Antidepressant use in children with congenital long QT syndrome

Antidepressant use in children with congenital long QT syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Antidepressant use in children with congenital long QT syndrome Nicholas E Rebhan, Liyun Zhang, Ke Yan, Anoop K Singh, Joshua Kovach This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7829018/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background Congenital long QT syndrome (LQTS) conveys a significant risk of cardiac events. Primary management includes avoiding medications that prolong the QTc. Many antidepressant medications are known to be QT-prolonging, but there is scant literature on whether their use increases event rate or prolongs the QTc in LQTS. Objective The objectives of this study are to determine the prevalence of depression and anxiety in patients with congenital LQTS, and to evaluate the effect of antidepressant treatment on frequency of LQTS-triggered events and QTc changes during antidepressant treatment. Methods This was a single-center, retrospective study. Patients were divided based on whether they were prescribed antidepressants during the study period. Incidence of LQTS-triggered events and QTc measurements before and after antidepressant use were recorded for comparison. Results Ninety-eight subjects were identified for analysis. Most (92%) were prescribed beta-blockers as treatment for LQTS. Twenty-seven percent (n = 27) of the cohort were diagnosed with anxiety and/or depression. Of these, 15 received antidepressant therapy. We found no significant difference in the LQTS event rate or QTc measurements in patients prescribed antidepressants. Baseline median (IQR) QTc 467 (460, 479) ms vs median (IQR) of first QTc post-antidepressant 482 (462, 487), p = 0.27. Conclusion In this single-center study, the prevalence of anxiety and depression in patients with LQTS was consistent with the general population. Rates of treatment were also comparable. Our findings suggest that certain antidepressant therapy may be safe in patients with LQTS on beta-blockers. Further study across multiple centers and with a larger cohort may help clarify the safety of these medications. Congenital Long QT Syndrome QT interval depression anxiety antidepressant Figures Figure 1 Figure 2 Introduction Congenital long QT syndrome (LQTS) is an inherited channelopathy characterized by a prolonged QTc on ECG, predisposing individuals to ventricular arrhythmias. It is estimated to affect 1 in every 2000-2,500 people. 1 , 2 Typically, the presenting symptoms include syncope, seizures, or sudden cardiac arrest (SCA), although diagnosis through family history and genetic testing is increasingly common. 3 The risk of SCA in LQTS patients varies based on factors such as QT interval (i.e. QTc > 500 ms), prior LQTS-triggered events, sex, and specific genetic variant. The overall prevalence of a first LQTS-triggered event before 40 years of age has been shown to range from 30–46 percent depending on the genetic locus of the variant 4 . Management focuses on reducing the risk of LQTS-triggered events, primarily with beta-blockers and avoiding QT-prolonging medications. Depression and anxiety are two prevalent psychiatric disorders in childhood, impacting psychosocial functioning and educational achievement. Studies indicate a one-year incidence of depression in adolescence of around 8%, with a lifetime prevalence of 11%, 5, 6 while the lifetime prevalence of anxiety disorders range from 10 to 30%. 7, 8 They are often comorbid with each other or with other psychiatric conditions and may frequently be undertreated. 9 Management often entails psychotherapy and pharmacotherapy, with selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) as first-line pharmacotherapy. 10 , 11 , 12 The management of depression and anxiety in patients with LQTS presents a unique dilemma. While population-based studies suggest minimal QT prolongation with some SSRIs, 13, 14 nearly all antidepressants pose a risk of prolonging the QTc and triggering torsades de pointes (TdP), warranting their inclusion on the “Drugs to Avoid in Patients with LQTS” list. 15 This may lead to provider uncertainty or confusion when trying to manage patients with these comorbid conditions. Studies conducted by Weeke, et al. and Wang, et al. have examined the effect of proarrhythmic pharmacotherapy, but these have focused primarily on adult populations 26 , 28 . This study aims to establish anxiety and depression prevalence in LQTS patients, determine LQTS-triggered event frequency during antidepressant treatment, and assess QTc changes while on antidepressant medications, specifically in a primarily adolescent and pediatric cohort. Methods Study Population This was a single-center retrospective study which was approved by the Medical College of Wisconsin Institutional Review Board. Patients with clinically and/or genetically diagnosed LQTS were identified through an electronic medical record query of patients followed by the Children’s Hospital of Wisconsin (CHW) Electrophysiology group. This query was compared against a separate registry of LQTS patients followed by the Electrophysiology group at CHW to ensure completeness. Patients are followed in EP clinic every 6–12 months depending on clinical status and patient/provider preference. ECGs were routinely performed during these visits for patients on QT prolonging drugs. Compliance with either beta-blocker or antidepressant was patient reported. All patients treated with beta-blockers were treated with either nadolol or propranolol based on weight and assessment of response on ambulatory monitors and exercise stress testing. Patients were included in this study if they had been diagnosed with LQTS between 2012 and 2020 and were followed by the Electrophysiology group at CHW. LQTS is diagnosed primarily based on phenotypic presentation based on current Schwartz score criteria with genetic testing performed for confirmation and subtype determination. Some patients were identified based on family member cascade testing with phenotype confirmed with clinical testing. QTcs were calculated using Bazett’s formula with measurement of the termination of the QT interval based on when the tangent of the downslope crossed the baseline 29 . All measurements were performed by electrophysiologists. Exclusion criteria included structural heart disease or prescription of other QT-prolonging medications prior to antidepressant initiation. Patients were divided into two cohorts based on whether they had been prescribed antidepressants during the study period. Data Collection and Endpoints The electronic medical record was reviewed for basic demographic information, LQTS genotype, LQTS therapy, and any LQTS-triggered events either prior to or after diagnosis of LQTS. For patients started on antidepressant therapy, additional information was gathered on the specific type of antidepressant drug used, age at initiation, and treatment duration. For all patients, QTc measurements from up to 10 separate ECGs were obtained while not on antidepressants. For those patients who were started on antidepressants, QTc measurements were obtained from up to 10 ECGs after initiation of antidepressant, and any LQTS-triggered events while on antidepressant therapy were recorded. LQTS-triggered events were defined as syncope or seizures that were otherwise unexplained, documented ventricular arrhythmia, appropriate implantable cardioverter-defibrillator (ICD) shock, or sudden cardiac arrest/death. The primary endpoint of the study was the incidence of LQTS-triggered events without antidepressants compared to while being on antidepressant therapy. The secondary endpoint of this study was any difference in QTc after initiating antidepressant therapy. Statistical Analysis Continuous variables were summarized as median and interquartile range (IQR), and categorical variables were summarized as frequency count and percentage (%). To compare antidepressant groups, the Mann-Whitney Wilcoxon test was used for continuous variables and the Chi-square test or a Fisher’s exact test was used for categorical variables. The Wilcoxon Signed rank test was used to assess