Paxil Study 329 – lest we forget

Thanks to Healthy Skepticism and Pharmagossip for this:

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 they wrote to the Editor of JAACAP raising concerns about the misleading reporting by the authors that exaggerated benefit and downplayed adverse effects. (They 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, HS 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.