6% vs. 8.8%, p < 0.001), benzodiazepines (58.8% vs. 44.4%, p < 0.001), SSRIs (70.6% vs. 58.5%, p < 0.001), and SNRIs (40.1% vs. 30.5%, p = 0.002). They were also more likely to have been treated with antidepressants without a mood stabilizer (14.6% vs. 8.7%, p < 0.001). Pharmacotherapeutic differences among individuals with BD-I and ANX (n = 878) and those without ANX (n = 573) Among individuals with BD-I (ANX n = 878; No ANX n = 573), significant differences were observed in several pharmacotherapeutic variables ( Supplementary Table 1 , Fig. 2 ). Individuals with BD-I + ANX were less likely to be currently prescribed lithium (37.1% vs. 50.7%, p = 0.009), while valproic acid (22.4% vs. 31.2%, p = 0.137) and lamotrigine use (34.6% vs. 31.8%, p = 0.092) showed no statistically significant differences. There was a trend toward higher use of gabapentinoids (7.8% vs. 4.8%, p = 0.041) and significantly higher use of benzodiazepines (39.4% vs. 27.7%, p < 0.001). Olanzapine prescriptions trended lower among ANX individuals (9.4% vs. 16.9%, p = 0.023), while no significant differences were observed for carbamazepine, quetiapine, aripiprazole, risperidone, FGAs, or SGA overall. Regarding antidepressants, individuals with BD-I + ANX were more likely to be prescribed any antidepressant (48.8% vs. 37.0%, p < 0.001), two or more concurrent antidepressants (10.5% vs. 4.0%, p < 0.001), and SSRIs (26.5% vs. 15.5%, p < 0.001), and to receive antidepressants without a concomitant mood stabilizer (15.9% vs. 7.7%, p = 0.001). Thyroid hormone use was also lower among ANX individuals (17.2% vs. 27.2%, p = 0.014). Lifetime treatment patterns reflected similar trends: individuals with BD-I + ANX show a trend toward lower lithium use (54.6% vs. 61.9%, p = 0.035) and a trend toward higher use of gabapentinoids (15.6% vs. 9.0%, p = 0.015), benzodiazepines (59.2% vs. 46.7%, p < 0.001), SSRIs (70.9% vs. 56.6%, p < 0.001), and quetiapine (41.3% vs. 35.7%, p = 0.052), with only benzodiazepines and SSRIs reaching statistical significance. Pharmacotherapeutic differences among individuals with BD-II and ANX (n = 460) and those without ANX (n = 263) Among individuals with BD-II (ANX n = 460; No ANX n = 263), similar differences emerged in pharmacotherapy patterns ( Supplementary Table 2 , Fig. 2 ). Individuals with BD-II + ANX were more likely to receive gabapentinoids (9.5% vs. 3.5%, p = 0.005) and benzodiazepines (40.3% vs. 24.1%, p < 0.001) compared to those without ANX. They were also significantly more likely to be prescribed SSRIs (31.8% vs. 18.9%, p < 0.001) and any antidepressant (62.6% vs. 43.9%, p < 0.001), including antidepressants without a mood stabilizer (19.2% vs. 13.0%, p = 0.046). Current use of lamotrigine (51.4% vs. 46.6%, p = 0.313) and valproic acid (21.0% vs. 24.9%, p = 0.452) did not differ significantly, nor did prescriptions for carbamazepine, quetiapine, aripiprazole, risperidone, FGAs, or thyroid hormones. Lifetime treatment patterns reflected similar trends: individuals with BD-II + ANX show a trend toward higher gabapentinoids use (15.0% vs. 8.5%, p = 0.015), benzodiazepines (57.2% vs. 37.7%, p < 0.001), and SNRIs (48.2% vs. 35.2%, p = 0.002). There was a trend toward higher use of quetiapine (39.0% vs. 30.2%, p = 0.030) and overall SGAs (64.2% vs. 51.7%, p = 0.003). In contrast, lifetime lithium and valproate use showed no significant differences. Effect of Comorbid ANX on Pharmacological Treatment Response in BD Individuals with BD + ANX demonstrated lower treatment responses to lithium (4.91 vs. 6.05, p < 0.001), MSACs (5.16 vs. 6.01, p = 0.005), and SGAs (4.67 vs. 5.73, p < 0.001) compared to those with BD + NoANX, as measured by Alda A scores (Table 3 ). This pattern of reduced treatment response was evident in both BD-I and BD-II subtypes. However, the differences between groups were less pronounced in BD-II than in BD-I, and the bipolar II comparisons were further limited by smaller sample sizes. Table 3 Treatment responses of lithium, mood-stabilizing anticonvulsants (MSACs) and second-generation antipsychotics (SGAs), measured by Alda A scores, in individuals with bipolar disorder with and without comorbid anxiety (ANX). All* BD-I BD-II No ANX ANX p -value No ANX ANX p -value No ANX ANX p -value Lithium response (Alda-A) , n 289 404 < 0.001 218 300 0.004 66 92 0.183 Mean (SD) 6.05 (2.65) 4.91 (2.93) 6.28 (2.59) 5.07 (2.88) 5.21 (2.78) 4.39 (3.03) MSACs (Alda-A) , n 232 387 0.005 153 248 0.011 78 138 0.165 Mean (SD) 6.01 (2.56) 5.16 (2.59) 6.12 (2.46) 5.08 (2.53) 5.77 (2.76) 5.26 (2.67) SGAs (Alda-A) , n 230 309 < 0.001 131 257 0.002 46 100 0.080 Mean (SD) 5.73 (2.56) 4.67 (2.69) 5.87 (2.58) 4.69 (2.70) 5.48 (2.51) 4.65 (2.71) *Including BD-I, BD-II and schizoaffective (bipolar type). DISCUSSION This study represents one of the largest systematic examinations of the clinical, demographic, and pharmacotherapeutic differences between individuals with BD + ANX and BD + NoANX. Our findings reveal that anxiety comorbidity in BD is associated with a more complex clinical presentation, greater psychiatric and somatic burden, distinct prescribing patterns, and poorer treatment response to mood stabilizers. These observations have important implications for clinical management and highlight the need for tailored therapeutic approaches in this phenotypically distinct subgroup. Clinical and Demographic Characteristics Individuals with BD + ANX demonstrated a significantly more severe clinical profile compared to those of BD + NoANX. The higher prevalence of rapid cycling, suicide attempts, and multiple SUDs in the BD + ANX group suggests a more treatment-refractory illness course. Consistent with previous research showing that ANX emerge earlier and are more common in women (Simon et al., 2004 ; Vazquez et al., 2014 ), our BD + ANX group demonstrated younger age and female predominance. This pattern supports the hypothesis that anxiety may be an early predictor of bipolar disorder onset (McElroy et al., 2001 ). Our findings align with a prior systematic review showing greater SUD prevalence and poorer treatment response in individuals with BD and concurrent ANX (Vazquez et al., 2014 ). The association with a history of suicide attempts is consistent with data from the Systematic Treatment Enhancement Program for Bipolar Disorder (Simon et al., 2004 ), reinforcing that the anxiety phenotype reflects a more severe clinical profile. The substantially elevated rates of PTSD, BED, and OCD in the BD + ANX cohort further underscore the complex psychiatric burden characterizing this population. The familial aggregation patterns observed in our study are particularly noteworthy. Individuals with BD + ANX had significantly higher rates of family history across multiple psychiatric conditions, including BD, anxiety, depression, and alcohol use disorder. This suggests potential shared genetic vulnerabilities (Williams et al., 2024 )or environmental factors that predispose to both mood and anxiety pathology, consistent with emerging evidence of common neurobiological substrates underlying these disorders (Lopes et al., 2020 ; Maki et al., 2025 ). Both disorders share a core fronto-limbic network, characterized by overlapping amygdala hyperactivation and impaired prefrontal cortex regulation (Bi et al., 2022 ). The increased medical comorbidity burden, as reflected by higher MCIRS scores and elevated migraine prevalence in the BD + ANX group, aligns with the growing recognition that psychiatric comorbidity often parallels increased somatic illness (Romo-Nava et al., 2021 ). The substantially higher medication burden—both current and lifetime—in the anxiety comorbid group likely reflects both the greater clinical complexity and the challenges in achieving symptom control in this population (Feske et al., 2000 ). Pharmacotherapeutic Patterns and Implications A key finding of this study is the distinct pharmacotherapeutic patterns observed between individuals with and without comorbid anxiety. Individuals with BD + ANX were significantly less likely to receive lithium and valproic acid, medications with robust evidence for mood stabilization and suicide prevention in BD. Conversely, they were more likely to be prescribed monoaminergic antidepressants, including SSRIs and SNRIs, as well as adjunctive agents such as benzodiazepines and gabapentinoids. Our findings are consistent with prior reports showing higher rates of antidepressant prescriptions among individuals with BD + ANX (Galimberti et al., 2020 ; Keck et al., 2006 ; Vazquez et al., 2014 ). Notably, a substantial proportion of individuals with BD + ANX received one or more antidepressants without concurrent mood stabilizer coverage—a prescribing pattern that may increase the risk of affective instability, rapid cycling, and mood switching, particularly in BD-I. It remains unclear whether unimodal antidepressant use or lower rates of lithium and anticonvulsant mood stabilizer use confer greater risk, or whether anxiety comorbidity itself or associated substance use comorbidity drives illness severity measures such as cycle acceleration and mood switching (Altshuler et al., 1995 ). The lower utilization of lithium and valproate in the BD + ANX group may reflect multiple factors. Clinicians may avoid these agents due to concerns about tolerability, narrow therapeutic windows, or monitoring requirements in patients already managing complex medication regimens. The reduced valproate prescribing may also reflect growing safety concerns, particularly in women of childbearing potential due to teratogenic risks (Freeman, 2022 ) and, more recently, emerging recommendations in European guidelines to exercise caution even in men (Singh et al., 2025b ). Lamotrigine emerged as a notable exception, with slightly higher utilization in the BD + ANX group, particularly among those with BD-II. This pattern may reflect lamotrigine's favorable tolerability profile and its efficacy in preventing depressive episodes (Keck et al., 2006 ). The preference for antidepressants may stem from attempts to target depressive and anxious symptoms concurrently, despite limited evidence supporting antidepressant monotherapy in BD (Elmosalamy et al., 2025 ). The increased prescription of benzodiazepines and gabapentinoids likely represents symptomatic management of anxiety, though benzodiazepines carry risks of dependence and may not address underlying mood dysregulation. The relative safety of gabapentinoids, and their evidence base for use in GAD and SAD, without increasing the risk of affective switching, highlight their potential role in this specific phenotype (Frye and Singh, 2024 ; Rickels et al., 2005 ). The observation that individuals with BD + ANX received significantly more lifetime medications underscores the complexity of treating this difficult-to-treat population. Treatment Response and Clinical Outcomes Perhaps most clinically significant is the substantially poorer treatment response to mood stabilizers among individuals with BD + ANX, as measured by the Alda-A score. Mean response scores for lithium, MSACs, and SGAs were all significantly lower in the anxiety comorbid group across both BD subtypes, with the most pronounced differences in BD-I. These findings suggest anxiety comorbidity may represent a negative prognostic indicator associated with attenuated response to standard mood stabilizers. This finding aligns with previous research indicating that anxiety is a predictor of poor outcomes in BD (Feske et al., 2000 ; Gaudiano and Miller, 2005 ; Simon et al., 2004 ). This treatment resistance may reflect distinct neurobiological underpinnings—such as hyperactive fear circuitry, dysregulated stress response systems, or altered serotonergic, GABAergic, and dopaminergic neurotransmission—not adequately addressed by conventional mood stabilizers (Freeman et al., 2002 ). Additionally, chronic anxiety symptoms may perpetuate mood instability (Coryell et al., 2012 )through behavioral mechanisms including sleep disruption and substance use as self-medication. The BD + ANX group showed diminished lithium response, consistent with earlier reports of reduced efficacy in comorbid anxiety (Feske et al., 2000 ; Young et al., 1993 ), despite lithium's antisuicidal effects. A recent open-label trial suggests lithium may improve comorbid anxiety in bipolar disorder, with similar effects at low ( 0.5) doses, and improvements correlated with depressive symptoms (Jones et al., 2022 ). We lack lithium data and adherence information in our cohort, which should be addressed in future studies. However, randomized controlled trial evidence for this population remains limited (Kauer-Sant'Anna et al., 2009 ; Yatham et al., 2018 ). It is unclear whether anxiety comorbidity alters the neurobiology of BD, reducing lithium responsiveness, or whether factors such as suboptimal dosing, adherence challenges, or early discontinuation contribute. The cross-sectional design of this study limits causal conclusions, highlighting the need for future research using longitudinal treatment data and objective adherence measures. Subtype-Specific Considerations Subgroup analyses revealed shared and distinct patterns in BD-I and BD-II with comorbid anxiety. In both subtypes, anxiety was associated with increased antidepressant use, higher rates of benzodiazepine and gabapentinoid prescriptions, and reduced lithium utilization. However, several differences emerged. Among individuals with BD-I, anxiety comorbidity was associated with significantly lower olanzapine use and reduced thyroid hormone supplementation. In contrast, BD-II individuals with anxiety showed higher lifetime use of SGAs, particularly quetiapine, possibly reflecting its dual FDA indication for both BD depression and GAD. GAD was more prevalent in BD-II than BD-I, consistent with the depressive predominance of BD-II and the frequent co-occurrence of anxiety with depressive states. The particularly high rate of antidepressant monotherapy in BD-II individuals with anxiety (19.2% without mood stabilizer coverage) raises concerns about potential mood destabilization, even though the risk of treatment-emergent mania may be lower in BD-II than BD-I. Clinical and Research Implications The findings of this study have several important clinical implications. First, the presence of comorbid ANX should be recognized as a marker of illness severity and treatment complexity in BD. Clinicians should maintain heightened vigilance for suicide risk, substance use, and somatic comorbidities in this population, implementing comprehensive assessment and monitoring strategies. Second, the prevalent use of antidepressant monotherapy in the BD + ANX group—particularly without mood stabilizer coverage—warrants critical reconsideration. While anxiety symptoms are distressing and merit treatment, antidepressant monotherapy in BD carries risks of mood destabilization. Current clinical guidelines recommend mood stabilizer therapy as the foundation of BD treatment, with adjunctive agents added as needed for residual symptoms. Our data suggest this principle may be frequently overlooked in individuals with prominent anxiety, potentially contributing to the poorer outcomes observed in this group. Third, the reduced treatment response to standard mood stabilizers in BD + ANX highlights the need for alternative or augmentation strategies. Potential approaches might include psychotherapy (particularly cognitive-behavioral therapy with anxiety-specific modules), optimization of mood stabilizer dosing before adding additional agents, or investigation of novel pharmacological targets. Short term (8 weeks) data support quetiapine as a helpful option for BD + ANX (Hirschfeld et al., 2006 ; Sheehan et al., 2013 ). Limitations Several limitations of this study merit consideration. First, the cross-sectional design precludes causal inferences about the relationships between anxiety comorbidity, prescribing patterns, and treatment outcomes. Longitudinal studies tracking symptom trajectories and medication changes over time would provide more definitive insights. Second, anxiety diagnoses were determined at enrollment and may not reflect the full longitudinal course of anxiety symptoms, which can fluctuate with mood state. Third, our sample was predominantly recruited from U.S. sites and largely composed of white participants, with limited representation from Mexico and Chile, which may limit generalizability. Finally, we did not have detailed data on antidepressant treatment duration, dosing, or specific indications, which would help clarify whether these agents were prescribed primarily for anxiety, depression, or both. CONCLUSIONS This large-scale study highlights that 60% of individuals with bipolar disorder have comorbid anxiety, forming a clinically distinct subgroup with greater psychiatric and somatic complexity, unique pharmacotherapy patterns, and reduced response to standard mood stabilizers. Widespread antidepressant use—often without adequate mood stabilizer coverage—and high benzodiazepine use raise concerns about current prescribing practices. These findings emphasize the need for anxiety-informed treatment strategies, further research into neurobiological mechanisms of treatment resistance, and more intensive monitoring and tailored interventions for this high-risk population. Declarations Ethics approval and consent to participate Ethics approval for The Mayo Clinic Bipolar Disorder Biobank has been obtained from the Mayo Clinic Institutional Review Board (reference ID: 08-008794). Written informed consent was obtained from all participants. Consent for publication Not applicable. Competing Interests BS reports research grant support from Mayo Clinic, the National Network of Depression Centers, and Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2). He is a KL2 Mentored Career Development Program scholar, supported by CTSA Grant Number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS). He has received honoraria (to Mayo Clinic) from Elsevier for editing a Clinical Overview on Treatment-Resistant Depression. DJB reports research grant support from Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2).MAF received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories and American Physician Institute, and has Financial Interest/Stock ownership/Royalties from Chymia LLC. SLM is a consultant to, or member of the scientific advisory boards of, in the past year: Axsome, Idorsia, Levo, Kallyope, Novo Nordisk, Otsuka, and Soleno. SLM is presently or has been in the past year a principal or co-investigator