Cited by 253Cardiac electrophysiology and arrhythmiasCardiac Health and Mental HealthTreatment of Major Depression

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Meta-Analysis of Selective Serotonin Reuptake Inhibitor–Associated QTc Prolongation

Beach, Scott R., Kostis, William J., Celano, Christopher M., Januzzi, James L., Ruskin, Jeremy N., Noseworthy, Peter A., Huffman, Jeff C.·2014·The Journal of Clinical Psychiatry

DOI 10.4088/jcp.13r08672

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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.

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“The most common CNS-related adverse effects include insomnia, anxiety, tremor, drowsiness, sedation, dizziness, ataxia, cognitive impairment, and confusion (Beach et al. 2014 ; Rux-ton et al. 2015 ; Riediger et al. 2017 ).”
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Increased Odds of Ventricular Arrhythmias Associated with Selective Serotonin Reuptake Inhibitor Use among the Pediatric and Young Adult Population: A Case–Control Study
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“However, initiations of TCAs and SNRIs were not common in our study.”
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“However, the risks differ depending on the antidepressant class and the specific agents.(13,14) Comparing the frequency of cardiovascular adverse drug reactions defined according to the “AMSP study guidelines,”(15) selective serotonin reuptake inhibitors (SSRIs) show a significantly lower risk than tricyclic antidepre…”
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“QTcF prolongation occurred in only a small number of subjects in this study, which is reminiscent of the mild prolongations that are reported for most SSRIs.40 Taken together, this study demonstrated a CNS effect pattern for ALKS 7119 that is in line with the drug's pharmacological binding profile.”
Result
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“46 Consequently, we do not expect any bias or inaccuracies in the estimation of drug-specific parameters based on the data obtained at steady state on treatment days 7, 14 and 21.”
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“Similarly, a meta-analysis found that SSRIs increased corrected QT by 6.1 ms versus placebo, while a greater increase was observed for TCAs [ 32 ].”
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Background
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“In adult patients ( N = 1692) treated with SSRIs, a recent meta-analysis revealed a modest, but statistically signiﬁcant increase in the QTc interval ( + 6.10 milliseconds, 95% CI: 3.47– 8.73), although to a lesser extent than tricyclic antidepressants (Beach et al. 2014).”
Influential

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: Beach, Scott R.
Kostis, William J.
Celano, Christopher M.
Januzzi, James L.
Ruskin, Jeremy N.
Noseworthy, Peter A.
Huffman, Jeff C.
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)
DOI: 10.4088/jcp.13r08672
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

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Meta-Analysis of Selective Serotonin Reuptake Inhibitor–Associated QTc Prolongation

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