Antipsychotics and the Risks of Sudden Cardiac Death and All-Cause Death: Cohort Studies in Medicaid and Dually-Eligible Medicaid-Medicare Beneficiaries of Five States.
CONTEXT
Antipsychotic drugs have been linked to QT-interval prolongation, a presumed marker of cardiac risk, and torsade de pointes.


OBJECTIVE
To examine the associations between antipsychotics and 1) outpatient-originated sudden cardiac death and ventricular arrhythmia (SD/VA) and 2) all-cause death.


DESIGN
Two retrospective cohort studies.


SETTING
Medicaid programs of California, Florida, New York, Ohio and Pennsylvania.


PATIENTS
Incident antipsychotic users aged 30-75 years.


MAIN OUTCOME MEASURES
1) Incident, first-listed emergency department or principal inpatient SD/VA diagnoses; and 2) death reported in the Social Security Administration Death Master File.


RESULTS
Among 459,614 incident antipsychotic users, the incidences of SD/VA and death were 3.4 and 35.1 per 1,000 person-years, respectively. Compared to olanzapine as the referent, adjusted hazard ratios (HRs) for SD/VA were 2.06 (95% CI, 1.20-3.53) for chlorpromazine, 1.72 (1.28-2.31) for haloperidol, and 0.73 (0.57-0.93) for quetiapine. Adjusted HRs for perphenazine and risperidone were consistent with unity. In a subanalysis limited to first prescription exposures, HRs for chlorpromazine and haloperidol were further elevated (2.54 [1.07-5.99] and 2.68 [1.59-4.53], respectively), with the latter exhibiting a dose-response relationship. Results for death were similar.


CONCLUSIONS
Haloperidol and chlorpromazine had less favorable cardiac safety profiles than olanzapine. Among atypical agents, risperidone had a similar cardiac safety profile to olanzapine, whereas quetiapine was associated with 30% and 20% lower risks of SD/VA and death, respectively, compared to olanzapine. These measured risks do not correlate well with average QT prolongation, further supporting the notion that average QT prolongation may be a poor surrogate of antipsychotic arrhythmogenicity.
['Leonard|Charles E|CE|', 'Freeman|Cristin P|CP|', 'Newcomb|Craig W|CW|', 'Bilker|Warren B|WB|', 'Kimmel|Stephen E|SE|', 'Strom|Brian L|BL|', 'Hennessy|Sean|S|']
Death Cohort studies Medicaid Torsades de pointes Antipsychotic agents Cardiac arrhythmias International classification of diseases Pharmacoepidemiology Proportional hazards models Sudden death