on research studies sponsored by: Axsome, Idorsia, Marriott Foundation, National Institute of Mental Health, Novo Nordisk, and Otsuka. Patents: SLM is also inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and, along with the patent’s assignee, University of Cincinnati, Cincinnati, OH, has received payments from Johnson & Johnson Pharmaceutical Research & Development, L.L.C., which has exclusive rights under the patent. FRN is supported in part by NIMH grants K23MH120503 and 1R61MH133770-01A1; is the inventor on a U.S. Patent and Trademark Office patent # 10,857,356. MGR receives research support from Conahcyt CONAHCYT (Mexico). The rest of the co-authors have no conflict of interest to declare. CRediT authorship contribution statement: Balwinder Singh: Writing – review & editing, Writing – original draft, Visualization, Validation, Project administration, Methodology, Investigation, Data curation, Conceptualization. Ada Man-Choi Ho: Writing – original draft, Writing – review & editing, Investigation, Visualization, Validation, Conceptualization. Brandon J. Coombes: Writing – review & editing, Methodology, Formal analysis, Data curation. Richard Pendegraft: Methodology, Formal analysis, Data curation. Manuel Gardea-Resendez: Writing – review & editing, Methodology, Investigation. Aysegul Ozerdem: Writing – review & editing, Methodology, Investigation. David J. Bond: Writing – review & editing, Methodology, Investigation. Miguel L. Prieto: Writing – review & editing, Methodology, Investigation. Marin Veldic: Writing – review & editing, Methodology, Investigation. Susan L. McElroy: Writing – review & editing, Validation, Methodology. Joanna M. Biernacka: review & editing, Investigation, Funding acquisition. Aysegul Ozerdem: Writing – review & editing. Alfredo Cuellar-Barboza: Writing – review & editing, Methodology, Investigation. Francisco Romo-Nava: Writing – review & editing, Methodology, Investigation. Mark A. Frye: Writing – review & editing, Investigation, Funding acquisition. All authors contributed to reviewing and editing the manuscript. Declaration of AI-assisted technologies in the manuscript preparation process The authors disclose the use of Claude Sonnet 4.5 (Anthropic) only to assist with language editing and formatting. No AI tools were used for data analysis, interpretation, or content generation. All scientific content, analysis, and interpretation are the original work of the authors, who take full responsibility for all content accuracy. Funding The Mayo Clinic Bipolar Disorder Biobank was supported by the Marriott Foundation, and by the Thomas and Elizabeth Grainger Fund in Bipolar Functional Genomics and Drug Development. Project Generation was supported in part by Mayo Clinic Center for Individualized Medicine. This publication was supported by CTSA Grant Number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Author Contribution Balwinder Singh: Writing – review & editing, Writing – original draft, Visualization, Validation, Project administration, Methodology, Investigation, Data curation, Conceptualization.Ada Man-Choi Ho: Writing – original draft, Writing – review & editing, Investigation, Visualization, Validation, Conceptualization.Brandon J. Coombes: Writing – review & editing, Methodology, Formal analysis, Data curation.Richard Pendegraft: Methodology, Formal analysis, Data curation.Manuel Gardea-Resendez: Writing – review & editing, Methodology, Investigation.Aysegul Ozerdem: Writing – review & editing, Methodology, Investigation.David J. Bond: Writing – review & editing, Methodology, Investigation.Miguel L. Prieto: Writing – review & editing, Methodology, Investigation.Marin Veldic: Writing – review & editing, Methodology, Investigation.Susan L. McElroy: Writing – review & editing, Validation, Methodology.Joanna M. Biernacka: review & editing, Investigation, Funding acquisition.Aysegul Ozerdem: Writing – review & editing.Alfredo Cuellar-Barboza: Writing – review & editing, Methodology, Investigation.Francisco Romo-Nava: Writing – review & editing, Methodology, Investigation.Mark A. Frye: Writing – review & editing, Investigation, Funding acquisition.All authors contributed to reviewing and editing the manuscript. Acknowledgement We deeply thank the Mayo Clinic Bipolar Disorder Biobank participants for their time and generous contributions. Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. References Altshuler LL, Post RM, Leverich GS, Mikalauskas K, Rosoff A, Ackerman L. Antidepressant-induced mania and cycle acceleration: a controversy revisited. Am J Psychiatry. 1995;152:1130–8. https://doi.org/10.1176/ajp.152.8.1130 . Bi B, Che D, Bai Y. Neural network of bipolar disorder: Toward integration of neuroimaging and neurocircuit-based treatment strategies. Transl Psychiatry. 2022;12:143. https://doi.org/10.1038/s41398-022-01917-x . Burdick KE, Millett CE, Yocum AK, Altimus CM, Andreassen OA, Aubin V, Belzeaux R, Berk M, Biernacka JM, Blumberg HP, Cleare AJ, Diaz-Byrd C, Dubertret C, Etain B, Eyler LT, Forester BP, Fullerton JM, Frye MA, Gard S, Godin O, Haffen E, Klaus F, Lagerberg TV, Leboyer M, Martinez-Aran A, McElroy S, Mitchell PB, Olie E, Olorunfemi P, Passerieux C, Peters AT, Pham DL, Polosan M, Potter JR, Sajatovic M, Samalin L, Schwan R, Shanahan M, Sole B, Strawbridge R, Stuart AL, Torres I, Ueland T, Vieta E, Williams LJ, Wrobel AL, Yatham LN, Young AH, Nierenberg AA, McInnis MG. Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative. Bipolar Disord. 2022. https://doi.org/10.1111/bdi.13208 . Coryell W, Fiedorowicz JG, Solomon D, Leon AC, Rice JP, Keller MB. Effects of anxiety on the long-term course of depressive disorders. Br J Psychiatry. 2012;200:210–5. https://doi.org/10.1192/bjp.bp.110.081992 . Cuellar-Barboza AB, McElroy SL, Veldic M, Singh B, Kung S, Romo-Nava F, Nunez NA, Cabello-Arreola A, Coombes BJ, Prieto M, Betcher HK, Moore KM, Winham SJ, Biernacka JM, Frye MA. Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection. Int J Bipolar Disord. 2020;8:23. https://doi.org/10.1186/s40345-020-00184-3 . Cullen C, Kappelmann N, Umer M, Abdolizadeh A, Husain MO, Bonato S, Sharma G, Xue S, Ortiz A, Kloiber SM, Mulsant BH, Husain MI. Efficacy and acceptability of pharmacotherapy for comorbid anxiety symptoms in bipolar disorder: A systematic review and meta-analysis. Bipolar Disord. 2021;23:754–66. https://doi.org/10.1111/bdi.13125 . Elmosalamy A, Keeth N, Park JH, Gerberi DJ, McElroy SL, Frye MA, Singh B. Systematic Review of Second-Generation Antidepressant Monotherapy for Acute Bipolar-II Depression. Psychopharmacol Bull. 2025;55:79–103. https://doi.org/https://doi.org/10.64719/pb.4545 . Feske U, Frank E, Mallinger AG, Houck PR, Fagiolini A, Shear MK, Grochocinski VJ, Kupfer DJ. Anxiety as a correlate of response to the acute treatment of bipolar I disorder. Am J Psychiatry. 2000;157:956–62. https://doi.org/10.1176/appi.ajp.157.6.956 . Freeman MP. Prescribing Guideline for Valproic Acid and Women of Reproductive Potential: Forget It Exists. J Clin Psychiatry. 2022;83. https://doi.org/10.4088/JCP.22ed14609 . Freeman MP, Freeman SA, McElroy SL. The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues. J Affect Disord. 2002;68:1–23. https://doi.org/10.1016/s0165-0327(00)00299-8 . Frye MA, McElroy SL, Fuentes M, Sutor B, Schak KM, Galardy CW, Palmer BA, Prieto ML, Kung S, Sola CL, Ryu E, Veldic M, Geske J, Cuellar-Barboza A, Seymour LR, Mori N, Crowe S, Rummans TA, Biernacka JM. Development of a bipolar disorder biobank: differential phenotyping for subsequent biomarker analyses. Int J Bipolar Disord. 2015;3:30. https://doi.org/10.1186/s40345-015-0030-4 . Frye MA, Singh B. Other anticonvulsants: Pregabalin, gabapentin, and topiramate. In: Nemeroff CB, Craighead WE, editors. Anxiety and Depression Association of America patient guide to mood and anxiety disorders. Amer Psychiatric Pub Inc; 2024. pp. 275–80. Galimberti C, Caricasole V, Bosi MF, Vigano CA, Ketter TA, Dell'Osso B. Clinical features and patterns of psychopharmacological prescription in bipolar patients with vs without anxiety disorders at onset. Early Interv Psychiatry. 2020;14:714–22. https://doi.org/10.1111/eip.12900 . Gardea-Resendez M, Winham SJ, Romo-Nava F, Cuellar-Barboza A, Clark MM, Andreazza AC, Cabello-Arreola A, Veldic M, Bond DJ, Singh B, Prieto ML, Nunez NA, Betcher H, Moore KM, Blom T, Colby C, Pendegraft RS, Kelpin SS, Ozerdem A, Miola A, De Filippis E, Biernacka JM, McElroy SL, Frye MA. Quantification of diet quality utilizing the rapid eating assessment for participants-shortened version in bipolar disorder: Implications for prospective depression and cardiometabolic studies. J Affect Disord. 2022;310:150–5. https://doi.org/10.1016/j.jad.2022.05.037 . Gaudiano BA, Miller IW. Anxiety disorder comobidity in Bipolar I Disorder: relationship to depression severity and treatment outcome. Depress Anxiety. 2005;21:71–7. https://doi.org/10.1002/da.20053 . Grof P, Duffy A, Cavazzoni P, Grof E, Garnham J, MacDougall M, O'Donovan C, Alda M. Is response to prophylactic lithium a familial trait? J Clin Psychiatry. 2002;63:942–7. Hirschfeld RM, Weisler RH, Raines SR, Macfadden W, Group BS. Quetiapine in the treatment of anxiety in patients with bipolar I or II depression: a secondary analysis from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2006;67:355–62. https://doi.org/10.4088/jcp.v67n0304 . Ho AM, Coombes BJ, Nguyen TTL, Liu D, McElroy SL, Singh B, Nassan M, Colby CL, Larrabee BR, Weinshilboum RM, Frye MA, Biernacka JM. Mood-Stabilizing Antiepileptic Treatment Response in Bipolar Disorder: A Genome-Wide Association Study. Clin Pharmacol Ther. 2020;108:1233–42. https://doi.org/10.1002/cpt.1982 . Jones G, Rong C, Vecera CM, Gurguis CI, Chudal R, Khairova R, Leung E, Ruiz AC, Shahani L, Zanetti MV, de Sousa RT, Busatto G, Soares J, Gattaz WF, Machado-Vieira R. The role of lithium treatment on comorbid anxiety symptoms in patients with bipolar depression. J Affect Disord. 2022;308:71–5. https://doi.org/10.1016/j.jad.2022.04.025 . Joseph B, Nunez NA, Pazdernik V, Kumar R, Pahwa M, Ercis M, Ozerdem A, Cuellar-Barboza AB, Romo-Nava F, McElroy SL, Coombes BJ, Biernacka JM, Stan MN, Frye MA, Singh B. Long-Term Lithium Therapy and Thyroid Disorders in Bipolar Disorder: A Historical Cohort Study. Brain Sci. 2023;13. https://doi.org/10.3390/brainsci13010133 . Kauer-Sant'Anna M, Kapczinski F, Vieta E. Epidemiology and management of anxiety in patients with bipolar disorder. CNS Drugs. 2009;23:953–64. https://doi.org/10.2165/11310850-000000000-00000 . Keck PE Jr., Strawn JR, McElroy SL. Pharmacologic treatment considerations in co-occurring bipolar and anxiety disorders. J Clin Psychiatry. 2006;67(Suppl 1):8–15. Kinrys G, Bowden CL, Nierenberg AA, Hearing CM, Gold AK, Rabideau DJ, Sylvia LG, Gao K, Kamali M, Bobo WV, Tohen M, Deckersbach T, McElroy SL, Ketter TA, Shelton RC, Friedman ES, Calabrese JR, McInnis MG, Kocsis J, Thase ME, Singh V, Reilly-Harrington NA. Comorbid anxiety in bipolar CHOICE: Insights from the bipolar inventory of symptoms scale. J Affect Disord. 2019;246:126–31. https://doi.org/10.1016/j.jad.2018.12.039 . Lopes FL, Zhu K, Purves KL, Song C, Ahn K, Hou L, Akula N, Kassem L, Bergen SE, Landen M, Veras AB, Nardi AE, Study BG, McMahon C, F.J. Polygenic risk for anxiety influences anxiety comorbidity and suicidal behavior in bipolar disorder. Transl Psychiatry. 2020;10:298. https://doi.org/10.1038/s41398-020-00981-5 . Maki H, Sakai N, Kataoka M, Fujii K, Kageyama Y, Hayama T, Matsuo K, Nishioka M, Kato T. Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent-of-origin effect. PCN Rep. 2025;4:e70071. https://doi.org/10.1002/pcn5.70071 . McElroy SL, Altshuler LL, Suppes T, Keck PE Jr., Frye MA, Denicoff KD, Nolen WA, Kupka RW, Leverich GS, Rochussen JR, Rush AJ, Post RM. Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder. Am J Psychiatry. 2001;158:420–6. https://doi.org/10.1176/appi.ajp.158.3.420 . McIntyre RS, Soczynska JK, Bottas A, Bordbar K, Konarski JZ, Kennedy SH. Anxiety disorders and bipolar disorder: a review. Bipolar Disord. 2006;8:665–76. https://doi.org/10.1111/j.1399-5618.2006.00355.x . Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, Kessler RC. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007;64:543–52. https://doi.org/10.1001/archpsyc.64.5.543 . Mitchell PB, Johnston AK, Frankland A, Slade T, Green MJ, Roberts G, Wright A, Corry J, Hadzi-Pavlovic D. Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms. Acta Psychiatr Scand. 2013;127:381–93. https://doi.org/10.1111/acps.12005 . Pahwa M, Joseph B, Nunez NA, Jenkins GD, Colby CL, Kashani KB, Marin V, Moore KM, Betcher HK, Ozerdem A, Cuellar-Barboza AB, McElroy SL, Biernacka JM, Frye MA, Singh B. Long-term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study. Bipolar Disord. 2021a;23:715–23. https://doi.org/10.1111/bdi.13052 . Pahwa M, Joseph B, Nunez NA, Jenkins GD, Colby CL, Kashani KB, Marin V, Moore KM, Betcher HK, Ozerdem A, Cuellar-Barboza AB, McElroy SL, Biernacka JM, Frye MA, Singh B. 2021b. Long-term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study. Bipolar Disord. https://doi.org/10.1111/bdi.13052 Park JH, Nunez NA, Gardea-Resendez M, Gerberi DJ, Breitinger S, Veldic M, Frye MA, Singh B. Short Term Second-Generation Antidepressant Monotherapy in Acute Depressive Episodes of Bipolar II Disorder: A Systematic Review and Meta-Analysis. Psychopharmacol Bull. 2022;52:45–72. Pavlova B, Perlis RH, Alda M, Uher R. Lifetime prevalence of anxiety disorders in people with bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry. 2015;2:710–7. https://doi.org/10.1016/S2215-0366(15)00112-1 . Rickels K, Pollack MH, Feltner DE, Lydiard RB, Zimbroff DL, Bielski RJ, Tobias K, Brock JD, Zornberg GL, Pande AC. Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry. 2005;62:1022–30. https://doi.org/10.1001/archpsyc.62.9.1022 . Romo-Nava F, Blom T, Cuellar-Barboza AB, Awosika OO, Martens BE, Mori NN, Colby CL, Prieto ML, Veldic M, Singh B, Gardea-Resendez M, Nunez NA, Ozerdem A, Biernacka JM, Frye MA, McElroy SL. Revisiting the bipolar disorder with migraine phenotype: Clinical features and comorbidity. J Affect Disord. 2021;295:156–62. https://doi.org/10.1016/j.jad.2021.08.026 . Salvi F, Miller MD, Grilli A, Giorgi R, Towers AL, Morichi V, Spazzafumo L, Mancinelli L, Espinosa E, Rappelli A, Dessi-Fulgheri P. A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients. J Am Geriatr Soc. 2008;56:1926–31. https://doi.org/10.1111/j.1532-5415.2008.01935.x . Schaffer A, McIntosh D, Goldstein BI, Rector NA, McIntyre RS, Beaulieu S, Swinson R, Yatham LN, Canadian Network for, Task MAT. F., 2012. The CANMAT task force recommendations for the management of patients with mood disorders and comorbid anxiety disorders. Ann Clin Psychiatry. 24, 6–22. Sheehan DV, Harnett-Sheehan K, Hidalgo RB, Janavs J, McElroy SL, Amado D, Suppes T. Randomized, placebo-controlled trial of quetiapine XR and divalproex ER monotherapies in the treatment of the anxious bipolar patient. J Affect Disord. 2013;145:83–94. https://doi.org/10.1016/j.jad.2012.07.016 . Simon NM, Otto MW, Wisniewski SR, Fossey M, Sagduyu K, Frank E, Sachs GS, Nierenberg AA, Thase ME, Pollack MH. Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry. 2004;161:2222–9. https://doi.org/10.1176/appi.ajp.161.12.2222 . Singh B, Ho AM, Coombes BJ, Romo-Nava F, Bond DJ, Veldic M, Pendegraft RS, Batzler A, Cuellar-Barboza AB, Gardea-Resendez M, Prieto ML, Ozerdem A, McElroy SL, Biernacka JM, Frye MA. Antipsychotic use in bipolar disorder: clinical and genomic correlates- a Mayo clinic bipolar disorder biobank study. Int J Bipolar Disord. 2025a. https://doi.org/10.1186/s40345-025-00405-7 . Singh B, Swartz HA, Cuellar-Barboza AB, Schaffer A, Kato T, Dols A, Sperry SH, Vassilev AB, Burdick KE, Frye MA. Bipolar disorder Lancet. 2025b;406:963–78. https://doi.org/10.1016/S0140-6736(25)01140-7 . Singh B, Yocum AK, Strawbridge R, Burdick KE, Millett CE, Peters AT, Sperry SH, Fico G, Vieta E, Verdolini N, Godin O, Leboyer M, Etain B, Tso IF, Coombes BJ, McInnis MG, Nierenberg AA, Young AH, Ashton MM, Berk M, Williams LJ, Keramatian K, Yatham LN, Overs BJ, Fullerton JM, Roberts G, Mitchell PB, Andreassen OA, Andreazza AC, Zandi PP, Pham D, Biernacka JM, Frye MA, Collaborators F-B. T.G.B.C.C., 2024. Patterns of pharmacotherapy for bipolar disorder: A GBC survey. Bipolar Disord. 26, 22–32. https://doi.org/10.1111/bdi.13366 Smith JP, Book SW. Anxiety and Substance Use Disorders: A Review. Psychiatr Times. 2008;25:19–23. Vazquez GH, Baldessarini RJ, Tondo L. Co-occurrence of anxiety and bipolar disorders: clinical and therapeutic overview. Depress Anxiety. 2014;31:196–206. https://doi.org/10.1002/da.22248 . Williams CM, Peyre H, Wolfram T, Lee YH, Seidlitz J, Ge T, Smoller JW, Mallard TT, Ramus F. Characterizing the phenotypic and genetic structure of psychopathology in UK Biobank. Nat Ment Health. 2024;2:960–74. https://doi.org/10.1038/s44220-024-00272-8 . Yapici Eser H, Kacar AS, Kilciksiz CM, Yalcinay-Inan M, Ongur D. Prevalence and Associated Features of Anxiety Disorder Comorbidity in Bipolar Disorder: A Meta-Analysis and Meta-Regression Study. Front Psychiatry. 2018;9:229. https://doi.org/10.3389/fpsyt.2018.00229 . Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, Sharma V, Goldstein BI, Rej S, Beaulieu S, Alda M, MacQueen G, Milev RV, Ravindran A, O'Donovan C, McIntosh D, Lam RW, Vazquez G, Kapczinski F, McIntyre RS, Kozicky J, Kanba S, Lafer B, Suppes T, Calabrese JR, Vieta E, Malhi G, Post RM, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20:97–170. https://doi.org/10.1111/bdi.12609 . Yocum AK, Singh B. Global Trends in the Use of Pharmacotherapy for the Treatment of Bipolar Disorder. Curr psychiatry Rep. 2025;27:239–47. https://doi.org/10.1007/s11920-025-01606-8 . Young LT, Cooke RG, Robb JC, Levitt AJ, Joffe RT. Anxious and non-anxious bipolar disorder. J Affect Disord. 