Excess cardiometabolic risk in children and adolescents initiating antipsychotic treatment compared to young adults: results from a nationwide cohort study

Antipsychotic treatment is associated with cardiometabolic risks that may be especially detrimental to children and adolescents. In this Danish population-based cohort study, we included individuals with psychiatric diagnoses who initiated antipsychotics in 2000-2021 at age 6-31 years. We assessed the risk of cardiometabolic adverse events up to 10 years following incident exposure to antipsychotics, compared to age- and sex-matched unexposed individuals with psychiatric diagnoses. Cox regression models were used to calculate hazard ratios (HRs) after adjustment using high-dimensional propensity scores, including age, sex, calendar time, hospital diagnoses, and prescription drug use. HRs were compared between incident exposure in youths (6-17 years) and young adults (18-31 years), and between incident exposure in children (6-11 years) and adolescents (12-17 years). The total cohort consisted of 335,093 individuals, including 36,092 subjects exposed to antipsychotics (children and adolescents: 8,547, mean follow-up: 6.8±3.2 years; young adults: 27,545, mean follow-up: 6.5±3.4 years) and 299,001 age-, sex- and calendar-matched unexposed subjects. The incidence rate of cardiometabolic events was higher for young adults initiating antipsychotics than for children and adolescents (23.2 vs. 14.1 events/1,000 person-years). However, the adjusted excess risk of cardiometabolic events was significantly higher in exposed compared to unexposed children and adolescents (HR=1.87, 95% CI: 1.71-2.05) than in exposed compared to unexposed young adults (HR=1.46, 95% CI: 1.40-1.51) (p<0.001). The excess risk of cardiometabolic events was even higher when antipsychotic treatment was initiated before age 12 years (HR=2.44; 95% CI: 1.99-2.98) than at age 12-17 years (HR=1.69, 95% CI: 1.52-1.87) (p=0.012). Concerning specific cardiometabolic outcomes, there was an effect of age at antipsychotic initiation on the risks of metabolic syndrome (p=0.011) and obesity (p<0.001), that were higher among children and adolescents than young adults. Thus, initiation of antipsychotic treatment before age 18 years is associated with an excess risk of cardiometabolic events compared to age- and sex-matched youths with psychiatric disorders but unexposed to antipsychotics. The excess cardiometabolic risk is significantly higher than that of individuals who start antipsychotic treatment in early adulthood, and significantly higher for treatment onset in childhood compared to adolescence. On the basis of these findings, recommendations are provided about the use of antipsychotics in children and adolescents.