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Antipsychotics Pose Risk of Fatal Cardiac Effects

Because several antipsychotic medications are associated with prolonged QT interval, vulnerable patients are exposed to the risk of cardiac arrhythmias and arrest. Hennessy and colleagues attempted to estimate the overall risk of ventricular arrhythmia and cardiac arrest in treated schizophrenic patients and to compare the risk with the two most frequently prescribed medications, haloperidol and thioridazine.

They studied patients identified in U.S. Medicaid databases as being diagnosed with schizophrenia and receiving more than one prescription for oral thioridazine, haloperidol, risperidone, or clozapine between 1993 and 1996. Two control groups of patients were selected by diagnosis of psoriasis or open-angle glaucoma. The average daily dosage of each of the study medications was calculated for each patient. All patients were followed until the end of the prescription or occurrence of ventricular arrhythmia or cardiac arrest.

Although the control patients with glaucoma were older than patients in the other groups, patients taking antipsychotic medications had between 1.7 and 3.2 times the rate of cardiac arrest and ventricular arrhythmia compared with the control group. These patients also had rates of death between 2.6 and 5.8 times that of the control groups (see accompanying table). Risperidone had the highest risk of cardiac arrest, ventricular arrhythmia, and death, followed by haloperidol. The risk of cardiac arrest and ventricular arrhythmia was 1.5 times greater for risperidone than for haloperidol. Paradoxically, the highest risk for risperidone was associated with the lowest dosage. The authors speculate that this finding reflects the use of very low dosages in frail patients who are at the greatest risk. The risk with thioridazine was associated with dosages of 600 mg per day or more, and the risk was dose-related.

Cardiac Arrest and Ventricular Arrhythmia in Patients Taking Antipsychotic Drugs--a Comparison Drug Cardiac arrest and ventricular arrhythmia Death Glaucoma* Psoriasis† Haloperidol‡ Glaucoma§ Psoriasis|| Haloperidol‡ Clozapine 1.7 (1.0 to 2.9) 1.9 (1.0 to 3.7) 0.7 (0.4 to 1.2) 3.4 (2.1 to 5.5) 2.6 (1.5 to 4.5) 0.8 (0.5 to 1.2) Haloperidol 2.2 (1.7 to 3.0) 2.4 (1.5 to 3.9) 1.0 (reference) 4.5 (3.6 to 5.7) 3.2 (2.2 to 4.8) 1.0 (reference) Risperidone 3.1 (2.2 to 4.5) 3.2 (1.9 to 5.4) 1.5 (1.1 to 2.1) 5.8 (4.3 to 8.0) 4.1 (2.7 to 6.4) 1.4 (1.1 to 1.9) Thioridazine 2.2 (1.6 to 3.0) 2.4 (1.4 to 3.9) 0.9 (0.7 to 1.2) 4.0 (3.1 to 5.2) 2.9 (2.0 to 4.4) 0.8 (0.7 to 1.0) *--Adjusted for age, sex, state, heart failure, ischemic heart disease, conduction disorder, other heart disease, ever use of angiotensin-converting enzyme inhibitor, ever use of antianginal drug, ever use of calcium channel blocker, ever use of antidiabetic drug, and ever use of coagulation modifier. †--Adjusted for age, sex, state, heart failure, other heart disease, cancer, ever use of adrenergic bronchodilators, ever use of angiotensin-converting enzyme inhibitor, ever use of antianginal drug, ever use of calcium channel blocker, ever use of coagulation modifier, and current use of any one of the following drugs: loop diuretics, potassium-sparing diuretics, terfenadine, astemizole, cisapride, antiarrhythmic drugs, antidepressants, gatifloxacin, sparfloxacin, erythromycin, felbamate, sumatriptan, probucol, sotalol, perphenazine, or pindolol. ‡--Adjusted for age, sex, and state. No factor affected the rate ratio by >=10 percent. §--Adjusted for age, sex, state, heart failure, other heart disease, ever use of angiotensin-converting enzyme inhibitor, ever use of antianginal drug, ever use of calcium channel blocker, and ever use of coagulation modifier. ||--Adjusted for age, sex, state, heart failure, cancer, ever use of inhaled corticosteroid, ever use of systemic corticosteroid, ever use of adrenergic bronchodilators, ever use of antiretroviral drug, ever use of calcium channel blocker, and current use of any one of the following drugs: loop diuretics, potassium-sparing diuretics, terfenadine, astemizole, cisapride, antiarrhythmic drugs, antidepressants, gatifloxacin, sparfloxacin, erythromycin, felbamate, sumatriptan, probucol, sotalol, perphenazine, or pindolol. Adapted with permission from Hennessy S, Bilker WB, Knauss JS, Margolis DJ, Kimmel SE, Reynolds RF, et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ 2002;325:1071.

The authors conclude that antipsychotic drugs are associated with increased risk of cardiac arrest and ventricular arrhythmia. The greatest risk may be for those taking high dosages of thioridazine, but all patients should be prescribed the lowest antipsychotic dosage necessary for optimal therapeutic effect.

ANNE D. WALLING, M.D.

Hennessy S, et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ November 9, 2002;325: 1070-2.

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