1993;29:49–52. https://doi.org/10.1016/0165-0327(93)90118-4 . Additional Declarations Competing interest reported. BS reports research grant support from Mayo Clinic, the National Network of Depression Centers, and Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2). He is a KL2 Mentored Career Development Program scholar, supported by CTSA Grant Number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS). He has received honoraria (to Mayo Clinic) from Elsevier for editing a Clinical Overview on Treatment-Resistant Depression. DJB reports research grant support from Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2). MAF received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories and American Physician Institute, and has Financial Interest/Stock ownership/Royalties from Chymia LLC. SLM is a consultant to, or member of the scientific advisory boards of, in the past year: Axsome, Idorsia, Levo, Kallyope, Novo Nordisk, Otsuka, and Soleno. SLM is presently or has been in the past year a principal or co-investigator on research studies sponsored by: Axsome, Idorsia, Marriott Foundation, National Institute of Mental Health, Novo Nordisk, and Otsuka. Patents: SLM is also inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and, along with the patent’s assignee, University of Cincinnati, Cincinnati, OH, has received payments from Johnson & Johnson Pharmaceutical Research & Development, L.L.C., which has exclusive rights under the patent. FRN is supported in part by NIMH grants K23MH120503 and 1R61MH133770-01A1; is the inventor on a U.S. Patent and Trademark Office patent # 10,857,356. MGR receives research support from Conahcyt CONAHCYT (Mexico). The rest of the co-authors have no conflict of interest to declare. 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05:41:03","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":298638,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8503080/v1/102227bde281b008f5293442.html"},{"id":100006591,"identity":"a05262e2-f385-4a94-87b6-fd3bb361c99e","added_by":"auto","created_at":"2026-01-12 05:41:02","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":281889,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of Anxiety Disorders, PTSD, and OCD in Bipolar I and Bipolar II disorders. GAD: generalized anxiety disorder; OCD: obsessive-compulsive disorder; PTSD: post-traumatic stress disorder; SAD: social anxiety disorder. *\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8503080/v1/02511e83362ac62f49ee4fe4.jpeg"},{"id":100360753,"identity":"303e4789-2560-4522-acea-ff822cde017d","added_by":"auto","created_at":"2026-01-16 07:41:38","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":630830,"visible":true,"origin":"","legend":"\u003cp\u003eCurrent and lifetime pharmacotherapeutic prescribing patterns among individuals with bipolar disorder, with and without comorbid anxiety (ANX), by Bipolar I and Bipolar II subtypes. Benzo: benzodiazepines; CBZ: carbamazepine; FGA: first-generation antipsychotics; SGA: second-generation antipsychotics; SNRI: serotonin-norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressants.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8503080/v1/5f76fb504fbd0d803115fa36.jpeg"},{"id":103765569,"identity":"acd83a4b-650f-4f50-9518-e7a005e67c56","added_by":"auto","created_at":"2026-03-02 16:04:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3733019,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8503080/v1/d20066d5-ecfd-4cd3-9db4-a1e8146f1998.pdf"},{"id":100006587,"identity":"ee383753-a25a-4bc7-98a9-c293abeedafe","added_by":"auto","created_at":"2026-01-12 05:41:02","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":47113,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-8503080/v1/b605f8aed7748a0361f62206.docx"}],"financialInterests":"Competing interest reported. BS reports research grant support from Mayo Clinic, the National Network of Depression Centers, and Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2). He is a KL2 Mentored Career Development Program scholar, supported by CTSA Grant Number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS). He has received honoraria (to Mayo Clinic) from Elsevier for editing a Clinical Overview on Treatment-Resistant Depression. \nDJB reports research grant support from Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2).\nMAF received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories and American Physician Institute, and has Financial Interest/Stock ownership/Royalties from Chymia LLC. \nSLM is a consultant to, or member of the scientific advisory boards of, in the past year: Axsome, Idorsia, Levo, Kallyope, Novo Nordisk, Otsuka, and Soleno. SLM is presently or has been in the past year a principal or co-investigator on research studies sponsored by: Axsome, Idorsia, Marriott Foundation, National Institute of Mental Health, Novo Nordisk, and Otsuka. Patents: SLM is also inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and, along with the patent’s assignee, University of Cincinnati, Cincinnati, OH, has received payments from Johnson \u0026 Johnson Pharmaceutical Research \u0026 Development, L.L.C., which has exclusive rights under the patent. \nFRN is supported in part by NIMH grants K23MH120503 and 1R61MH133770-01A1; is the inventor on a U.S. Patent and Trademark Office patent # 10,857,356. \nMGR receives research support from Conahcyt CONAHCYT (Mexico). \nThe rest of the co-authors have no conflict of interest to declare.","formattedTitle":"The Anxious Bipolar Phenotype: Clinical Complexity and Treatment Resistance","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eA significant challenge in effectively managing bipolar disorder (BD) is the high prevalence of comorbidities, particularly anxiety disorders (ANX) (Pavlova et al., \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Singh et al., \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), with clinical estimates up to 60% (Kinrys et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; McIntyre et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Pavlova et al., \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Singh et al., \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2025b\u003c/span\u003e). Those with ANX are at increased risk for developing substance use disorders (SUD) and frequently self-medicate with alcohol (Smith and Book, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). Previous research has indicated that BD with comorbid ANX (BD\u0026thinsp;+\u0026thinsp;ANX) correlates with substantial functional impairment, risk for suicidality, and poor quality of life (Burdick et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Simon et al., \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2004\u003c/span\u003e). A recent systematic review reported the current prevalence of ANX in BD at approximately 38%, with generalized anxiety disorder (GAD) being the most common subtype (Yapici Eser et al., \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Although some studies suggest the lifetime risk of ANX may be as high as 60\u0026ndash;85% (Merikangas et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Mitchell et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2013\u003c/span\u003e), there remains a lack of consistent data on prevalence rates across bipolar I and bipolar II subtypes, as well as on associated clinical outcomes (Cullen et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Galimberti et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Kauer-Sant'Anna et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Keck et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Kinrys et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Schaffer et al., \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Vazquez et al., \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). There is a paucity of recent data examining pharmacotherapeutic approaches and treatment response differences among bipolar individuals with (BD\u0026thinsp;+\u0026thinsp;ANX) and without lifetime anxiety (BD\u0026thinsp;+\u0026thinsp;NoANX).\u003c/p\u003e \u003cp\u003eA critical discussion within the field of BD concerns the prescription rates of monoaminergic antidepressants (Elmosalamy et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Park et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), which may vary between 30\u0026ndash;70%, depending on the region and study populations (Singh et al., \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Yocum and Singh, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Evidence suggests that individuals with ANX are frequently prescribed monoaminergic antidepressants (Yatham et al., \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2018\u003c/span\u003e), which may increase the risk of affective switching in BD. This raises the question of whether pharmacotherapy patterns differ between individuals with BD\u0026thinsp;+\u0026thinsp;ANX and BD\u0026thinsp;+\u0026thinsp;NoANX, with the former typically receiving higher rates of antidepressant prescriptions (Keck et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). Understanding these prescribing trends can inform clinical practices and contribute to strategies aimed at enhancing treatment outcomes in future research.\u003c/p\u003e \u003cp\u003eRecent data from the Global Bipolar Cohort Collaboration showed prevalence rates of comorbid ANX as high as 60% in the North American cohorts compared to 30% in the European cohorts (Singh et al., \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). We also observed regional variations in prescription patterns; however, data regarding the BD\u0026thinsp;+\u0026thinsp;ANX phenotype were not available. Leveraging data from the Mayo Clinic Bipolar Disorder Bank, this study examined the differences in clinical and demographic characteristics as well as pharmacotherapeutic prescription patterns among individuals with BD\u0026thinsp;+\u0026thinsp;ANX and BD\u0026thinsp;+\u0026thinsp;NoANX. Furthermore, we analyzed prescription patterns among individuals with bipolar I (BD-I) and bipolar II disorder (BD-II) with and without ANX, as those with BD-II tend to be prescribed more monoaminergic antidepressants (Singh et al., \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eDetailed information about the Mayo Clinic Bipolar Disorder Biobank has been previously published (Frye et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). In summary, cross-sectional data was collected from study participants at enrollment (Gardea-Resendez et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Pahwa et al., 2021b). Participants were recruited from five sites: Mayo Clinic, Rochester, Minnesota; Lindner Center of HOPE/University of Cincinnati College of Medicine, Cincinnati, Ohio; University of Minnesota, Minneapolis, Minnesota; Universidad Aut\u0026oacute;noma de Nuevo Le\u0026oacute;n, Mexico; and Universidad de los Andes, Chile. The inclusion criteria consisted of adults aged 18\u0026ndash;80 with BD who spoke English at the U.S. sites and Spanish at Mexico and Chile sites, provided informed consent, and met DSM-IV-TR criteria for BD-I/BD-II or schizoaffective BD. Participants exhibiting active psychosis or suicidal ideation were excluded.\u003c/p\u003e \u003cp\u003eAt the time of study enrollment, data were collected on demographics, family history, psychiatric conditions (including adult and childhood attention deficit hyperactivity disorder [ADHD], anorexia nervosa, bulimia nervosa, binge eating disorder (BED), GAD, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD), medications, and somatic comorbidities. For this study, GAD, panic disorder, SAD, and phobias were categorized under the ANX category. Since most ANX persist as psychiatric diagnoses throughout an individual's life, our study concentrated on lifetime ANX diagnoses. The overall burden of medical illness was measured using the Modified Cumulative Illness Rating Scale (MCIRS) (Salvi et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2008\u003c/span\u003e), with psychiatric comorbidity data excluded. Data for additional somatic comorbidities were extracted using structured surveys.\u003c/p\u003e \u003cp\u003eWe collected data on current and lifetime prescriptions for second-generation antipsychotics (SGAs) and mood stabilizers, including lithium and mood-stabilizing anticonvulsants (MSACs) such as valproate, carbamazepine, and lamotrigine. Additional data were obtained for first-generation antipsychotics (FGAs), monoaminergic antidepressants\u0026mdash;including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs)\u0026mdash;as well as benzodiazepines, gabapentinoids (gabapentin or pregabalin), stimulants, wakefulness-promoting agents, and dopamine agonists. We examined patterns of polypharmacotherapy, defined as the concurrent use of two or more SGAs or mood stabilizers, and assessed the frequency of monoaminergic antidepressant prescriptions without a concurrent mood stabilizer.\u003c/p\u003e \u003cp\u003eTreatment response to lithium, SGAs, and MSACs was assessed using the Alda-A score from the Alda Scale (Grof et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). The Alda-A score measures clinical improvement in illness severity during the treatment, rated from 0 (no improvement or worsening) to 10 (full recovery or absence of symptoms). Although initially developed to retrospectively measure response to lithium, it has been modified to assess response to other mood stabilizers in previous studies (Cuellar-Barboza et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Ho et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Joseph et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Pahwa et al., \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2021a\u003c/span\u003e; Singh et al., \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2025a\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eClinical and demographic characteristics were compared between participants with and without a lifetime anxiety diagnosis (BD\u0026thinsp;+\u0026thinsp;ANX and BD\u0026thinsp;+\u0026thinsp;NoANX, respectively) using the \u003cem\u003earsenal\u003c/em\u003e package in R. The \u003cem\u003emodelsum\u003c/em\u003e function was applied to perform multiple univariate tests, using linear models for continuous variables and logistic models for categorical variables. All models were adjusted for age, sex, and recruitment site (Mayo Clinic, Lindner Center of HOPE, University of Minnesota, Chile, or Mexico). Given the large number of comparisons, a threshold of \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 was used to define statistical significance. Analyses were conducted using R version 4.2.2.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe study cohort consisted of 2,225 adults with BD (1,451 BD-I, 723 BD-II, 51 schizoaffective disorder BD). The mean age was 41.6 years; 62.1% were female, 84.0% White, and 12.4% Hispanic (\u003cb\u003eTable-1\u003c/b\u003e). Rapid cycling was prevalent in 57.1% of individuals, with a history of psychosis in 39.6%, and 38.1% had early onset of BD.\u003c/p\u003e \u003cp\u003eNinety percent of ANX data came from the US, with the rest from Mexico and Chile. Overall, 61.4% (n\u0026thinsp;=\u0026thinsp;1366) had ANX, with similar rates in BD-I (66.7%) and BD-II (64.3%). Among individuals with BD-I and BD-II, the most common ANX was GAD (50%), followed by panic disorder (30.3%), SAD (21.8%), and phobias (9.6%). There is a trend toward a higher prevalence of GAD in BD-II compared to BD-I (54.0% vs. 47.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021), while rates of other ANX disorders were similar across BD subtypes (\u003cb\u003eFigure-1\u003c/b\u003e).\u003c/p\u003e\n\u003ch3\u003eComparison of individuals with BD + ANX (n = 1366) and BD + NoANX (n = 859)\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the comparisons of demographic and clinical characteristics between individuals with BD\u0026thinsp;+\u0026thinsp;ANX and BD\u0026thinsp;+\u0026thinsp;NoANX, adjusted for age, sex, and recruitment site. Individuals with BD\u0026thinsp;+\u0026thinsp;ANX were younger (mean age 40.4 vs. 43.6 years, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and more likely female (66.6% vs. 54.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to those with BD\u0026thinsp;+\u0026thinsp;NoANX. They exhibited higher rates of rapid cycling (64.2% vs. 45.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), BED (12.3% vs. 7.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), PTSD (34.6% vs. 12.6%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), OCD (21.3% vs. 8.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and SUDs (63.5% vs. 54.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Suicidal attempts (40.4% vs. 24.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), tobacco use disorder (43.1% vs. 35.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), cocaine use disorder (16.6% vs. 10.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), alcohol use disorder (42.3% vs. 36.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), cannabis use disorder (33.3% vs. 24.4%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), methamphetamine use disorder (10.4% vs. 7.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), and opioid use disorder (12.8% vs. 6.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were more prevalent in individuals with BD\u0026thinsp;+\u0026thinsp;ANX. A family history of BD (51.5% vs. 40.3%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), anxiety (68.5% vs. 49.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), depression (84.8% vs. 72.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and alcohol use disorder (54.0% vs. 40.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) was also more common. Individuals with BD\u0026thinsp;+\u0026thinsp;ANX had higher MCIRS scores (6.68 vs. 5.42, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), more migraines (36.8% vs. 18.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and more current (2.86 vs. 2.50, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and lifetime use of psychotropics (7.27 vs. 5.74, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparisons of demographic and clinical characteristics between individuals with BD, with and without ANX, adjusted for age, sex, and recruitment site.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2225)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo ANX\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;859)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eANX\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1366)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSite of recruitment\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e859\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMayo, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1154 (51.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e495 (57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e659 (48.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLindner, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e770 (34.