Background: Antipsychotic-related weight gain and metabolic adverse effects have become a major focus, especially in youth.
Methods: Review of randomized, cohort, and pharmacoepidemiologic studies of antipsychotic-related weight gain and metabolic adverse effects and of interventions for their reduction in youth.
Results: Across 34 published head-to-head and placebo-controlled studies in youth with psychotic and bipolar disorders, weight gain ranged from 3.8 to 16.2 kg with olanzapine (n=353), 0.9-9.5 kg with clozapine (n=97), 1.9-7.2 kg with risperidone (n=571), 2.3-6.1 kg with quetiapine (n=133), and 0-4.4 kg with aripiprazole (n=451). In 24 placebo-controlled trials, the numbers-needed-to-harm for weight gain ≥7% in youth with bipolar disorder and schizophrenia were 39 (confidence interval [CI]: -1 to +6, not significant) for aripiprazole, 36 (CI: -1 to +7, not significant) for ziprasidone, 9 (CI: 7-14) for quetiapine, 6 (CI: 5-8) for risperidone, and 3 (CI: 3-4) for olanzapine. Data in youth with autism and disruptive behavior disorders, available only for some antipsychotics, suggest greater weight gain, possibly due to less prior antipsychotic exposure. Three-month results from a large cohort study in antipsychotic-naïve youth indicated that metabolic effects differ among second-generation antipsychotics, despite significant weight gain with all studied agents, suggesting additional, weight-independent effects. Further, pharmacoepidemiologic work indicates that antipsychotic polypharmacy increases the risk for obesity (odds ratio [OR]: 2.28 [CI: 1.49-3.65]) or any cardiovascular, cerebrovascular, or hypertensive adverse event (OR: 1.72 [CI: 1.10-2.69]). However, despite marked weight gain and its greater impact on youth, monitoring rates are low and studies of pharmacologic and behavioral interventions are extremely limited.
Conclusions: More research is needed to develop strategies to minimize antipsychotic-related weight gain and metabolic effects in youth and to discover treatments with lower risk potential.