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.
Integrity signals
Registry
Cites
Statistics
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?
The QTc prolongation was dose dependent.
“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]
Among SSRIs, citalopram prolonged the QTc to the greatest extent.
“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]
A meta-analysis including 16 prospective controlled studies showed that SSRIs caused significantly greater QTc interval prolongation than did placebo by 6 milliseconds.
“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]
TCAs prolong the QTc to a greater extent than SSRIs.
“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]
Cited by
Sorted by citations
Correll, C. U., Detraux, J., De Lepeleire, J., & De Hert, M. (2015) · World Psychiatry · doi:10.1002/wps.20204 · Cited by 820 · see citing works
“, citalopram) (125,126) may be associated with (modest) QTc prolongation.”
BackgroundCarvalho, A. F., Sharma, M. S., Brunoni, A. R., Vieta, E., & Fava, G. A. (2016) · Psychotherapy and Psychosomatics · doi:10.1159/000447034 · Cited by 650 · see citing works
Depression and anxiety in heart failure: a review.
Celano, C. M., Villegas, A. C., Albanese, A. M., Gaggin, H. K., & Huffman, J. C. (2018) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000162 · Cited by 610 · see citing works
Comorbid depression in medical diseases
Gold, S. M., Köhler‐Forsberg, O., Moss-Morris, R. E., Mehnert, A., Miranda, J. J., Bullinger, M., Steptoe, A., Whooley, M. A., & Otte, C. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-0200-2 · Cited by 547 · see citing works
Anxiety Disorders and Cardiovascular Disease
Celano, C. M., Daunis, D. J., Lokko, H. N., Campbell, K. A., & Huffman, J. C. (2016) · Current Psychiatry Reports · doi:10.1007/s11920-016-0739-5 · Cited by 422 · see citing works
Self-citationBerk, M., Köhler‐Forsberg, O., Turner, M., Penninx, B. W. J. H., Wrobel, A., Firth, J., Loughman, A., Reavley, N. J., McGrath, J. J., Momen, N. C., et al. (2023) · World Psychiatry · doi:10.1002/wps.21110 · Cited by 336 · see citing works
Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review
Wang, S.-M., Han, C., Bahk, W.-M., Lee, S.-J., Patkar, A. A., Masand, P. S., & Pae, C.-U. (2018) · Chonnam Medical Journal · doi:10.4068/cmj.2018.54.2.101 · Cited by 299 · see citing works
“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) The QTc prolongation was also dose dependent.”
MethodStrawn, J. R., Geracioti, L., Rajdev, N., Clemenza, K., & Levine, A. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1491966 · Cited by 214 · see citing works
“' Additionally, the r-enantiomer may have greater histamine affinity and associated antihistaminergic effects as well as more QTc-prolongation compared to escitalopram [31] and compared to other SSRIs [32].”
BackgroundResultQT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update
Beach, S. R., Celano, C. M., Sugrue, A. M., Adams, C. N., Ackerman, M. J., Noseworthy, P. A., & Huffman, J. C. (2017) · Psychosomatics · doi:10.1016/j.psym.2017.10.009 · Cited by 195 · see citing works
Self-citationMajor Depressive Disorder Is Associated with Impaired Interoceptive Accuracy: A Systematic Review
Eggart, M., Lange, A., Binser, M. J., Queri, S., & Müller-Oerlinghausen, B. (2019) · Brain Sciences · doi:10.3390/brainsci9060131 · Cited by 189 · see citing works
“Moreover, SSRI intake is associated with a dose-dependent corrected QT interval prolongation [46] which could alter IAc.”
