The DOI matches its Crossref record.
Meta-Analysis of Selective Serotonin Reuptake Inhibitor–Associated QTc Prolongation
Abstract
OBJECTIVE: To evaluate the association between selective serotonin reuptake inhibitors (SSRIs) and corrected QT interval (QTc) prolongation via meta-analysis of prospective studies. DATA SOURCES: PubMed/MEDLINE database (January 1, 1975-August 15, 2012), with additional reports identified using hand searches of reference lists of relevant articles. Key words searched were QT, torsades de pointes, and sudden cardiac death, combined with antidepressants, citalopram, escitalopram, fluoxetine, sertraline, paroxetine, and fluvoxamine. English-, Spanish-, and German-language articles were included. STUDY SELECTION: Two reviewers independently identified prospective controlled studies in adults that reported data related to QTc intervals prior to and following treatment with SSRIs. DATA EXTRACTION AND SYNTHESIS: Three reviewers independently extracted study-level data including population characteristics, method of QTc measurement and treatment and outcome data. Two independent reviewers critiqued study quality. Publication bias was assessed visually using a funnel plot and quantitatively. Heterogeneity was measured using Cochran Q statistic. RESULTS: Sixteen articles (with 25 distinct data subsets) involving 4,292 patients were included. SSRIs were associated with a dose-dependent increase in QTc interval compared to placebo (+6.10 milliseconds; 95% CI, 3.47-8.73; P < .001). Tricyclic antidepressants (TCAs) were associated with a significantly greater QTc increase than SSRIs (TCA prolongation, 7.05 milliseconds; 95% CI, 3.84-10.27 greater than SSRIs; P < .001). With respect to specific SSRI agents, citalopram was associated with significantly greater QTc prolongation than sertraline, paroxetine, and fluvoxamine. CONCLUSIONS: SSRIs were associated with a modest but statistically significant increase in the QTc interval, although to a lesser extent than TCAs; this finding was not limited to any single study. Citalopram was associated with more QTc prolongation than most other SSRIs.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The QTc prolongation was also dose dependent.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [24]
In the citing paper
“Among SSRIs, citalopram prolonged the QTc to the greatest extent.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [24]
In the citing paper
“A meta-analysis, which included 16 prospective controlled studies, showed that SSRIs caused significantly greater QTc interval prolongation than did placebo by 6 milliseconds.24”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [24]
In the citing paper
“Moreover, the study further showed that TCAs prolong the QTc to a greater extent than SSRIs.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [24]
Citations
Cited by
Sorted by citations
Items 201–251 of 251
Anksioznost in koronarna bolezen srca
Palandačić, A. K., & Šarotar, B. N. (2018) · Slovenian Medical Journal · doi:10.6016/zdravvestn.2430 · Cited by 3
Dagenais, R., Leung, M., Poinen, K., & Landsberg, D. N. (2018) · Annals of Pharmacotherapy · doi:10.1177/1060028018809318 · Cited by 1
Wolff-Parkinson-White syndrome in an adolescent with depression
Chen, F., Richard, S., d’Andrea, G., Grandjean, C., & Eap, C. B. (2016) · Swiss Archives of Neurology Psychiatry and Psychotherapy · doi:10.4414/sanp.2016.00399 · Cited by 1
Metabolic Abnormalities and Drugs
Rowan, C. J. (2018) · Oxford University Press eBooks · doi:10.1093/med/9780190225483.003.0023 · Cited by 1
Psychopharmacology in the Treatment of Patients with Cardiovascular Disease
Beach, S. R., Celano, C. M., Huffman, J. C., & Stern, T. A. (2016) · Springer eBooks · doi:10.1007/978-981-287-206-7_53 · Cited by 1
Self-citationDepression and Anxiety Disorders
(2021) · Wiley eBooks · doi:10.1002/9781119870203.mpg003 · Cited by 1
Pharmaco-Epidemiological Studies on Antidepressant Use in Older Adults
Noordam, R. (2015) · RePub (Erasmus University Rotterdam)
Escitalopram y extrasístoles ventriculares
Criado‐Álvarez, J. J., González, J. G., Martín, S. C., et al. (2015) · Revista Clínica de Medicina de Familia · doi:10.4321/s1699-695x2015000100010
Psychopharmacology in the Treatment of Patients with Cardiovascular Disease
Beach, S. R., Celano, C. M., Huffman, J. C., & Stern, T. A. (2015) · Springer eBooks · doi:10.1007/978-981-4560-53-5_53-1
Self-citationVries, D. Y. A., de Jonge, P., Kalverdijk, L. J., Bos, J., Schuiling‐Veninga, C. C. M., & Hak, E. (2016) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Survey on the management of physical risks induced by psychotropic agents in Japan
Orime, N., Suzuki, Y., & Someya, T. (2017) · Clinical Neuropsychopharmacology and Therapeutics · doi:10.5234/cnpt.8.42
A Psychopharmacology Guide by Psychiatrists for Non-psychiatrists
Heinrich, T. W., Owen, J. R., & Pawar, D. S. (2019) · Springer eBooks · doi:10.1007/978-3-030-18218-2_3
Cardiovascular side effects of neuropsychiatric medication: an update
APETREI-CORDUNEANU, O., Fildan, A. P., Radu, R., Stătescu, C., Nemțeanu, R., & Lupușoru, E. C. (2020) · Archives of the Balkan Medical Union · doi:10.31688/abmu.2020.55.1.17
Optimizando farmacoterapia mediante la deprescripción: reporte de caso
Narváez, Á. V., & Correal, G. M. P. (2020) · Revista Colombiana de Ciencias Químico Farmacéuticas · doi:10.15446/rcciquifa.v49n1.86736
“12 Fluoxetina y trazodona Aumento de riesgo de síndrome de serotoninérgico y prolongación del intervalo QT en el electrocardiograma [15, 16].”