the changes of QTc measurements in antidepressant patients’ pre vs. post antidepressant use. A two-sided p-value < 0.05 was used as the term of statistically significant. All data analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC) and Graphpad Prism v10. Results LQTS Demographics We identified a cohort of 98 patients diagnosed with LQTS who met our inclusion criteria (Table 1 ). The median (IQR) age at LQTS diagnosis was 6 (1, 11) years with median (IQR) average baseline QTc 465 (451, 478) ms. Only 14% (n = 14) of the patients were symptomatic at presentation, while 84% (n = 82) had a family history of LQTS, and 36% (n = 35) having a family history of SCA. Genotype testing revealed an expected subtype distribution with LQTS type 1 in 67% (n = 66) of the cohort, LQTS type 2 in 24% (n = 23), and LQTS type 3 in only one patient. Eight percent (n = 8) of the patients either had other rare variants or an unidentified genotype. Table 1 Cohort demographics and comparisons Column1 Column2 Entire cohort LQTS alone LQTS + antidepressants P- value Total Patients 98 83 (85) 15 (15) Sex male/female (% male) 45/53 (46) 43/40 (52) 2/13 (13) 0.006 § Age at LQTS diagnosis (yrs), median (IQR) 6 (1, 11) 5 (0, 11) 11 (5, 14) 0.06 Average baseline QTc (ms), median (IQR) 465 (451, 478) 464 (450, 477) 467 (460, 479) 0.39 Symptomatic Presentation 14 (14) 11 (13) 3 (20) 0.45 Family history of LQTS 84 (85) 69 (85) 13 (86) > 0.99 Family history of SCD 35 (36) 27 (32) 8 (53) 0.12 LQTS genotype > 0.99 LQTS 1 66 (67) 55 (66) 11 (73) LQTS 2 23 (24) 20 (24) 3 (20) LQTS 3 1 (1) 1 (1) 0 (0) Other € 3 (3) 3 (4) 0 (0) Unknown 5 (5) 4 (5) 1 (7) LQTS Treatment Beta-blocker 90 (92) 76 (92) 14 (93) > 0.99 ICD 3 (3) 0 (0) 3 (2) 0.003 § LCSD 2 (2) 2 (2) 0 (0) > 0.99 Psychiatric diagnosis None 71 (72) 12 (14) 0 (0) < 0.0001 § Anxiety 19 (19) 6 (7) 13 (73) < 0.0001 § Depression 18 (18) 6 (7) 12 (80) 0.99 LQTS = long QT syndrome; SCD = sudden cardiac death; ICD = implantable cardioverter-defibrillator; LCSD = left cardiac sympathetic denervation †Values are given as no. (%) unless otherwise indicated ‡Autism spectrum disorder + ADHD €Other genotypes: SNTA (1), LQT5 (2) §Statistically significant Following diagnosis, ninety patients (92%) received beta-blocker therapy, while only three patients underwent implantation of an ICD for secondary prevention, and two patients underwent LCSD. All three ICD patients received antidepressants, whereas neither of the LCSD patients did. Depression/Anxiety A total of 27 LQTS patients were diagnosed with anxiety, depression, or both (Fig. 1 ). Nineteen percent (n = 19) of the entire cohort were diagnosed with anxiety, 18% (n = 18) with depression, and one patient was diagnosed with attention deficit hyperactivity disorder (ADHD) comorbid with autism spectrum disorder. Of the 27 patients diagnosed with anxiety or depression, 15 (56%) were prescribed antidepressant therapy. There was a significant difference in the prescription rates of antidepressants between female and male patients (25% vs. 4%; p = 0.006). There was no known interruption in antidepressant therapy based on patient reporting and patients already on antidepressant therapy at the time of their LQTS diagnosis were not included in the analysis. The median (IQR) average baseline QTc in these 15 patients was 467 (460, 479) ms. Only four patients had experienced a LQTS-related event at the time of psychiatric diagnosis. Similar to the broader cohort, the majority (87%) of these patients had a family history of LQTS, and 53% had a family history of SCA. All patients but one had a confirmed positive genotype test, with the majority being LQTS type 1 (11 with LQTS1, 3 with LQTS2, and 1 patient with unknown genotyping). Like the overall cohort, the LQTS patients managed with antidepressant medications were almost all concurrently treated with beta-blockers (93%). Antidepressant Therapy The median age (IQR) at which antidepressant therapy was initiated was 15 (12, 18) years (see Table 2 ). SSRIs were the most prescribed class of antidepressants (80%), followed by bupropion alone in two patients and buspirone alone in one patient. Sertraline was the predominant SSRI, prescribed to six patients, followed by fluoxetine in five patients. One patient required multiple medications, including various combinations of buspirone, fluoxetine, lamotrigine, and sertraline, due to refractory anxiety and depression. Table 2 LQTS and Antidepressant Treatment Column2 Column1 No. of patients on antidepressants 15 Age at initiation (yrs), median (IQR) 15 (12, 18) Antidepressant Treatment SSRI/SNRI 12 (80) Buproprion 3 (20) Buspirone 1 (7) LQTS = long QT syndrome; SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin/norepinephrine reuptake inhibitor. †Values are given as no. (%) unless otherwise indicated. Table 3 Individual characteristics of the antidepressant cohort Case M/F Gene Age at LQTS diagnosis (yrs) Baseline Avg QTc (ms) Symptomatic presentation Family hx LQTS Family hx SCD ICD Beta-blocker therapy Psychiatric diagnosis Antidepressant Age at initiation (yrs) Duration of therapy (yrs) LQTS event on antidepressant 1 F LQTS 1 11 483 Y - - + Y Anxiety, Depression Sertraline 21 2 Syncope 2 F LQTS 1 8 497 N + + - Y Depression Sertraline 13 6 3 F LQTS 1 14 † N + - - Y Anxiety, Depression Fluoxetine Not documented - 4 F LQTS 1 15 470 N + + - Y Anxiety, Depression Escitalopram 15 2 5 F LQTS 1 14 † N + + - Y Anxiety, Depression Multiple‡ 12 10 6 F LQTS 2 2 475 N + + - Y Anxiety, Depression Fluoxetine 19 1 7 M LQTS 2 11 464 N + - - Y Anxiety, Depression Sertraline 13 2 8 F LQTS 2 4 425 Y - - + N Anxiety, Depression Sertraline 15 2 9 F LQTS 1 10 457 Y + - - Y Depression Buproprion 12 < 1 10 M LQTS 1 < 1 464 N + - - Y Anxiety Sertraline 11 1 Syncope 11 F Unknown 8 496 N + - - Y Anxiety, Depression Fluoxetine 15 6 Syncope 12 F LQTS 1 14 467 N + + - Y Anxiety, Depression Buproprion 16 1 Syncope 13 F LQTS 1 14 452 N + + - Y Anxiety, Depression Buspirone 20 2 14 F LQTS 1 16 460 N + + - Y Anxiety Fluoxetine 18 3 15 F LQTS 1 5 479 N + + + Y Anxiety, Depression Fluoxetine + Sertraline 11 4 Arrhythmia †No baseline QTc available (i.e., patient was diagnosed with LQTS while already on antidepressant medication) ‡Buspirone, fluoxetine, lamotrigine, and sertraline There was no significant association found between LQTS genotype and antidepressant treatment. Notably, all patients (n = 3) who received ICDs were also treated with antidepressants, compared to only 13% of those who did not receive ICDs (p = 0.003). Two out of the 15 patients prescribed antidepressants were diagnosed with LQTS after initiating treatment with antidepressants. Overall, there was no significant difference observed in the rate of LQTS-related events between patients who received antidepressants and those who did not (Table 4 ). Syncope was the most frequently reported event in both groups post antidepressants, with no significant disparity (22% and 27%, respectively; p = 0.74). Only two of the patients who were not prescribed antidepressants experienced documented ventricular arrhythmia compared to one patient while on antidepressants (p = 0.40). Furthermore, there was no significant variance between the baseline QTc and the QTc recorded on ECGs obtained after the initiation of antidepressant therapy, either by paired analysis or longitudinal monitoring on antidepressant therapy (Fig. 2 ). Table 4 Comparison of LQTS events Event Antidepressant (-) Antidepressant (+) P value Syncope 18 (22) 4 (27) 0.74 Seizure 5 (6) 0 > 0.99 Arrhythmia 2 (2) 1 (7) 0.4 SCD 1 (1) 0 > 0.99 Overall 21 (25) 5 (33) 0.53 LQTS = long QT syndrome; SCA = sudden cardiac arrest †Values are given as no. (% of cohort) Discussion Prescribing antidepressant therapy to individuals with congenital LQTS presents a significant and frequently encountered dilemma. These medications lack specific testing in LQTS patients, and the few studies which have examined the effect of proarrhythmic pharmacotherapies have centered mostly on adult populations whereas our population is primarily pediatric 26 , 28 . As such, there are no specific recommendations for follow up of patients with LQTS who are prescribed antidepressant therapy. Among the SSRIs available in the US market, such as fluoxetine, paroxetine, and sertraline, some are categorized as having a “Conditional Risk” of Torsades de Pointes (TdP) on the CredibleMeds website, while others, like citalopram and escitalopram, are labeled as “Known Risk” of TdP. 15 However, asserting any antidepressant as universally “safe” for use in this population remains challenging. Moreover, various subtypes of LQTS may exhibit distinct sensitivities to these medications depending on the specific ion channel affected. 