BackgroundBueno, H., Deaton, C., Farrero, M., Forsyth, F., Braunschweig, F., Buccheri, S., Dragan, S. R., Gevaert, S., Held, C., Kurpas, D., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf191 · Cited by 209 · see citing works
Anxiety in Patients with Schizophrenia: Epidemiology and Management
Temmingh, H., & Stein, D. J. (2015) · CNS Drugs · doi:10.1007/s40263-015-0282-7 · Cited by 173 · see citing works
Kovacs, A. H., Brouillette, J., Ibeziako, P. I., Jackson, J. L., Kasparian, N. A., Kim, Y. Y., Livecchi, T., Sillman, C., & Kochilas, L. K. (2022) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/hcq.0000000000000110 · Cited by 180 · see citing works
Cubeddu, L. X. (2016) · Current Cardiology Reviews · doi:10.2174/1573403x12666160301120217 · Cited by 141 · see citing works
Psychopharmacology and Cardiovascular Disease
Piña, I. L., Di Palo, K. E., & Ventura, H. O. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.03.458 · Cited by 126 · see citing works
Management of Treatment-Resistant Depression in Children and Adolescents
DeFilippis, M., & Wagner, K. D. (2014) · Pediatric Drugs · doi:10.1007/s40272-014-0088-y · Cited by 77 · see citing works
Treatment of Depression in Patients with Concomitant Cardiac Disease
Teply, R. M., Packard, K. A., White, N. D., Hilleman, D. E., & DiNicolantonio, J. J. (2015) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2015.11.003 · Cited by 76 · see citing works
Assimon, M. M., Brookhart, M. A., & Flythe, J. E. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018101032 · Cited by 69 · see citing works
A comparative study of QT prolongation with serotonin reuptake inhibitors
Senard, A., Bénevent, J., Bondon‐Guitton, E., Durrieu, G., Chebane, L., Araujo, M., Montastruc, F., & Montastruc, J. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4685-7 · Cited by 69 · see citing works
Impact of Age and Sex on QT Prolongation in Patients Receiving Psychotropics
Rabkin, S. W. (2015) · The Canadian Journal of Psychiatry · doi:10.1177/070674371506000502 · Cited by 67 · see citing works
Ladwig, K.-H., Baghai, T. C., Doyle, F., Hamer, M., Herrmann‐Lingen, C., Kunschitz, E., Lemogne, C., Beresnevaitė, M., Compare, A., von Känel, R., et al. (2022) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwac006 · Cited by 66 · see citing works
Antidepressant use and risk of adverse outcomes: population-based cohort study
Bansal, N., Hudda, M. T., Payne, R., Smıth, D. J., Kessler, D. S., & Wiles, N. (2022) · BJPsych Open · doi:10.1192/bjo.2022.563 · Cited by 64 · see citing works
Bellet, M., Ahmad, F., Villanueva-Vázquez, R., Valdivia, C., Palomino-Doza, J., Ruiz, A. I., González, X., Adrover, E., Azaro, A., Valls-Margarit, M., et al. (2019) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835919833867 · Cited by 63 · see citing works
Nosè, M., Bighelli, I., Castellazzi, M., Martinotti, G., Carrà, G., Lucii, C., Ostuzzi, G., Sozzi, F., Barbui, C., & the STAR NETWORK GROUP (2015) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796015000906 · Cited by 56 · see citing works
“The review found that the association between citalopram and QTc prolongation was stronger than for most other SSRIs (Beach et al. 2014).”
BackgroundDrug-induced cardiac toxicity and adverse drug reactions, a narrative review
Destère, A., Merino, D., Lavrut, T., Rocher, F., Viard, D., Drici, M., & Gérard, A. O. (2023) · Therapies · doi:10.1016/j.therap.2023.10.008 · Cited by 55 · see citing works
Central Neuromodulators in Irritable Bowel Syndrome: Why, How, and When
Hanna-Jairala, I., & Drossman, D. A. (2024) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002800 · Cited by 56 · see citing works
“A meta-analysis found that among SSRIs, cit-alopramappears tobetheagentmostsigni fi cantly associatedwith QTc prolongation (57).”
BackgroundStatins in the treatment of depression: Hype or hope?
