New-Onset Antidepressant Use After Cardiothoracic Intensive Care is Associated with Increased Long-Term Mortality

New-Onset Antidepressant Use After Cardiothoracic Intensive Care is Associated with Increased Long-Term Mortality | 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 Article New-Onset Antidepressant Use After Cardiothoracic Intensive Care is Associated with Increased Long-Term Mortality Erik von Oelreich, Emma Larsson, Mikael Eriksson, Anders Oldner, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9136479/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Survival after cardiothoracic intensive care has improved, yet long-term psychological and physical morbidities remain common. Depression is frequent after intensive care, and initiation of antidepressant therapy may serve as a proxy for clinically significant psychological distress. We investigated the incidence, associated factors, and outcomes related to new-onset antidepressant use among cardiothoracic ICU survivors in Sweden. Methods: Nationwide, population-based cohort study using linked Swedish registers. We included 27,006 patients who survived ≥ 90 days after their first cardiothoracic ICU admission (2010–2017) and were naïve to antidepressants during the preceding 6 months. The primary outcome was new-onset SSRI use within 12 months after discharge. Multivariable logistic regression identified associated factors, and Cox models assessed long-term mortality. Results: Overall, 2,051 patients (7.6%) initiated SSRI therapy within one year. Factors associated with new-onset antidepressant use included psychiatric comorbidity, substance abuse, higher somatic comorbidity (CCI > 1), and ICU length of stay > 7 days, while male sex was associated with lower odds. New-onset SSRI use was independently associated with higher long-term mortality (adjusted HR 1.9; 95% CI 1.4–2.6). Patients prescribed SSRIs also had fewer care days alive and at home within 90 days after ICU discharge (DAH90), indicating delayed recovery or greater post-ICU morbidity. Conclusions: New-onset SSRI use after cardiothoracic critical illness was associated with markers of higher mortality and fewer early days at home. These findings underscore the importance of addressing mental health in post-ICU care. Health sciences/Cardiology Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Health sciences/Risk factors Intensive Care Units Depression Antidepressive Agents Socioeconomic Factors Mortality Figures Figure 1 Figure 2 Figure 3 Methods Study Design and Setting This nationwide, retrospective, population-based cohort study was conducted using data from several Swedish national health registers. Ethical approval was obtained from the Regional Ethical Review Board in Stockholm, Sweden (approval numbers 2018/2541-31 and 2019 − 00213). All methods were performed in accordance with the relevant guidelines and regulations. The requirement for informed consent was waived by the Stockholm Regional Ethics Review Board, Division 4 (Stockholm Avdelning 4), in accordance with Swedish legislation. The study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines 17 . Study Population and Data Sources The study cohort was identified from the Swedish Intensive Care Registry (SIR) and enriched with individual-level data from additional Swedish registers using the unique personal identity number assigned to every Swedish resident 18 . The National Board of Health and Welfare (Socialstyrelsen) performed pseudonymization by converting each personal identity number into an encrypted study-specific identifier prior to data release. Data on ICU admissions and ICU care and interventions were obtained from the Swedish Intensive Care Registry (SIR), a nationwide quality registry covering all Swedish ICUs. Information on pre-existing comorbidities was retrieved from the Swedish National Patient Register, which captures both inpatient and outpatient diagnoses, for the five-year period preceding ICU admission 19 . Socioeconomic data, including income and educational attainment, were obtained from the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA) 20 . Prescription data were collected from the Swedish Prescribed Drug Register, which records all dispensed medications nationwide 21 . Mortality data were retrieved from the Swedish Cause of Death Register 22 . Patients admitted to a cardiothoracic ICU between January 1, 2010, and December 31, 2017, were eligible for inclusion. To focus on new-onset antidepressant use, patients with any dispensed antidepressant (Anatomical Therapeutic Chemical [ATC] codes beginning with N06A) in the six months preceding ICU admission were excluded. To assess long-term outcomes, individuals who died within 90 days after ICU discharge were also excluded. When multiple cardiothoracic ICU admissions occurred, only the first episode was considered. Outcomes The primary outcome was new-onset SSRI use, defined as at least one dispensed prescription for a selective serotonin reuptake inhibitor (ATC code N06AB) within 12 months following discharge from the index ICU admission. The secondary outcome was all-cause mortality occurring between 12 and 18 months after ICU admission. An additional secondary outcome was care days alive and at home within 90 days after ICU discharge (DAH90). Statistical Analysis Baseline characteristics were summarized using descriptive statistics. Categorical variables were presented as counts and percentages, while continuous variables were expressed as medians with interquartile ranges (IQR). Univariable and multivariable logistic regression analyses were used to identify factors independently associated with new-onset SSRI use. Covariates included age, sex, income, education level, somatic comorbidity (measured by the Charlson Comorbidity Index, CCI), psychiatric comorbidity, substance abuse, surgical procedures, and ICU length of stay. Results were reported as odds ratios (OR) with corresponding 95% confidence intervals (CI). To evaluate the association between new-onset SSRI use and long-term mortality, Cox proportional hazards regression models were applied. The models were adjusted for age, sex, income, education, comorbidities, and ICU length of stay. Hazard ratios (HR) with 95% CI were reported. The DAH90 metric, a validated patient-centered outcome measure, was derived from mortality and hospitalization records for each quarter before and after ICU admission, following the general methodology described by Myles and colleagues 23 . For patients who died within respective quarter, the duration of hospital stay was, as suggested by Myles, given a value of zero. A p -value of < 0.05 was considered statistically significant. All analyses were performed using Stata/SE 16.1 (StataCorp, College Station, TX, USA). Results A total of 31,358 patients were initially identified as having been admitted to a cardiothoracic intensive care unit (ICU) in Sweden between 2010 and 2017. After excluding patients who died within 90 days of ICU discharge ( n = 1,700) and those with a history of antidepressant use within six months prior to admission ( n = 2,652), the final study cohort consisted of 27,006 patients (Fig. 1 ). The baseline characteristics of the study cohort are summarized in Table 1 . The median age was 68 years (interquartile range [IQR] 60–74), and 74.0% were male. A substantial proportion had pre-existing comorbidities, with 38.6% showing a Charlson Comorbidity Index (CCI) greater than 1. Psychiatric comorbidity was present in 3.4%, and 1.8% had a diagnosis of substance abuse. Table 1 General characteristics for patients included. Cardiothoracic ICU patients Count 27 006 Age, median (IQR) 68 (60, 74) Male, count (%) 19 991 (74.0) Income categories, count (%) Low Medium High 2594 (9.6) 22 015 (81.8) 2290 (8.5) Education level, count (%) Low Medium High 8700 (32.7) 11 396 (42.9) 6487 (24.4) CCI categories, count (%) CCI 0 CCI 1 CCI > 1 7978 (29.5) 8608 (31.9) 10 420 (38.6) Psychiatric comorbidity, count (%) 913 (3.4) Substance abuse, count (%) 483 (1.8) Acute myocardial infarction 8048 (29.8) Congestive heart failure 5035 (18.6) Peripheral vascular disease 3981 (14.7) Cerebrovascular disease 2208 (8.2) Dementia 46 (0.2) COPD 2703 (10.0) Rheumatoid disease 887 (3.3) Peptic ulcer disease 468 (1.7) Mild liver disease 352 (1.3) Moderate/severe liver disease 79 (0.3) Diabetes w/o complications 5558 (20.6) Diabetes with complications 1549 (5.7) Hemiplegia or paraplegia 155 (0.6) Renal disease 1101 (4.1) Cancer 2481 (9.2) Metastatic cancer 221 (0.8) AIDS 30 (0.1) ICU length of stay, days 0–2 3–7 > 7 19 827 (73.4) 5789 (21.4) 1390 (5.1) Surgery Acute care Elective No surgery 1560 (5.8) 24 026 (89.0) 1420 (5.3) Categorical parameters are presented as n (%), continuous