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e219 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e551 (40.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUniversity of Minnesota, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChile, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMexico, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e151 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e86 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e856\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1363\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.6 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.6 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.4 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e859\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1366\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e844 (37.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e388 (45.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e456 (33.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1381 (62.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e471 (54.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e910 (66.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRace\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2191\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e840\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1351\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1840 (84.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e705 (83.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1135 (84.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (1.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e97 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiracial, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHispanic\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e271 (12.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody mass index\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e818\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.9 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.4 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.2 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.094\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrently married\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2201\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1353\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e997 (45.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e403 (47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e594 (43.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.821\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEmployment\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e809\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1297\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFull-time, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e544 (25.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e226 (27.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e318 (24.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePart-time, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e401 (19.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e170 (21.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e231 (17.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot working for pay at present, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1161 (55.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e413 (51.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e748 (57.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEducation\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e814\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school or less, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.271\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school graduated, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e284 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97 (11.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e187 (14.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeyond high school graduation, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1789 (83.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e691 (84.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1098 (83.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eBipolar Disorder Characteristics\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBipolar type\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e859\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1366\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBipolar I, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1451 (65.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e573 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e878 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBipolar II, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e723 (32.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e263 (30.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e460 (33.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSchizoaffective, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRapid cycling\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2083\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1189 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e354 (45.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e835 (64.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of psychosis\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e874 (39.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e352 (41.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e522 (38.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.302\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eManic psychosis\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e693 (31.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e301 (35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e392 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEarly onset (\u0026le;\u0026thinsp;19 years old)\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2094\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e791\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e797 (38.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e275 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e522 (40.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuicide attempt\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1357\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e760 (34.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e212 (24.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e548 (40.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuicide attempt (\u0026le;\u0026thinsp;19 years old)\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e571\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e256 (44.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (42.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e190 (45.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eLifetime Psychiatric Illness History\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChild ADHD\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e853\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e347 (15.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e237 (17.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnorexia or bulimia\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e857\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1343\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBinge eating disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e855\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1347\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e270 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e206 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePost-traumatic stress disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e855\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1347\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e574 (26.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108 (12.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e466 (34.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eObsessive compulsive disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2196\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e857\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1339\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e358 (16.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e285 (21.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eLifetime Substance Use Disorder\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSubstance use disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e836\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1283 (60.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e458 (54.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e825 (63.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTobacco use disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e880 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e300 (35.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e580 (43.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlcohol use disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e856\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1351\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e879 (39.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e308 (36.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e571 (42.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCocaine use disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2193\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e313 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (10.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e223 (16.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCannabis use disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e855\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1350\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e658 (29.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e209 (24.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e449 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMethamphetamine use disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e855\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (7.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e140 (10.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOpioid use disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e230 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e171 (12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eFamily History (First-degree Relatives)\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBipolar disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1692\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e648\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e799 (47.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e261 (40.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e538 (51.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnxiety\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e722\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e426\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e439 (60.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e147 (49.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e292 (68.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDepression\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1877\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e707\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1505 (80.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e513 (72.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e992 (84.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlcohol use disorder\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1894\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e721\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e928 (49.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e294 (40.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e634 (54.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuicide\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1873\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e721\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e167 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e112 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMCIRS\u003c/b\u003e, \u003cb\u003emean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.191 (6.570)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.421 (6.207)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.676 (6.746)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedical comorbidities\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e758\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e446\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78 (17.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.522\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMusculoskeletal, integumentary, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.707\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEczema, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.275\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsoriasis, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.721\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitiligo, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.390\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCOS, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyroid, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e135 (17.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (19.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 (16.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.734\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRheum arthritis, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibromyalgia, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (7.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.882\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpilepsy, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (6.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstructive sleep apnea, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (11.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.666\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMigraines, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e223 (29.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (18.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e164 (36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOsteoporosis, \u003cem\u003en (\u003c/em\u003e%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (4.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOsteoarthritis, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (12.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (9.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66 (14.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eObese\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e818\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e888 (41.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e317 (38.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e571 (43.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent psychotropics\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1362\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.723 (1.581)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.502 (1.469)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.861 (1.632)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLifetime psychotropics\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1362\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.681 (5.456)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.737 (4.765)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.273 (5.772)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntidepressant-induced mania\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e672\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.207\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e384 (20.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e266 (22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTardive dyskinesia\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e729\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e436\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (9.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Not adjusted for age, sex, and site of recruitment.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003ePharmacotherapeutic differences among individuals with BD + ANX (n = 1366) and BD + NoANX (n = 859)\u003c/h3\u003e\n\u003cp\u003eIndividuals with BD\u0026thinsp;+\u0026thinsp;ANX (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1366) differed significantly from those with BD\u0026thinsp;+\u0026thinsp;NoANX (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;859) across multiple pharmacotherapeutic variables (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Individuals with BD\u0026thinsp;+\u0026thinsp;ANX were less likely to be currently prescribed lithium (37.1% vs. 47.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) and showed a trend towards lower valproic acid use (21.7% vs. 29.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047), but more likely to receive gabapentinoids (8.5% vs. 4.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and benzodiazepines (39.9% vs. 26.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). They were also significantly more likely to receive antidepressant treatment (53.8% vs. 39.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), including two or more concurrent antidepressants (13.0% vs. 6.9%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), particularly SSRIs (28.8% vs. 16.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and to be prescribed antidepressants without a concomitant mood stabilizer (17.3% vs. 9.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Olanzapine prescriptions were lower among BD\u0026thinsp;+\u0026thinsp;ANX individuals (8.0% vs. 14.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008), while there was a trend toward slightly higher lamotrigine use (39.7% vs. 35.