Papers

Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data

Sean Hennessy, assistant professor, ^a Warren B Bilker, associate professor, ^a Jill S Knauss, biostatistician, ^a David J Margolis, associate professor, ^a Stephen E Kimmel, assistant professor, ^a Robert F Reynolds, director, epidemiology, ^b Dale B Glasser, medical director, sexual health, ^b Mary F Morrison, assistant professor, ^c Brian L Strom, professor. ^a

^a Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA, ^b Pfizer, New York, NY 10017, USA, ^c Department of Psychiatry, University of Pennsylvania School of Medicine

Correspondence to: S Hennessy shenness{at}cceb.med.upenn.edu

Objective: To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls.
Design: Cohort study of outpatients using administrative data.
Setting: 3 US Medicaid programmes.
Participants: Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis.
Main outcome measure: Diagnosis of cardiac arrest or ventricular arrhythmia.
Results: Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses 600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038).
Conclusions: The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect.

What is already known on this topic Thioridazine seems to prolong the electrocardiographic QT interval more than haloperidol Although QT prolongation is used as a marker of arrhythmogenicity, it is unknown whether thioridazine is any worse than haloperidol with regard to cardiac safety What this study adds Patients taking antipsychotic drugs had higher risks of cardiac events than control patients with glaucoma or psoriasis Overall, the risk of cardiac arrest and ventricular arrhythmia was not higher with thioridazine than haloperidol Thioridazine may carry a greater risk than haloperidol at high doses Patients should be treated with the lowest dose of thioridazine needed to treat their symptoms