parameters as median with interquartile range (IQR), CCI, Charlson Comorbidity Index; COPD, Chronic Obstructive Pulmonary Disease; AIDS, Acquired Immune Deficiency Syndrome; ICU, Intensive Care Unit. Of the 27,006 patients, 2,051 (7.6%) initiated SSRI therapy within the first year after discharge. Table 2 compares baseline characteristics between new SSRI users and non-users. Compared to non-users, SSRI initiators were more often female (66.0% vs. 74.7%), had lower income (11.7% vs. 9.5%), and a higher prevalence of comorbidities (CCI > 1: 49.1% vs. 37.7%). Psychiatric comorbidity (10.2% vs. 2.8%) and substance abuse (4.4% vs. 1.6%) were also more frequent among new SSRI users. Moreover, these patients had a longer median ICU stay. The proportion of patients with a dispensed SSRI prescription increased consistently throughout the follow-up period of two years (Fig. 2 ). Table 2 General characteristics in included cardiothoracic ICU patients stratified by use of antidepressant medication during the first twelve months after ICU care Count Non-SSRI user SSRI user 24 955 2051 Age, median (IQR) 68 (60, 74) 68 (58, 75) Male, count (%) 18 637 (74.7) 1354 (66.0) Income categories, count (%) Low Medium High 2355 (9.5) 20 344 (81.9) 2156 (8.7) 239 (11.7) 1671 (81.8) 134 (6.6) Education level, count (%) Low Medium High 7978 (32.5) 10 519 (42.8) 6072 (24.7) 722 (35.8) 877 (43.5) 415 (20.6) CCI categories, count (%) CCI 0 CCI 1 CCI > 1 7527 (30.2) 8016 (32.1) 9412 (37.7) 451 (22.0) 592 (28.9) 1008 (49.1) Psychiatric comorbidity, count (%) 704 (2.8) 209 (10.2) Substance abuse, count (%) 393 (1.6) 90 (4.4) Acute myocardial infarction 7391 (29.6) 657 (32.0) Congestive heart failure 4584 (18.4) 451 (22.0) Peripheral vascular disease 3605 (14.4) 376 (18.3) Cerebrovascular disease 1947 (7.8) 261 (12.7) Dementia 42 (0.2) 4 (0.2) COPD 2407 (9.6) 296 (14.4) Rheumatoid disease 793 (3.2) 94 (4.6) Peptic ulcer disease 423 (1.7) 45 (2.2) Mild liver disease 312 (1.3) 40 (2.0) Moderate/severe liver disease 69 (0.3) 10 (0.5) Diabetes w/o complications 5062 (20.3) 496 (24.2) Diabetes with complications 1397 (5.6) 152 (7.4) Hemiplegia or paraplegia 125 (0.5) 30 (1.5) Renal disease 987 (4.0) 114 (5.6) Cancer 2249 (9.0) 232 (11.3) Metastatic cancer 196 (0.8) 25 (1.2) AIDS 28 (0.1) 2 (0.1) ICU length of stay, days 0–2 3–7 > 7 18 595 (74.5) 5274 (21.1) 1086 (4.4) 1232 (60.1) 515 (25.1) 304 (14.8) Surgery Acute care Elective No surgery 1367 (5.5) 22 345 (89.5) 1243 (5.0) 193 (9.4) 1681 (82.0) 177 (8.6) Categorical parameters are presented as n (%), continuous parameters as median with interquartile range (IQR), CCI, Charlson Comorbidity Index; COPD, Chronic Obstructive Pulmonary Disease; AIDS, Acquired Immune Deficiency Syndrome; ICU, Intensive Care Unit. The proportion of patients with a dispensed SSRI prescription increased progressively during the follow-up period. As shown in Fig. 2 , 3.28% had initiated SSRI therapy during the first quarter after discharge, increasing to 4.93% by the eighth quarter. Results from the univariable and multivariable logistic regression analyses are presented in Table 3 . After adjustment for potential confounders, several variables remained independently associated with an increased risk of new-onset SSRI use. These included pre-existing psychiatric comorbidity (odds ratio [OR] 3.21; 95% confidence interval [CI] 2.69–3.83), substance abuse (OR 1.67; 95% CI 1.29–2.17), and higher somatic comorbidity (CCI > 1: OR 1.62; 95% CI 1.44–1.83). An ICU length of stay exceeding seven days was also a significant risk factor (OR 3.47; 95% CI 2.98–4.03). In contrast, male sex was independently associated with lower odds of new-onset SSRI use (OR 0.68; 95% CI 0.61–0.75). Table 3 Univariate and multivariable logistic regression analyses, associations with initiation of antidepressant medication presented as OR (95% CI). Age categories 18–45 46–60 61–70 71–80 80- Univariate P value Multivariable P value Ref. 0.92 (0.76–1.12) 0.66 (0.55–0.79) 0.76 (0.63–0.91) 1.01 (0.81–1.26) 0.42 < 0.001 0.003 0.93 Ref. 1.05 (0.86–1.29) 0.75 (0.61–0.92) 0.83 (0.68–1.02) 1.09 (0.85–1.38) 0.64 0.006 0.082 0.50 Male 0.66 (0.60–0.72) < 0.001 0.68 (0.61–0.75) < 0.001 Income categories Low Medium High Ref. 0.81 (0.70–0.93) 0.61 (0.49–0.76) 0.004 < 0.001 Ref. 0.95 (0.82–1.03) 0.93 (0.73–1.18) 0.51 0.54 Education level Low Medium High Ref. 0.92 (0.83–1.02) 0.76 (0.67–0.86) 0.12 1 Ref. 1.23 (1.09–1.40) 1.79 (1.59–2.01) 0.001 < 0.001 Ref. 1.21 (1.06–1.37) 1.62 (1.44–1.83) 0.005 < 0.001 Psychiatric comorbidity 3.91 (3.33–4.59) < 0.001 3.21 (2.69–3.83) < 0.001 Substance abuse 2.87 (2.27–3.62) < 0.001 1.67 (1.29–2.17) 7 Ref. 1.47 (1.32–1.64) 4.23 (3.67–4.86) < 0.001 < 0.001 Ref. 1.31 (1.17–1.47) 3.47 (2.98–4.03) < 0.001 < 0.001 Surgery No surgery Elective Acute care Ref. 0.53 (0.45–0.62) 0.99 (0.80–1.23) < 0.001 0.94 Ref. 0.68 (0.57–0.81) 0.91 (0.72–1.14) < 0.001 0.42 CCI, Charlson Comorbidity Index; ICU, Intensive Care Unit Between 12 and 18 months post-ICU admission, 298 patients died, including 49 who had initiated SSRI therapy. In unadjusted analyses, new-onset SSRI use was associated with an increased risk of mortality (hazard ratio [HR] 2.5; 95% CI 1.8–3.4). This association persisted after adjusting for age, sex, comorbidities, and ICU length of stay (adjusted HR 1.9; 95% CI 1.4–2.6). Further analysis of causes of death revealed that mental and behavioral disorders accounted for a significantly greater proportion of deaths among new SSRI users compared with non-users (Supplemental Digital Content. Figure S1 ). Figure 3 displays care days alive out of hospital. Values are shown separately for patients with and without SSRI treatment. Discussion This large, nationwide cohort study provides insights into the long-term psychological burden following cardiothoracic intensive care. We found that a substantial proportion of patients (7.6%) who were previously naïve to antidepressants initiated SSRI therapy within one year of discharge. This finding underscores the importance of systematic screening for psychological morbidity in the post-ICU population 24 , 25 . The steady increase in antidepressant use observed throughout the follow-up period suggests that psychological sequelae may have a delayed onset or progress gradually, emphasizing the need for extended follow-up beyond hospital discharge. Pre-existing psychiatric comorbidity and substance abuse were associated with an increased likelihood of new-onset SSRI use, aligning with previous studies suggesting that these factors may contribute to greater vulnerability to post-ICU psychological morbidity 26 , 27 . While causality cannot be inferred, these findings indicate that patients with such pre-existing conditions could benefit from more attentive follow-up. A more individualized and risk-informed approach to post-ICU care, where psychosocial vulnerabilities are taken into consideration, may help identify patients in need of early assessment or support. Socioeconomic disparities also played a notable role. Patients with lower income or education had significantly higher odds of initiating SSRI therapy. This aligns with earlier studies demonstrating that social disadvantage is associated with poorer health outcomes and higher mortality among ICU survivors 28 , 29 . Multiple mechanisms may underlie this association, including greater financial stress, limited access to mental health services, and differences in health literacy. Such inequities can lead to delayed recognition or undertreatment of psychological distress, resulting in a greater reliance on pharmacological therapy. Addressing these disparities is crucial for ensuring equitable, high-quality post-ICU care. Clinical characteristics of the ICU stay also influenced SSRI initiation. A longer ICU length of stay was an independent risk factor, indicating that prolonged exposure to critical illness and intensive interventions may contribute to psychological distress. Extended ICU stays often involve increased sedation, sleep disruption, delirium, and invasive monitoring, all of which have been associated with long-term mental health impairment 30 , 31 . Among cardiothoracic patients, additional factors such as cardiopulmonary bypass may trigger neuroinflammatory and microembolic processes that could affect cognitive and psychological outcomes 32 – 34 . Moreover, the experience of an acute, unplanned surgical event, as opposed to elective surgery, has been associated with heightened psychological trauma and distress, potentially contributing to the elevated odds of SSRI use observed in this study 35 . These findings highlight the importance of early psychological support and preventive interventions during and after ICU care 36 . The relationship between new-onset SSRI use