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027). No significant differences were observed for carbamazepine, quetiapine, FGAs, thyroid hormones, stimulants, or dopamine agonists.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDifferences in pharmacotherapeutic prescriptions among individuals with bipolar disorder, with and without comorbid anxiety (ANX).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2225)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo ANX\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;859)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eANX\u003c/p\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1366)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCurrent Prescriptions\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLithium\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1516\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e579\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e937\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e625 (41.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e277 (47.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e348 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLamotrigine\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e628\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1072\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e651 (38.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e225 (35.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e426 (39.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eValproic acid\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1638\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e631\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e406 (24.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e187 (29.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e219 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCarbamazepine\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1543\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e578\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e965\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.807\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGabapentinoids\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1350\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153 (7.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBenzodiazepines\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1985\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e693 (34.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e198 (26.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e495 (39.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-BZD sedatives\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e740\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1234\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.387\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e154 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (7.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSGA\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.635\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1110 (53.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e418 (52.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e692 (53.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOlanzapine\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1544\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e601\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e943\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e159 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (14.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClozapine\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1514\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e585\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.740\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eQuetiapine\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e620\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e461 (28.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e171 (27.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e290 (28.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAripiprazole\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1566\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e599\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e967\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.353\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e250 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (14.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e166 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRisperidone\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1551\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e597\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e954\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.735\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80 (8.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFGA\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1583\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e602\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e981\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.388\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAny antidepressants\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1018 (48.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e309 (39.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e709 (53.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTwo or more antidepressants\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e226 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e172 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSSRI\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e772\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e506 (24.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130 (16.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e376 (28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSNRI\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1764\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e656\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.254\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e228 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (11.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e151 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCA\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1894\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e684\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntidepressant without MS\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e828\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e311 (14.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e231 (17.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThyroid hormone\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e431\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e754\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e262 (22.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113 (26.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e149 (19.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStimulants/wakefulness agents\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1675\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1065\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.939\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e199 (11.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (11.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132 (12.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDopamine agonist\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1684\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e618\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.769\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTwo or more SGA\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.430\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOne or more MS\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1503 (69.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e617 (74.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e886 (66.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTwo or more MSs\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.597\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e220 (10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 (10.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e133 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThree or more MSs\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.957\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo MS\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e662 (30.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e216 (25.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e446 (33.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo medications\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1362\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.762\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e183 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLifetime Prescriptions\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLithium ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e717\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1159\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1009 (53.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e415 (57.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e594 (51.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLamotrigine ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e781\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1282\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e880 (42.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e310 (39.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e570 (44.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eValproate ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2071\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e769 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e323 (41.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e446 (34.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGabapentinoids ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1350\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e286 (13.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e211 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBenzodiazepines ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1985\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1060 (53.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e330 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e730 (58.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFGA ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1583\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e602\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e981\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.897\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e163 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (11.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e97 (9.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSGA ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1457 (69.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e534 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e923 (71.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOlanzapine ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e788\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e374 (18.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e171 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e203 (16.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eQuetiapine ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e788\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e787 (38.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e274 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e513 (40.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAripiprazole ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.386\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e543 (26.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e178 (22.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e365 (29.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRisperidone ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e789\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1256\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.773\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e419 (20.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e153 (19.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e266 (21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAny antidepressant ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1710 (81.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e590 (75.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1120 (84.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSSRI ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e772\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1373 (66.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e452 (58.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e921 (70.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSNRI ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1764\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e656\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e644 (36.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200 (30.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e444 (40.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCA ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1894\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e684\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e350 (18.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e245 (20.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntidepressant without MS ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e831\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e267 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e195 (14.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThyroid hormone ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e431\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e754\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.300\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120 (10.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStimulants/wakefulness agents ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1675\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1065\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e432 (25.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e303 (28.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDopamine agonist ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1684\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e618\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.736\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTwo or more SGAs ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.866\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e640 (30.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e229 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e411 (31.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOne or more MS ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1799 (83.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e714 (85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1085 (81.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTwo or more MSs ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.873\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e721 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e279 (33.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e442 (33.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThree or more MSs ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.415\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e249 (11.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101 (12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e148 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo MS ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e833\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e366 (16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e247 (18.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo medications ever, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1362\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.827\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e*Models adjusted for age, sex, and recruitment site.\u003c/p\u003e \u003cp\u003eANX: anxiety disorders; BZD: benzodiazepines; FGA: first-generation antipsychotics; MS: mood stabilizer (includes valproate, lamotrigine, carbamazepine, and lithium); SGA: second-generation antipsychotic; SNRI: serotonin-norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLifetime treatment patterns mirrored these trends: individuals with BD\u0026thinsp;+\u0026thinsp;ANX show a trend toward lower use of lithium (51.3% vs. 57.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030) and valproate (34.6% vs. 41.3%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013) but were more likely to have received gabapentinoids (15.6% vs. 8.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), benzodiazepines (58.8% vs. 44.4%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), SSRIs (70.6% vs. 58.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and SNRIs (40.1% vs. 30.5%, p\u0026thinsp;=\u0026thinsp;0.002). They were also more likely to have been treated with antidepressants without a mood stabilizer (14.6% vs. 8.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003ch3\u003ePharmacotherapeutic differences among individuals with BD-I and ANX (n = 878) and those without ANX (n = 573)\u003c/h3\u003e\n\u003cp\u003eAmong individuals with BD-I (ANX \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;878; No ANX \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;573), significant differences were observed in several pharmacotherapeutic variables (\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Individuals with BD-I\u0026thinsp;+\u0026thinsp;ANX were less likely to be currently prescribed lithium (37.1% vs. 50.