Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence

作者：Joanna Le Noury, John M. Nardo, David Healy, Jon Jureidini, Melissa Raven, Cătălin Tufănaru, Elia Abi‐Jaoude · 发表于：BMJ · 年份：2015 · DOI：10.1136/bmj.h4320 · 被引用次数：336 · 研究领域：Child and Adolescent Psychosocial and Emotional Development、Treatment of Major Depression、Attention Deficit Hyperactivity Disorder

OBJECTIVES: To reanalyse SmithKline Beecham's Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine. DESIGN: Double blind randomised placebo controlled trial. SETTING: 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. PARTICIPANTS: 275 adolescents with major depression of at least eight weeks in duration. Exclusion criteria included a range of comorbid psychiatric and medical disorders and suicidality. INTERVENTIONS: Participants were randomised to eight weeks double blind treatment with paroxetine (20-40 mg), imipramine (200-300 mg), or placebo. MAIN OUTCOME MEASURES: The prespecified primary efficacy variables were change from baseline to the end of the eight week acute treatment phase in total Hamilton depression scale (HAM-D) score and the proportion of responders (HAM-D score ≤8 or ≥50% reduction in baseline HAM-D) at acute endpoint. Prespecified secondary outcomes were changes from baseline to endpoint in depression items in K-SADS-L, clinical global impression, autonomous functioning checklist, self-perce...