Sudden cardiac and sudden unexpected death related to antipsychotics: a meta-analysis of observational studies

Salvo, F., Pariente, A., Shakir, S., Robinson, P., Arnaud, M., Thomas, S.H., Raschi, E., Fourrier-Reglat, A., Moore, N., Sturkenboom, M. and Hazell, L. (2016) Sudden cardiac and sudden unexpected death related to antipsychotics: a meta-analysis of observational studies. Clinical Pharmacology and Therapeutics, 99 (3), 306-314. (doi:10.1002/cpt.250).

Abstract

To estimate the risk of sudden cardiac death (SCD) or sudden unexpected death (SUD) related to individual antipsychotics, a meta-analysis of observational studies was performed. Adjusted odds ratio (OR) of SCD/SUD with 95% confidence intervals (CI) were extracted and pooled; heterogeneity was studied using Q statistic and I 2 index, and its potential causes (e.g., hERG blockade potency) explored using meta-regression. Two cohort (740,306 person-years) and four case-control (2,557 cases; 17,670 controls) studies, investigating nine antipsychotics, were included. Compared with nonusers, the risk was increased for quetiapine (OR = 1.72, 95% CI: 1.33-2.23), olanzapine (OR = 2.04, 1.52-2.74), risperidone (OR = 3.04, 2.39-3.86), haloperidol (OR = 2.97, 1.59-5.54), clozapine (OR = 3.67, 1.94-6.94), and thioridazine (OR = 4.58, 2.09-10.05). Heterogeneity was found (Q = 20.0, P = 0.01; I 2 = 60.0%), and the increasing mean hERG blockade potency (P = 0.01) accounted for 43% of this. The SCD/SUD risk differed between individual antipsychotics, and mean hERG blockade potency could be an explanatory factor. This should be considered when initiating antipsychotic treatment.

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Contributors

Author: L. Hazell

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