Tolerability and pharmacokinetics of aripiprazole in children and adolescents with psychiatric disorders: An open-label, dose-escalation study

This multicenter, open-label, sequential-cohort, dose-escalation study explored the tolerability and pharmacokinetics (PK) of aripiprazole up to the maximum approved adult dose (30 mg/d) in children and adolescents (aged 10-17 years) preferentially with primary psychiatric diagnoses of a bipolar or schizophrenia spectrum disorder. During a dose-escalation phase, patients received aripiprazole for up to 12 days using forced titration to achieve doses of 20, 25, or 30 mg/d. In the subsequent fixed-dose phase, patients received the maximum dose for that cohort for an additional 14 days. Tolerability in each fixed-dose cohort was assessed by measures including evaluation of spontaneously reported adverse events (AEs) and vital signs. If 4 of 6 patients tolerated the maximum dose for the cohort, the dose was considered tolerated, and enrollment in the next dose level began. Of 21 enrolled patients, 17 completed the fixed-dose phase. Aripiprazole treatment was generally well tolerated, with criteria for tolerability met for all doses tested. All patients experienced at least 1 AE, none of which met the regulatory criteria for a serious AE. There were no deaths or clinically relevant changes in vital signs or weight. Aripiprazole PK seemed to be linear across the tested dose range and was comparable with previous PK observations in adults. This study provides information regarding the tolerability and PK of aripiprazole up to the maximum adult dose in children and adolescents. These data provided support for exploration of a 30-mg/d dose in child/adolescent schizophrenia and bipolar disorder.