Children and young people who received antipsychotic doses higher than 50-mg chlorpromazine equivalents had an 80% increased risk of death at follow-up, compared with a control group, according to a study of young Medicaid enrollees who recently had begun medication.
“The study findings seem to reinforce existing guidelines for improving the outcomes of antipsychotic therapy in children and youths,” wrote lead author, of the department of health policy at the Vanderbilt University in Nashville, Tenn., and his coauthors. Those guidelines include using “psychosocial interventions when possible, cardiometabolic assessment before treatment and monitoring after treatment, and limiting therapy to the lowest dose and shortest duration possible,” they wrote.
The study, published online in, analyzed children and young adults from Tennessee, aged 5-24 years, who were new medication users, and had been enrolled in Medicaid between 1999 and 2014.
They were split into three groups: a control group (189,361) with users primarily taking attention-deficit/hyperactivity disorder medications and antidepressants; a group (28,377) with users who received antipsychotic doses of 50 mg or less chlorpromazine equivalents; and a group (30,120) with users who received doses higher than 50-mg chlorpromazine equivalents.
At follow-up, the incidence of death in the higher-dose group was 146.2 per 100,000 person-years (95% confidence interval, 107.3-199.4 per 100,000 person-years), compared with 49.5 in the lower-dose group (95% CI, 24.8-99.0) and 54.5 in the control group (95% CI, 42.9-69.2). This difference was attributed to unexpected deaths, which accounted for 52.5% of deaths in the higher-dose group. No increased risk of death was noted for injuries or suicides. “The elevated risk persisted for unexpected deaths not due to overdose, with a 4.3-fold increased risk of death from cardiovascular or metabolic causes,” Dr. Ray and his coauthors wrote.
The authors shared potential limitations of their study, including a relatively small number of deaths during follow-up and subsequent statistical adjustment during analysis. They also recognized that their data did not factor in important characteristics such as body mass index and family history, and that a “single-state Medicaid cohort may limit the study’s generalizability.”
Nonetheless, they emphasized Medicaid’s relevance as coverage provider for an estimated 39% of U.S. children, along with noting that
“Further studies are needed that compare antipsychotic users and controls within more narrow comorbidity ranges or in analyses that include richer clinical data,” they wrote.
The study was supported by grants from the National Heart, Lung, and Blood Institute, and the National Institute for Child Health and Human Development. No conflicts of interest were reported.
SOURCE: Ray WA et al. JAMA Psychiatry. 2018 Dec 12. doi: .