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The cardiac safety of aripiprazole treatment in patients at high risk for torsade: a systematic review with a meta-analytic approach

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Abstract

Rationale

Certain antipsychotics increase the risk of heart rate-corrected QT (QTc) prolongation and consequently Torsades de Pointes (TdP) and sudden cardiac death (SCD). Drug-induced Brugada syndrome (BrS) is also associated with SCD. Most SCDs occur in patients with additional cardiac risk factors.

Objectives

Aripiprazole’s cardiac safety has not been assessed in patients at high risk for torsade, where QTc prolongation risk is highly increased.

Methods

MEDLINE, Embase, and The Cochrane Library were searched for preclinical, clinical, and epidemiological studies. Eligible studies were reviewed and cardiac safety data were extracted. Continuous and dichotomous QTc data were used in the meta-analysis.

Results

Preclinical studies suggested that aripiprazole has limited affinity for the delayed rectifier potassium current. TdP was reported in two case reports and SCD was reported in one case report and one case series. No clinical studies assessing aripiprazole’s cardiac safety in patients at high risk for torsade were found. No thorough QT (TQT) study with aripiprazole was found. The meta-analysis revealed that the mean ΔQTc interval was decreased with aripiprazole and QTc prolongation risk was lower compared with placebo and active controls. Epidemiological studies linked aripiprazole to weak/moderate torsadogenicity. No studies were found associating aripiprazole with BrS suggesting low affinity for the fast sodium current.

Conclusions

Aripiprazole is a low-risk antipsychotic regarding cardiac safety in healthy patients. However, baseline and steady state electrocardiogram is recommended in patients at high risk for torsade due to marked QTc prolongation, absence of a TQT study, and lack of data in this group.

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Acknowledgments

None.

Conflict of interest

J. Nielsen has received research grants from H. Lundbeck, Pfizer, and Chempaq for clinical studies, and received speaking fees from Bristol-Myers Squibb, Lundbeck, Janssen Pharmaceuticals, and Hemocue. J. Meyer has received speaking or advising fees from Arbor Scientia, Bristol-Myers Squibb, Forum Pharmaceuticals, Genentech, Merck, Otsuka America, Inc., and Sunovion Pharmaceuticals. All other authors declare that they have no conflict of interest. C. Polcwiartek had full control of all the primary data and was responsible for the manuscript.

Funding

This work was supported by the Danish Strategic Research Foundation (HEARTSAFE grant number: 10–092799). The funding had no influence on the study design or findings.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark

    Christoffer Polcwiartek, Benjamin Sneider & Jimmi Nielsen

  2. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    Christoffer Polcwiartek & Jimmi Nielsen

  3. Department of Health Science and Technology, Aalborg University, Aalborg, Denmark

    Claus Graff

  4. Department of Pharmacy, Maudsley Hospital, London, UK

    David Taylor

  5. Department of Psychiatry, University of California, San Diego, USA

    Jonathan Meyer

  6. Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

    Jørgen K. Kanters

  7. Department of Cardiology, Herlev and Gentofte University Hospitals, Copenhagen, Denmark

    Jørgen K. Kanters

  8. Centre for Schizophrenia, Aalborg University Hospital, Brandevej 5, 9220, Aalborg Ø, Denmark

    Jimmi Nielsen

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  1. Christoffer Polcwiartek
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  2. Benjamin Sneider
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  7. Jimmi Nielsen
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Correspondence to Jimmi Nielsen.

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Polcwiartek, C., Sneider, B., Graff, C. et al. The cardiac safety of aripiprazole treatment in patients at high risk for torsade: a systematic review with a meta-analytic approach. Psychopharmacology 232, 3297–3308 (2015). https://doi.org/10.1007/s00213-015-4024-9

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  • DOI: https://doi.org/10.1007/s00213-015-4024-9

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