and long-term mortality is likely complex. On one hand, SSRI initiation may serve as a proxy for underlying depression, a condition itself known to be associated with increased mortality risk 37 . On the other hand, it is reasonable to assume that, for patients suffering from such psychological distress, antidepressant therapy represents an appropriate and often necessary intervention. It cannot be excluded that the observed mortality might have been even higher in the absence of treatment. However, this hypothesis cannot be evaluated within the framework of the present observational design and should therefore be interpreted with caution. The higher proportion of deaths attributed to mental and behavioral disorders among new SSRI users in our cohort further suggests that these prescriptions may identify a subgroup experiencing more severe or persistent psychological distress. Previous studies have shown that depression following critical illness is not only associated with impaired quality of life but also constitutes an independent predictor of mortality 38 , 39 . Potential mechanisms include reduced physical activity, poorer adherence to rehabilitation, substance use, and other maladaptive health behaviors 9 . Collectively, these findings highlight the importance of recognizing and addressing psychological morbidity as an integral component of post-ICU care. Patients prescribed SSRIs had fewer care days alive and at home for each quarter after ICU admission compared with those without such prescriptions. This association should be interpreted with caution, as it may reflect differences in underlying health status rather than a direct effect of SSRI treatment. It is possible that patients who required SSRIs were more severely ill during their ICU stay or experienced greater physical and psychological vulnerability after discharge. Thus, SSRI use may serve as a proxy for greater morbidity or reduced recovery potential, although this cannot be determined from the present data. Further studies are warranted to explore the mechanisms underlying this association and to clarify whether it reflects pre-existing factors, illness severity, or post-ICU sequelae. This study has several strengths, including its large, population-based design, comprehensive data linkage across national registries, and focus on antidepressant-naïve patients, enabling a clear evaluation of new-onset use. However, certain limitations must be acknowledged. First, while SSRI dispensing is a validated epidemiological proxy for depression, it does not confirm a clinical diagnosis, and we could neither capture patients with untreated depression nor distinguish prescriptions for anxiety or other indications. Second, registry-based data restrict available variables, preventing adjustment for unmeasured confounders such as delirium, sedation strategy, or social support. Third, excluding patients who died within 90 days of discharge may have introduced selection bias by underestimating early mortality risk. Fourth, the study period (2010–2017) may not fully reflect current clinical practice, as awareness of post-ICU psychological morbidity and patterns of antidepressant prescribing may have evolved in recent years. Finally, residual confounding cannot be completely ruled out despite adjustment for multiple key variables. Nevertheless, the study’s robust design, large sample size, and minimal loss to follow-up enhance both its internal and external validity. Our findings have important implications for clinical practice and healthcare policy. Targeted interventions for high-risk cardiothoracic ICU survivors are needed, particularly for high-risk groups identified in this study. These programs should adopt a multidisciplinary approach that includes early psychological screening, timely referral to mental health professionals, and access to evidence-based non-pharmacological interventions. In addition, awareness of the potential link between post-ICU SSRI initiation and long-term mortality highlights the need for careful medication review and coordination between intensive care, cardiology, and primary care services. Conclusion In summary, new-onset SSRI use is a frequent outcome following cardiothoracic ICU care and is independently associated with increased long-term mortality. These findings emphasize that psychological well-being is not merely a quality-of-life issue but a potentially important factor in long-term prognosis. Future research should focus on prospective studies using standardized assessments of psychological morbidity and interventional trials testing early, structured psychological follow-up to determine whether early identification and treatment of mental health needs can improve outcomes after cardiothoracic intensive care. Abbreviations ATC Anatomical Therapeutic Chemical code CCI Charlson Comorbidity Index CI Confidence Interval(s) HR Hazard ratio ICU Intensive Care Unit IQR Interquartile Range LISA Longitudinal Integration Database for Health Insurance and Labour Market Studies OR Odds ratio PICS Post-Intensive Care Syndrome SIR Swedish Intensive Care Registry SSRI Selective Serotonin Reuptake Inhibitor STROBE Strengthening the Reporting of Observational Studies in Epidemiology Declarations Data Availability The datasets supporting the findings of this study are held under license and are not publicly available due to restrictions imposed by the Swedish Intensive Care Registry (SIR) and the National Board of Health and Welfare (NBHW). Data may, however, be made available from the authors upon reasonable request and contingent upon obtaining formal permission from the SIR and the NBHW. Acknowledgements We extend our sincere gratitude to all participating ICUs and their dedicated staff for their essential contributions and tireless work in collecting and submitting data to the Swedish Intensive Care Registry (SIR). This research was made possible through financial support from the following organizations: Region Stockholm, the David and Astrid Hagelén foundation, Svenska Läkaresällskapet, Stiftelsen Serafimerlasarettet, the Fredrik and Ingrid Thuring’s foundation, and Magnus Bergvall’s foundation. Author Contributions EvO and JE served as the main investigators, taking primary responsibility for study design, data collection, statistical analysis, and drafting of the manuscript. ME, EL, and AO contributed significantly to all phases of the project, including study design, data interpretation, critical revision of the analysis, and final manuscript writing. All authors read and approved the final manuscript. Funding AO, EL, and ME declare no competing interests. EvO discloses receiving funding from the Svenska Läkaresällskapet, and Stiftelsen Serafimerlasarettet. Both EvO and JE received funding from Region Stockholm. Crucially, none of the funding agents were involved in the study design, data collection, data analysis, manuscript preparation, or the decision to publish. References Morgan, A. Long-term outcomes from critical care. Surg. (Oxf) . 39 , 53–57. 10.1016/j.mpsur.2020.11.005 (2021). Rudd, K. E. et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet 395 , 200–211. 10.1016/S0140-6736(19)32989-7 (2020). Needham, D. M. et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference. Crit Care Med ; 40: 502–509. (2012). 10.1097/CCM.0b013e318232da75 Ramnarain, D. et al. 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Cardiac surgery, the brain, and inflammation. J. Extra Corpor. Technol. 46 , 15–22 (2014). Dillstrom, M., Bjersa, K. & Engstrom, M. Patients' experience of acute unplanned surgical reoperation. J. Surg. Res. 209 , 199–20520161026. 10.1016/j.jss.2016.09.060 (2017). Schandl, A. et al. Developing an early screening instrument for predicting psychological morbidity after critical illness. Crit. Care . 17 , R210. 10.1186/cc13018 (2013). Chan, J. K. N. et al. All-cause and cause-specific mortality in people with depression: a large-scale systematic review and meta-analysis of relative risk and aggravating or attenuating factors, including antidepressant treatment. World Psychiatry . 24 , 404–421. 10.1002/wps.21354 (2025). Yoo, K. H. et al. Depression or anxiety and long-term mortality among adult survivors of intensive care unit: a population-based cohort study. Crit. Care . 29 , 179. 10.1186/s13054-025-05381-z (2025). Hatch, R. et al. Anxiety, Depression and Post Traumatic Stress Disorder after critical illness: a UK-wide prospective cohort study. Crit. Care . 22 , 310. 