Antipsychotic Drugs and the Risk of Ventricular Arrhythmia and/or Sudden Cardiac Death: A Nation-wide Case-Crossover Study
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BACKGROUND: Antipsychotics have been linked to prolongation of the QT interval. However, little is known about the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with individual antipsychotic drug use. This study was designed to investigate the association between specific antipsychotic drugs and the risk of VA and/or SCD. METHODS AND RESULTS: We conducted a case-crossover study using a nation-wide population-based sample obtained from Taiwan's National Health Insurance Research Database. A total of 17 718 patients with incident VA and/or SCD were enrolled. Conditional logistic regression models were applied to examine the effects of antipsychotic drug use on the risk of VA/SCD during various case and control time windows of 7, 14, and 28 days. The effect of the potency of a human ether-à-go-go-related gene (hERG) potassium channel blockade was also assessed. Antipsychotic drug use was associated with a 1.53-fold increased risk of VA and/or SCD. Antipsychotic drugs with increased risk included clothiapine, haloperidol, prochlorperazine, thioridazine, olanzapine, quetiapine, risperidone, and sulpiride. The association was significantly higher among those with short-term use. Antipsychotics with a high potency of the hERG potassium channel blockade had the highest risk of VA and/or SCD. CONCLUSION: Use of antipsychotic drugs is associated with an increased risk of VA and/or SCD. Careful evaluations of the risks and benefits of antipsychotic treatment are highly recommended.
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Antipsychotic exposure is associated with a 1.5-fold higher risk of ventricular arrhythmia or sudden cardiac death, especially with short-term use and agents showing high hERG-blocking potency.
“Wu et al. (2015) conducted a nationwide case-crossover study in over 17,000 patients and found a 1.5-fold higher risk of ventricular arrhythmia or sudden cardiac death during antipsychotic exposure, especially with short-term use and agents showing high hERG-blocking potency such as haloperidol, thioridazine, and risperidone [33].”
From Trends in Sudden Death Among Schizophrenia Inpatients (2025) · cites this paper as [33]
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References 34 · Cited by 191
- Authors
- Wu, C., Tsai, Y., & Tsai, H.
- Affiliations
- National Taiwan University (TW)
- National Health Research Institutes (TW)
- Northwestern University (US)
- Corresponding author
- Tsai, Hui‐Ju
- Venue
- Journal of the American Heart Association
- Published
- 2015-01-30
- Volume
- 4
- Issue
- 2
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC4345877
- OpenAlex
- W2125156044
- Cited by
- 191
- References
- 34
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 17 · 2023: 18 · 2022: 20 · 2021: 15 · 2020: 18 · 2019: 17 · 2018: 17 · 2017: 20 · 2016: 21 · 2015: 6
- FWCI
- 15.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- World Health Organization
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- antipsychotic drugs, ventricular arrhythmias, sudden cardiac death, QT prolongation, clozapine, haloperidol, thioridazine, olanzapine, quetiapine, risperidone, prochlorperazine, sulpiride, drug safety, adverse drug reactions
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Arrhythmias, Cardiac, Female, Humans, Male, Middle Aged, Risk Factors, Taiwan, Time Factors, Antipsychotic Agents, Death, Sudden, Cardiac, Cross-Over Studies, Potassium Channel Blockers, Ether-A-Go-Go Potassium Channels, Young Adult
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