Atypical anti-psychotics (AAP) are being used with increased frequency to treat psychiatric illness in children and adolescents. Although AAP treatment has resulted in symptomatic improvement, therapeutic success is often accompanied by significant weight gain, with the result in increased risk of developing insulin resistance syndromes (including diabetes), cardiovascular disease, and other complications of obesity. Weight gain is also a major reason for medication non-compliance and discontinuation, often necessitating changes in pharmacotherapy that may eliminate therapeutic gains and contribute to disease recurrence. Dr. Klein has undertaken a project to prevent AAP-induced obesity by using the insulin sensitizing agent Metformin.
Metformin has been shown to act directly on the hypothalamic appetite centers. In earlier studies, Dr. Klein and other investigators noted that Metformin prevents further weight gain in AAP treated subjects who had previously gained weight on these agents and also improved insulin sensitivity. He is now undertaking a project to determine whether Metformin given at the initiation of anti-psychotic treatment can prevent weight accretion, which occurs commonly in children on these agents. Dr. Klein will be working with colleagues in the Department of Psychiatry. He will establish a database that will follow patients started on AAPs at CCHMC, and look for risk factors that predict weight gain on these agents. The pathophysiology of weight gain will be studied by performing mixed meal challenge tests and analyzing gut hormone feedback in patients who do and do not gain weight on AAP. Preventing AAP-induced weight gain will not only help to better understand obesity but will also improve patient outcomes on AAPs by avoiding serious side effects.