10.1186/s13054-018-2223-6 (2018). Additional Declarations No competing interests reported. Supplementary Files SupplementalDigitalContent.docx FigureS1.tif Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9136479","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":615084194,"identity":"1031928f-9506-48f0-a7bd-fadaf10c28ff","order_by":0,"name":"Erik von Oelreich","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIie3OsUoDMRjA8S8Id8tB1xSHvsJXOuhw1FdJEOIidnC5QSRHIJPUB/AlXN2+cJAueQDFqQjO9wClGlpQoURLJ4f8IRA+8uMLQC73L2Pm60YAHLC0QPsS2JLK/0Xg6CcBQK5+fz847gwyW19BaahrmtPRyfBdEqzqJBnOpRHMqmuovHAh8PHTgyKKkyTBwAxB6KTml+haywW+XmhiukuSs28y6127juRloePHPtJbKmYENJst4FodyXNBBAUlCY9bUDRK2sqj056PH4MSJO15kgzuyjfeYy3vS7Nc6pvbES78pO9X0yTZJOIpdia5XC6XO7xPQ/NYPtCW8fUAAAAASUVORK5CYII=","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":true,"prefix":"","firstName":"Erik","middleName":"","lastName":"von Oelreich","suffix":""},{"id":615084195,"identity":"d3a86e4d-3c01-4988-aee9-87ab9ef81a03","order_by":1,"name":"Emma Larsson","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Emma","middleName":"","lastName":"Larsson","suffix":""},{"id":615084196,"identity":"fa78570d-5e94-4b4e-b54f-ead226ea2451","order_by":2,"name":"Mikael Eriksson","email":"","orcid":"","institution":"Uppsala University","correspondingAuthor":false,"prefix":"","firstName":"Mikael","middleName":"","lastName":"Eriksson","suffix":""},{"id":615084197,"identity":"18e165f9-0460-42f2-8b2c-fcb2ba815393","order_by":3,"name":"Anders Oldner","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Anders","middleName":"","lastName":"Oldner","suffix":""},{"id":615084200,"identity":"4f23b34b-d4a9-498b-8386-b34a98fa9c22","order_by":4,"name":"Jesper Eriksson","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Jesper","middleName":"","lastName":"Eriksson","suffix":""}],"badges":[],"createdAt":"2026-03-16 10:23:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9136479/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9136479/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106094020,"identity":"35a33de4-c62d-4261-99fe-00ca802ec719","added_by":"auto","created_at":"2026-04-03 11:40:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":102279,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eFlow chart of included patients\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9136479/v1/8284b4bcf45878b3662ab18c.png"},{"id":106093587,"identity":"3926f591-a1d6-4081-ae6f-d6cc181660d3","added_by":"auto","created_at":"2026-04-03 11:38:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":65896,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eProportion of patients initiating dispensed antidepressant prescriptions by quarter. This figure illustrates the median proportion (with Interquartile Range, IQR) of patients who received an antidepressant prescription in each calendar quarter following their ICU admission. The dashed line indicates the time of initial ICU admission.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9136479/v1/1ba616cfe2325fdd2f950e9e.png"},{"id":106093518,"identity":"a70578c3-f41e-4ef5-940d-6b9d652bea3e","added_by":"auto","created_at":"2026-04-03 11:37:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":91334,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eDays alive and out of hospital per quarter from two quarters before to eight quarters after cardiothoracic ICU admission, comparing patients with and without SSRI use. Diamonds represent patients without SSRI use, and circles represent patients with SSRI use.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9136479/v1/a99eb0092bcb79842cce4acd.png"},{"id":107827882,"identity":"d7f6b9b2-5f1d-432e-bfec-49ba02c475d2","added_by":"auto","created_at":"2026-04-26 13:40:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":649634,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9136479/v1/cf8672ca-aabd-4644-9e53-2cbeac2402dd.pdf"},{"id":105985027,"identity":"f21d6ac8-771b-4e4c-991f-f3f32b94bbd9","added_by":"auto","created_at":"2026-04-02 07:19:54","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":162811,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalDigitalContent.docx","url":"https://assets-eu.researchsquare.com/files/rs-9136479/v1/5adf002a7373ab56d75378ba.docx"},{"id":106093888,"identity":"d0ca3fe5-5685-40aa-9902-206e8e8b1719","added_by":"auto","created_at":"2026-04-03 11:39:52","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":55145,"visible":true,"origin":"","legend":"","description":"","filename":"FigureS1.tif","url":"https://assets-eu.researchsquare.com/files/rs-9136479/v1/cba2f007a7632cb9cc01db44.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"New-Onset Antidepressant Use After Cardiothoracic Intensive Care is Associated with Increased Long-Term Mortality","fulltext":[{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eThis nationwide, retrospective, population-based cohort study was conducted using data from several Swedish national health registers. Ethical approval was obtained from the Regional Ethical Review Board in Stockholm, Sweden (approval numbers 2018/2541-31 and 2019\u0026thinsp;\u0026minus;\u0026thinsp;00213). All methods were performed in accordance with the relevant guidelines and regulations. The requirement for informed consent was waived by the Stockholm Regional Ethics Review Board, Division 4 (Stockholm Avdelning 4), in accordance with Swedish legislation. The study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population and Data Sources\u003c/h3\u003e\n\u003cp\u003eThe study cohort was identified from the Swedish Intensive Care Registry (SIR) and enriched with individual-level data from additional Swedish registers using the unique personal identity number assigned to every Swedish resident\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. The National Board of Health and Welfare (Socialstyrelsen) performed pseudonymization by converting each personal identity number into an encrypted study-specific identifier prior to data release.\u003c/p\u003e \u003cp\u003eData on ICU admissions and ICU care and interventions were obtained from the Swedish Intensive Care Registry (SIR), a nationwide quality registry covering all Swedish ICUs. Information on pre-existing comorbidities was retrieved from the Swedish National Patient Register, which captures both inpatient and outpatient diagnoses, for the five-year period preceding ICU admission\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Socioeconomic data, including income and educational attainment, were obtained from the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA)\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Prescription data were collected from the Swedish Prescribed Drug Register, which records all dispensed medications nationwide\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Mortality data were retrieved from the Swedish Cause of Death Register\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePatients admitted to a cardiothoracic ICU between January 1, 2010, and December 31, 2017, were eligible for inclusion. To focus on new-onset antidepressant use, patients with any dispensed antidepressant (Anatomical Therapeutic Chemical [ATC] codes beginning with N06A) in the six months preceding ICU admission were excluded. To assess long-term outcomes, individuals who died within 90 days after ICU discharge were also excluded. When multiple cardiothoracic ICU admissions occurred, only the first episode was considered.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was new-onset SSRI use, defined as at least one dispensed prescription for a selective serotonin reuptake inhibitor (ATC code N06AB) within 12 months following discharge from the index ICU admission. The secondary outcome was all-cause mortality occurring between 12 and 18 months after ICU admission. An additional secondary outcome was care days alive and at home within 90 days after ICU discharge (DAH90).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eBaseline characteristics were summarized using descriptive statistics. Categorical variables were presented as counts and percentages, while continuous variables were expressed as medians with interquartile ranges (IQR). Univariable and multivariable logistic regression analyses were used to identify factors independently associated with new-onset SSRI use. Covariates included age, sex, income, education level, somatic comorbidity (measured by the Charlson Comorbidity Index, CCI), psychiatric comorbidity, substance abuse, surgical procedures, and ICU length of stay. Results were reported as odds ratios (OR) with corresponding 95% confidence intervals (CI).\u003c/p\u003e \u003cp\u003eTo evaluate the association between new-onset SSRI use and long-term mortality, Cox proportional hazards regression models were applied. The models were adjusted for age, sex, income, education, comorbidities, and ICU length of stay. Hazard ratios (HR) with 95% CI were reported.