Increased Risk for Death in Youths Taking High-Dose Antipsychotics

In youths taking a high dose of antipsychotic medication, the risk for an unexpected death is >3.5-fold than in youths not taking one, according to study results published in JAMA Psychiatry.

Researchers retrospectively analyzed Medicaid data to create 3 study cohorts of youths 5 to 24 years old not diagnosed with schizophrenia or related psychoses. The first cohort was composed of young people taking an oral antipsychotic at a dosage >50 mg; the second cohort was composed of children taking an oral antipsychotic medication ≤50 mg; the third cohort was composed of children taking a control medication, such as attention-deficit/hyperactivity disorder medications, antidepressants, or mood stabilizers. Deaths during the study were classified as either injury or suicide, unexpected death not because of overdose, or unexpected death because of cardiovascular or metabolic causes.

Of the 30,120 participants taking a high dose of antipsychotic medication, 39.2% were women, the mean age was 14.5±4.8 years old, and the most commonly prescribed medication was quetiapine. Of the 28,377 participants taking a low dose of antipsychotic medication, 32.3% were women, the mean age was 11.7±4.4 years old, and the most commonly prescribed medication was risperidone. Of the 189,361 participants taking a control medication, 43.4% were women, the mean age was 12±5.1 years old, 49.6% were prescribed antidepressants, 42.9% were prescribed attention-deficit/hyperactivity disorder medications, and 7.5% were prescribed mood stabilizers.

The high-dose cohort had 40 deaths, which translated to 146.2 per 100,000 person-years (95% CI, 107.3-199.4), which was significantly higher than the control cohort (P <.001). The low-dose cohort had 8 deaths, which translated to 49.5 (95% CI, 24.8-99.0) per 100,000 person-years. The control-medication cohort had 67 deaths, which translated to 54.5 (95% CI, 42.9-69.2) per 100,000 person-years. The risk for death was 80% greater in the high-dose cohort than in the control cohort (hazard ratio (HR)1.80; 95% CI, 1.06-3.07), for any type of unexpected death (HR 3.51; 95% CI, 1.54-7.96), for injury or suicide (HR 1.03; 95% CI, 0.53-2.01), for unexpected deaths from unintentional drug overdose (HR 3.51; 95% CI, 0.99-12.43), and for unexpected death because of cardiovascular or metabolic causes (HR 4.29; 95% CI, 1.33-13.89).

Future studies should consider increasing sample size to further evaluate the association of specific antipsychotic medications, analyze potential drug interactions, and differentiate between cardiovascular and metabolic events.

The researchers concluded young people prescribed a high dose of antipsychotic medication “had a 3.5-fold increased risk [for] unexpected deaths… [and t]hese results appear to reinforce recommendations for careful prescribing and monitoring of antipsychotic regimens for children and youths and the need for larger antipsychotic safety studies in this population.”

Reference

Ray WA, Stein CM, Murray KT, et al. Association of antipsychotic treatment with risk of unexpected death among children and youths [published online December 12, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.3421