Aripiprazole for the treatment of pediatric bipolar I disorder: a 30-week, randomized, placebo-controlled study

Objective: To evaluate the long-term efficacy, safety, and tolerability of aripiprazole in pediatric subjects with bipolar I disorder. Methods: A randomized, double-blind, 30-week, placebo-controlled study of aripiprazole (10 or 30mg/day) in youths (1017years) with bipolar I disorder (manic or mixed) +/- psychotic features (n=296) was performed. After four weeks, acute treatment completers continued receiving 26weeks of double-blind treatment (n=210). The primary outcome was Young Mania Rating Scale (YMRS) total score change. Results: Of the 210 subjects who entered the 26-week extension phase, 32.4% completed the study (45.3% for aripiprazole 10mg/day, 31.0% for aripiprazole 30mg/day, and 18.8% for placebo). Both aripiprazole doses demonstrated significantly (p<0.001) greater improvements in YMRS total score at endpoint compared with placebo in protocol-specified last observation carried forward analyses, but not in observed case or mixed-model repeated measures at week 30. Overall time to all-cause discontinuation was longer for aripiprazole 10mg/day (15.6weeks) and aripiprazole 30mg/day (9.5weeks) compared with placebo (5.3weeks; both p<0.05 versus placebo). Both aripiprazole doses were significantly superior to placebo regarding response rates, Children's Global Assessment of Functioning and Clinical Global Impressions-Bipolar severity of overall and mania scores at endpoint in all analyses. Commonly reported adverse events included headache, somnolence, and extrapyramidal disorder. Conclusions: Aripiprazole 10mg/day and 30mg/day were superior to placebo and generally well tolerated in pediatric subjects with bipolar I disorder up to 30weeks. Despite the benefits of treatment, completion rates were low in all treatment arms.