\u003c/p\u003e \u003cp\u003eThe DAH90 metric, a validated patient-centered outcome measure, was derived from mortality and hospitalization records for each quarter before and after ICU admission, following the general methodology described by Myles and colleagues\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. For patients who died within respective quarter, the duration of hospital stay was, as suggested by Myles, given a value of zero.\u003c/p\u003e \u003cp\u003eA \u003cem\u003ep\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. All analyses were performed using Stata/SE 16.1 (StataCorp, College Station, TX, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 31,358 patients were initially identified as having been admitted to a cardiothoracic intensive care unit (ICU) in Sweden between 2010 and 2017. After excluding patients who died within 90 days of ICU discharge (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1,700) and those with a history of antidepressant use within six months prior to admission (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2,652), the final study cohort consisted of 27,006 patients (Fig. \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe baseline characteristics of the study cohort are summarized in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age was 68 years (interquartile range [IQR] 60\u0026ndash;74), and 74.0% were male. A substantial proportion had pre-existing comorbidities, with 38.6% showing a Charlson Comorbidity Index (CCI) greater than 1. Psychiatric comorbidity was present in 3.4%, and 1.8% had a diagnosis of substance abuse.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eGeneral characteristics for patients included.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCardiothoracic ICU patients\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCount\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e27 006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e68 (60, 74)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e19 991 (74.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncome categories, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e2594 (9.6)\u003c/p\u003e\n \u003cp\u003e22 015 (81.8)\u003c/p\u003e\n \u003cp\u003e2290 (8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation level, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e8700 (32.7)\u003c/p\u003e\n \u003cp\u003e11 396 (42.9)\u003c/p\u003e\n \u003cp\u003e6487 (24.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCCI categories, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI 0\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI\u0026thinsp;\u0026gt;\u0026thinsp;1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e7978 (29.5)\u003c/p\u003e\n \u003cp\u003e8608 (31.9)\u003c/p\u003e\n \u003cp\u003e10 420 (38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003ePsychiatric comorbidity, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e913 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubstance abuse, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e483 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcute myocardial infarction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e8048 (29.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCongestive heart failure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e5035 (18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeripheral vascular disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e3981 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCerebrovascular disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e2208 (8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eDementia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e46 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOPD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e2703 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eRheumatoid disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e887 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeptic ulcer disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e468 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild liver disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e352 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate/severe liver disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e79 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes w/o complications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e5558 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes with complications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1549 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemiplegia or paraplegia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e155 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eRenal disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1101 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e2481 (9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetastatic cancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e221 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eAIDS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e30 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU length of stay, days\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0\u0026ndash;2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3\u0026ndash;7\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt; 7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e19 827 (73.4)\u003c/p\u003e\n \u003cp\u003e5789 (21.4)\u003c/p\u003e\n \u003cp\u003e1390 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAcute care\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eElective\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo surgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e1560 (5.8)\u003c/p\u003e\n \u003cp\u003e24 026 (89.0)\u003c/p\u003e\n \u003cp\u003e1420 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eCategorical parameters are presented as n (%), continuous parameters as median with interquartile range (IQR), CCI, Charlson Comorbidity Index; COPD, Chronic Obstructive Pulmonary Disease; AIDS, Acquired Immune Deficiency Syndrome; ICU, Intensive Care Unit.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eOf the 27,006 patients, 2,051 (7.6%) initiated SSRI therapy within the first year after discharge. Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e compares baseline characteristics between new SSRI users and non-users. Compared to non-users, SSRI initiators were more often female (66.0% vs. 74.7%), had lower income (11.7% vs. 9.5%), and a higher prevalence of comorbidities (CCI\u0026thinsp;\u0026gt;\u0026thinsp;1: 49.1% vs. 37.7%). Psychiatric comorbidity (10.2% vs. 2.8%) and substance abuse (4.4% vs. 1.6%) were also more frequent among new SSRI users. Moreover, these patients had a longer median ICU stay. The proportion of patients with a dispensed SSRI prescription increased consistently throughout the follow-up period of two years (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eGeneral characteristics in included cardiothoracic ICU patients stratified by use of antidepressant medication during the first twelve months after ICU care\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCount\u003c/strong\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eNon-SSRI user\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eSSRI user\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e24 955\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e2051\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e68 (60, 74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e68 (58, 75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e18 637 (74.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e1354 (66.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncome categories, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e2355 (9.5)\u003c/p\u003e\n \u003cp\u003e20 344 (81.9)\u003c/p\u003e\n \u003cp\u003e2156 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e239 (11.7)\u003c/p\u003e\n \u003cp\u003e1671 (81.8)\u003c/p\u003e\n \u003cp\u003e134 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation level, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e7978 (32.5)\u003c/p\u003e\n \u003cp\u003e10 519 (42.8)\u003c/p\u003e\n \u003cp\u003e6072 (24.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e722 (35.8)\u003c/p\u003e\n \u003cp\u003e877 (43.5)\u003c/p\u003e\n \u003cp\u003e415 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCCI categories, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI 0\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI\u0026thinsp;\u0026gt;\u0026thinsp;1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e7527 (30.2)\u003c/p\u003e\n \u003cp\u003e8016 (32.1)\u003c/p\u003e\n \u003cp\u003e9412 (37.