Atypical antipsychotic drugs and the risk of sudden cardiac death
Open accessAbstract
BACKGROUND: Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice. METHODS: We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs). RESULTS: Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval [CI], 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score. CONCLUSIONS: Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death.
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Both first-generation and second-generation antipsychotics can prolong cardiac repolarization (QT interval), increasing the risk of ventricular arrhythmias such as torsades de pointes.
“Both first-generation (typical) and second-generation (atypical) antipsychotics can prolong cardiac repolarization (QT interval), increasing the risk of ventricular arrhythmias such as torsades de pointes [27,28].”
From Trends in Sudden Death Among Schizophrenia Inpatients (2025) · cites this paper as [27]
The introductory passages say typical antipsychotics prolong the QT interval and that several atypical antipsychotics prolong ventricular repolarization; the Discussion also notes reports of torsade de pointes with both classes. But the Discussion says the study did not assess the mechanism of sudden cardiac death and describes increased ventricular-arrhythmia risk through prolonged repolarization as the most plausible explanation, not an established causal finding for both classes. (LLM, conf=0.85)
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Research works printed but not linked: 4
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“Antipsychotic medications may increase the risk of serious ventricular arrhythmias such as TdP, probably QT interval prolongation through blockade of potassium ion channels (Ray et al., 2009; Straus et al., 2004).”
BackgroundA Study of Sudden Cardiac Death in Schizophrenia
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“Both first-generation (typical) and second-generation (atypical) antipsychotics can prolong cardiac repolarization (QT interval), increasing the risk of ventricular arrhythmias such as torsades de pointes [27,28].”
- Authors
- Ray, W. A., Chung, C. P., Murray, K. T., Hall, K., & Stein, C. M.
- Affiliations
- Vanderbilt University (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2009-01-15
- Volume
- 360
- Issue
- 3
- Pages
- 225-235
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2713724
- OpenAlex
- W2171956687
- Cited by
- 1,194
- References
- 61
- Citations by year
- 2026: 30 · 2025: 33 · 2024: 42 · 2023: 34 · 2022: 49 · 2021: 43 · 2020: 66 · 2019: 66 · 2018: 96 · 2017: 69 · 2016: 67 · 2015: 76 · 2014: 79 · 2013: 87 · 2012: 88
- FWCI
- 73.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Agency for Healthcare Research and Quality (HS 10384)
- National Heart, Lung, and Blood Institute (R01HL081707, R56HL081707, HL081707)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- atypical antipsychotics, typical antipsychotics, sudden cardiac death, drug safety, ventricular arrhythmias, antipsychotic dosing, propensity score matching, Medicaid enrollees, schizophrenia, residual confounding, cardiovascular risk
- MeSH terms
- Adult, Aged, Mental Disorders, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Regression Analysis, Retrospective Studies, Risk, Antipsychotic Agents, Cohort Studies, Incidence, Poisson Distribution, Death, Sudden, Cardiac
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