Healthy Skepticism International News

January 2010

Paxil Study 329: Paroxetine vs Imipramine vs Placebo in Adolescents

by Jon Jureidini

This page was published earlier in 2008 in our old website at:
http://www.healthyskepticism.org/documents/PaxilStudy329.php

GlaxoSmithKline’s Study 329 of medication for adolescent depression failed to demonstrate any benefit for paroxetine over placebo in adolescents and demonstrated a worrying profile of adverse events for paroxetine.  The study was ultimately published in 2001 by the Journal of the American Academy of Child and Adolescent Psychiatry with Keller as the primary author. This misleading paper has been a focus of interest for Healthy Skepticism since 2002.  In 2003 we wrote to the Editor of JAACAP raising concerns about the misleading reporting by the authors that exaggerated benefit and downplayed adverse effects.  (We also questioned editorial functioning, which drew an angry response from the Editor).  In 2004 CMAJ published an Editorial which showed that in 1998 an internal GSK document clearly acknowledged that GSK were aware that 329 was negative.  A subsequent law suit by New York Attorney General, Eliot Spitzer, was settled out of court. 

In 2006, we wrote to the Lancet to point out that internal documents from another United States law suit (Smith versus GSK) revealed further concerns about study 329: -

• The study was ghostwritten - see here.
• Misleadingly positive interpretations of the study were promoted to drug reps and other GSK staff - see here.
• An illusion of efficacy was achieved by re-inventing primary and secondary end points - see here.
• Eventually GSK had to acknowledge the failure of all three of their child and adolescent paroxetine depression studies - see here.

Click here for Peter Mansfield's summary of all trials of newer antidepressants in children and adolescents

Click here for J & E Jureidini's summary of citations of the Keller paper

Documents regarding study 329

Jon Jureidini, Leemon McHenry and Peter Mansfield's analysis of these documents is published as

Jureidini JN, McHenry LB, Mansfield PR.
Clinical trials and drug promotion: Selective reporting of study 329
International Journal of Risk and Safety in Medicine 2008 May;20(1-2):73-81
Link to source with long URL

The confidential internal Final Clinical Report 24 November 1998

DRAFTS/PEER REVIEWS

1. Draft I. 18 Dec 1998
2. Draft ?II with ?Keller’s annotations. 11 Feb, 1999.
3. Draft III. 22 Mar, 1999.
4. Draft submitted to JAMA, 30 July 1999.
5. JAMA Reviews, Oct 22, 1999
6. Response to JAMA reviews, 10 Dec, 1999.
7. Draft VI, submitted to JAACAP, 25 Apr, 2000.
8. JAACAP Reviews
9. Response to JAACAP reviewers.
10. Response to Dulcan.
11. Comparison of first to final draft

POSTERS

1. Keller M et al. American Psychiatric Association, Toronto, 2 Jun, 1998
2. Wagner K et al. NCDEU. Boca Raton, Florida. 11 Jun, 1998.
3. Berard R, Ryan N. European College of Neuropsychopharmacology, Paris, Oct 1998.
4. Gagiono C. World Congress of Psychiatry, Hamburg, Oct, 1999.

LETTERS/ MEMOS/EMAILS/MINUTES

1. Minutes:Teleconference.Paroxetine Study 329 Efficacy Analysis. 22 Apr, 1997
2. Top Line Results 21 Jan, 1998
3. Keller to Laden 11 Feb, 1999
4. Oakes to McCafferty 5 Mar, 1999
5. McCafferty to Laden 9 Mar, 1999
6. Clarke to Ryan 30 Mar, 1999
7. Klein to B. Ryan 15 Apr, 1999
8. Katz to Kline, 18 May, 1999
9. McCafferty to Laden, 19 Jul, 1999
10. McCafferty to Laden, 21 Jul, 1999
11. Laden to McCafferty 26 Apr 2000
12. Dulcan to Keller 27 Jul, 2000
13. Laden to Keller 4 Oct 2000
14. Laden to Brand et al, 11 Jan, 2001
15. Pretre to Keller, 6 Feb, 2001
16. White to Hood, 5 Mar, 2001
17. Battin to Laden, 27 Apr, 2001
18. Laden to McCafferty, 7 Aug, 2001
19. Hawkins to all sales representatives selling Paxil, Aug 16, 2001
20. Ryan to Keller and Strober, 4 Feb, 2004
21. Keller to Carpenter et al, 14 May, 2004
22. Keller to Ryan et al, 13 Jun, 2004

MEDICAL QUERIES/DEAR HEALTH CARE PROFESSIONAL LETTERS

1. SKB Med Query. Jul, 1998
2. SKB Med Query. Jul, 1999
3. GSK Med Query. Jan, 2000
4. GSK Med Query. Sep, 2001
5. GSK Med Query. Feb, 2002
6. Dear Health Care Professional. Jul, 2003 (Canada)
7. Dear Health Care Professional. Jul, 2003
8. Dear Health Care Professional. May, 2004

INFORMATION FOR SALES REPRESENTATIVES

1. SmithKline Beecham. Nulli Secundus. 8 Dec, 1999
2. GlaxoSmithKline. GSK Sales Connection. 10 Sep, 2003

OTHER

1. Proposal: 'Adolescent Unipolar Major Depression: Multisite Psychopharmacology Study' Dec, 1992
2. Investigator Agreement, August, 1993
3. The study protocol, as amended March 24,1994
4. Position piece on the phase III clinical studies, 14 Oct, 1998
5. STI proposal for a journal article, 3 April, 1998
6. STI Release Form for JAACAP paper, 3 Nov, 2000
7. FDA Clinical Review, 2002
8. Statement of David Wheadon Sep 9, 2004

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