16 Anxiety and depression are often under-addressed in the general population, with individuals with LQTS potentially facing even greater under treatment due to the risk of QT prolongation and TdP. While normal population-based studies suggest minimal QT prolongation with some SSRIs (hence their “conditional risk” categorization), no published research has yet examined the actual event rate while patients are on these medications. The use of antidepressants, particularly widely prescribed SSRIs and SNRIs, may be imperative for patients with LQTS who develop one or both comorbid conditions. Patients exhibiting symptoms of both anxiety and depression may find it challenging to fully engage with cognitive behavioral therapy (CBT) and may therefore necessitate pharmacotherapy as a primary treatment. The Treatment for Adolescents with Depression Study, a randomized controlled trial evaluating the effectiveness of CBT vs pharmacotherapy vs combined therapy vs placebo, for treatment of major depressive disorder demonstrated that combination therapy (pharmacotherapy plus cognitive-behavioral therapy/CBT) yielded twice as many patients with significant symptom improvement compared to a pill placebo 30 . Evidence also suggests that short-term combination therapy for depression surpasses either psychotherapy or pharmacotherapy alone. 17 Furthermore, SSRIs and SNRIs are deemed effective for anxiety disorders in both children and adults, particularly in cases of comorbid anxiety and depression. 12 In this single-center pilot study, we investigated the prevalence of anxiety and depression among patients with LQTS, the utilization of antidepressants, and their impact on LQTS-triggered events and the QTc. We identified 19% of patients diagnosed with anxiety and 18% of patients diagnosed with depression, consistent with national prevalence estimates. 8 Similarly, only approximately half of these patients received antidepressant therapy (15 out of 27 diagnosed patients), aligning with national treatment rates, though we are unable to assess if treatment was deferred in our population due to their LQTS diagnosis. The demographic characteristics of LQTS patients who received antidepressants closely resembled those who did not, except for a higher proportion of female patients who received antidepressant than males (25% vs 4%, p = 0.006). During a cumulative 42 years of antidepressant treatment, only 5 of the 15 patients who received antidepressants experienced a LQTS-triggered event, with a comparable event rate observed among patients with LQTS not on antidepressant therapy. Observed event rate on antidepressants was not significantly increased when examining specific event types. Additionally, we noted no discernible increase in the QTc when analyzing serial ECGs during antidepressant therapy. A recent study out of Mayo Clinic has drawn a similar conclusion that LQTS patients with concomitant mental health issues may be safely and effectively treated with QT prolonging medications. This study represents a pioneering effort, focusing specifically on the safety profile of antidepressants in patients with LQTS and their effects on the QTc. Our findings suggest that antidepressants, particularly SSRIs, may be safely employed to manage depression and anxiety in this high-risk cohort, provided patients also receive beta-blocker therapy. Study Limitations/Future Directions This retrospective, single-center cohort provided a modest sample size, making adequate statistical power to explore certain relationships challenging, such as the correlation between LQTS genotype and events during antidepressant use. Future endeavors, such as larger multi-center studies or evaluation of data in the international congenital LQTS registry focused on adolescents and children, could substantially enhance statistical power. This increased power would facilitate more nuanced analyses, such as stratifying results based on LQTS genotype or specific antidepressant medications. It may also shed further light on the significant difference in antidepressant prescription rate between males and females, especially considering female sex has been shown to be an independent risk factor for ventricular arrhythmia in patients with LQTS. 18 Furthermore, gathering information on psychiatric conditions was often restricted as patients typically received antidepressant prescriptions from external offices (e.g., primary care or psychiatry) not affiliated with our institution. Consequently, details regarding diagnosis, initiation, and duration of antidepressant treatment were constrained by the available documentation. Conclusions This pilot study marks the first endeavor to assess the prevalence and outcomes of patients with LQTS undergoing treatment with antidepressants for anxiety and/or depression. Among individuals with LQTS, the prevalence of anxiety and depression mirrors that of the broader reported adolescent and adult population, with similar rates of antidepressant utilization observed. Patients with LQTS undergoing antidepressant therapy did not exhibit an increase in LQTS-triggered events, nor was there significant alteration in their QTc during treatment. This finding underscores the potential safety of prescribing certain antidepressants to patients with LQTS, particularly when accompanied by beta-blocker therapy. However, further research is imperative to reinforce this conclusion. Physicians must continue to carefully balance the risks of undertreating anxiety and/or depression and the potential QT-prolonging effects of antidepressant medications. Abbreviations CBT Cognitive behavioral therapy SCA Sudden cardiac arrest ICD Implantable cardioverter-[AS1] defibrillator SNRI Serotonin and norepinephrine reuptake inhibitor IQR Interquartile range SSRI Selective serotonin reuptake inhibitor LQTS Congenital long QT syndrome[AS2] [NR3] TdP Torsades de Pointes Declarations Author Contribution N.R. collected the data, wrote the main manuscript text, and prepared all figures and tables. L.Z and K.Y. provided data analysis and wrote portions of the results section. All authors reviewed the manuscript and provided edits and alterations throughout the writing process. Acknowledgements: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Data Availability Data is provided within the manuscript. References Priori, S. G., Wilde, A. A., Horie, M., et al. (2013). 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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-7829018","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":533579862,"identity":"11d13241-2f6c-4c7d-bfb3-00fb9053f877","order_by":0,"name":"Nicholas E Rebhan","email":"data:image/png;base64,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","orcid":"","institution":"University of Louisville","correspondingAuthor":true,"prefix":"","firstName":"Nicholas","middleName":"E","lastName":"Rebhan","suffix":""},{"id":533579864,"identity":"08910d63-5c39-479d-acf3-874460f951aa","order_by":1,"name":"Liyun Zhang","email":"","orcid":"","institution":"Medical College of Wisconsin","correspondingAuthor":false,"prefix":"","firstName":"Liyun","middleName":"","lastName":"Zhang","suffix":""},{"id":533579866,"identity":"a9fdd808-c266-4c6b-a966-903c2e8c66e3","order_by":2,"name":"Ke Yan","email":"","orcid":"","institution":"Medical College of Wisconsin","correspondingAuthor":false,"prefix":"","firstName":"Ke","middleName":"","lastName":"Yan","suffix":""},{"id":533579868,"identity":"885946b4-f890-4d4f-aed8-c3bfb261d4e2","order_by":3,"name":"Anoop K Singh","email":"","orcid":"","institution":"Medical College of