Associations of common antipsychotic medications with weight gain in youth and adults: a target trial emulation study

Few real-world studies have estimated differences in weight gain between antipsychotic medications. This study estimated effects of initiating 4 first-line antipsychotic medications on weight change in adults and children/adolescents.

Electronic health record data were collected from 31,270 adults (≥20 years) and 29,496 children/adolescents (<20 years) newly prescribed 1 of 4 antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone) from 2010 to 2019 across 15 U.S. health systems. Target trial emulation estimated the effect of initiating each medication on weight change in adults and body mass index z-score (BMIz) in children/adolescents at 6 (primary) and 12 months (secondary) versus aripiprazole (reference). Inverse probability weighted estimation of repeated outcome marginal structural models adjusted for baseline confounding and informative outcome measurement.

In adults, initiation of aripiprazole was associated with greater 6-month weight change than initiation of olanzapine (difference = -0.60 kg [95% CI: -0.97, -0.25]), quetiapine (difference = -1.17 kg [-1.43, -0.91]), and risperidone (difference = -0.35 kg [-0.73, 0.03]); 12-month weight gain was similar between aripiprazole and olanzapine (difference = -0.11 [-0.61, 0.38]). In children/adolescents, olanzapine was associated with greater 6-month BMIz change than aripiprazole (difference = 0.15 [0.10, 0.20]); quetiapine and risperidone were associated with slightly smaller BMIz increases than aripiprazole. Six-month adherence was lower for olanzapine (5-7%) than other medications (15-21%) in adults and children/adolescents.

Among 4 first-line antipsychotic medications, aripiprazole was associated with the greatest 6-month weight gain in adults and olanzapine was associated with the greatest 6-month BMIz increase in children/adolescents, though adherence was lower for olanzapine than other medications. Clinicians should consider these differences in weight gain when initiating antipsychotic medications.