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J Child Adolesc Psychopharmacol. 2013 Mar;23(2):72-9. doi: 10.1089/cap.2012.0024. Epub 2013 Mar 12.

Clinical significance of treatment effects with aripiprazole versus placebo in a study of manic or mixed episodes associated with pediatric bipolar I disorder.

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Department of Psychology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.



Published studies in adult and pediatric bipolar disorder have used different definitions of treatment response. This analysis aimed to compare different definitions of response in a large sample of children and adolescents.


Anexploratory analysis of a 4-week, multicenter, placebo-controlled study assessed patients (n=296; ages, 10-17 years) with an acute manic/mixed episode associated with BIPOLAR I disorder who were randomized to aripiprazole (10 or 30 mg/day) or placebo. The primary efficacy endpoint was mean change from baseline to week 4 in young mania rating scale (YMRS) total score. Additional assessments included: clinical global impressions-bipolar disorder (CGI-BP) Overall and mania scales, child global assessment scale (CGAS), and parent and subject general behavior inventory. Response was compared across seven operational definitions. Cohen's κ and Spearman's correlation tested relationships between various response definitions or changes in outcome measures and clinically meaningful improvement (defined as a CGI-BP overall improvement score of 1 or 2).


Response rates varied depending upon the operational definition, but were highest for 95% reliable change (statistical method used to determine individual change from previous assessment) and ≥33% reduction in YMRS total score. Response rate definitions with the highest validity in terms of predicting clinically meaningful improvement were: ≥50% reduction on YMRS (κ=0.64), a composite definition of response (YMRS <12.5, children's depression rating scale-revised (CDRS-R) ≤40, and CGAS ≥51; κ=0.59), and 95% reliable change on the CGAS or 33% reduction on YMRS (κ=0.56). Parent ratings of symptoms were generally better at detecting symptom improvement than were subject ratings (κ=∼0.4-0.5 vs. ∼0.2 when compared with CGI-BP overall improvement score).


Clinically meaningful definitions of response in acute treatment of a manic/mixed episode in pediatric subjects include a 50% change in YMRS and a composite measure of response. Parent-reported measures of symptom improvement appear reliable for assessing symptom change.


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