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e451 (22.0)\u003c/p\u003e\n \u003cp\u003e592 (28.9)\u003c/p\u003e\n \u003cp\u003e1008 (49.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003ePsychiatric comorbidity, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e704 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e209 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubstance abuse, count (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e393 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e90 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcute myocardial infarction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e7391 (29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e657 (32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCongestive heart failure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e4584 (18.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e451 (22.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeripheral vascular disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e3605 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e376 (18.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCerebrovascular disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1947 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e261 (12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eDementia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e42 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e4 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOPD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e2407 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e296 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eRheumatoid disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e793 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e94 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeptic ulcer disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e423 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e45 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild liver disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e312 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e40 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate/severe liver disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e69 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e10 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes w/o complications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e5062 (20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e496 (24.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetes with complications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e1397 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e152 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemiplegia or paraplegia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e125 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e30 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eRenal disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e987 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e114 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e2249 (9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e232 (11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetastatic cancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e196 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e25 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eAIDS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e28 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e2 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU length of stay, days\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0\u0026ndash;2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3\u0026ndash;7\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt; 7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e18 595 (74.5)\u003c/p\u003e\n \u003cp\u003e5274 (21.1)\u003c/p\u003e\n \u003cp\u003e1086 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e1232 (60.1)\u003c/p\u003e\n \u003cp\u003e515 (25.1)\u003c/p\u003e\n \u003cp\u003e304 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAcute care\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eElective\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo surgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e1367 (5.5)\u003c/p\u003e\n \u003cp\u003e22 345 (89.5)\u003c/p\u003e\n \u003cp\u003e1243 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e193 (9.4)\u003c/p\u003e\n \u003cp\u003e1681 (82.0)\u003c/p\u003e\n \u003cp\u003e177 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003eCategorical parameters are presented as n (%), continuous parameters as median with interquartile range (IQR), CCI, Charlson Comorbidity Index; COPD, Chronic Obstructive Pulmonary Disease; AIDS, Acquired Immune Deficiency Syndrome; ICU, Intensive Care Unit.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eThe proportion of patients with a dispensed SSRI prescription increased progressively during the follow-up period. As shown in Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, 3.28% had initiated SSRI therapy during the first quarter after discharge, increasing to 4.93% by the eighth quarter.\u003c/p\u003e\n\u003cp\u003eResults from the univariable and multivariable logistic regression analyses are presented in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. After adjustment for potential confounders, several variables remained independently associated with an increased risk of new-onset SSRI use. These included pre-existing psychiatric comorbidity (odds ratio [OR] 3.21; 95% confidence interval [CI] 2.69\u0026ndash;3.83), substance abuse (OR 1.67; 95% CI 1.29\u0026ndash;2.17), and higher somatic comorbidity (CCI\u0026thinsp;\u0026gt;\u0026thinsp;1: OR 1.62; 95% CI 1.44\u0026ndash;1.83). An ICU length of stay exceeding seven days was also a significant risk factor (OR 3.47; 95% CI 2.98\u0026ndash;4.03). In contrast, male sex was independently associated with lower odds of new-onset SSRI use (OR 0.68; 95% CI 0.61\u0026ndash;0.75).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\" class=\"fr-table-selection-hover\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eUnivariate and multivariable logistic regression analyses, associations with initiation of antidepressant medication presented as OR (95% CI).\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\n \u003cp\u003eAge categories\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e18\u0026ndash;45\u003c/p\u003e\n \u003cp\u003e46\u0026ndash;60\u003c/p\u003e\n \u003cp\u003e61\u0026ndash;70\u003c/p\u003e\n \u003cp\u003e71\u0026ndash;80\u003c/p\u003e\n \u003cp\u003e80-\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003eMultivariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.92 (0.76\u0026ndash;1.12)\u003c/p\u003e\n \u003cp\u003e0.66 (0.55\u0026ndash;0.79)\u003c/p\u003e\n \u003cp\u003e0.76 (0.63\u0026ndash;0.91)\u003c/p\u003e\n \u003cp\u003e1.01 (0.81\u0026ndash;1.26)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.05 (0.86\u0026ndash;1.29)\u003c/p\u003e\n \u003cp\u003e0.75 (0.61\u0026ndash;0.92)\u003c/p\u003e\n \u003cp\u003e0.83 (0.68\u0026ndash;1.02)\u003c/p\u003e\n \u003cp\u003e1.09 (0.85\u0026ndash;1.38)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e0.66 (0.60\u0026ndash;0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003e0.68 (0.61\u0026ndash;0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncome categories\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.81 (0.70\u0026ndash;0.93)\u003c/p\u003e\n \u003cp\u003e0.61 (0.49\u0026ndash;0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.95 (0.82\u0026ndash;1.03)\u003c/p\u003e\n \u003cp\u003e0.93 (0.73\u0026ndash;1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation level\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLow\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHigh\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.92 (0.83\u0026ndash;1.02)\u003c/p\u003e\n \u003cp\u003e0.76 (0.67\u0026ndash;0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.92 (0.83\u0026ndash;1.03)\u003c/p\u003e\n \u003cp\u003e0.80 (0.70\u0026ndash;0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eCCI categories\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI 0\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCCI\u0026thinsp;\u0026gt;\u0026thinsp;1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.23 (1.09\u0026ndash;1.40)\u003c/p\u003e\n \u003cp\u003e1.79 (1.59\u0026ndash;2.