Wednesday, December 12, 2018

Youth Prescribed High Doses of Antipsychotics Off Label May Be at Heightened Risk of Death, Study Finds

Medicaid-enrolled youth aged 5 to 24 years who begin taking high doses of antipsychotics for psychiatric disorders other than psychosis appear to be at an increased risk of death compared with those taking other psychiatric medications, reports a study published today in JAMA Psychiatry. The findings serve as a reminder of the importance of careful prescribing and monitoring of young patients on antipsychotics, according to the study authors.

Wayne R. Ray, Ph.D., of Vanderbilt University School of Medicine and colleagues conducted a retrospective cohort study of youth aged 5 to 24 years who were enrolled in Medicaid in Tennessee between 1999 and 2014. The researchers specifically focused on deaths of patients who began taking oral antipsychotics and/or other medications commonly prescribed for the same indications as antipsychotics (such as mood stabilizers or antidepressants) for recently diagnosed psychiatric disorders. Patients who had a diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder were excluded from the analysis.

Of the 247,858 patients included in the cohort, 70.6% had a diagnosis of behavioral symptoms (ADHD, conduct disorder, or impulsivity). A total of 28,377 began taking a low dose of antipsychotics (defined as 50-mg or less chlorpromazine equivalents); 30,120 began taking a high dose of antipsychotics (higher than 50-mg chlorpromazine equivalents); 81,310 began taking ADHD medications (most frequently psychostimulants); 93,864 began taking antidepressants (most frequently selective serotonin reuptake inhibitors); and 14,187 began taking mood stabilizers (most frequently anticonvulsants). The patients were tracked from the filling of the first prescription for an antipsychotic or other medication until the end of 2014, five years after entering the cohort, loss of Medicaid enrollment, they reached age 25, or death—whichever came first.

The researchers found that “those receiving doses higher than 50-mg chlorpromazine equivalents during follow-up had an 80% increased risk of death that was attributable to a 3.5-fold increased risk of unexpected deaths,” Ray and colleagues wrote. “In contrast, the risk of deaths from injuries or suicides was not increased. 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.”

“These results demonstrate a significant increase in the incidence of unexplained deaths in young people treated with higher doses of antipsychotics,” David Fassler, M.D., a clinical professor of psychiatry at the University of Vermont College of Medicine, told Psychiatric News. Although additional studies are needed to begin to understand how family history, undiagnosed cardiovascular abnormalities, or specific drug interactions as the result of polypharmacy may contribute to this increased risk of death in those taking higher doses of antipsychotics, Fassler said that “the findings represent an important contribution to the field.”

In an accompanying editorial, Barbara Geller, M.D., a professor emerita of child psychiatry at Washington University School of Medicine in St. Louis, added: The “[r]esults in the study by Ray et al heighten the already increased caution about prescribing antipsychotics to children and adolescents…. Concerns about excess deaths are likely to increase because the prevalence of some disorders for which antipsychotics are prescribed off-label (e.g., attention-deficit/hyperactivity disorder) and the number of prescriptions for indicated and off-label use are rising.”

For related information, see the Psychiatric Services article “The Impact of a State Medicaid Peer-Review Authorization Program on Pediatric Use of Antipsychotic Medications.”

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