Köhler‐Forsberg, O., Otte, C., Gold, S. M., & Østergaard, S. D. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107625 · Cited by 51 · see citing works
Baba, H., Kito, S., Nukariya, K., Takeshima, M., Fujise, N., Iga, J., Oshibuchi, H., Kawano, M., Kimura, M., Mizukami, K., et al. (2022) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13349 · Cited by 50 · see citing works
“Careful consideration should be given to QT prolongation associated with the TCAs, citalopram and escitalopram.(55,56) Rare but serious adverse reactions to SSRIs include upper gastrointestinal bleeding.”
BackgroundPashaei, Y. (2021) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2021.03.010 · Cited by 46 · see citing works
“It is also worth noting that all six SSRIs have QT-prolonging capabilities [135].”
Citalopram, QTc Prolongation, and Torsades de Pointes
Tampi, R. R., Balderas, M., Carter, K. V., Tampi, D. J., Moca, M., Knudsen, A., & May, J. T. (2014) · Psychosomatics · doi:10.1016/j.psym.2014.09.002 · Cited by 44 · see citing works
Maljurić, N., Noordam, R., Aarts, N., Niemeijer, M. N., van den Berg, M. E., Albert Hofman, D., Kors, J. A., Stricker, B. H. C., & Visser, L. E. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12681 · Cited by 42 · see citing works
Late-life depression: issues for the general practitioner
Damme, A. V., Declercq, T., Lemey, L., Tandt, H. L. N., & Petrović, M. (2018) · International Journal of General Medicine · doi:10.2147/ijgm.s154876 · Cited by 43 · see citing works
“(QTc prolongation), which is why sertraline is preferred over citalopram.(67) TCAs are as effective as SSRIs for LLD, but are less often used because of frequent side effects.”
Nomikos, G. G., Tomori, D., Zhong, W., Affinito, J., & Palo, W. A. (2016) · CNS Spectrums · doi:10.1017/s1092852916000626 · Cited by 40 · see citing works
Psychological and Psychopharmacological Interventions in Psychocardiology
Kahl, K. G., Stapel, B., & Correll, C. U. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.831359 · Cited by 39 · see citing works
“A meta-analysis revealed that SSRIs as a class increase QTc interval for an average of 6 ms (32).”
Nonopioid Medications for Pain
Tauben, D. J. (2015) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2015.01.005 · Cited by 37 · see citing works
Cardiovascular Safety of Psychiatric Agents: A Cautionary Tale
Manolis, T. A., Manolis, A. S., & Manolis, A. S. (2018) · Angiology · doi:10.1177/0003319718780145 · Cited by 39 · see citing works
Association between citalopram, escitalopram and QTc prolongation in a real-world geriatric setting
Crépeau‐Gendron, G., Brown, H. K., Shorey, C., Madan, R., Szabuniewicz, C., Koh, S. J., Veinish, S. L., & Mah, L. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.02.060 · Cited by 36 · see citing works
Cardiovascular toxicity induced by SSRIs: Analysis of spontaneous reports submitted to FAERS
Chen, Y., Fan, Q., Liu, Y., Shi, Y., & Luo, H. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115300 · Cited by 34 · see citing works
Neuroinflammation and Natural Antidepressants: Balancing Fire with Flora
Godoy, A. C. F., Frota, F. F., Araújo, L. P., Valenti, V. E., Pereira, E. D. S. B. M., Detregiachi, C. R. P., Galhardi, C. M., Caracio, F. C. C., Haber, R. S. A., Laurindo, L. F., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13051129 · Cited by 33 · see citing works
Effects of antidepressants on QT interval in people with mental disorders
Aronow, W. S., & Shamliyan, T. (2020) · Archives of Medical Science · doi:10.5114/aoms.2019.86928 · Cited by 34 · see citing works
“04) 892 (6 RCTs) [7, 71, 94, 96, 107] Moderate Favors control”
InfluentialChen, A., Copeli, F., Metzger, E. D., Cloutier, A. A., & Osser, D. N. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2020.113641 · Cited by 31 · see citing works
“5-7 ms and in a dose-related pattern (Beach et al., 2014; Thase et al., 2013), but does it less so than citalopram, and does not carry an FDA warning.”