Wisconsin","correspondingAuthor":false,"prefix":"","firstName":"Anoop","middleName":"K","lastName":"Singh","suffix":""},{"id":533579870,"identity":"ec90cb9a-79e2-43d5-aa80-52b3c16fa9c8","order_by":4,"name":"Joshua Kovach","email":"","orcid":"","institution":"Medical College of Wisconsin","correspondingAuthor":false,"prefix":"","firstName":"Joshua","middleName":"","lastName":"Kovach","suffix":""}],"badges":[],"createdAt":"2025-10-10 16:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7829018/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7829018/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94408948,"identity":"331f61b5-8bd0-47df-8e26-261341912cae","added_by":"auto","created_at":"2025-10-27 14:03:57","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":190634,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptSubmissionformatv4.0.docx","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/432c67c8609ec9e069f0ad98.docx"},{"id":94409174,"identity":"9abf50d4-637a-450c-aefd-8634e9f853d6","added_by":"auto","created_at":"2025-10-27 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14:04:18","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":71616,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/303d9c6d83512aa5b0bf2ae2.png"},{"id":94409847,"identity":"a9afe81b-2e6e-427d-9be0-6cfb4909c432","added_by":"auto","created_at":"2025-10-27 14:04:20","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":53664,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/4be0366d72cbde8b59ee7656.png"},{"id":94410355,"identity":"bf422676-a18f-41d0-9c87-ca7b173c3d65","added_by":"auto","created_at":"2025-10-27 14:04:41","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":33389,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/075affd4caed4a5d18e835fd.png"},{"id":94409348,"identity":"ed3c601a-2c87-4808-b012-79e1f5402b4e","added_by":"auto","created_at":"2025-10-27 14:04:05","extension":"xml","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":86588,"visible":true,"origin":"","legend":"","description":"","filename":"9eee4de4a6e7409b92e266d1da08f9da1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/61645dfe48c157fef7858f8d.xml"},{"id":94410273,"identity":"06e15251-8d26-4c8a-90dc-32e1f824a6cf","added_by":"auto","created_at":"2025-10-27 14:04:37","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":94134,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/a3c9137c61967d0969bf08e4.html"},{"id":94409167,"identity":"2d948913-fb0b-4816-b0b7-8529edf139d9","added_by":"auto","created_at":"2025-10-27 14:04:01","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":163101,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eLQTS patient cohort – 27 patients were diagnosed with depression, anxiety, or a combination of both. Of those patients, 15 were prescribed antidepressants during the study period. D = depression, A = anxiety\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e92% of all LQTS patients were treated with beta-blockers\u003c/em\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/cc7deb4ca1de04e2965acd6f.jpeg"},{"id":94408399,"identity":"f85079f3-05d9-42ea-8ae0-c282569ec98c","added_by":"auto","created_at":"2025-10-27 14:03:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":71616,"visible":true,"origin":"","legend":"\u003cp\u003eSerial QTc changes after starting antidepressants, displayed longitudinally. Again, there was no significant change in QTc over time once starting antidepressants. EKGs were obtained at EP follow up appointments. Baseline = QTc prior to starting antidepressants; Post ‘n’ = QTc from nth EKG after starting antidepressants\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e†\u003c/sup\u003eP-values generated by comparing QTc at each time point after starting antidepressants to baseline QTc\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/aa44387a81e2ce6a57cfe4fb.png"},{"id":94460740,"identity":"19e90339-bb4e-42ab-b48a-e183d31a804a","added_by":"auto","created_at":"2025-10-27 14:57:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1004906,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7829018/v1/96346a1b-d9ae-4616-8982-4664331efee4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Antidepressant use in children with congenital long QT syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCongenital long QT syndrome (LQTS) is an inherited channelopathy characterized by a prolonged QTc on ECG, predisposing individuals to ventricular arrhythmias. It is estimated to affect 1 in every 2000-2,500 people.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Typically, the presenting symptoms include syncope, seizures, or sudden cardiac arrest (SCA), although diagnosis through family history and genetic testing is increasingly common.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The risk of SCA in LQTS patients varies based on factors such as QT interval (i.e. QTc \u0026gt; 500 ms), prior LQTS-triggered events, sex, and specific genetic variant. The overall prevalence of a first LQTS-triggered event before 40 years of age has been shown to range from 30–46 percent depending on the genetic locus of the variant\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Management focuses on reducing the risk of LQTS-triggered events, primarily with beta-blockers and avoiding QT-prolonging medications.\u003c/p\u003e\u003cp\u003eDepression and anxiety are two prevalent psychiatric disorders in childhood, impacting psychosocial functioning and educational achievement. Studies indicate a one-year incidence of depression in adolescence of around 8%, with a lifetime prevalence of 11%,\u003csup\u003e5, 6\u003c/sup\u003e while the lifetime prevalence of anxiety disorders range from 10 to 30%.\u003csup\u003e7, 8\u003c/sup\u003e They are often comorbid with each other or with other psychiatric conditions and may frequently be undertreated.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Management often entails psychotherapy and pharmacotherapy, with selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) as first-line pharmacotherapy.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe management of depression and anxiety in patients with LQTS presents a unique dilemma. While population-based studies suggest minimal QT prolongation with some SSRIs,\u003csup\u003e13, 14\u003c/sup\u003e nearly all antidepressants pose a risk of prolonging the QTc and triggering torsades de pointes (TdP), warranting their inclusion on the “Drugs to Avoid in Patients with LQTS” list.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e This may lead to provider uncertainty or confusion when trying to manage patients with these comorbid conditions. Studies conducted by Weeke, et al. and Wang, et al. have examined the effect of proarrhythmic pharmacotherapy, but these have focused primarily on adult populations\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. This study aims to establish anxiety and depression prevalence in LQTS patients, determine LQTS-triggered event frequency during antidepressant treatment, and assess QTc changes while on antidepressant medications, specifically in a primarily adolescent and pediatric cohort.\u003c/p\u003e\n\n"},{"header":"Methods","content":"\u003ch3\u003eStudy Population\u003c/h3\u003e\u003cp\u003e This was a single-center retrospective study which was approved by the Medical College of Wisconsin Institutional Review Board. Patients with clinically and/or genetically diagnosed LQTS were identified through an electronic medical record query of patients followed by the Children’s Hospital of Wisconsin (CHW) Electrophysiology group. This query was compared against a separate registry of LQTS patients followed by the Electrophysiology group at CHW to ensure completeness. Patients are followed in EP clinic every 6–12 months depending on clinical status and patient/provider preference. ECGs were routinely performed during these visits for patients on QT prolonging drugs. Compliance with either beta-blocker or antidepressant was patient reported. All patients treated with beta-blockers were treated with either nadolol or propranolol based on weight and assessment of response on ambulatory monitors and exercise stress testing.