Schizophrenia is still all too frequently associated with a chronic relapsing course, poor functional outcome, and decreased life expectancy. The chronicity and refractoriness of this illness is particularly pronounced in early onset schizophrenia (EOS=onset <18 years). Although the limited data suggest that clozapine is the most efficacious option for youth with refractory EOS (Kumra et al. 1996;Shaw et al. 2006;Kumra et al. 2008a,b) it is still underutilized, in part due to a profound negative impact on weight and metabolic parameters. To improve the benefit/risk ratio of clozapine in refractory youth, the development of concurrent interventions to limit cardiometabolic effects and enhance effectiveness is sorely needed. For this reason, other medications, often a second antipsychotic, are commonly combined with clozapine in clinical practice. However, a sound evidence base for this clinical strategy is absent, particularly in youth. To fill this critical gap in knowledge, we propose a 12-week, placebo-controlled trial of clozapine supplementation with aripiprazole in 50 youths (age 10-18 years) with refractory schizophrenia.
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