BackgroundInfluentialFirst-generation antipsychotics and QTc: any role for mediating variables?
Carrà, G., Crocamo, C., Bartoli, F., Lax, A., Tremolada, M., Lucii, C., Martinotti, G., Nosè, M., Bighelli, I., Ostuzzi, G., et al. (2016) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2540 · Cited by 30 · see citing works
“, 2011), the effects on QTc of other drugs, from multiple therapeutic classes, including antibiotics, tricyclic antidepressants, antihistamines, selective-serotonin reuptake inhibitors, and antiemetics (Beach et al., 2014; Woosley and Romero, 2015).”
BackgroundEffect of Abrupt Discontinuation of Antidepressants in Critically Ill Hospitalized Adults
Bainum, T. B., Fike, D. S., Mechelay, D., & Haase, K. K. (2017) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1992 · Cited by 28 · see citing works
Erritzøe, D., Barba, T., Spriggs, M. J., Rosas, F. E., Nutt, D., & Carhart-Harris, R. L. (2024) · Journal of Psychopharmacology · doi:10.1177/02698811241237870 · Cited by 33 · see citing works
“High doses of psilocybin could indeed lead to transient QTc increases up to 10 ms (Dahmane et al., 2021), and most common SSRI/SNRIs used at clinical doses are also associated with QTc prolongation (Beach et al., 2014).”
BackgroundRamalho, D., & Freitas, J. P. (2018) · Revista Portuguesa de Cardiologia · doi:10.1016/j.repc.2017.07.010 · Cited by 27 · see citing works
de Geus, E. J. C. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.019861 · Cited by 26 · see citing works
Psychological sequelae of myocardial infarction
Kumar, M., & Nayak, P. K. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.08.109 · Cited by 26 · see citing works
Use of Sertraline in Hemodialysis Patients
Kubanek, A., Paul, P., Przybylak, M., Kanclerz, K., Rojek, J. J., Renke, M., Bidzan, L., & Grabowski, J. (2021) · Medicina · doi:10.3390/medicina57090949 · Cited by 26 · see citing works
“SSRIs can cause prolongation of QTc interval, with citalopram and escitalopram having the greatest impact [62,68] with the effect increasing with the dose [69].”
BackgroundBupleurum in Treatment of Depression Disorder: A Comprehensive Review
Ran, S., Peng, R., Guo, Q., Cui, J., Chen, G., & Wang, Z. (2024) · Pharmaceuticals · doi:10.3390/ph17040512 · Cited by 26 · see citing works
High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death
Ray, W. A., Chung, C. P., Murray, K. T., Hall, K., & Stein, C. M. (2016) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.15m10324 · Cited by 25 · see citing works
Effects of psychopharmacological treatment with antidepressants on the vascular system
Kahl, K. G., Westhoff‐Bleck, M., & Krüger, T. H. C. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.07.004 · Cited by 23 · see citing works
Hartz, I., Skurtveit, S. O., Hjellvik, V., Furu, K., Nesvåg, R., & Handal, M. (2016) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12633 · Cited by 23 · see citing works
“There have, however, been warnings on an increased risk for QT interval prolongation on an ECG with citalopram (36, 37) which may explain the preference for escitalopram observed in the present study.”