\u003c/p\u003e\u003cp\u003ePatients were included in this study if they had been diagnosed with LQTS between 2012 and 2020 and were followed by the Electrophysiology group at CHW. LQTS is diagnosed primarily based on phenotypic presentation based on current Schwartz score criteria with genetic testing performed for confirmation and subtype determination. Some patients were identified based on family member cascade testing with phenotype confirmed with clinical testing. QTcs were calculated using Bazett’s formula with measurement of the termination of the QT interval based on when the tangent of the downslope crossed the baseline\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. All measurements were performed by electrophysiologists. Exclusion criteria included structural heart disease or prescription of other QT-prolonging medications prior to antidepressant initiation. Patients were divided into two cohorts based on whether they had been prescribed antidepressants during the study period.\u003c/p\u003e\u003ch2\u003eData Collection and Endpoints\u003c/h2\u003e\u003cp\u003eThe electronic medical record was reviewed for basic demographic information, LQTS genotype, LQTS therapy, and any LQTS-triggered events either prior to or after diagnosis of LQTS. For patients started on antidepressant therapy, additional information was gathered on the specific type of antidepressant drug used, age at initiation, and treatment duration. For all patients, QTc measurements from up to 10 separate ECGs were obtained while not on antidepressants. For those patients who were started on antidepressants, QTc measurements were obtained from up to 10 ECGs after initiation of antidepressant, and any LQTS-triggered events while on antidepressant therapy were recorded. LQTS-triggered events were defined as syncope or seizures that were otherwise unexplained, documented ventricular arrhythmia, appropriate implantable cardioverter-defibrillator (ICD) shock, or sudden cardiac arrest/death.\u003c/p\u003e\u003cp\u003eThe primary endpoint of the study was the incidence of LQTS-triggered events without antidepressants compared to while being on antidepressant therapy. The secondary endpoint of this study was any difference in QTc after initiating antidepressant therapy.\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were summarized as median and interquartile range (IQR), and categorical variables were summarized as frequency count and percentage (%). To compare antidepressant groups, the Mann-Whitney Wilcoxon test was used for continuous variables and the Chi-square test or a Fisher’s exact test was used for categorical variables. The Wilcoxon Signed rank test was used to assess the changes of QTc measurements in antidepressant patients’ pre vs. post antidepressant use. A two-sided p-value \u0026lt; 0.05 was used as the term of statistically significant. All data analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC) and Graphpad Prism v10.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eLQTS Demographics\u003c/h2\u003e\u003cp\u003eWe identified a cohort of 98 patients diagnosed with LQTS who met our inclusion criteria (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median (IQR) age at LQTS diagnosis was 6 (1, 11) years with median (IQR) average baseline QTc 465 (451, 478) ms. Only 14% (n\u0026thinsp;=\u0026thinsp;14) of the patients were symptomatic at presentation, while 84% (n\u0026thinsp;=\u0026thinsp;82) had a family history of LQTS, and 36% (n\u0026thinsp;=\u0026thinsp;35) having a family history of SCA. Genotype testing revealed an expected subtype distribution with LQTS type 1 in 67% (n\u0026thinsp;=\u0026thinsp;66) of the cohort, LQTS type 2 in 24% (n\u0026thinsp;=\u0026thinsp;23), and LQTS type 3 in only one patient. Eight percent (n\u0026thinsp;=\u0026thinsp;8) of the patients either had other rare variants or an unidentified genotype.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCohort demographics and comparisons\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eColumn1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColumn2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEntire cohort\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLQTS alone\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eLQTS\u0026thinsp;+\u0026thinsp;antidepressants\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTotal Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e83 (85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSex male/female (% male)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45/53 (46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43/40 (52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2/13 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.006\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge at LQTS diagnosis (yrs), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (1, 11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (0, 11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11 (5, 14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAverage baseline QTc (ms), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e465 (451, 478)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e464 (450, 477)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e467 (460, 479)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSymptomatic Presentation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.45\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eFamily history of LQTS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e84 (85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e69 (85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13 (86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eFamily history of SCD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003eLQTS genotype\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55 (66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11 (73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLQTS 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLQTS 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOther\u003csup\u003e\u0026euro;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003eLQTS Treatment\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBeta-blocker\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e90 (92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76 (92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14 (93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eICD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.003\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLCSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003ePsychiatric diagnosis\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71 (72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13 (73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDepression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12 (80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOther\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1) \u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eLQTS\u0026thinsp;=\u0026thinsp;long QT syndrome; SCD\u0026thinsp;=\u0026thinsp;sudden cardiac death; ICD\u0026thinsp;=\u0026thinsp;implantable cardioverter-defibrillator; LCSD\u0026thinsp;=\u0026thinsp;left cardiac sympathetic denervation\u003c/p\u003e\u003cp\u003e\u0026dagger;Values are given as no. (%) unless otherwise indicated\u003c/p\u003e\u003cp\u003e\u0026Dagger;Autism spectrum disorder\u0026thinsp;+\u0026thinsp;ADHD\u003c/p\u003e\u003cp\u003e\u0026euro;Other genotypes: SNTA (1), LQT5 (2)\u003c/p\u003e\u003cp\u003e\u0026sect;Statistically significant\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFollowing diagnosis, ninety patients (92%) received beta-blocker therapy, while only three patients underwent implantation of an ICD for secondary prevention, and two patients underwent LCSD. All three ICD patients received antidepressants, whereas neither of the LCSD patients did.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDepression/Anxiety\u003c/h3\u003e\n\u003cp\u003eA total of 27 LQTS patients were diagnosed with anxiety, depression, or both (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Nineteen percent (n\u0026thinsp;=\u0026thinsp;19) of the entire cohort were diagnosed with anxiety, 18% (n\u0026thinsp;=\u0026thinsp;18) with depression, and one patient was diagnosed with attention deficit hyperactivity disorder (ADHD) comorbid with autism spectrum disorder.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eOf the 27 patients diagnosed with anxiety or depression, 15 (56%) were prescribed antidepressant therapy. There was a significant difference in the prescription rates of antidepressants between female and male patients (25% vs. 4%; p\u0026thinsp;=\u0026thinsp;0.006). There was no known interruption in antidepressant therapy based on patient reporting and patients already on antidepressant therapy at the time of their LQTS diagnosis were not included in the analysis. The median (IQR) average baseline QTc in these 15 patients was 467 (460, 479) ms. Only four patients had experienced a LQTS-related event at the time of psychiatric diagnosis. Similar to the broader cohort, the majority (87%) of these patients had a family history of LQTS, and 53% had a family history of SCA. All patients but one had a confirmed positive genotype test, with the majority being LQTS type 1 (11 with LQTS1, 3 with LQTS2, and 1 patient with unknown genotyping). Like the overall cohort, the LQTS patients managed with antidepressant medications were almost all concurrently treated with beta-blockers (93%).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eAntidepressant Therapy\u003c/h2\u003e\u003cp\u003eThe median age (IQR) at which antidepressant therapy was initiated was 15 (12, 18) years (see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). SSRIs were the most prescribed class of antidepressants (80%), followed by bupropion alone in two patients and buspirone alone in one patient. Sertraline was the predominant SSRI, prescribed to six patients, followed by fluoxetine in five patients. One patient required multiple medications, including various combinations of buspirone, fluoxetine, lamotrigine, and sertraline, due to refractory anxiety and depression.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLQTS and Antidepressant Treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eColumn2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColumn1\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo. of patients on antidepressants\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at initiation (yrs), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (12, 18)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntidepressant Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSSRI/SNRI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (80)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBuproprion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBuspirone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eLQTS\u0026thinsp;=\u0026thinsp;long QT syndrome; SSRI\u0026thinsp;=\u0026thinsp;selective serotonin reuptake inhibitor; SNRI\u0026thinsp;=\u0026thinsp;serotonin/norepinephrine reuptake inhibitor.\u003c/p\u003e\u003cp\u003e\u0026dagger;Values are given as no. (%) unless otherwise indicated.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eIndividual characteristics of the antidepressant cohort\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"15\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM/F\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGene\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAge at LQTS diagnosis (yrs)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBaseline Avg QTc (ms)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSymptomatic presentation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eFamily hx LQTS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eFamily hx SCD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eICD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eBeta-blocker therapy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePsychiatric diagnosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eAntidepressant\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eAge at initiation (yrs)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c14\"\u003e\u003cp\u003eDuration of therapy (yrs)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c15\"\u003e\u003cp\u003eLQTS event on antidepressant\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e483\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSertraline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eSyncope\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e497\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDepression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSertraline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026dagger;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eFluoxetine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNot documented\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e470\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eEscitalopram\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026dagger;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eMultiple\u0026Dagger;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e475\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eFluoxetine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e464\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSertraline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e425\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSertraline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e457\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDepression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eBuproprion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e464\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eSertraline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eSyncope\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e496\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eFluoxetine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eSyncope\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e467\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eBuproprion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eSyncope\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e452\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eBuspirone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e460\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eFluoxetine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLQTS 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e479\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eY\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnxiety, Depression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eFluoxetine\u0026thinsp;+\u0026thinsp;Sertraline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eArrhythmia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"15\" nameend=\"c15\" namest=\"c1\"\u003e\u003cp\u003e\u0026dagger;No baseline QTc available (i.e., patient was diagnosed with LQTS while already on antidepressant medication)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"15\" nameend=\"c15\" namest=\"c1\"\u003e\u003cp\u003e\u0026Dagger;Buspirone, fluoxetine, lamotrigine, and sertraline\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThere was no significant association found between LQTS genotype and antidepressant treatment. Notably, all patients (n\u0026thinsp;=\u0026thinsp;3) who received ICDs were also treated with antidepressants, compared to only 13% of those who did not receive ICDs (p\u0026thinsp;=\u0026thinsp;0.003). Two out of the 15 patients prescribed antidepressants were diagnosed with LQTS after initiating treatment with antidepressants. Overall, there was no significant difference observed in the rate of LQTS-related events between patients who received antidepressants and those who did not (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Syncope was the most frequently reported event in both groups post antidepressants, with no significant disparity (22% and 27%, respectively; p\u0026thinsp;=\u0026thinsp;0.74). Only two of the patients who were