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.21 (1.06\u0026ndash;1.37)\u003c/p\u003e\n \u003cp\u003e1.62 (1.44\u0026ndash;1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003ePsychiatric comorbidity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e3.91 (3.33\u0026ndash;4.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003e3.21 (2.69\u0026ndash;3.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubstance abuse\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e2.87 (2.27\u0026ndash;3.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003e1.67 (1.29\u0026ndash;2.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU length of stay, days\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0\u0026ndash;2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3\u0026ndash;7\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt; 7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.47 (1.32\u0026ndash;1.64)\u003c/p\u003e\n \u003cp\u003e4.23 (3.67\u0026ndash;4.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e1.31 (1.17\u0026ndash;1.47)\u003c/p\u003e\n \u003cp\u003e3.47 (2.98\u0026ndash;4.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo surgery\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eElective\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAcute care\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.53 (0.45\u0026ndash;0.62)\u003c/p\u003e\n \u003cp\u003e0.99 (0.80\u0026ndash;1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c4\" style=\"width: 22.245%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003cp\u003e0.68 (0.57\u0026ndash;0.81)\u003c/p\u003e\n \u003cp\u003e0.91 (0.72\u0026ndash;1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colname=\"c5\" style=\"width: 10.6121%;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eCCI, Charlson Comorbidity Index; ICU, Intensive Care Unit\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eBetween 12 and 18 months post-ICU admission, 298 patients died, including 49 who had initiated SSRI therapy. In unadjusted analyses, new-onset SSRI use was associated with an increased risk of mortality (hazard ratio [HR] 2.5; 95% CI 1.8\u0026ndash;3.4). This association persisted after adjusting for age, sex, comorbidities, and ICU length of stay (adjusted HR 1.9; 95% CI 1.4\u0026ndash;2.6). Further analysis of causes of death revealed that mental and behavioral disorders accounted for a significantly greater proportion of deaths among new SSRI users compared with non-users (Supplemental Digital Content. Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e displays care days alive out of hospital. Values are shown separately for patients with and without SSRI treatment.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis large, nationwide cohort study provides insights into the long-term psychological burden following cardiothoracic intensive care. We found that a substantial proportion of patients (7.6%) who were previously na\u0026iuml;ve to antidepressants initiated SSRI therapy within one year of discharge. This finding underscores the importance of systematic screening for psychological morbidity in the post-ICU population\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. The steady increase in antidepressant use observed throughout the follow-up period suggests that psychological sequelae may have a delayed onset or progress gradually, emphasizing the need for extended follow-up beyond hospital discharge.\u003c/p\u003e \u003cp\u003ePre-existing psychiatric comorbidity and substance abuse were associated with an increased likelihood of new-onset SSRI use, aligning with previous studies suggesting that these factors may contribute to greater vulnerability to post-ICU psychological morbidity\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. While causality cannot be inferred, these findings indicate that patients with such pre-existing conditions could benefit from more attentive follow-up. A more individualized and risk-informed approach to post-ICU care, where psychosocial vulnerabilities are taken into consideration, may help identify patients in need of early assessment or support.\u003c/p\u003e \u003cp\u003eSocioeconomic disparities also played a notable role. Patients with lower income or education had significantly higher odds of initiating SSRI therapy. This aligns with earlier studies demonstrating that social disadvantage is associated with poorer health outcomes and higher mortality among ICU survivors\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Multiple mechanisms may underlie this association, including greater financial stress, limited access to mental health services, and differences in health literacy. Such inequities can lead to delayed recognition or undertreatment of psychological distress, resulting in a greater reliance on pharmacological therapy. Addressing these disparities is crucial for ensuring equitable, high-quality post-ICU care.\u003c/p\u003e \u003cp\u003eClinical characteristics of the ICU stay also influenced SSRI initiation. A longer ICU length of stay was an independent risk factor, indicating that prolonged exposure to critical illness and intensive interventions may contribute to psychological distress. Extended ICU stays often involve increased sedation, sleep disruption, delirium, and invasive monitoring, all of which have been associated with long-term mental health impairment\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Among cardiothoracic patients, additional factors such as cardiopulmonary bypass may trigger neuroinflammatory and microembolic processes that could affect cognitive and psychological outcomes\u003csup\u003e\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, the experience of an acute, unplanned surgical event, as opposed to elective surgery, has been associated with heightened psychological trauma and distress, potentially contributing to the elevated odds of SSRI use observed in this study\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. These findings highlight the importance of early psychological support and preventive interventions during and after ICU care\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe relationship between new-onset SSRI use and long-term mortality is likely complex. On one hand, SSRI initiation may serve as a proxy for underlying depression, a condition itself known to be associated with increased mortality risk\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. On the other hand, it is reasonable to assume that, for patients suffering from such psychological distress, antidepressant therapy represents an appropriate and often necessary intervention. It cannot be excluded that the observed mortality might have been even higher in the absence of treatment. However, this hypothesis cannot be evaluated within the framework of the present observational design and should therefore be interpreted with caution.\u003c/p\u003e \u003cp\u003eThe higher proportion of deaths attributed to mental and behavioral disorders among new SSRI users in our cohort further suggests that these prescriptions may identify a subgroup experiencing more severe or persistent psychological distress. Previous studies have shown that depression following critical illness is not only associated with impaired quality of life but also constitutes an independent predictor of mortality\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. Potential mechanisms include reduced physical activity, poorer adherence to rehabilitation, substance use, and other maladaptive health behaviors\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Collectively, these findings highlight the importance of recognizing and addressing psychological morbidity as an integral component of post-ICU care.\u003c/p\u003e \u003cp\u003ePatients prescribed SSRIs had fewer care days alive and at home for each quarter after ICU admission compared with those without such prescriptions. This association should be interpreted with caution, as it may reflect differences in underlying health status rather than a direct effect of SSRI treatment. It is possible that patients who required SSRIs were more severely ill during their ICU stay or experienced greater physical and psychological vulnerability after discharge. Thus, SSRI use may serve as a proxy for greater morbidity or reduced recovery potential, although this cannot be determined from the present data. Further studies are warranted to explore the mechanisms underlying this association and to clarify whether it reflects pre-existing factors, illness severity, or post-ICU sequelae.