DOI: 10.5061/dryad.bv8j6
title: Data from: Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence

description: 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-perception profile, and
 sickness impact scale; predictors of response; and number of patients who
 relapse during the maintenance phase. Adverse experiences were to be
 compared primarily by using descriptive statistics. No coding dictionary
 was prespecified. Results: The efficacy of paroxetine and imipramine was
 not statistically or clinically significantly different from placebo for
 any prespecified primary or secondary efficacy outcome. HAM-D scores
 decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to
 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for
 the paroxetine, imipramine and placebo groups (P=0.20). There were
 clinically significant increases in harms, including suicidal ideation and
 behaviour and other serious adverse events in the paroxetine group and
 cardiovascular problems in the imipramine group. Conclusions: Neither
 paroxetine nor high dose imipramine showed efficacy for major depression
 in adolescents, and there was an increase in harms with both drugs. Access
 to primary data from trials has important implications for both clinical
 practice and research, including that published conclusions about efficacy
 and safety should not be read as authoritative. The reanalysis of Study
 329 illustrates the necessity of making primary trial data and protocols
 available to increase the rigour of the evidence base.
description: RIAT Restoring Study 329
 data filesZip file containing:
 Original SKB CSR (both Appendix D & Appendix G); ii) RIAT Excel
 spreadsheet for Harms/Adverse Event data; RIAT Excel spreadsheet for
 Withdrawals/dropouts from the study. R code used to analyse Efficacy data;
 Original SKB Study 329 Trial protocol which was followed in Restoring
 Study 329 (RIAT).Dryad.zip