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009), while valproic acid (22.4% vs. 31.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.137) and lamotrigine use (34.6% vs. 31.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.092) showed no statistically significant differences. There was a trend toward higher use of gabapentinoids (7.8% vs. 4.8%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041) and significantly higher use of benzodiazepines (39.4% vs. 27.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Olanzapine prescriptions trended lower among ANX individuals (9.4% vs. 16.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023), while no significant differences were observed for carbamazepine, quetiapine, aripiprazole, risperidone, FGAs, or SGA overall. Regarding antidepressants, individuals with BD-I\u0026thinsp;+\u0026thinsp;ANX were more likely to be prescribed any antidepressant (48.8% vs. 37.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), two or more concurrent antidepressants (10.5% vs. 4.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and SSRIs (26.5% vs. 15.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and to receive antidepressants without a concomitant mood stabilizer (15.9% vs. 7.7%, p\u0026thinsp;=\u0026thinsp;0.001). Thyroid hormone use was also lower among ANX individuals (17.2% vs. 27.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014).\u003c/p\u003e \u003cp\u003eLifetime treatment patterns reflected similar trends: individuals with BD-I\u0026thinsp;+\u0026thinsp;ANX show a trend toward lower lithium use (54.6% vs. 61.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035) and a trend toward higher use of gabapentinoids (15.6% vs. 9.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015), benzodiazepines (59.2% vs. 46.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), SSRIs (70.9% vs. 56.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and quetiapine (41.3% vs. 35.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.052), with only benzodiazepines and SSRIs reaching statistical significance.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePharmacotherapeutic differences among individuals with BD-II and ANX (n\u0026thinsp;=\u0026thinsp;460) and those without ANX (n\u0026thinsp;=\u0026thinsp;263)\u003c/h2\u003e \u003cp\u003eAmong individuals with BD-II (ANX \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;460; No ANX \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;263), similar differences emerged in pharmacotherapy patterns (\u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Individuals with BD-II\u0026thinsp;+\u0026thinsp;ANX were more likely to receive gabapentinoids (9.5% vs. 3.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) and benzodiazepines (40.3% vs. 24.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to those without ANX. They were also significantly more likely to be prescribed SSRIs (31.8% vs. 18.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and any antidepressant (62.6% vs. 43.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), including antidepressants without a mood stabilizer (19.2% vs. 13.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.046). Current use of lamotrigine (51.4% vs. 46.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.313) and valproic acid (21.0% vs. 24.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.452) did not differ significantly, nor did prescriptions for carbamazepine, quetiapine, aripiprazole, risperidone, FGAs, or thyroid hormones.\u003c/p\u003e \u003cp\u003eLifetime treatment patterns reflected similar trends: individuals with BD-II\u0026thinsp;+\u0026thinsp;ANX show a trend toward higher gabapentinoids use (15.0% vs. 8.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015), benzodiazepines (57.2% vs. 37.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and SNRIs (48.2% vs. 35.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). There was a trend toward higher use of quetiapine (39.0% vs. 30.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030) and overall SGAs (64.2% vs. 51.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003). In contrast, lifetime lithium and valproate use showed no significant differences.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEffect of Comorbid ANX on Pharmacological Treatment Response in BD\u003c/h3\u003e\n\u003cp\u003eIndividuals with BD\u0026thinsp;+\u0026thinsp;ANX demonstrated lower treatment responses to lithium (4.91 vs. 6.05, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), MSACs (5.16 vs. 6.01, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005), and SGAs (4.67 vs. 5.73, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to those with BD\u0026thinsp;+\u0026thinsp;NoANX, as measured by Alda A scores (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This pattern of reduced treatment response was evident in both BD-I and BD-II subtypes. However, the differences between groups were less pronounced in BD-II than in BD-I, and the bipolar II comparisons were further limited by smaller sample sizes.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment responses of lithium, mood-stabilizing anticonvulsants (MSACs) and second-generation antipsychotics (SGAs), measured by Alda A scores, in individuals with bipolar disorder with and without comorbid anxiety (ANX).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eAll*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eBD-I\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003eBD-II\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo ANX\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eANX\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo ANX\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eANX\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo ANX\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eANX\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLithium response (Alda-A)\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e404\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.05 (2.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.91 (2.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.28 (2.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.07 (2.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.21 (2.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4.39 (3.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMSACs (Alda-A)\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e248\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.01 (2.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.16 (2.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.12 (2.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.08 (2.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.77 (2.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5.26 (2.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSGAs (Alda-A)\u003c/b\u003e, \u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e309\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.73 (2.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.67 (2.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.87 (2.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.69 (2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.48 (2.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e4.65 (2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003e*Including BD-I, BD-II and schizoaffective (bipolar type).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study represents one of the largest systematic examinations of the clinical, demographic, and pharmacotherapeutic differences between individuals with BD\u0026thinsp;+\u0026thinsp;ANX and BD\u0026thinsp;+\u0026thinsp;NoANX. Our findings reveal that anxiety comorbidity in BD is associated with a more complex clinical presentation, greater psychiatric and somatic burden, distinct prescribing patterns, and poorer treatment response to mood stabilizers. These observations have important implications for clinical management and highlight the need for tailored therapeutic approaches in this phenotypically distinct subgroup.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinical and Demographic Characteristics\u003c/h2\u003e \u003cp\u003eIndividuals with BD\u0026thinsp;+\u0026thinsp;ANX demonstrated a significantly more severe clinical profile compared to those of BD\u0026thinsp;+\u0026thinsp;NoANX. The higher prevalence of rapid cycling, suicide attempts, and multiple SUDs in the BD\u0026thinsp;+\u0026thinsp;ANX group suggests a more treatment-refractory illness course. Consistent with previous research showing that ANX emerge earlier and are more common in women (Simon et al., \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2004\u003c/span\u003e; Vazquez et al., \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2014\u003c/span\u003e), our BD\u0026thinsp;+\u0026thinsp;ANX group demonstrated younger age and female predominance. This pattern supports the hypothesis that anxiety may be an early predictor of bipolar disorder onset (McElroy et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). Our findings align with a prior systematic review showing greater SUD prevalence and poorer treatment response in individuals with BD and concurrent ANX (Vazquez et al., \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). The association with a history of suicide attempts is consistent with data from the Systematic Treatment Enhancement Program for Bipolar Disorder (Simon et al., \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2004\u003c/span\u003e), reinforcing that the anxiety phenotype reflects a more severe clinical profile. The substantially elevated rates of PTSD, BED, and OCD in the BD\u0026thinsp;+\u0026thinsp;ANX cohort further underscore the complex psychiatric burden characterizing this population.\u003c/p\u003e \u003cp\u003eThe familial aggregation patterns observed in our study are particularly noteworthy. Individuals with BD\u0026thinsp;+\u0026thinsp;ANX had significantly higher rates of family history across multiple psychiatric conditions, including BD, anxiety, depression, and alcohol use disorder. This suggests potential shared genetic vulnerabilities (Williams et al., \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2024\u003c/span\u003e)or environmental factors that predispose to both mood and anxiety pathology, consistent with emerging evidence of common neurobiological substrates underlying these disorders (Lopes et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Maki et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Both disorders share a core fronto-limbic network, characterized by overlapping amygdala hyperactivation and impaired prefrontal cortex regulation (Bi et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe increased medical comorbidity burden, as reflected by higher MCIRS scores and elevated migraine prevalence in the BD\u0026thinsp;+\u0026thinsp;ANX group, aligns with the growing recognition that psychiatric comorbidity often parallels increased somatic illness (Romo-Nava et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). The substantially higher medication burden\u0026mdash;both current and lifetime\u0026mdash;in the anxiety comorbid group likely reflects both the greater clinical complexity and the challenges in achieving symptom control in this population (Feske et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2000\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePharmacotherapeutic Patterns and Implications\u003c/h2\u003e \u003cp\u003eA key finding of this study is the distinct pharmacotherapeutic patterns observed between individuals with and without comorbid anxiety. Individuals with BD\u0026thinsp;+\u0026thinsp;ANX were significantly less likely to receive lithium and valproic acid, medications with robust evidence for mood stabilization and suicide prevention in BD. Conversely, they were more likely to be prescribed monoaminergic antidepressants, including SSRIs and SNRIs, as well as adjunctive agents such as benzodiazepines and gabapentinoids. Our findings are consistent with prior reports showing higher rates of antidepressant prescriptions among individuals with BD\u0026thinsp;+\u0026thinsp;ANX (Galimberti et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Keck et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Vazquez et al., \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Notably, a substantial proportion of individuals with BD\u0026thinsp;+\u0026thinsp;ANX received one or more antidepressants without concurrent mood stabilizer coverage\u0026mdash;a prescribing pattern that may increase the risk of affective instability, rapid cycling, and mood switching, particularly in BD-I. It remains unclear whether unimodal antidepressant use or lower rates of lithium and anticonvulsant mood stabilizer use confer greater risk, or whether anxiety comorbidity itself or associated substance use comorbidity drives illness severity measures such as cycle acceleration and mood switching (Altshuler et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1995\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe lower utilization of lithium and valproate in the BD\u0026thinsp;+\u0026thinsp;ANX group may reflect multiple factors. Clinicians may avoid these agents due to concerns about tolerability, narrow therapeutic windows, or monitoring requirements in patients already managing complex medication regimens. The reduced valproate prescribing may also reflect growing safety concerns, particularly in women of childbearing potential due to teratogenic risks (Freeman, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) and, more recently, emerging recommendations in European guidelines to exercise caution even in men (Singh et al., \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2025b\u003c/span\u003e). Lamotrigine emerged as a notable exception, with slightly higher utilization in the BD\u0026thinsp;+\u0026thinsp;ANX group, particularly among those with BD-II. This pattern may reflect lamotrigine's favorable tolerability profile and its efficacy in preventing depressive episodes (Keck et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). The preference for antidepressants may stem from attempts to target depressive and anxious symptoms concurrently, despite limited evidence supporting antidepressant monotherapy in BD (Elmosalamy et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). The increased prescription of benzodiazepines and gabapentinoids likely represents symptomatic management of anxiety, though benzodiazepines carry risks of dependence and may not address underlying mood dysregulation. The relative safety of gabapentinoids, and their evidence base for use in GAD and SAD, without increasing the risk of affective switching, highlight their potential role in this specific phenotype (Frye and Singh, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Rickels et al., \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). The observation that individuals with BD\u0026thinsp;+\u0026thinsp;ANX received significantly more lifetime medications underscores the complexity of treating this difficult-to-treat population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eTreatment Response and Clinical Outcomes\u003c/h2\u003e \u003cp\u003ePerhaps most clinically significant is the substantially poorer treatment response to mood stabilizers among individuals with BD\u0026thinsp;+\u0026thinsp;ANX, as measured by the Alda-A score. Mean response scores for lithium, MSACs, and SGAs were all significantly lower in the anxiety comorbid group across both BD subtypes, with the most pronounced differences in BD-I. These findings suggest anxiety comorbidity may represent a negative prognostic indicator associated with attenuated response to standard mood stabilizers. This finding aligns with previous research indicating that anxiety is a predictor of poor outcomes in BD (Feske et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2000\u003c/span\u003e; Gaudiano and Miller, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2005\u003c/span\u003e; Simon et al., \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2004\u003c/span\u003e). This treatment resistance may reflect distinct neurobiological underpinnings\u0026mdash;such as hyperactive fear circuitry, dysregulated stress response systems, or altered serotonergic, GABAergic, and dopaminergic neurotransmission\u0026mdash;not adequately addressed by conventional mood stabilizers (Freeman et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). Additionally, chronic anxiety symptoms may perpetuate mood instability (Coryell et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2012\u003c/span\u003e)through behavioral mechanisms including sleep disruption and substance use as self-medication.\u003c/p\u003e \u003cp\u003eThe BD\u0026thinsp;+\u0026thinsp;ANX group showed diminished lithium response, consistent with earlier reports of reduced efficacy in comorbid anxiety (Feske et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2000\u003c/span\u003e; Young et al., \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e1993\u003c/span\u003e), despite lithium's antisuicidal effects. A recent open-label trial suggests lithium may improve comorbid anxiety in bipolar disorder, with similar effects at low (\u0026lt;\u0026thinsp;0.5) and high (\u0026gt;\u0026thinsp;0.5) doses, and improvements correlated with depressive symptoms (Jones et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). We lack lithium data and adherence information in our cohort, which should be addressed in future studies. However, randomized controlled trial evidence for this population remains limited (Kauer-Sant'Anna et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Yatham et al., \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). It is unclear whether anxiety comorbidity alters the neurobiology of BD, reducing lithium responsiveness, or whether factors such as suboptimal dosing, adherence challenges, or early discontinuation contribute. The cross-sectional design of this study limits causal conclusions, highlighting the need for future research using longitudinal treatment data and objective adherence measures.