BackgroundDirect and indirect effects of psychopharmacological treatment on the cardiovascular system
Kahl, K. G. (2018) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2018-0054 · Cited by 23 · see citing works
Batelaan, N. M., Seldenrijk, A., van den Heuvel, O. A., van Balkom, A. J. L. M., Kaiser, A., Reneman, L., & Tan, H. L. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.813518 · Cited by 24 · see citing works
Effect of 3 Single Doses of Trazodone on QTc Interval in Healthy Subjects
Tellone, V., Rosignoli, M. T., Picollo, R., et al. (2020) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1640 · Cited by 22 · see citing works
Rossi, M., Marzi, F., Natale, M., Porceddu, A., Tuccori, M., Lazzerini, P. E., Pasini, F. L., & Capecchi, P. L. (2021) · Drugs - Real World Outcomes · doi:10.1007/s40801-021-00234-x · Cited by 23 · see citing works
“Despite general agreement in the literature, including a recent meta-analysis [40], that citalopram is the selective serotonin reuptake inhibitor more consistently associated with QTc prolongation, and recommendations from the FDA [41] and other regulatory authorities, awareness of this issue in older patients seems t…”
ResultJohnson, C. F. A., Maxwell, M., Williams, B., Dougall, N. J., & MacGillivray, S. A. (2022) · BMJ Medicine · doi:10.1136/bmjmed-2021-000017 · Cited by 26 · see citing works
Pittenger, C., Brennan, B. P., Koran, L. M., Mathews, C. A., Nestadt, G., Pato, M. T., Phillips, K. A., Rodríguez, C. I., Simpson, H. B., Skapinakis, P., et al. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.113853 · Cited by 22 · see citing works
SSRIs: Applications in inflammatory lung disease and implications for COVID‐19
Meikle, C. K., Creeden, J. F., McCullumsmith, C. B., & Worth, R. G. (2021) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12194 · Cited by 20 · see citing works
A Practical Approach to Avoiding Cardiovascular Adverse Effects of Psychoactive Medications
Brouillette, J., & Nattel, S. (2017) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.09.001 · Cited by 21 · see citing works
Evidence for cardiotoxicity associated with sertraline in rats
Ilgın, S., Kılıç, V., Baysal, M., Kılıç, G., Uçarcan, Ş., Dermenci, B., & Atlı, Ö. (2018) · Toxicology Research · doi:10.1039/c8tx00072g · Cited by 21 · see citing works
“According to Beach et al. (2014), SSRIs have given rise to slight QT interval prolongation, which is statistically significant and dose-dependent.”
BackgroundPharmacokinetic evaluation of fluvoxamine for the treatment of anxiety disorders
Altamura, A. C., Caldiroli, A., & Buoli, M. (2015) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2015.1021331 · Cited by 20 · see citing works
“A recent meta-analysis has highlighted how the administration of SSRIs is effectively associated with a dose-dependent QTc prolongation, although less than tricyclic antidepressants [99].”
BackgroundUnintended Consequences of Adjusting Citalopram Prescriptions Following the 2011 FDA Warning
Gerlach, L. B., Kales, H. C., Maust, D. T., Chiang, C., Stano, C., Choe, H. M., & Zivin, K. (2016) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2016.11.010 · Cited by 20 · see citing works
“Although not subject to the FDA warning, studies have demonstrated a dose-dependent increase in the QT interval for escitalopram as well.(7,8,18) Patients who were switched to a new antidepressant were significantly more likely to have concomitant psychotropic medications prescribed, including new prescriptions for be…”
BackgroundSafer, D. J. (2016) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000564 · Cited by 19 · see citing works
Hussaarts, K. G. A. M., Berger, F. A., Binkhorst, L., et al. (2019) · Pharmaceutical Research · doi:10.1007/s11095-019-2746-9 · Cited by 19 · see citing works
Should We be Worried About QTc Prolongation Using Citalopram? A Review
Hutton, L. M. J., Cave, A., Jean, R. S., & Banh, H. L. (2016) · Journal of Pharmacy Practice · doi:10.1177/0897190015624862 · Cited by 19 · see citing works
“Two recently published, well-conducted reviews of citalopram include either supratherapeutic doses of citalopram or a wider scope of antidepressant medications than the current review.(24,25) Neither of these reviews reports in detail on patient-specific confounding factors for LQTS in their included citalopram trials.”
BackgroundResultInfluentialBayas, A., Schuh, K., Baier, M. L., Vormfelde, S. V., for the REGAIN Study Group, Koppai-Reiner, J., Strauss, E., Haerting, B., Wiehler, S., Boehringer, J., et al. (2016) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285616651197 · Cited by 20 · see citing works
“73) was described, especially for citalopram, although absolute prolongations (>450 ms) were only rarely seen [Beach et al. 2014].”
