Portal latinoamericano de toxicología
Typical and atypical antipsychotics both increase risk of sudden cardiac
6 March, 2009
Clinical Question: How safe are the newer atypical antipsychotic drugs? (March 06, 2009)
Bottom Line:
Both typical and atypical antipsychotic drugs increase the risk of sudden cardiac death. The absolute risk of sudden cardiac death in patients taking these drugs is 1.8 per 100 persons taking the drugs for 10 years, which is approximately twice as high as for patients in the general population. Newer drugs are not safer than older drugs with respect to cardiovascular outcomes, and thioridazine, clozapine, and risperidone in high doses appear to be slightly more risky. (See; http://www.essentialevidenceplus.com/levels.html)
Reference: Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009;360(3):225-235.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=19144938dopt=Abstract>
Bottom Line:
Both typical and atypical antipsychotic drugs increase the risk of sudden cardiac death. The absolute risk of sudden cardiac death in patients taking these drugs is 1.8 per 100 persons taking the drugs for 10 years, which is approximately twice as high as for patients in the general population. Newer drugs are not safer than older drugs with respect to cardiovascular outcomes, and thioridazine, clozapine, and risperidone in high doses appear to be slightly more risky. (See; http://www.essentialevidenceplus.com/levels.html)
Reference: Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 2009;360(3):225-235.
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=19144938dopt=Abstract>
Synopsis:
Older typical antipsychotic drugs, such as thioridazine, are associated with an increased risk of sudden cardiac death. In this study, data from Tennessee Medicaid were used to identify adults aged between 30 years and 74 years who had taken an antipsychotic drug and matched control patients who had not. Drug use was linked to death records. Deaths occurring in a hospital and within 30 days of hospital discharge were not included since the Medicaid database did not include drugs dispensed in hospital. Use was
divided into current use, indeterminate use (within 90 days after last current use), and nonuse. The study population included 93,300 users of antipsychotic drugs and 186,600 matched control patients. Groups were fairly well matched demographically, but differed by psychiatric diagnoses. Compared with nonusers, the risk of sudden cardiac death was increased among patients taking typical (incidence rate ratio [IRR] = 1.99; 95% CI, 1.68 – 2.34) and atypical (IRR = 2.26; 1.88 – 2.72) antipsychotic drugs. The direct comparison of mortality risk for patients taking typical or atypical agents was nonsignificant (1.14; 0.93-1.39). Subanalyses of patients with shorter use, no use in the prior 2 years, or more recent use (1998-2005) had similar results to the main analysis. There was a dose-response relationship, and the risk was highest among current users of high doses of thioridazine. As in any observational study, confounding was possible (for example, by increased smoking among patients taking these drugs), but the authors attempted to control for this by adjusting the analysis for the presence of comorbid cardiovascular disease.
A secondary analysis compared 67,824 users of antipsychotics with a control group of 116,069 patients matched according to their psychiatric illness profile for the likelihood that they would be a user of antipsychotic drugs. These patients typically had mood disorders for which antipsychotic drugs are an option but are not the standard of care. These groups were better matched than those in the primary analysis. Results were similar for this group of patients as for the primary analysis.
Older typical antipsychotic drugs, such as thioridazine, are associated with an increased risk of sudden cardiac death. In this study, data from Tennessee Medicaid were used to identify adults aged between 30 years and 74 years who had taken an antipsychotic drug and matched control patients who had not. Drug use was linked to death records. Deaths occurring in a hospital and within 30 days of hospital discharge were not included since the Medicaid database did not include drugs dispensed in hospital. Use was
divided into current use, indeterminate use (within 90 days after last current use), and nonuse. The study population included 93,300 users of antipsychotic drugs and 186,600 matched control patients. Groups were fairly well matched demographically, but differed by psychiatric diagnoses. Compared with nonusers, the risk of sudden cardiac death was increased among patients taking typical (incidence rate ratio [IRR] = 1.99; 95% CI, 1.68 – 2.34) and atypical (IRR = 2.26; 1.88 – 2.72) antipsychotic drugs. The direct comparison of mortality risk for patients taking typical or atypical agents was nonsignificant (1.14; 0.93-1.39). Subanalyses of patients with shorter use, no use in the prior 2 years, or more recent use (1998-2005) had similar results to the main analysis. There was a dose-response relationship, and the risk was highest among current users of high doses of thioridazine. As in any observational study, confounding was possible (for example, by increased smoking among patients taking these drugs), but the authors attempted to control for this by adjusting the analysis for the presence of comorbid cardiovascular disease.
A secondary analysis compared 67,824 users of antipsychotics with a control group of 116,069 patients matched according to their psychiatric illness profile for the likelihood that they would be a user of antipsychotic drugs. These patients typically had mood disorders for which antipsychotic drugs are an option but are not the standard of care. These groups were better matched than those in the primary analysis. Results were similar for this group of patients as for the primary analysis.