not prescribed antidepressants experienced documented ventricular arrhythmia compared to one patient while on antidepressants (p\u0026thinsp;=\u0026thinsp;0.40). Furthermore, there was no significant variance between the baseline QTc and the QTc recorded on ECGs obtained after the initiation of antidepressant therapy, either by paired analysis or longitudinal monitoring on antidepressant therapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of LQTS events\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEvent\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAntidepressant (-)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAntidepressant (+)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSyncope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSeizure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eArrhythmia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eLQTS\u0026thinsp;=\u0026thinsp;long QT syndrome; SCA\u0026thinsp;=\u0026thinsp;sudden cardiac arrest\u003c/p\u003e\u003cp\u003e\u0026dagger;Values are given as no. (% of cohort)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrescribing antidepressant therapy to individuals with congenital LQTS presents a significant and frequently encountered dilemma. These medications lack specific testing in LQTS patients, and the few studies which have examined the effect of proarrhythmic pharmacotherapies have centered mostly on adult populations whereas our population is primarily pediatric\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. As such, there are no specific recommendations for follow up of patients with LQTS who are prescribed antidepressant therapy. Among the SSRIs available in the US market, such as fluoxetine, paroxetine, and sertraline, some are categorized as having a \u0026ldquo;Conditional Risk\u0026rdquo; of Torsades de Pointes (TdP) on the CredibleMeds website, while others, like citalopram and escitalopram, are labeled as \u0026ldquo;Known Risk\u0026rdquo; of TdP.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e However, asserting any antidepressant as universally \u0026ldquo;safe\u0026rdquo; for use in this population remains challenging. Moreover, various subtypes of LQTS may exhibit distinct sensitivities to these medications depending on the specific ion channel affected.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAnxiety and depression are often under-addressed in the general population, with individuals with LQTS potentially facing even greater under treatment due to the risk of QT prolongation and TdP. While normal population-based studies suggest minimal QT prolongation with some SSRIs (hence their \u0026ldquo;conditional risk\u0026rdquo; categorization), no published research has yet examined the actual event rate while patients are on these medications. The use of antidepressants, particularly widely prescribed SSRIs and SNRIs, may be imperative for patients with LQTS who develop one or both comorbid conditions.\u003c/p\u003e\u003cp\u003ePatients exhibiting symptoms of both anxiety and depression may find it challenging to fully engage with cognitive behavioral therapy (CBT) and may therefore necessitate pharmacotherapy as a primary treatment. The Treatment for Adolescents with Depression Study, a randomized controlled trial evaluating the effectiveness of CBT vs pharmacotherapy vs combined therapy vs placebo, for treatment of major depressive disorder demonstrated that combination therapy (pharmacotherapy plus cognitive-behavioral therapy/CBT) yielded twice as many patients with significant symptom improvement compared to a pill placebo\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Evidence also suggests that short-term combination therapy for depression surpasses either psychotherapy or pharmacotherapy alone. \u003csup\u003e17\u003c/sup\u003e Furthermore, SSRIs and SNRIs are deemed effective for anxiety disorders in both children and adults, particularly in cases of comorbid anxiety and depression.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn this single-center pilot study, we investigated the prevalence of anxiety and depression among patients with LQTS, the utilization of antidepressants, and their impact on LQTS-triggered events and the QTc. We identified 19% of patients diagnosed with anxiety and 18% of patients diagnosed with depression, consistent with national prevalence estimates.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Similarly, only approximately half of these patients received antidepressant therapy (15 out of 27 diagnosed patients), aligning with national treatment rates, though we are unable to assess if treatment was deferred in our population due to their LQTS diagnosis. The demographic characteristics of LQTS patients who received antidepressants closely resembled those who did not, except for a higher proportion of female patients who received antidepressant than males (25% vs 4%, p\u0026thinsp;=\u0026thinsp;0.006).\u003c/p\u003e\u003cp\u003eDuring a cumulative 42 years of antidepressant treatment, only 5 of the 15 patients who received antidepressants experienced a LQTS-triggered event, with a comparable event rate observed among patients with LQTS not on antidepressant therapy. Observed event rate on antidepressants was not significantly increased when examining specific event types. Additionally, we noted no discernible increase in the QTc when analyzing serial ECGs during antidepressant therapy. A recent study out of Mayo Clinic has drawn a similar conclusion that LQTS patients with concomitant mental health issues may be safely and effectively treated with QT prolonging medications. This study represents a pioneering effort, focusing specifically on the safety profile of antidepressants in patients with LQTS and their effects on the QTc. Our findings suggest that antidepressants, particularly SSRIs, may be safely employed to manage depression and anxiety in this high-risk cohort, provided patients also receive beta-blocker therapy.\u003c/p\u003e\n\u003ch3\u003eStudy Limitations/Future Directions\u003c/h3\u003e\n\u003cp\u003eThis retrospective, single-center cohort provided a modest sample size, making adequate statistical power to explore certain relationships challenging, such as the correlation between LQTS genotype and events during antidepressant use. Future endeavors, such as larger multi-center studies or evaluation of data in the international congenital LQTS registry focused on adolescents and children, could substantially enhance statistical power. This increased power would facilitate more nuanced analyses, such as stratifying results based on LQTS genotype or specific antidepressant medications. It may also shed further light on the significant difference in antidepressant prescription rate between males and females, especially considering female sex has been shown to be an independent risk factor for ventricular arrhythmia in patients with LQTS.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eFurthermore, gathering information on psychiatric conditions was often restricted as patients typically received antidepressant prescriptions from external offices (e.g., primary care or psychiatry) not affiliated with our institution. Consequently, details regarding diagnosis, initiation, and duration of antidepressant treatment were constrained by the available documentation.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis pilot study marks the first endeavor to assess the prevalence and outcomes of patients with LQTS undergoing treatment with antidepressants for anxiety and/or depression. Among individuals with LQTS, the prevalence of anxiety and depression mirrors that of the broader reported adolescent and adult population, with similar rates of antidepressant utilization observed. Patients with LQTS undergoing antidepressant therapy did not exhibit an increase in LQTS-triggered events, nor was there significant alteration in their QTc during treatment. This finding underscores the potential safety of prescribing certain antidepressants to patients with LQTS, particularly when accompanied by beta-blocker therapy. However, further research is imperative to reinforce this conclusion. Physicians must continue to carefully balance the risks of undertreating anxiety and/or depression and the potential QT-prolonging effects of antidepressant medications.