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Antipsychotics and the Risk of Sudden Cardiac Death
Wayne A. Ray, PhD;
Sarah Meredith, MBBS, MSc;
Purushottam B. Thapa, MBBS, MPH;
Keith G. Meador, MD, MPH;
Kathi Hall, BS;
Katherine T. Murray, MD
Arch Gen Psychiatry. 2001;58:1161-1167.
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.
From the Division of Pharmacoepidemiology, Department of Preventive
Medicine (Drs Ray and Meredith and Ms Hall), and the Divisions of Cardiology
and Clinical Pharmacology, Departments of Medicine and Pharmacology (Dr Murray),
Vanderbilt University School of Medicine, Geriatric Research, Education, and
Clinical Center, Nashville Veterans Affairs Medical Center (Dr Ray), Nashville,
Tenn; the Department of Psychiatry, University of Arkansas for Medical Sciences,
Little Rock (Dr Thapa); and the Department of Psychiatry and Behavioral Sciences,
Duke University Medical Center and Durham Veterans Affairs Medical Center,
Durham, NC (Dr Meador).
Corresponding author and reprints: Wayne A. Ray, PhD, Department
of Preventive Medicine, Medical Center North, Room A-1124, Vanderbilt University
Medical Center, Nashville, TN 37232 (e-mail: wayne.ray{at}mcmail.vanderbilt.edu).
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