Published in JAMA Psychiatry, results of a randomized clinical trial indicate that antipsychotic medication use may be associated with adverse changes in adiposity and insulin sensitivity in youths.

Participants aged 6 to 18 years with a diagnosis of 1 or more psychiatric disorders and clinically significant aggression were enrolled in the study ( identifier: NCT00205699). Participants were randomly assigned (1:1:1) to 12 weeks of treatment with oral aripiprazole (n=49), olanzapine (n=46), or risperidone (n=49). Primary outcome measures included total body fat percentage and insulin sensitivity in muscle, measured by dual-energy X-ray absorptiometry (DXA) and hyperinsulinemic clamps with stable isotopically labeled tracers, respectively. Abdominal adiposity was captured using magnetic resonance imaging, and adipose and hepatic tissue insulin sensitivity were analyzed via clamps with tracers.

The total cohort included 144 patients (68.1% boys; mean age, 11.3 years), of whom 43 (29.9%) were overweight or obese at baseline. Behavioral improvements were observed for all treatment modes during the study course. From baseline to week 12, total body fat percentage increased by 1.18% for risperidone, 4.12% for olanzapine, and 1.66% for aripiprazole. According to time by treatment interaction analyses, olanzapine had a significantly greater effect on DXA percentage compared with risperidone and aripiprazole (P <.001). Reductions in insulin sensitivity from baseline were observed in the pooled sample, shown by substantial decreases in insulin-stimulated glucose rate of disappearance (P <.001). Magnetic resonance imaging-measured abdominal fat increased across the 12 weeks, with subcutaneous fat increase significantly greater for olanzapine compared with risperidone and aripiprazole (time by treatment, P =.003).

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Adverse changes in adiposity and insulin sensitivity are potential risk factors for premature cardiometabolic morbidity, researchers said, and should be considered by clinicians in planning antipsychotic treatment course for youths.

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Disclosures: Dr Nicol reported research funding from the National Institute of Mental Health, Otsuka America Pharmaceutical Inc, Alkermes PLC, The Sidney R. Baer Jr Foundation, and the Center for Brain Research in Mood Disorders at Washington University in St Louis. Dr Schechtman reported research funding from the National Institute of Mental Health; the National Heart, Lung, and Blood Institute; the National Institute of Aging; the National Cancer Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Institute of Allergy and Infectious Diseases. Dr Newcomer reported research funding from the National Institutes of Health and Otsuka America Pharmaceutical Inc in the 3 years before this study, serving as a consultant for Reviva Pharmaceuticals, Sunovion Pharmaceuticals Inc, Indivior, Otsuka America Pharmaceutical Inc, and Alkermes PLC, and serving as a consultant to litigation; serving on a data safety monitoring board for Amgen Inc; and receiving honoraria for continuing medical education from the American Society for Clinical Psychopharmacology. No other disclosures were reported.


Nicol GE, Yingling MD, Flavin KS, et al. Metabolic effects of antipsychotics on adiposity and insulin sensitivity in youths [published online June 13, 2018]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2018.1088