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSubtype-Specific Considerations\u003c/h2\u003e \u003cp\u003eSubgroup analyses revealed shared and distinct patterns in BD-I and BD-II with comorbid anxiety. In both subtypes, anxiety was associated with increased antidepressant use, higher rates of benzodiazepine and gabapentinoid prescriptions, and reduced lithium utilization. However, several differences emerged. Among individuals with BD-I, anxiety comorbidity was associated with significantly lower olanzapine use and reduced thyroid hormone supplementation. In contrast, BD-II individuals with anxiety showed higher lifetime use of SGAs, particularly quetiapine, possibly reflecting its dual FDA indication for both BD depression and GAD.\u003c/p\u003e \u003cp\u003eGAD was more prevalent in BD-II than BD-I, consistent with the depressive predominance of BD-II and the frequent co-occurrence of anxiety with depressive states. The particularly high rate of antidepressant monotherapy in BD-II individuals with anxiety (19.2% without mood stabilizer coverage) raises concerns about potential mood destabilization, even though the risk of treatment-emergent mania may be lower in BD-II than BD-I.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eClinical and Research Implications\u003c/h2\u003e \u003cp\u003eThe findings of this study have several important clinical implications. First, the presence of comorbid ANX should be recognized as a marker of illness severity and treatment complexity in BD. Clinicians should maintain heightened vigilance for suicide risk, substance use, and somatic comorbidities in this population, implementing comprehensive assessment and monitoring strategies. Second, the prevalent use of antidepressant monotherapy in the BD\u0026thinsp;+\u0026thinsp;ANX group\u0026mdash;particularly without mood stabilizer coverage\u0026mdash;warrants critical reconsideration. While anxiety symptoms are distressing and merit treatment, antidepressant monotherapy in BD carries risks of mood destabilization. Current clinical guidelines recommend mood stabilizer therapy as the foundation of BD treatment, with adjunctive agents added as needed for residual symptoms. Our data suggest this principle may be frequently overlooked in individuals with prominent anxiety, potentially contributing to the poorer outcomes observed in this group. Third, the reduced treatment response to standard mood stabilizers in BD\u0026thinsp;+\u0026thinsp;ANX highlights the need for alternative or augmentation strategies. Potential approaches might include psychotherapy (particularly cognitive-behavioral therapy with anxiety-specific modules), optimization of mood stabilizer dosing before adding additional agents, or investigation of novel pharmacological targets. Short term (8 weeks) data support quetiapine as a helpful option for BD\u0026thinsp;+\u0026thinsp;ANX (Hirschfeld et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Sheehan et al., \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2013\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eSeveral limitations of this study merit consideration. First, the cross-sectional design precludes causal inferences about the relationships between anxiety comorbidity, prescribing patterns, and treatment outcomes. Longitudinal studies tracking symptom trajectories and medication changes over time would provide more definitive insights. Second, anxiety diagnoses were determined at enrollment and may not reflect the full longitudinal course of anxiety symptoms, which can fluctuate with mood state. Third, our sample was predominantly recruited from U.S. sites and largely composed of white participants, with limited representation from Mexico and Chile, which may limit generalizability. Finally, we did not have detailed data on antidepressant treatment duration, dosing, or specific indications, which would help clarify whether these agents were prescribed primarily for anxiety, depression, or both.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis large-scale study highlights that 60% of individuals with bipolar disorder have comorbid anxiety, forming a clinically distinct subgroup with greater psychiatric and somatic complexity, unique pharmacotherapy patterns, and reduced response to standard mood stabilizers. Widespread antidepressant use\u0026mdash;often without adequate mood stabilizer coverage\u0026mdash;and high benzodiazepine use raise concerns about current prescribing practices. These findings emphasize the need for anxiety-informed treatment strategies, further research into neurobiological mechanisms of treatment resistance, and more intensive monitoring and tailored interventions for this high-risk population.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e Ethics approval for The Mayo Clinic Bipolar Disorder Biobank has been obtained from the Mayo Clinic Institutional Review Board (reference ID: 08-008794). Written informed consent was obtained from all participants.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eCompeting Interests\u003c/h2\u003e\u003cp\u003eBS reports research grant support from Mayo Clinic, the National Network of Depression Centers, and Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2). He is a KL2 Mentored Career Development Program scholar, supported by CTSA Grant Number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS). He has received honoraria (to Mayo Clinic) from Elsevier for editing a Clinical Overview on Treatment-Resistant Depression. DJB reports research grant support from Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2).MAF received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories and American Physician Institute, and has Financial Interest/Stock ownership/Royalties from Chymia LLC. SLM is a consultant to, or member of the scientific advisory boards of, in the past year: Axsome, Idorsia, Levo, Kallyope, Novo Nordisk, Otsuka, and Soleno. SLM is presently or has been in the past year a principal or co-investigator on research studies sponsored by: Axsome, Idorsia, Marriott Foundation, National Institute of Mental Health, Novo Nordisk, and Otsuka. Patents: SLM is also inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and, along with the patent\u0026rsquo;s assignee, University of Cincinnati, Cincinnati, OH, has received payments from Johnson \u0026amp; Johnson Pharmaceutical Research \u0026amp; Development, L.L.C., which has exclusive rights under the patent. FRN is supported in part by NIMH grants K23MH120503 and 1R61MH133770-01A1; is the inventor on a U.S. Patent and Trademark Office patent # 10,857,356. MGR receives research support from Conahcyt CONAHCYT (Mexico). The rest of the co-authors have no conflict of interest to declare.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e \u003ch2\u003eCRediT authorship contribution statement:\u003c/h2\u003e \u003cp\u003eBalwinder Singh: Writing \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft, Visualization, Validation, Project administration, Methodology, Investigation, Data curation, Conceptualization.\u003c/p\u003e \u003cp\u003eAda Man-Choi Ho: Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing, Investigation, Visualization, Validation, Conceptualization.\u003c/p\u003e \u003cp\u003eBrandon J. Coombes: Writing \u0026ndash; review \u0026amp; editing, Methodology, Formal analysis, Data curation.\u003c/p\u003e \u003cp\u003eRichard Pendegraft: Methodology, Formal analysis, Data curation.\u003c/p\u003e \u003cp\u003eManuel Gardea-Resendez: Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.\u003c/p\u003e \u003cp\u003eAysegul Ozerdem: Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.\u003c/p\u003e \u003cp\u003eDavid J. Bond: Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.\u003c/p\u003e \u003cp\u003eMiguel L. Prieto: Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.\u003c/p\u003e \u003cp\u003eMarin Veldic: Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.\u003c/p\u003e \u003cp\u003eSusan L. McElroy: Writing \u0026ndash; review \u0026amp; editing, Validation, Methodology.\u003c/p\u003e \u003cp\u003eJoanna M. Biernacka: review \u0026amp; editing, Investigation, Funding acquisition.\u003c/p\u003e \u003cp\u003eAysegul Ozerdem: Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e \u003cp\u003eAlfredo Cuellar-Barboza: Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.\u003c/p\u003e \u003cp\u003eFrancisco Romo-Nava: Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.\u003c/p\u003e \u003cp\u003eMark A. Frye: Writing \u0026ndash; review \u0026amp; editing, Investigation, Funding acquisition.\u003c/p\u003e \u003cp\u003e All authors contributed to reviewing and editing the manuscript.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eDeclaration of AI-assisted technologies in the manuscript preparation process\u003c/h2\u003e \u003cp\u003eThe authors disclose the use of Claude Sonnet 4.5 (Anthropic) only to assist with language editing and formatting. No AI tools were used for data analysis, interpretation, or content generation. All scientific content, analysis, and interpretation are the original work of the authors, who take full responsibility for all content accuracy.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe Mayo Clinic Bipolar Disorder Biobank was supported by the Marriott Foundation, and by the Thomas and Elizabeth Grainger Fund in Bipolar Functional Genomics and Drug Development. Project Generation was supported in part by Mayo Clinic Center for Individualized Medicine. This publication was supported by CTSA Grant Number KL2 TR002379 from the National Center for Advancing Translational Science (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.\u003c/p\u003e \u003cp\u003eThe funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eBalwinder Singh:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft, Visualization, Validation, Project administration, Methodology, Investigation, Data curation, Conceptualization.Ada Man-Choi Ho:\u0026nbsp;Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing, Investigation, Visualization, Validation, Conceptualization.Brandon J. Coombes:\u0026nbsp; Writing \u0026ndash; review \u0026amp; editing, Methodology, Formal analysis, Data curation.Richard Pendegraft:\u0026nbsp;Methodology, Formal analysis, Data curation.Manuel Gardea-Resendez:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.Aysegul Ozerdem:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.David J. Bond:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.Miguel L. Prieto:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.Marin Veldic:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.Susan L. McElroy:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Validation, Methodology.Joanna M. Biernacka:\u0026nbsp;review \u0026amp; editing, Investigation, Funding acquisition.Aysegul Ozerdem:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing.Alfredo Cuellar-Barboza:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.Francisco Romo-Nava:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Methodology, Investigation.Mark A. Frye:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Investigation, Funding acquisition.All authors contributed to reviewing and editing the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe deeply thank the Mayo Clinic Bipolar Disorder Biobank participants for their time and generous contributions.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAltshuler LL, Post RM, Leverich GS, Mikalauskas K, Rosoff A, Ackerman L. Antidepressant-induced mania and cycle acceleration: a controversy revisited. Am J Psychiatry. 1995;152:1130\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1176/ajp.152.8.1130\u003c/span\u003e\u003cspan address=\"10.1176/ajp.152.8.1130\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBi B, Che D, Bai Y. Neural network of bipolar disorder: Toward integration of neuroimaging and neurocircuit-based treatment strategies. Transl Psychiatry. 2022;12:143. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41398-022-01917-x\u003c/span\u003e\u003cspan address=\"10.1038/s41398-022-01917-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurdick KE, Millett CE, Yocum AK, Altimus CM, Andreassen OA, Aubin V, Belzeaux R, Berk M, Biernacka JM, Blumberg HP, Cleare AJ, Diaz-Byrd C, Dubertret C, Etain B, Eyler LT, Forester BP, Fullerton JM, Frye MA, Gard S, Godin O, Haffen E, Klaus F, Lagerberg TV, Leboyer M, Martinez-Aran A, McElroy S, Mitchell PB, Olie E, Olorunfemi P, Passerieux C, Peters AT, Pham DL, Polosan M, Potter JR, Sajatovic M, Samalin L, Schwan R, Shanahan M, Sole B, Strawbridge R, Stuart AL, Torres I, Ueland T, Vieta E, Williams LJ, Wrobel AL, Yatham LN, Young AH, Nierenberg AA, McInnis MG. Predictors of functional impairment in bipolar disorder: Results from 13 cohorts from seven countries by the global bipolar cohort collaborative. Bipolar Disord. 2022. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/bdi.13208\u003c/span\u003e\u003cspan address=\"10.1111/bdi.13208\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoryell W, Fiedorowicz JG, Solomon D, Leon AC, Rice JP, Keller MB. Effects of anxiety on the long-term course of depressive disorders. Br J Psychiatry. 2012;200:210\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1192/bjp.bp.110.081992\u003c/span\u003e\u003cspan address=\"10.1192/bjp.bp.110.081992\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCuellar-Barboza AB, McElroy SL, Veldic M, Singh B, Kung S, Romo-Nava F, Nunez NA, Cabello-Arreola A, Coombes BJ, Prieto M, Betcher HK, Moore KM, Winham SJ, Biernacka JM, Frye MA. Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection. Int J Bipolar Disord. 2020;8:23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s40345-020-00184-3\u003c/span\u003e\u003cspan address=\"10.1186/s40345-020-00184-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCullen C, Kappelmann N, Umer M, Abdolizadeh A, Husain MO, Bonato S, Sharma G, Xue S, Ortiz A, Kloiber SM, Mulsant BH, Husain MI. Efficacy and acceptability of pharmacotherapy for comorbid anxiety symptoms in bipolar disorder: A systematic review and meta-analysis. Bipolar Disord. 2021;23:754\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/bdi.13125\u003c/span\u003e\u003cspan address=\"10.1111/bdi.13125\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElmosalamy A, Keeth N, Park JH, Gerberi DJ, McElroy SL, Frye MA, Singh B. Systematic Review of Second-Generation Antidepressant Monotherapy for Acute Bipolar-II Depression. Psychopharmacol Bull. 2025;55:79\u0026ndash;103. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/https://doi.org/10.64719/pb.4545\u003c/span\u003e\u003cspan address=\"10.64719/pb.4545\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeske U, Frank E, Mallinger AG, Houck PR, Fagiolini A, Shear MK, Grochocinski VJ, Kupfer DJ. Anxiety as a correlate of response to the acute treatment of bipolar I disorder. Am J Psychiatry. 2000;157:956\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1176/appi.ajp.157.6.956\u003c/span\u003e\u003cspan address=\"10.1176/appi.ajp.157.6.956\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreeman MP. Prescribing Guideline for Valproic Acid and Women of Reproductive Potential: Forget It Exists. J Clin Psychiatry. 2022;83. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4088/JCP.22ed14609\u003c/span\u003e\u003cspan address=\"10.4088/JCP.22ed14609\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreeman MP, Freeman SA, McElroy SL. The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues. J Affect Disord. 2002;68:1\u0026ndash;23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0165-0327(00)00299-8\u003c/span\u003e\u003cspan address=\"10.1016/s0165-0327(00)00299-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrye MA, McElroy SL, Fuentes M, Sutor B, Schak KM, Galardy CW, Palmer BA, Prieto ML, Kung S, Sola CL, Ryu E, Veldic M, Geske J, Cuellar-Barboza A, Seymour LR, Mori N, Crowe S, Rummans TA, Biernacka JM. Development of a bipolar disorder biobank: differential phenotyping for subsequent biomarker analyses. Int J Bipolar Disord. 2015;3:30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s40345-015-0030-4\u003c/span\u003e\u003cspan address=\"10.1186/s40345-015-0030-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrye MA, Singh B. Other anticonvulsants: Pregabalin, gabapentin, and topiramate. In: Nemeroff CB, Craighead WE, editors. Anxiety and Depression Association of America patient guide to mood and anxiety disorders. Amer Psychiatric Pub Inc; 2024. pp. 275\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalimberti C, Caricasole V, Bosi MF, Vigano CA, Ketter TA, Dell'Osso B. Clinical features and patterns of psychopharmacological prescription in bipolar patients with vs without anxiety disorders at onset. Early Interv Psychiatry. 2020;14:714\u0026ndash;22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/eip.12900\u003c/span\u003e\u003cspan address=\"10.1111/eip.12900\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGardea-Resendez M, Winham SJ, Romo-Nava F, Cuellar-Barboza A, Clark MM, Andreazza AC, Cabello-Arreola A, Veldic M, Bond DJ, Singh B, Prieto ML, Nunez NA, Betcher H, Moore KM, Blom T, Colby C, Pendegraft RS, Kelpin SS, Ozerdem A, Miola A, De Filippis E, Biernacka JM, McElroy SL, Frye MA. Quantification of diet quality utilizing the rapid eating assessment for participants-shortened version in bipolar disorder: Implications for prospective depression and cardiometabolic studies. J Affect Disord. 2022;310:150\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jad.2022.05.037\u003c/span\u003e\u003cspan address=\"10.1016/j.jad.2022.05.037\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGaudiano BA, Miller IW. Anxiety disorder comobidity in Bipolar I Disorder: relationship to depression severity and treatment outcome. Depress Anxiety. 2005;21:71\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/da.20053\u003c/span\u003e\u003cspan address=\"10.1002/da.20053\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrof P, Duffy A, Cavazzoni P, Grof E, Garnham J, MacDougall M, O'Donovan C, Alda M. Is response to prophylactic lithium a familial trait? J Clin Psychiatry. 