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Antipsychotic use in young people tied to 80% increased risk of death

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Results heighten ‘already increased caution’

This study by Wayne A. Ray, PhD, and his colleagues addresses the risks of antipsychotic use in childhood while highlighting the contradictions in how psychiatrically ill children are treated and medicated, according to Barbara Geller, MD, of the department of psychiatry at Washington University in St. Louis.

Before commenting on the study itself, Dr. Geller noted that child psychiatry is not a subspecialty that deals with “little patients and little problems,” despite that lingering perception among some. “Fifty percent of psychiatry disorders begin by age 14 years,” she wrote, “and childhood age at onset is a risk factor for a more severe longitudinal course in mood and other disorders.”

In addition, though it seems instinctually that antipsychotic medications would have lesser side effects on healthy children, that is not always the case. “The opposite is true for certain metabolic and endocrine effects,” she explained, “such as relatively greater weight gain and prolactin level elevation than adults and the onset of type 2 diabetes within the first year of treatment.”

When it came to the study, Dr. Geller posed questions about the findings, including whether an increase in unexpected deaths among the higher-dose group could be attributed to suicide. She also recommended that future investigations “examine outcomes within child, adolescent, and young adult age subgroups, as opposed to combining all youth 6 to 24 years old.”

That said, this research does probe depths that require continued exploration. “Results in the study by Ray et al. heighten the already increased caution about prescribing antipsychotics to children and adolescents,” she wrote, “and emphasize the need to consider situational triggers of psychopathology to avoid medicating the environment.”

These comments are adapted from an accompanying editorial (JAMA Psychiatry. 2018 Dec 12. doi: 10.1001/jamapsychiatry.2018.3409). No conflicts of interest were reported.



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 Wayne A. Ray, PhD, 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 JAMA Psychiatry, 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 this was a first step toward better understanding the consequences of prescribing antipsychotics in younger populations.

“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: 10.1001/jamapsychiatry.2018.3421.

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