OBJECTIVE: 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. METHODS: 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). RESULTS: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). CONCLUSIONS: 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.
RCT Entities:
OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.
Authors: Liliana Dell'Osso; Stefano Pini; Giovanni B Cassano; Concettina Mastrocinque; Regine Anna Seckinger; Marco Saettoni; Alessandra Papasogli; Scott A Yale; Xavier F Amador Journal: Bipolar Disord Date: 2002-10 Impact factor: 6.744
Authors: Robert L Findling; Nora K McNamara; Barbara L Gracious; Eric A Youngstrom; Robert J Stansbrey; Michael D Reed; Christine A Demeter; Lisa A Branicky; Kathryn E Fisher; Joseph R Calabrese Journal: J Am Acad Child Adolesc Psychiatry Date: 2003-08 Impact factor: 8.829
Authors: Laura L Pendergast; Eric A Youngstrom; Christopher Brown; Dane Jensen; Lyn Y Abramson; Lauren B Alloy Journal: Psychol Assess Date: 2014-09-15
Authors: Benjamin I Goldstein; Boris Birmaher; Gabrielle A Carlson; Melissa P DelBello; Robert L Findling; Mary Fristad; Robert A Kowatch; David J Miklowitz; Fabiano G Nery; Guillermo Perez-Algorta; Anna Van Meter; Cristian P Zeni; Christoph U Correll; Hyo-Won Kim; Janet Wozniak; Kiki D Chang; Manon Hillegers; Eric A Youngstrom Journal: Bipolar Disord Date: 2017-09-25 Impact factor: 6.744