\u003c/p\u003e \u003cp\u003eThis study has several strengths, including its large, population-based design, comprehensive data linkage across national registries, and focus on antidepressant-na\u0026iuml;ve patients, enabling a clear evaluation of new-onset use. However, certain limitations must be acknowledged. First, while SSRI dispensing is a validated epidemiological proxy for depression, it does not confirm a clinical diagnosis, and we could neither capture patients with untreated depression nor distinguish prescriptions for anxiety or other indications. Second, registry-based data restrict available variables, preventing adjustment for unmeasured confounders such as delirium, sedation strategy, or social support. Third, excluding patients who died within 90 days of discharge may have introduced selection bias by underestimating early mortality risk. Fourth, the study period (2010\u0026ndash;2017) may not fully reflect current clinical practice, as awareness of post-ICU psychological morbidity and patterns of antidepressant prescribing may have evolved in recent years. Finally, residual confounding cannot be completely ruled out despite adjustment for multiple key variables. Nevertheless, the study\u0026rsquo;s robust design, large sample size, and minimal loss to follow-up enhance both its internal and external validity.\u003c/p\u003e \u003cp\u003eOur findings have important implications for clinical practice and healthcare policy. Targeted interventions for high-risk cardiothoracic ICU survivors are needed, particularly for high-risk groups identified in this study. These programs should adopt a multidisciplinary approach that includes early psychological screening, timely referral to mental health professionals, and access to evidence-based non-pharmacological interventions. In addition, awareness of the potential link between post-ICU SSRI initiation and long-term mortality highlights the need for careful medication review and coordination between intensive care, cardiology, and primary care services.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, new-onset SSRI use is a frequent outcome following cardiothoracic ICU care and is independently associated with increased long-term mortality. These findings emphasize that psychological well-being is not merely a quality-of-life issue but a potentially important factor in long-term prognosis. Future research should focus on prospective studies using standardized assessments of psychological morbidity and interventional trials testing early, structured psychological follow-up to determine whether early identification and treatment of mental health needs can improve outcomes after cardiothoracic intensive care.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eATC Anatomical Therapeutic Chemical code\u003c/p\u003e\u003cp\u003eCCI Charlson Comorbidity Index\u003c/p\u003e\u003cp\u003eCI Confidence Interval(s)\u003c/p\u003e\u003cp\u003eHR Hazard ratio\u003c/p\u003e\u003cp\u003eICU Intensive Care Unit\u003c/p\u003e\u003cp\u003eIQR Interquartile Range\u003c/p\u003e\u003cp\u003eLISA Longitudinal Integration Database for Health Insurance and Labour Market Studies\u003c/p\u003e\u003cp\u003eOR Odds ratio\u003c/p\u003e\u003cp\u003ePICS Post-Intensive Care Syndrome\u003c/p\u003e\u003cp\u003eSIR Swedish Intensive Care Registry\u003c/p\u003e\u003cp\u003eSSRI Selective Serotonin Reuptake Inhibitor\u003c/p\u003e\u003cp\u003eSTROBE Strengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eData Availability\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets supporting the findings of this study are held under license and are not publicly available due to restrictions imposed by the Swedish Intensive Care Registry (SIR) and the National Board of Health and Welfare (NBHW). Data may, however, be made available from the authors upon\u0026nbsp;reasonable request\u0026nbsp;and contingent upon obtaining formal permission from the SIR and the NBHW.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe extend our sincere gratitude to all participating ICUs and their dedicated staff for their essential contributions and tireless work in collecting and submitting data to the Swedish Intensive Care Registry (SIR).\u003c/p\u003e\n\u003cp\u003eThis research was made possible through financial support from the following organizations: Region Stockholm, the David and Astrid Hagelén foundation, Svenska Läkaresällskapet, Stiftelsen Serafimerlasarettet, the Fredrik and Ingrid Thuring’s foundation, and Magnus Bergvall’s foundation.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthor Contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEvO\u0026nbsp;and JE served as the main investigators, taking primary responsibility for study design, data collection, statistical analysis, and drafting of the manuscript. ME, EL, and AO contributed significantly to all phases of the project, including study design, data interpretation, critical revision of the analysis, and final manuscript writing. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAO, EL, and ME declare no competing interests. EvO discloses receiving funding from the Svenska Läkaresällskapet, and Stiftelsen Serafimerlasarettet. Both EvO and JE received funding from Region Stockholm. Crucially, none of the funding agents were involved in the study design, data collection, data analysis, manuscript preparation, or the decision to publish.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMorgan, A. Long-term outcomes from critical care. \u003cem\u003eSurg. 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Care\u003c/em\u003e. \u003cb\u003e22\u003c/b\u003e, 310. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13054-018-2223-6\u003c/span\u003e\u003cspan address=\"10.1186/s13054-018-2223-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Intensive Care Units, Depression, Antidepressive Agents, Socioeconomic Factors, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-9136479/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9136479/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eSurvival after cardiothoracic intensive care has improved, yet long-term psychological and physical morbidities remain common. Depression is frequent after intensive care, and initiation of antidepressant therapy may serve as a proxy for clinically significant psychological distress. We investigated the incidence, associated factors, and outcomes related to new-onset antidepressant use among cardiothoracic ICU survivors in Sweden.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eNationwide, population-based cohort study using linked Swedish registers. We included 27,006 patients who survived\u0026thinsp;\u0026ge;\u0026thinsp;90 days after their first cardiothoracic ICU admission (2010\u0026ndash;2017) and were na\u0026iuml;ve to antidepressants during the preceding 6 months. The primary outcome was new-onset SSRI use within 12 months after discharge. Multivariable logistic regression identified associated factors, and Cox models assessed long-term mortality.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eOverall, 2,051 patients (7.6%) initiated SSRI therapy within one year. Factors associated with new-onset antidepressant use included psychiatric comorbidity, substance abuse, higher somatic comorbidity (CCI\u0026thinsp;\u0026gt;\u0026thinsp;1), and ICU length of stay\u0026thinsp;\u0026gt;\u0026thinsp;7 days, while male sex was associated with lower odds. New-onset SSRI use was independently associated with higher long-term mortality (adjusted HR 1.9; 95% CI 1.4\u0026ndash;2.6). Patients prescribed SSRIs also had fewer care days alive and at home within 90 days after ICU discharge (DAH90), indicating delayed recovery or greater post-ICU morbidity.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eNew-onset SSRI use after cardiothoracic critical illness was associated with markers of higher mortality and fewer early days at home. These findings underscore the importance of addressing mental health in post-ICU care.\u003c/p\u003e","manuscriptTitle":"New-Onset Antidepressant Use After Cardiothoracic Intensive Care is Associated with Increased Long-Term Mortality","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 07:19:50","doi":"10.21203/rs.3.rs-9136479/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"16caf3a6-bef5-41b6-b9a7-bf773251b697","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":65447903,"name":"Health sciences/Cardiology"},{"id":65447904,"name":"Health sciences/Diseases"},{"id":65447905,"name":"Health sciences/Health care"},{"id":65447906,"name":"Health sciences/Medical research"},{"id":65447907,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-04-26T13:39:45+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 07:19:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9136479","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9136479","identity":"rs-9136479","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}