BackgroundKaliuzhna, M., Kirschner, M., Carruzzo, F., Hartmann-Riemer, M. N., Bischof, M., Seifritz, E., Tobler, P. N., & Kaiser, S. (2021) · Schizophrenia Research · doi:10.1016/j.schres.2021.08.007 · Cited by 18 · see citing works
Efficacy and acceptability of antidepressants in patients with ischemic heart disease
Ostuzzi, G., Turrini, G., Gastaldon, C., Papola, D., Rayner, L., Caruso, R., Grassi, L. G., Hotopf, M. H., & Barbui, C. (2018) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000248 · Cited by 18 · see citing works
Toward a personalized therapy for panic disorder: preliminary considerations from a work in progress
Caldirola, D., & Perna, G. (2019) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s174433 · Cited by 17 · see citing works
“…seemed to have very limited clinical signi fi cance in the vast majority of patients, particularly in those with no other risk factors for torsades de pointes, 84,85 while more attention should be paid to patients taking multiple medications due to possible additive effects on QT length.”
BackgroundCorponi, F., Fabbri, C., Boriani, G., Diemberger, I., Albani, D., Forloni, G., & Serretti, A. (2018) · Neuropsychobiology · doi:10.1159/000493400 · Cited by 18 · see citing works
Abbas, R., Riley, S., LaBadie, R. R., Bachinsky, M., Chappell, P. B., Crownover, P. H., & Damle, B. D. (2019) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.749 · Cited by 17 · see citing works
Risk of out‐of‐hospital cardiac arrest in antidepressant drug users
Eroglu, T. E., Barcella, C. A., Gerds, T. A., Kessing, L. V., Zylyftari, N., Mohr, G. H., Kragholm, K. H., Polcwiartek, C., Wissenberg, M., Folke, F., et al. (2022) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15224 · Cited by 17 · see citing works
“line with a previous study that investigated the effects of antidepressants on QT interval in which was reported that QT prolongation among SSRIs were largely caused by citalopram and escitalopram (the effects of mirtazapine was not studied).(19) The individual antidepressants differ substantially between each other i…”
Resultde Vries, Y. A., de Jonge, P., Kalverdijk, L. J., Bos, J., Schuiling‐Veninga, C. C. M., & Hak, E. (2016) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-016-0836-3 · Cited by 17 · see citing works
“Among the SSRIs, citalopram has also been most strongly associated with QT interval prolongation (particularly at higher doses), which may increase the risk for torsade de pointes and sudden cardiac death [25, 26] and which may be an additional safety-related reason, apart from treatment-emergent suicidality, to prefe…”
BackgroundPain medication and long QT syndrome
Klivinyi, C., & Bornemann‐Cimenti, H. (2018) · The Korean journal of pain · doi:10.3344/kjp.2018.31.1.3 · Cited by 16 · see citing works
Bandt, D. D., Haile, S. R., Devillers, L., Bourrion, B., & Menges, D. (2024) · BMJ Mental Health · doi:10.1136/bmjment-2024-301026 · Cited by 17 · see citing works
“38 Anxiolytic sales demonstrated a declining trend from 2012 to 2019 in line with other studies, as their utilisation—especially the prescription of benzodiazepines—was increasingly discour-aged in clinical practice guidelines due to their risk for adverse effects and dependence.”
ResultAssimon, M. M., Pun, P. H., Al‐Khatib, S. M., Brookhart, M. A., Gaynes, B. N., Winkelmayer, W. C., & Flythe, J. E. (2022) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.5428 · Cited by 15 · see citing works
“to follow-up, (6) index SSRI discontinuation (using a 7-day grace period), (7) switch to a non-index SSRI, (8) PPI discontinuation (using a 7-day grace period) among those using a PPI on the SSRI index date, (9) PPI initiation among those not using a PPI on the index date, (10) completion of 1-year of follow-up, and (…”
MethodYamazaki-Hashimoto, Y., Nakamura, Y., Ohara, H., Cao, X., Kitahara, K., Izumi‐Nakaseko, H., Ando, K., Yamazaki, H., Ikeda, T., Yamazaki, J., et al. (2014) · The Journal of Toxicological Sciences · doi:10.2131/jts.40.33 · Cited by 15 · see citing works
Criticisms of drugs in early development for the treatment of depression: what can be improved?
