Nicol GE, et al. - Using criterion standard assessments of body composition and insulin sensitivity, researchers characterized the metabolic effects of first exposure to antipsychotics in youths. Researchers noted that in children, antipsychotic medications are commonly used for the treatment of disruptive behavior disorders. However, their potential benefits are recommended to be carefully weighed against the risk for adverse changes in total and abdominal adiposity and insulin sensitivity, known contributors to the development of early-onset type 2 diabetes, cardiovascular disease, and other illnesses associated with premature morbidity and mortality.

Methods

• Researchers undertook this randomized clinical trial recruiting antipsychotic-naive youths aged 6 to 18 years in the St Louis, Missouri, metropolitan area.
• The youths were those who were diagnosed with 1 or more psychiatric disorders and clinically significant aggression and in whom antipsychotic treatment was considered.
• From June 12, 2006, through November 10, 2010, they enrolled the participants.
• Randomization of enrolled participants (1:1:1) to 1 of 3 antipsychotics commonly used in children with disruptive behavioral disorders was performed.
• Evaluation of the participants was performed for 12 weeks.
• From January 17, 2011, through August 9, 2017, they performed data analysis.
• The participants received 12 weeks of treatment with oral aripiprazole (n=49), olanzapine (n=46), or risperidone (n=49).
• Percentage total body fat measured by dual-energy x-ray absorptiometry (DXA) and insulin sensitivity in muscle measured via hyperinsulinemic clamps with stable isotopically labeled tracers were assessed as primary outcomes.
• Abdominal adiposity measured by magnetic resonance imaging (MRI) and adipose and hepatic tissue insulin sensitivity measured via clamps with tracers were the secondary outcomes assessed.

Results

• Researchers included 144 participants (98 males [68.1%]; mean [SD] age, 11.3 [2.8] years) in the intention-to-treat sample; 74 (51.4%) were African American, and 43 (29.9%) were overweight or obese at baseline.
• For the primary outcomes, they noted increase in DXA percentage total body fat by 1.18% with risperidone, 4.12% with olanzapine, and 1.66% with aripiprazole from baseline to week 12; the increase was significantly greater for olanzapine than risperidone or aripiprazole (time by treatment interaction P < .001).
• Insulin-stimulated change in glucose rate of disappearance increased by 2.30% for risperidone and decreased by 29.34% for olanzapine and 30.26% for aripiprazole from baseline to week 12; no significant difference across medications was observed(time by treatment interaction, P < .07).
• During 12 weeks, significant decrease in this primary measure of insulin sensitivity was observed in the pooled study sample (effect of time, F = 17.38; P < .001).
• For the secondary outcomes, MRI measured abdominal fat increased, with subcutaneous fat increase significantly greater for olanzapine than risperdone or aripiprazole from baseline to week 12 (time by treatment, P=.003).
• All treatments resulted in behavioral improvements.