High doses of antipsychotics may increase mortality among adolescents without diagnosed psychosis: JAMA

The key findings of the study are

• A total of 2 067 507 patients beginning study medication treatment filled 21 749 825 prescriptions during follow-up with 5 415 054 for antipsychotic doses of 100 mg or less, 2 813 796 for doses greater than 100 mg, and 13 520 975 for control medications.

• Mortality was not associated with antipsychotic doses of 100 mg or less (RD, 3.3) but was associated with doses greater than 100 mg (RD, 22.4).

• For higher doses, antipsychotic treatment was significantly associated with overdose deaths (RD, 8.3) and other unintentional injury deaths (RD, 12.3) but was not associated with nonoverdose suicide deaths or cardiovascular/metabolic deaths.

• Mortality for children aged 5 to 17 years was not significantly associated with either antipsychotic dose, whereas young adults aged 18 to 24 years had increased risk for doses greater than 100 mg (RD, 127.5).

Researchers concluded that “In this cohort study of more than 2 million children and young adults without severe somatic disease or diagnosed psychosis, antipsychotic treatment in doses of 100 mg or less of chlorpromazine equivalents or in children aged 5 to 17 years was not associated with increased risk of death. For doses greater than 100 mg, young adults aged 18 to 24 years had significantly increased risk of death, with 127.5 additional deaths per 100 000 person-years.”

Reference: Ray WA, Fuchs DC, Olfson M, et al. Antipsychotic Medications and Mortality in Children and Young Adults. JAMA Psychiatry. Published online November 29, 2023. doi:10.1001/jamapsychiatry.2023.4573.