Second generation antipsychotics are known to produce negative metabolic adverse effects including obesity, hyperglycemia and dyslipidemia. These effects are also known to occur more often and more quickly in children and young adults. While many observational trials have been published demonstrating these risks, a randomized, controlled trial was published last week providing definitive evidence of the extent and speed of metabolic changes in young children (mean age 11.3 years) with psychiatric disorders and aggressive behavior who were previously naïve to antipsychotic treatment. Patients (n = 144) were randomly assigned to treatment with aripiprazole, olanzapine or risperidone for 12 weeks. In this trial, primary outcomes included percentage total body fat (measured by dual-energy x-ray absorptiometry) and insulin sensitivity in muscle (measured with stable isotopically labeled tracers).
While behavioral improvements were observed in all treatment groups, significant metabolic changes occurred within the 12 week study period. Percentage total body fat increased by 1.18% for risperidone, 4.12% for olanzapine and 1.66% for aripiprazole. Insulin-stimulated change in glucose rate of disappearance (the gold standard measure for insulin resistance) increased by 2.30% for risperidone, but decreased by 29.34% for olanzapine and 30.26% for aripiprazole. The combined rates of overweight and obesity increased from the baseline rate of 29.9% (43 of 144 participants) to 46.5% (60 of 144 participants) after the 12 week trial.
These results reinforce the importance of careful monitoring of metabolic parameters in patients from the start of treatment, and underscores the risk of diabetes and cardiovascular disease secondary to treatment with these agents.
Additional information about aripiprazole, olanzapine and risperidone can be found in the Top 300 Pharmacy Drug Cards. If you or your institution subscribes to AccessPharmacy, use or create your MyAccess Profile to sign-in to the Top 300 Pharmacy Drug Cards. If your institution does not provide access, ask your medical librarian about subscribing.
Nicol GE, Yingling MD, Flavin KS, Schweiger JA, Patterson BW, Schechtman KB, Newcomer JW. Metabolic effects of antipsychotics on adiposity and insulin sensitivity in youths: A randomized clinical trial. JAMA Psychiatry 2018, June 13 (epub ahead of print); doi:10.1001/jamapsychiatry.2018.1088