Wang, S., Han, C., & Pae, C. (2014) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.985784 · Cited by 15 · see citing works
“Moreover, recent studies suggest that conventional antidepressants, selective serotonin reuptake inhibitors (SSRIs), are also associated with a significant increase in the QTc interval [2].”
BackgroundPromising new pharmacological targets for depression: The search for efficacy
Tsugiyama, L. E., de Moraes, R. C. M., Moraes, Y. A. C., & de Oliveira, J. F. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103804 · Cited by 14 · see citing works
The effectiveness and limitations of regulatory warnings for the safe prescribing of citalopram
Bugden, S., & Friesen, K. J. (2015) · Drug Healthcare and Patient Safety · doi:10.2147/dhps.s91046 · Cited by 14 · see citing works
Wu, C., Tsai, Y.-T., Hsiung, C. A., & Tsai, H. (2016) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000631 · Cited by 14 · see citing works
“Among SSRIs, previous reports indicated that citalopram was associated with the greatest QTc prolongation; however, there was no statistically significant difference between fluoxetine, paroxetine, and placebo.(6) Besides SSRIs, overdose of venlafaxine might also be associated with QTc prolongation.”
Behlke, L. M., Lenze, E. J., Pham, V., Miller, J. P., Smith, T. W., Saade, Y., Karp, J. F., Reynolds, C. F., Blumberger, D. M., Stefan, C., et al. (2020) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001287 · Cited by 14 · see citing works
“Increased QTc interval has become a proxy marker for drug-induced risk of sudden cardiac death,(10) and several studies have demonstrated that some specific antidepressants prolong the QTc.(11,12) Although some studies have raised concern regarding selective serotonin reuptake inhibitors such as citalopram and QTc pro…”
BackgroundInfluentialChang, L., & Liu, N. (2017) · Heart and Mind · doi:10.4103/hm.hm_6_16 · Cited by 14 · see citing works
“significantly greater than increases found in sertraline, paroxetine, or fluvoxamine.[45] This ultimately prompted the”
BackgroundSerial follow‐up of corrected QT interval in Rett syndrome
Clark, B. C., Kopp, A. R., Morey, W., et al. (2019) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.14419 · Cited by 13 · see citing works
“Certain medications, including selective serotonin reuptake inhibitors (SSRIs), are known to cause prolongation of the QT interval.(14) These medications and other agents with effects on serotonin have been shown to have a positive impact on behaviour, sleep, and respiratory patterns in patients with RTT.”
BackgroundAntidepressants and the Risk of Cardiovascular Events in Elderly Affected by Cardiovascular Disease
Biffi, A., Rea, F., Scotti, L., Lucenteforte, E., Vannacci, A., Lombardi, N., Chinellato, A., Onder, G., Vitale, C., Cascini, S., et al. (2020) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001189 · Cited by 14 · see citing works
Hines, L. J., Wilke, R. A., Myers, R. A., Mathews, C. A., Liu, M., Baye, J. F., Petry, N., Cicali, E. J., Duong, B. Q., Elwood, E. N., et al. (2024) · Clinical and Translational Science · doi:10.1111/cts.13822 · Cited by 13 · see citing works
“14,16,18,19 For CYP2C19 rapid and ultrara-pid metabolizers (carrying one or two increased function alleles), more rapid metabolism increases risk of therapeutic failure due to inadequate plasma drug concentrations of the active parent drug.”
BackgroundBehandlung der Depression bei koronarer Herzerkrankung
Agorastos, A., Lederbogen, F., & Otte, C. (2015) · Der Nervenarzt · doi:10.1007/s00115-014-4162-z · Cited by 12 · see citing works
“Während Citalopram mit der größten QTc-ZeitVerlängerung assoziiert ist, zeigen Substanzen wie Sertralin, Paroxetin und Fluoxetin im Vergleich ein niedrigeres Risiko [52, 53].”