BackgroundOpioid Alternative Medication and Clinical Dilemmas
Krazit, S. T. (2020) · Springer eBooks · doi:10.1007/978-3-030-39982-5_22
Agomelatine for treating depression in somatic diseases
Racková, S. (2018) · Praktické lékárenství · doi:10.36290/lek.2018.056
“Neuropsychiatr Dis Treat 2015; 27(11): 1307–1311.”
Gendermedizin: „Wir stehen erst am Anfang“
Keiner, D. (2017) · Deutsches Ärzteblatt · doi:10.3238/personko/2017.02.03.01
Oxytocin Exerts Harmful Cardiac Repolarization Prolonging Effects in Drug-Induced LQTSPreprint
Kreifels, P., Bódi, I., Hornyik, T., Franke, G., Perez‐Feliz, S., Lewetag, R. D., Moss, R., Castiglione, A., Ziupa, D., Zehender, M., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3975629
Anxiety, Anger, Personality, and Heart Disease
Fusar‐Poli, L., & Arillotta, D. (2020) · Springer eBooks · doi:10.1007/978-3-030-28008-6_19
Psychotropic agents and torsades de pointes
Funk, M. C., & Beach, S. R. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821446-6.00001-8
Self-citationQT interval prolongation, torsades de pointes and psychotropic medication
Kyziridis, T. C. (2022) · Hellenic Journal of Nursing Science · doi:10.24283/hjns.202215
Managing Risks and Side Effects of Antidepressant Medications
Kroll, D. S. (2022) · Springer eBooks · doi:10.1007/978-3-031-08495-9_4
Kroll, D. S. (2022) · Springer eBooks · doi:10.1007/978-3-031-08495-9_8
Laux, G. (2022) · Springer eBooks · doi:10.1007/978-3-030-62059-2_413 · Cited by 1
Antidepressants: Indications, Contraindications, Interactions, and Side Effects
Corponi, F., Fabbri, C., & Serretti, A. (2022) · Springer eBooks · doi:10.1007/978-3-030-62059-2_29
Ушкалова, Е. А., & Ushkalova, A. V. (2023) · Neurology neuropsychiatry Psychosomatics · doi:10.14412/2074-2711-2023-5-1-94-101
Cardiovascular eff ects of psychotropic drugs
Vardanyan, Y. Т. (2023) · Clinical Medicine (Russian Journal) · doi:10.30629/0023-2149-2023-101-9-10-467-473
Depressive Symptoms in Heart Failure: Pathophysiology and Diagnosis
Taskura, R. A., & Utami, M. P. (2023) · Scientia Psychiatrica · doi:10.37275/scipsy.v5i1.124
The Treatment of Depression in Patients with Heart Failure
Bachurska, D., Marek, J., Grygorczuk, O., & Czach, Z. (2024) · Journal of Education Health and Sport · doi:10.12775/jehs.2024.66.003
Grundlagen der Diagnostik und Therapie
(2024) · Elsevier eBooks · doi:10.1016/b978-3-437-22487-4.16001-0
Antidepressants and old age: the risks of pharmacotherapy
Kukushkin, G., Yurov, D. E., Kalinina, E., Burenkova, E. E., & Devushkin, D. A. (2025) · Russian Medicine · doi:10.17816/medjrf641965
Treatment-resistant depression in children and adolescents
DeFilippis, M., & Wagner, K. D. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824067-0.00027-x
Tricyclic antidepressants for treatment-resistant depression
Bobo, W. V., & Richelson, E. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824067-0.00008-6
Treiber, M., Baune, B. T., Gramser, A., Saelens, J., Grüll, N., Rössler, K., Novak, K., Bouzouina, A., Thanarajah, S. E., Reif-Leonhard, C., et al. (2025) · medRxiv · doi:10.1101/2025.08.31.25334709
“Antidepressant medication, such as Serotonin-Reuptake-Inhibitors and Tricyclic Antidepressants have been suggested to increase QTc intervals (Beach et al., 2014; Keshtkar et al., 2025).”
