Sudden Cardiac Death and Antipsychotic Drugs Do We Know Enough?

Zarate CA, Jr, Patel J. — Sat, 01 Dec 2001 00:00:00 GMT

ANTIPSYCHOTIC drugs have revolutionized the treatment of psychotic and mood disorders since their introduction 50 years ago. Although psychiatric patients have significantly benefited from the use of typical antipsychotic drugs, their limitations have become apparent and include extrapyramidal symptoms and tardive dyskinesia. The next generation of antipsychotic drugs (novel or atypical) offers advantages compared with the typical antipsychotic drugs: they are uniformly better tolerated and are more efficacious in certain symptom domains. However, current data do not suggest that these new medications offer advantages regarding cardiovascular adverse effects.

Antipsychotics and the Risk of Sudden Cardiac Death

Ray WA, Meredith S, Thapa PB, et al. — Sat, 01 Dec 2001 00:00:00 GMT

Background

Case reports link antipsychotic drugs with sudden cardiac deaths, which is consistent with dose-related electrophysiologic effects. Because this association has not been confirmed in controlled studies, we conducted a retrospective cohort study in Tennessee Medicaid enrollees, which included many antipsychotic users; there were also computer files describing medication use and comorbidity. The study was conducted before the introduction of risperidone and, thus, did not include the newer atypical agents.

Methods

The cohort included 481 744 persons with 1 282 996 person-years of follow-up. This included 26 749 person-years for current moderate-dose antipsychotic use (>100-mg thioridazine equivalents), 31 864 person-years for current low-dose antipsychotic use, 37 881 person-years for use in the past year only, and 1 186 501 person-years for no use. The cohort had 1487 confirmed sudden cardiac deaths; from these, we calculated multivariate rate ratios adjusted for potential confounding factors.

Results

When current moderate-dose antipsychotic use was compared with nonuse, the multivariate rate ratio was 2.39 (95% confidence interval, 1.77-3.22; P<.001). This was greater than that for current low-dose (rate ratio, 1.30; 95% confidence interval, 0.98-1.72; P = .003) and former (rate ratio, 1.20; 95% confidence interval, 0.91-1.58; P<.001) use. Among cohort members with severe cardiovascular disease, current moderate-dose users had a 3.53-fold (95% confidence interval, 1.66-7.51) increased rate relative to comparable nonusers (P<.001), resulting in 367 additional deaths per 10 000 person-years of follow-up.

Conclusions

Patients prescribed moderate doses of antipsychotics had large relative and absolute increases in the risk of sudden cardiac death. Although the study data cannot demonstrate causality, they suggest that the potential adverse cardiac effects of antipsychotics should be considered in clinical practice, particularly for patients with cardiovascular disease.

JAMA Psychiatry: Cardiac Arrest/Resuscitation Topic Collection

Sudden Cardiac Death and Antipsychotic Drugs Do We Know Enough?

Antipsychotics and the Risk of Sudden Cardiac Death