BackgroundRisk of Cardiac Events Associated With Antidepressant Therapy in Patients With Long QT Syndrome
Wang, M., Szepietowska, B., Polonsky, B., et al. (2017) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2017.10.010 · Cited by 12 · see citing works
Mortality among psychiatric inpatients in China: A national survey
Wu, X., Xia, L., Yang, Y., Zhang, L., Li, M., Liu, T., Liu, Y., Cotes, R. O., Jiang, F., Tang, Y., et al. (2022) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2022.103262 · Cited by 13 · see citing works
Guo, S., Chen, L., Cheng, S., & Xu, H. (2019) · Medicine · doi:10.1097/md.0000000000015786 · Cited by 12 · see citing works
“However, Beach et al[14] have conducted a meta-analysis to evaluate the association between SSRIs and correlated QT interval prolongation, and concluded that SSRIs were associated with a modest but statistically significant increase in the QTc interval.”
BackgroundMenchón, J. M., Bobes, J., Álamo, C., Alonso, P., García‐Portilla, M. P., Ibáñez, Á., Real, E., Bousoño, M., Sáiz-González, M. D., & Sáiz-Ruiz, J. (2019) · Revista de Psiquiatría y Salud Mental · doi:10.1016/j.rpsm.2019.01.003 · Cited by 11 · see citing works
Fung, K. W., Baye, F. M., Kapusnik-Uner, J., & McDonald, C. J. (2021) · Drugs - Real World Outcomes · doi:10.1007/s40801-021-00230-1 · Cited by 11 · see citing works
Lack of relationship between plasma levels of escitalopram and QTc-interval length
Carceller‐Sindreu, M., de Diego-Adeliño, J., Portella, M. J., García–Moll, X., Figueras, M., Fernández-Vidal, A., Queraltó, J. M., Puigdemont, D., & Álvarez, E. (2017) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-016-0758-6 · Cited by 11 · see citing works
Wei, A., Peng, J., Gu, Z., & Li, J. (2017) · Medicine · doi:10.1097/md.0000000000009071 · Cited by 12 · see citing works
“Compared with TCAs, SSRIs have shown significant antidepressant activity and good tolerability.([4]) When taken alone, fluoxetine was associated with a low risk of cardiac adverse effects.”
BackgroundAntidepressants: Indications, Contraindications, Interactions, and Side Effects
Corponi, F., Fabbri, C., & Serretti, A. (2020) · Springer eBooks · doi:10.1007/978-3-319-56015-1_29-1 · Cited by 11 · see citing works
Fabbri, C., Boriani, G., Diemberger, I., Filippi, M. G., Ravegnini, G., Hrelia, P., Minarini, A., Albani, D., Forloni, G., Angelini, S., et al. (2016) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12720 · Cited by 11 · see citing works
Acquired drug-induced long QTc: new insights coming from a retrospective study
Vecchis, R. D., Ariano, C., Biase, G. D., & Noutsias, M. (2018) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-018-2537-y · Cited by 11 · see citing works
Campbell, K. S. J., Collier, A. C., Irvine, M. A., Brain, U. M., Rurak, D. W., Oberlander, T. F., & Lim, K. I. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.680177 · Cited by 9 · see citing works
“Additionally, higher SRI doses may have cardiac side effects in adults, such as QT interval prolongation (93).”
BackgroundAnxiety Predicts Poor Prognosis in Patients With Hypertrophic Cardiomyopathy
He, C., Zhai, C., Huang, S.-D., Fan, H., Qian, Y., Zhu, C.-Y., & Hu, H. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.890506 · Cited by 10 · see citing works
“Finally, antidepressant medications including selective serotonin reuptake inhibitors have been associated with a modest effect on the QT interval, with citalopram appearing to cause the greatest QTc prolongation (36, 37).”
Background
- 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 › 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