Warrings, W., Taurines, R., Egberts, K. M., et al. (2025) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0000000000001379
Hämäläinen, I., Tiihonen, M., Hartikainen, S., & Tolppanen, A.-M. (2024) · Figshare · doi:10.6084/m9.figshare.26555480
Miller, C. O. G. (2025) · Springer eBooks · doi:10.1007/978-3-032-13315-1_2
Lavender Oil-Infused Mirtazapine Nanoemulsion for Direct Nose-to-Brain Targeting
Waqar, M. A., Ashfaq, A., Khalid, M., Khan, R., Zahra, S., Alvi, A. S., & Arshad, B. (2026) · BioNanoScience · doi:10.1007/s12668-026-02443-6
Central neuromodulators in gastroenterology and gastropsychology. Focus on irritable bowel syndrome
Gubska, O., & Vanchytskiy, A. O. (2026) · GASTROENTEROLOGY · doi:10.22141/2308-2097.60.1.2026.717
Burky, G. (2026) · Cureus · doi:10.7759/cureus.108196
“While selective serotonin reuptake inhibitors (SSRIs) as a class have variable effects on the QTc interval, sertraline has generally demonstrated minimal clinically significant QT prolongation at standard doses [6,7].”
Snapir, L., Elazar, M., Cohen, T., Weinberger, R., Schwartz-Lifshitz, M., Taler, M., & Gothelf, D. (2026) · Journal of Child and Adolescent Psychopharmacology · doi:10.1177/10445463261451798
“Individuals with WS are predisposed to cardiovascular abnormalities (Collins, 2018; Pober, 2010), and certain SSRIs have been associated with dose-dependent QTc prolongation (Beach et al., 2014).”
Kundnani, N. R., Mogos, A., Barbu, L. A., Mogoș, G. F. R., Buciu, V., Caraba, A., Borza, C., & Huţ, E. F. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15113995
Malik, M. M. U. D. (2026) · British Journal of Clinical Pharmacology · doi:10.1002/bcp.70658
Lin, J., & Zhang, T. (2026) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2026.06.012
Karevan, S., Heidari, Z., Momenzadeh, M., & Panahishokouh, M. (2026) · Heart and Mind · doi:10.4103/hm.hm-d-26-00005
Concurrent Use of Tasipimidine Oral Solution and Fluoxetine in Dogs
Lindstedt, J. M., Levijoki, J. M., Tuunainen, J., Häggström, J. U., Ramela, M., & Korpivaara, M. (2026) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/jvp.70098 · Cited by 1
Huang, J., Deng, L., Yao, B., Zhao, L., Xu, X., Liu, L., Liang, C., Shen, Y., Zhang, Y., & Wang, X. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118335
Dovgan, E. V., Andreeva, I. V., Anisimova, S. Y., Andreev, V. А., & Tsareva, V. M. (2026) · Safety and Risk of Pharmacotherapy · doi:10.30895/2312-7821-2026-577
Kahl, K. G., Deuschle, M., & Schneider, F. (2026) · Springer eBooks · doi:10.1007/978-3-662-70668-8_40
Management of fragile X-associated tremor ataxia syndrome: a review for clinicians
Hall, D. A., González, D. A., Klusek, J., Todd, P. K., O’Keefe, J. A., Maltman, N., Montanaro, F. A. M., Protic, D. D., Scorr, L., Malik, R., et al. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1870779
Sind Antidepressiva bei leichter Depression indiziert?
Nordhues, P., & Bschor, T. (2014) · DNP - Der Neurologe und Psychiater · doi:10.1007/s15202-014-1024-2
“Auch wenn die heutzutage eingesetzten Antidepressiva als sicher und insgesamt gut verträglich gelten, sind sie bei weitem nicht nebenwirkungsfrei: Bei den am häu gsten eingesetzten selektiven Serotonin-Wiederaufnahmehemmern (SSRI) ist zunächst einmal neben gastrointestinalen und sexuellen Nebenwirkungen eine dosisabhä…”
Background
Metadata
- Authors
- Beach, S. R., Kostis, W. J., Celano, C. M., Januzzi, J. L., Ruskin, J. N., Noseworthy, P. A., & Huffman, J. C.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- ORCID
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2014-05-15
- Volume
- 75
- Issue
- 05
- Pages
- e441-e449
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2092475629
- Cited by
- 253
- References
- 0
- Citations by year
- 2026: 23 · 2025: 18 · 2024: 18 · 2023: 17 · 2022: 30 · 2021: 20 · 2020: 18 · 2019: 19 · 2018: 22 · 2017: 17 · 2016: 22 · 2015: 21 · 2014: 7
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- selective serotonin reuptake inhibitors, QTc prolongation, torsades de pointes, sudden cardiac death, citalopram, tricyclic antidepressants, antidepressant side effects, sertraline, paroxetine, fluvoxamine, fluoxetine
- MeSH terms
- Antidepressive Agents, Tricyclic, Humans, Long QT Syndrome, Selective Serotonin Reuptake Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
