(JAMA Psychiatry) – Over the last 2 decades, there has been increasing widespread use of second-generation antipsychotic (SGA) medications in nonpsychotic pediatric populations in the United States and Europe. As the ubiquity of SGA drugs in treatment plans for these children and adolescents grows, so does the controversy surrounding them.
Antipsychotic medications can induce cardiometabolic abnormalities (such as obesity, hyperglycemia, and dyslipidemia) that are associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus (DM). These adverse effects tend to appear faster and to a greater extent in children and adolescents than in adults. In this vulnerable population, roughly the same hierarchy for risk of weight gain with these agents has been identified (with olanzapine having the highest risk, risperidone showing an intermediate risk, and aripiprazole having less effect on body weight) but at a higher rate. Generally, this weight gain is rapid during the first few weeks or months of medication use, slows gradually thereafter, and often reaches a plateau within 1 year. Although the occurrence of new cases of DM in antipsychotic-exposed youths remains small, SGA-treated children nevertheless have a 2-fold to 3-fold increased risk of developing type 2 DM compared with SGA-naive children. This risk increases with higher cumulative doses (particularly with olanzapine), longer treatment duration, and adjunctive antidepressant use, and it seems to remain high for a certain period of time after discontinuation. High interindividual variability of these adverse effects among patients treated with a given agent suggests that underlying biological or genetic factors predispose children to metabolic adverse effects during SGA treatment. This explains why not all children and adolescents show these adverse effects.