Ray WA, et al. - Given the occurrence of multiple, potentially fatal, dose-related cardiovascular, metabolic, and other adverse events among children and youths who are prescribed antipsychotic medications, researchers compared children and youths who are beginning treatment with antipsychotic vs control medications regarding their risk of unexpected death. In this cohort study of 247,858 Medicaid-enrolled children and youths in Tennessee, a significantly increased risk of unexpected death was noted in the group that received a higher dose of antipsychotic medication compared with the group that received control medication. This suggests the association of antipsychotic use with increased risk of unexpected death, reinforcing recommendations for careful prescribing and monitoring of antipsychotic treatment for children and youths.

Methods

• From 1999 through 2014, researchers performed this retrospective cohort study including Medicaid enrollees aged 5 to 24 years in Tennessee who had no diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder.
• They analyzed data from January 1, 2017, to August 15, 2018.
• Exposures comprised current, new antipsychotic medication use at doses higher than 50 mg (higher-dose group) or 50 mg or lower chlorpromazine equivalents (lower-dose group) as well as control medications (ie, attention-deficit/hyperactivity disorder medications, antidepressants, or mood stabilizers) (control group).
• They assessed deaths during study follow-up while out of hospital or within 7 days after hospital admission, classified as either deaths due to injury or suicide or unexpected deaths, as the main outcome and measures.
• Unexpected deaths not due to overdose and death due to cardiovascular or metabolic causes were assessed as the secondary outcomes.

Results

• The control group had 189,361 children and youths (mean [SD] age, 12.0 [5.1] years; 43.4% female), the lower-dose group had 28,377 (mean [SD] age, 11.7 [4.4] years; 32.3% female), and the higher-dose group had 30,120 (mean [SD] age, 14.5 [4.8] years; 39.2% female).
• The higher-dose group displayed the unadjusted incidence of death of 146.2 per 100,000 person-years (40 deaths per 27 354 person-years), which was significantly greater than that in the control group (54.5 per 100,000 population; 67 deaths per 123,005 person-years) (P < .001).
• The increased incidence of unexpected deaths in the higher-dose group (21 deaths; 76.8 per 100,000 population) compared with the control group (22 deaths; 17.9 per 100 000 population) was the primary difference observed.
• Following propensity score–adjusted hazard ratios were noted: all deaths (1.80; 95% CI, 1.06-3.07), deaths due to unintentional injury or suicide (1.03; 95% CI, 0.53-2.01), and unexpected deaths (3.51; 95% CI, 1.54-7.96).
• For unexpected deaths not due to overdose, the hazard ratio was 3.50 (95% CI, 1.35-9.11) and for deaths due to cardiovascular or metabolic causes, the hazard ratio was 4.29 (95% CI, 1.33-13.89).
• The lower-dose group and the control group did not differ significantly in terms of unadjusted as well as adjusted incidence of death.