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eCBT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 264px;\"\u003e\n \u003cp\u003eCognitive behavioral therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eSCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 264px;\"\u003e\n \u003cp\u003eSudden cardiac arrest\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eICD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 264px;\"\u003e\n \u003cp\u003eImplantable cardioverter-[AS1] defibrillator\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eSNRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 264px;\"\u003e\n \u003cp\u003eSerotonin and norepinephrine reuptake inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eIQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 264px;\"\u003e\n \u003cp\u003eInterquartile range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eSSRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 264px;\"\u003e\n \u003cp\u003eSelective serotonin reuptake inhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eLQTS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 264px;\"\u003e\n \u003cp\u003eCongenital long QT syndrome[AS2] [NR3]\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eTdP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 264px;\"\u003e\n \u003cp\u003eTorsades de Pointes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eN.R. collected the data, wrote the main manuscript text, and prepared all figures and tables. L.Z and K.Y. provided data analysis and wrote portions of the results section. All authors reviewed the manuscript and provided edits and alterations throughout the writing process.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements:\u003c/h2\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eData is provided within the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePriori, S. G., Wilde, A. A., Horie, M., et al. (2013). HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes. Heart Rhythm, 10(12), 1932\u0026ndash;1963. https://doi.org/10.1016/j.hrthm.2013.05.014\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchwartz, P. J., Stramba-Badiale, M., Crotti, L., et al. (2009). 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JAMA Pediatrics, 175(11), 1142\u0026ndash;1150. https://doi.org/10.1001/jamapediatrics.2021.2482\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarch, J. (2004). Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression. JAMA, 292(7), 807. https://doi.org/10.1001/jama.292.7.807\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYounis, A., Zareba, W., Goldenberg, I., et al. (2022). Biological life-stage and the burden of cardiac events in women with congenital long QT syndrome. Circulation: Arrhythmia and Electrophysiology, 15(12). https://doi.org/10.1161/circep.122.011247\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaracaldo-Santamar\u0026iacute;a, D., Llin\u0026aacute;s-Caballero, K., Corso-Ramirez, J. M., et al. (2021). Genetic and molecular aspects of drug-induced QT interval prolongation. 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S., Jespersen, C. B., Theilade, J., Kanters, J. K., Hansen, M. S., Christiansen, M., Marstrand, P., Gislason, G. H., Torp-Pedersen, C., Bundgaard, H., Jensen, H. K., \u0026amp; Tfelt-Hansen, J. (2019). Long-term proarrhythmic pharmacotherapy among patients with congenital long QT syndrome and risk of arrhythmia and mortality. European Heart Journal, 40(37), 3110\u0026ndash;3117. https://doi.org/10.1093/eurheartj/ehz228\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePostema PG, De Jong JSSG, Van der Bilt IAC, Wilde AAM (2008) Accurate electrocardiographic assessment of the QT interval: Teach the tangent. Heart Rhythm 5(7):1015\u0026ndash;1018. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.hrthm.2008.03.037\u003c/span\u003e\u003cspan address=\"10.1016/j.hrthm.2008.03.037\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarch J (2007) The Treatment for Adolescents with Depression Study (TADS). Arch Gen Psychiatry 64(10):1132. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/archpsyc.64.10.1132\u003c/span\u003e\u003cspan address=\"10.1001/archpsyc.64.10.1132\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Congenital Long QT Syndrome, QT interval, depression, anxiety, antidepressant","lastPublishedDoi":"10.21203/rs.3.rs-7829018/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7829018/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eCongenital long QT syndrome (LQTS) conveys a significant risk of cardiac events. Primary management includes avoiding medications that prolong the QTc. Many antidepressant medications are known to be QT-prolonging, but there is scant literature on whether their use increases event rate or prolongs the QTc in LQTS.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThe objectives of this study are to determine the prevalence of depression and anxiety in patients with congenital LQTS, and to evaluate the effect of antidepressant treatment on frequency of LQTS-triggered events and QTc changes during antidepressant treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis was a single-center, retrospective study. Patients were divided based on whether they were prescribed antidepressants during the study period. Incidence of LQTS-triggered events and QTc measurements before and after antidepressant use were recorded for comparison.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eNinety-eight subjects were identified for analysis. Most (92%) were prescribed beta-blockers as treatment for LQTS. Twenty-seven percent (n\u0026thinsp;=\u0026thinsp;27) of the cohort were diagnosed with anxiety and/or depression. Of these, 15 received antidepressant therapy. We found no significant difference in the LQTS event rate or QTc measurements in patients prescribed antidepressants. Baseline median (IQR) QTc 467 (460, 479) ms vs median (IQR) of first QTc post-antidepressant 482 (462, 487), p\u0026thinsp;=\u0026thinsp;0.27.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn this single-center study, the prevalence of anxiety and depression in patients with LQTS was consistent with the general population. Rates of treatment were also comparable. Our findings suggest that certain antidepressant therapy may be safe in patients with LQTS on beta-blockers. Further study across multiple centers and with a larger cohort may help clarify the safety of these medications.\u003c/p\u003e","manuscriptTitle":"Antidepressant use in children with congenital long QT syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-26 13:26:36","doi":"10.21203/rs.3.rs-7829018/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-29T16:48:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-29T04:31:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325035054231339757283325159392783595443","date":"2025-10-26T03:59:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-22T16:23:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"333682635233740279341010130341891095377","date":"2025-10-19T07:59:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"112560262605487711854009742816190459768","date":"2025-10-13T03:58:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"36090643438807716463015990533824900156","date":"2025-10-13T00:19:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-12T19:45:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-11T04:24:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-11T04:22:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2025-10-10T16:23:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8cdfa131-1848-4e56-88db-a325f40e3727","owner":[],"postedDate":"October 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T14:55:18+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-26 13:26:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7829018","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7829018","identity":"rs-7829018","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}