2002;63:942\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirschfeld RM, Weisler RH, Raines SR, Macfadden W, Group BS. Quetiapine in the treatment of anxiety in patients with bipolar I or II depression: a secondary analysis from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2006;67:355\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4088/jcp.v67n0304\u003c/span\u003e\u003cspan address=\"10.4088/jcp.v67n0304\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHo AM, Coombes BJ, Nguyen TTL, Liu D, McElroy SL, Singh B, Nassan M, Colby CL, Larrabee BR, Weinshilboum RM, Frye MA, Biernacka JM. Mood-Stabilizing Antiepileptic Treatment Response in Bipolar Disorder: A Genome-Wide Association Study. Clin Pharmacol Ther. 2020;108:1233\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/cpt.1982\u003c/span\u003e\u003cspan address=\"10.1002/cpt.1982\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJones G, Rong C, Vecera CM, Gurguis CI, Chudal R, Khairova R, Leung E, Ruiz AC, Shahani L, Zanetti MV, de Sousa RT, Busatto G, Soares J, Gattaz WF, Machado-Vieira R. The role of lithium treatment on comorbid anxiety symptoms in patients with bipolar depression. J Affect Disord. 2022;308:71\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jad.2022.04.025\u003c/span\u003e\u003cspan address=\"10.1016/j.jad.2022.04.025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoseph B, Nunez NA, Pazdernik V, Kumar R, Pahwa M, Ercis M, Ozerdem A, Cuellar-Barboza AB, Romo-Nava F, McElroy SL, Coombes BJ, Biernacka JM, Stan MN, Frye MA, Singh B. Long-Term Lithium Therapy and Thyroid Disorders in Bipolar Disorder: A Historical Cohort Study. Brain Sci. 2023;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/brainsci13010133\u003c/span\u003e\u003cspan address=\"10.3390/brainsci13010133\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKauer-Sant'Anna M, Kapczinski F, Vieta E. Epidemiology and management of anxiety in patients with bipolar disorder. CNS Drugs. 2009;23:953\u0026ndash;64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2165/11310850-000000000-00000\u003c/span\u003e\u003cspan address=\"10.2165/11310850-000000000-00000\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeck PE Jr., Strawn JR, McElroy SL. Pharmacologic treatment considerations in co-occurring bipolar and anxiety disorders. J Clin Psychiatry. 2006;67(Suppl 1):8\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKinrys G, Bowden CL, Nierenberg AA, Hearing CM, Gold AK, Rabideau DJ, Sylvia LG, Gao K, Kamali M, Bobo WV, Tohen M, Deckersbach T, McElroy SL, Ketter TA, Shelton RC, Friedman ES, Calabrese JR, McInnis MG, Kocsis J, Thase ME, Singh V, Reilly-Harrington NA. Comorbid anxiety in bipolar CHOICE: Insights from the bipolar inventory of symptoms scale. J Affect Disord. 2019;246:126\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jad.2018.12.039\u003c/span\u003e\u003cspan address=\"10.1016/j.jad.2018.12.039\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLopes FL, Zhu K, Purves KL, Song C, Ahn K, Hou L, Akula N, Kassem L, Bergen SE, Landen M, Veras AB, Nardi AE, Study BG, McMahon C, F.J. Polygenic risk for anxiety influences anxiety comorbidity and suicidal behavior in bipolar disorder. Transl Psychiatry. 2020;10:298. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41398-020-00981-5\u003c/span\u003e\u003cspan address=\"10.1038/s41398-020-00981-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaki H, Sakai N, Kataoka M, Fujii K, Kageyama Y, Hayama T, Matsuo K, Nishioka M, Kato T. Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent-of-origin effect. PCN Rep. 2025;4:e70071. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/pcn5.70071\u003c/span\u003e\u003cspan address=\"10.1002/pcn5.70071\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcElroy SL, Altshuler LL, Suppes T, Keck PE Jr., Frye MA, Denicoff KD, Nolen WA, Kupka RW, Leverich GS, Rochussen JR, Rush AJ, Post RM. Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder. Am J Psychiatry. 2001;158:420\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1176/appi.ajp.158.3.420\u003c/span\u003e\u003cspan address=\"10.1176/appi.ajp.158.3.420\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcIntyre RS, Soczynska JK, Bottas A, Bordbar K, Konarski JZ, Kennedy SH. Anxiety disorders and bipolar disorder: a review. Bipolar Disord. 2006;8:665\u0026ndash;76. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1399-5618.2006.00355.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1399-5618.2006.00355.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMerikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, Kessler RC. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007;64:543\u0026ndash;52. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/archpsyc.64.5.543\u003c/span\u003e\u003cspan address=\"10.1001/archpsyc.64.5.543\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitchell PB, Johnston AK, Frankland A, Slade T, Green MJ, Roberts G, Wright A, Corry J, Hadzi-Pavlovic D. Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms. Acta Psychiatr Scand. 2013;127:381\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/acps.12005\u003c/span\u003e\u003cspan address=\"10.1111/acps.12005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePahwa M, Joseph B, Nunez NA, Jenkins GD, Colby CL, Kashani KB, Marin V, Moore KM, Betcher HK, Ozerdem A, Cuellar-Barboza AB, McElroy SL, Biernacka JM, Frye MA, Singh B. Long-term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study. Bipolar Disord. 2021a;23:715\u0026ndash;23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/bdi.13052\u003c/span\u003e\u003cspan address=\"10.1111/bdi.13052\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePahwa M, Joseph B, Nunez NA, Jenkins GD, Colby CL, Kashani KB, Marin V, Moore KM, Betcher HK, Ozerdem A, Cuellar-Barboza AB, McElroy SL, Biernacka JM, Frye MA, Singh B. 2021b. Long-term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study. Bipolar Disord. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/bdi.13052\u003c/span\u003e\u003cspan address=\"10.1111/bdi.13052\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark JH, Nunez NA, Gardea-Resendez M, Gerberi DJ, Breitinger S, Veldic M, Frye MA, Singh B. Short Term Second-Generation Antidepressant Monotherapy in Acute Depressive Episodes of Bipolar II Disorder: A Systematic Review and Meta-Analysis. Psychopharmacol Bull. 2022;52:45\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePavlova B, Perlis RH, Alda M, Uher R. Lifetime prevalence of anxiety disorders in people with bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry. 2015;2:710\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S2215-0366(15)00112-1\u003c/span\u003e\u003cspan address=\"10.1016/S2215-0366(15)00112-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRickels K, Pollack MH, Feltner DE, Lydiard RB, Zimbroff DL, Bielski RJ, Tobias K, Brock JD, Zornberg GL, Pande AC. Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry. 2005;62:1022\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/archpsyc.62.9.1022\u003c/span\u003e\u003cspan address=\"10.1001/archpsyc.62.9.1022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRomo-Nava F, Blom T, Cuellar-Barboza AB, Awosika OO, Martens BE, Mori NN, Colby CL, Prieto ML, Veldic M, Singh B, Gardea-Resendez M, Nunez NA, Ozerdem A, Biernacka JM, Frye MA, McElroy SL. Revisiting the bipolar disorder with migraine phenotype: Clinical features and comorbidity. J Affect Disord. 2021;295:156\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jad.2021.08.026\u003c/span\u003e\u003cspan address=\"10.1016/j.jad.2021.08.026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalvi F, Miller MD, Grilli A, Giorgi R, Towers AL, Morichi V, Spazzafumo L, Mancinelli L, Espinosa E, Rappelli A, Dessi-Fulgheri P. A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients. J Am Geriatr Soc. 2008;56:1926\u0026ndash;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1532-5415.2008.01935.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1532-5415.2008.01935.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchaffer A, McIntosh D, Goldstein BI, Rector NA, McIntyre RS, Beaulieu S, Swinson R, Yatham LN, Canadian Network for, Task MAT. F., 2012. The CANMAT task force recommendations for the management of patients with mood disorders and comorbid anxiety disorders. Ann Clin Psychiatry. 24, 6\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheehan DV, Harnett-Sheehan K, Hidalgo RB, Janavs J, McElroy SL, Amado D, Suppes T. Randomized, placebo-controlled trial of quetiapine XR and divalproex ER monotherapies in the treatment of the anxious bipolar patient. J Affect Disord. 2013;145:83\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jad.2012.07.016\u003c/span\u003e\u003cspan address=\"10.1016/j.jad.2012.07.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimon NM, Otto MW, Wisniewski SR, Fossey M, Sagduyu K, Frank E, Sachs GS, Nierenberg AA, Thase ME, Pollack MH. Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry. 2004;161:2222\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1176/appi.ajp.161.12.2222\u003c/span\u003e\u003cspan address=\"10.1176/appi.ajp.161.12.2222\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh B, Ho AM, Coombes BJ, Romo-Nava F, Bond DJ, Veldic M, Pendegraft RS, Batzler A, Cuellar-Barboza AB, Gardea-Resendez M, Prieto ML, Ozerdem A, McElroy SL, Biernacka JM, Frye MA. Antipsychotic use in bipolar disorder: clinical and genomic correlates- a Mayo clinic bipolar disorder biobank study. Int J Bipolar Disord. 2025a. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s40345-025-00405-7\u003c/span\u003e\u003cspan address=\"10.1186/s40345-025-00405-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh B, Swartz HA, Cuellar-Barboza AB, Schaffer A, Kato T, Dols A, Sperry SH, Vassilev AB, Burdick KE, Frye MA. Bipolar disorder Lancet. 2025b;406:963\u0026ndash;78. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(25)01140-7\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(25)01140-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh B, Yocum AK, Strawbridge R, Burdick KE, Millett CE, Peters AT, Sperry SH, Fico G, Vieta E, Verdolini N, Godin O, Leboyer M, Etain B, Tso IF, Coombes BJ, McInnis MG, Nierenberg AA, Young AH, Ashton MM, Berk M, Williams LJ, Keramatian K, Yatham LN, Overs BJ, Fullerton JM, Roberts G, Mitchell PB, Andreassen OA, Andreazza AC, Zandi PP, Pham D, Biernacka JM, Frye MA, Collaborators F-B. T.G.B.C.C., 2024. Patterns of pharmacotherapy for bipolar disorder: A GBC survey. Bipolar Disord. 26, 22\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/bdi.13366\u003c/span\u003e\u003cspan address=\"10.1111/bdi.13366\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith JP, Book SW. Anxiety and Substance Use Disorders: A Review. Psychiatr Times. 2008;25:19\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVazquez GH, Baldessarini RJ, Tondo L. Co-occurrence of anxiety and bipolar disorders: clinical and therapeutic overview. Depress Anxiety. 2014;31:196\u0026ndash;206. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/da.22248\u003c/span\u003e\u003cspan address=\"10.1002/da.22248\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams CM, Peyre H, Wolfram T, Lee YH, Seidlitz J, Ge T, Smoller JW, Mallard TT, Ramus F. Characterizing the phenotypic and genetic structure of psychopathology in UK Biobank. Nat Ment Health. 2024;2:960\u0026ndash;74. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s44220-024-00272-8\u003c/span\u003e\u003cspan address=\"10.1038/s44220-024-00272-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYapici Eser H, Kacar AS, Kilciksiz CM, Yalcinay-Inan M, Ongur D. Prevalence and Associated Features of Anxiety Disorder Comorbidity in Bipolar Disorder: A Meta-Analysis and Meta-Regression Study. Front Psychiatry. 2018;9:229. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fpsyt.2018.00229\u003c/span\u003e\u003cspan address=\"10.3389/fpsyt.2018.00229\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, Sharma V, Goldstein BI, Rej S, Beaulieu S, Alda M, MacQueen G, Milev RV, Ravindran A, O'Donovan C, McIntosh D, Lam RW, Vazquez G, Kapczinski F, McIntyre RS, Kozicky J, Kanba S, Lafer B, Suppes T, Calabrese JR, Vieta E, Malhi G, Post RM, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20:97\u0026ndash;170. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/bdi.12609\u003c/span\u003e\u003cspan address=\"10.1111/bdi.12609\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYocum AK, Singh B. Global Trends in the Use of Pharmacotherapy for the Treatment of Bipolar Disorder. Curr psychiatry Rep. 2025;27:239\u0026ndash;47. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11920-025-01606-8\u003c/span\u003e\u003cspan address=\"10.1007/s11920-025-01606-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoung LT, Cooke RG, Robb JC, Levitt AJ, Joffe RT. Anxious and non-anxious bipolar disorder. J Affect Disord. 1993;29:49\u0026ndash;52. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/0165-0327(93)90118-4\u003c/span\u003e\u003cspan address=\"10.1016/0165-0327(93)90118-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-bipolar-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijbd","sideBox":"Learn more about [International Journal of Bipolar Disorders](http://journalbipolardisorders.springeropen.com/)","snPcode":"40345","submissionUrl":"https://submission.nature.com/new-submission/40345/3","title":"International Journal of Bipolar Disorders","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bipolar disorder, anxiety disorders, comorbidity, pharmacotherapy, treatment response, mood stabilizers, antidepressants","lastPublishedDoi":"10.21203/rs.3.rs-8503080/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8503080/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAnxiety disorders (ANX) affect 30\u0026ndash;60% of individuals with bipolar disorder (BD), yet limited research has systematically examined clinical characteristics and treatment patterns in this comorbid population. This study investigated demographic, clinical, and pharmacotherapeutic differences between individuals with BD with and without comorbid ANX.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eCross-sectional data from 2,225 adults with BD enrolled in the Mayo Clinic Bipolar Disorder Biobank were analyzed. Participants were assessed for comorbid ANX, demographics, clinical characteristics, medication use, and treatment response using the Alda-A scale.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOverall, 61% (n\u0026thinsp;=\u0026thinsp;1,366) had comorbid ANX. Individuals with BD\u0026thinsp;+\u0026thinsp;ANX were younger (40.4 vs. 43.6 years, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), more likely female (66.6% vs. 54.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and exhibited higher rates of rapid cycling (64.2% vs. 45.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), suicide attempts (40.4% vs. 24.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), substance use disorders (63.5% vs. 54.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and somatic comorbidities (MCIRS: 6.68 vs. 5.42, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Pharmacotherapeutically, BD\u0026thinsp;+\u0026thinsp;ANX individuals were less likely to receive lithium (37.1% vs. 47.8%, p\u0026thinsp;=\u0026thinsp;0.005) and valproic acid (21.7% vs. 29.6%, p\u0026thinsp;=\u0026thinsp;0.047), but more likely to receive antidepressants (53.8% vs. 39.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), benzodiazepines (39.9% vs. 26.6%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and gabapentinoids (8.5% vs. 4.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Notably, 17.3% of BD\u0026thinsp;+\u0026thinsp;ANX individuals received antidepressants without mood stabilizer coverage. Treatment response (Alda-A) scores were significantly lower in BD\u0026thinsp;+\u0026thinsp;ANX for lithium (4.91 vs. 6.05, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), mood-stabilizing anticonvulsants (5.09 vs. 6.22, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and second-generation antipsychotics (4.67 vs. 5.73, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similar patterns were observed in both BD-I and BD-II subtypes.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIndividuals with BD\u0026thinsp;+\u0026thinsp;ANX represent a more severely affected subgroup with distinct prescribing patterns favoring antidepressants over mood stabilizers and attenuated mood stabilizers response. These findings highlight the need for anxiety-informed treatment algorithms recognizing anxiety comorbidity as a negative prognostic factor.\u003c/p\u003e","manuscriptTitle":"The Anxious Bipolar Phenotype: Clinical Complexity and Treatment Resistance","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 05:40:54","doi":"10.21203/rs.3.rs-8503080/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-20T17:22:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-18T19:37:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-17T09:52:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"83432996926050388769948787717603293269","date":"2026-01-08T08:51:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-07T12:37:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"51124479899112208805372738957274687934","date":"2026-01-07T12:31:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"145732746033813616111198924656456619996","date":"2026-01-06T20:39:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-06T19:12:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-05T00:28:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-05T00:27:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Bipolar Disorders","date":"2026-01-02T19:48:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-bipolar-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijbd","sideBox":"Learn more about [International Journal of Bipolar Disorders](http://journalbipolardisorders.springeropen.com/)","snPcode":"40345","submissionUrl":"https://submission.nature.com/new-submission/40345/3","title":"International Journal of Bipolar Disorders","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2c99bf07-7589-4f91-a633-2ab359d13f56","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T16:01:33+00:00","versionOfRecord":{"articleIdentity":"rs-8503080","link":"https://doi.org/10.1186/s40345-026-00415-z","journal":{"identity":"international-journal-of-bipolar-disorders","isVorOnly":false,"title":"International Journal of Bipolar Disorders"},"publishedOn":"2026-02-26 15:58:26","publishedOnDateReadable":"February 26th, 2026"},"versionCreatedAt":"2026-01-12 05:40:54","video":"","vorDoi":"10.1186/s40345-026-00415-z","vorDoiUrl":"https://doi.org/10.1186/s40345-026-00415-z","workflowStages":[]},"version":"v1","identity":"rs-8503080","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8503080","identity":"rs-8503080","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}