In 2001, the results of a four-year studyâdubbed âStudy 329ââthat looked at the effects of the anti-depressant âPaxilâ was published. It showed the drug as being effective in adolescents. Now, a restored version of the study has been released that shows almost the exact opposite. A team of Australian researchers has found Study 329 to have numerous misrepresentations about Paxil’s effectiveness compared to a placebo and the risk of suicidal side effects in adolescents.
By gaining access to the full amount of data that the sponsoring company, GlaxoSmithKline (GSK), gathered for Study 329, the researchers performed a full review of the data. When possible, the same protocols used when Study 329 was first carried out were used for the review. In some cases more modern parsing techniques were employed to compare the published data with the documents GSK had previously made public, the individual patient data of the participants, and the raw initial data of the study.
Specifically, the Australian team found that, when using Study 329’s initial criteria, Paxil was not significantly better than a placebo. It was only when new secondary outcome variables were added after the fact that the results shifted to being more positive. It is not uncommon for studies to mention findings that are not part of the initial protocol or hypothesis, but they are normally included as considerations for future research rather than used to draw conclusions. What Study 329’s team did is similar to HARK, or Hypothesis After Results Known, a form of misrepresentation.
When serious adverse events were examined, the Australian team found that 11 (around 10%) of those on Paxil experienced side effects including headaches, euphoria, aggression, worsening depression, and suicidal thoughts or behavior. Of these, Study 329 only considered headaches to be related to Paxil. For comparison, only two of those on the placebo experienced a serious adverse event.
The findings of the restored study are not entirely surprising to anyone familiar with Paxil’s history. Methodology questions were raised shortly after Study 329 was published and there have been more than a few calls for its retraction, along with several class action lawsuits about the increased risk of suicide in teens.
Against critics of Study 329, GSK has had several defenses. First and foremost is that Paxil has never been marketing towards children and adolescents, which the drug is not actually approved for. However, since doctors can prescribe off-label use of medication, GSK’s marketing staff has touted Study 329 in its materials. The rate of Paxil use in teens and children subsequently rose. In fact, in a 1998 memo that was later released during the course of a lawsuit, GSK reportedly considered that âIt would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine [the chemical name of Paxil].â
In response to the Australian review of Study 329, GSK continues to stand by the original results and denies any misleading activities. It notes that Paxil has borne clear warnings for over a decade that it is not suitable for children, which is in line with the longstanding medical belief about similar types of antidepressants. In fact, in 2003, GSK released a statement specifically stating that Paxil should not be used by those under the age of 18.
Sources for Todayâs Article:
âArchived – Important Drug Warning – PaxilÂ® – Until further information is available, PAXILÂ® (paroxetine hydrochloride) should not be used in children and adolescents under 18 years of age â GlaxoSmithKline,â HealthyCanadians.gc.ca, July 10, 2003; http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2003/14226a-eng.php.
Grimm, N., âDamning Review Links Popular Anti-depressant to Youth Suicide,â ABC News web site, last updated September 17, 2015; http://www.abc.net.au/news/2015-09-17/anti-depressant-linked-to-youth-suicide-in-damning-review/6783332.
Kondro, W., et al., âDrug Company Experts Advised Staff To Withhold Data About SSRI Use In Children,â Canadian Medical Association Journal 2004; 170(5): 783, doi:10.1503/cmaj.1040213.
Le Noury, J., et al., âRestoring Study 329: Efficacy and Harms of Paroxetine and Imipramine in Treatment of Major Depression in Adolescence,â British Medical Journal 2015; 351, doi:10.1136/bmj.h4320.