Antipsychotics Raise Unexpected Death Risk in Young People

December 18, 2018

High-dose antipsychotic use in children and young adults without psychosis is associated with an increased risk of unexpected death, according to a study published online in JAMA Psychiatry.

Consequently, prescribers should be cautious about prescribing antipsychotics—especially at higher doses—to younger patients, researchers warned.

“Patients should be selected very carefully, after consideration of both drug- and nondrug-alternatives,” said senior author Wayne Ray, PhD, professor of health policy at Vanderbilt University School of Medicine, Nashville, Tennessee. “There should be a pretreatment evaluation for factors that might amplify antipsychotic effects, such as cardiac conditions. These children and young adults should also be thoroughly monitored during treatment if they are prescribed a high-dose antipsychotic.”

Antipsychotics May Increase Risk for Diabetes, Heart Disease in Young People

Dr. Ray and colleagues reached the finding after evaluating retrospective data for 247,858 patients aged 5 to 24 enrolled in Medicaid in Tennessee between 1999 and 2014. Participants were classified into one of three groups: a higher-dose group consisting of those who began antipsychotic treatment at doses higher than 50 mg of chlorpromazine equivalents, a lower-dose group of those who began antipsychotic treatment at doses of 50 mg or lower of chlorpromazine equivalents, or a control group of patients who received other medications such as attention-deficit/hyperactivity disorder treatments, antidepressants, or mood stabilizers.

The study focused on youths receiving antipsychotics for conditions other than schizophrenia or psychosis since there are no alternative treatments for those conditions.

The higher-dose group had a 3.5-fold increased risk of unexpected death, compared with the control group, researchers found. Their risk of cardiovascular- and metabolic-related deaths increased by 4.29 times, according to researchers. The unexpected death rate in the lower-dose group did not differ significantly from that of the control group.

“The findings suggest that antipsychotic use is associated with increased risk of unexpected death and appear to reinforce recommendations for careful prescribing and monitoring of antipsychotic treatment for children and youths,” researchers wrote, “and to underscore the need for larger antipsychotic treatment safety studies in this population.”

—Jolynn Tumolo


Ray WA, Stein CM, Murray KT, et al. Association of antipsychotic treatment with risk of unexpected death among children and youths. JAMA Psychiatry. 2018 December 12;[Epub ahead of print].

Boerner C. High-dose antipsychotics place children at increased risk of unexpected death [press release]. Nashville, Tennessee: Vanderbilt University; December 12, 2018.