Atypical antipsychotic drugs and the risk of sudden cardiac death - PubMed (original) (raw)

Atypical antipsychotic drugs and the risk of sudden cardiac death

Wayne A Ray et al. N Engl J Med. 2009.

Erratum in

Abstract

Background: Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice.

Methods: We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs).

Results: Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval [CI], 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score.

Conclusions: Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death.

2009 Massachusetts Medical Society

PubMed Disclaimer

Figures

Figure 1

Figure 1

Adjusted incidence rate-ratio for sudden cardiac death among current users of antipsychotics, according to antipsychotic type and dose (chlorpromazine equivalents: low, <100mg; moderate, 100mg–299mg; high, ≥300mg). The reference category is that of nonusers of any antipsychotic drug. Vertical bars denote 95% confidence intervals.

Figure 2

Figure 2

Adjusted incidence rate-ratio for sudden cardiac death among current users of six frequently prescribed individual antipsychotic drugs, according to dose( chlorpromazine equivalents: low, <100mg; moderate, 100mg–299mg; high, ≥300mg). The reference category is that of nonusers of any antipsychotic drug. Vertical bars denote 95% confidence intervals.

Comment in

Similar articles

Cited by

References

    1. Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs. 2002;62:1649–1671. - PubMed
    1. Kongsamut S, Kang J, Chen XL, Roehr J, Rampe D. A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs. Eur J Pharmacol. 2002;450:37–41. - PubMed
    1. Thomas SHL. Drugs, QT interval abnormalities and ventricular arrhythmias. Adverse Drug React Toxicol Rev. 1994;13:77–102. - PubMed
    1. Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas HL. QTc- interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet. 2000;355:1048–1052. - PubMed
    1. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013–1022. - PubMed

Reference List

    1. Ray WA, Meredith S, Thapa PB, Meador KG, Hall K, Murray KT. Cyclic antidepressants and the risk of sudden cardiac death. Clin Pharmacol Ther. 2003;75:234–241. - PubMed
    1. Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral erythromycin use and the risk of sudden cardiac death. N Engl J Med. 2004;351:1089–1096. - PubMed
    1. Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmacol Drug Safety. 2005;14:747–753. - PubMed
    1. Wiseman LR, Faulds D. Cisapride. An updated review of its pharmacology and therapeutic efficacy as a prokinetic agent in gastrointestinal motility disorders. Drugs. 1994;47:116–152. - PubMed
    1. Monahan BP, Ferguson CL, Killeavy ES, Lloyd BK, Troy J, Cantilena LR. Torsades de pointes occurring in association with terfenadine use. JAMA. 1990;264:2788–2790. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources