FDA Analysis Supports Mosholder Report on Antidepressants

An FDA draft document analysis reviewed by the Wall Street Journal indicates a link between antidepressants and suicidal behavior and thoughts among children and teenagers, "consistent with the controversial earlier analysis" written by FDA medical officer Dr. Andrew Mosholder (Wilde Mathews, Wall Street Journal, 8/5). In April, FDA officials acknowledged that agency managers did not allow Mosholder to testify at a February public hearing about a report he compiled that found antidepressants may lead to suicidal behavior in children because they considered the results preliminary. House and Senate Republican leaders at the end of March launched investigations into whether FDA managers prevented the release of the report. According to unnamed FDA sources, Mosholder planned to present a preliminary report that found selective serotonin reuptake inhibitors may increase the risk of suicide in children. A senior FDA official said that Mosholder did not present the report because the results were not finalized.

The 33-page report, based on an analysis of 22 studies that involved 4,250 children and seven antidepressants, found that children who took the medications were twice as likely as those who took placebos to become suicidal. However, FDA officials raised some concerns about how Mosholder classified suicidal behavior in the report (California Healthline, 6/21). The new analysis, dated July 19, conducted by researchers from Columbia University, focused on 25 clinical trials of nine antidepressants (Wall Street Journal, 8/5). FDA commissioned the analysis and planned to use the results to determine whether the agency should warn physicians not to prescribe antidepressants to children. The Columbia researchers sought to apply a consistent definition of "suicidal" in the clinical trials examined (California Healthline, 6/21). FDA in September will present a final version of the analysis, which the agency has not made public, to an advisory committee and ask for recommendations on revisions to antidepressant label warnings.

According to the Journal, the analysis, which is "supposed to be more definitive" than the report complied by Mosholder, focused on clinical trials of nine antidepressants, such as Zoloft, manufactured by Pfizer; Celexa, manufactured by Forest Laboratories; Effexor, manufactured by Wyeth; Wellbutrin and Paxil, both manufactured by GlaxoSmithKline; and Prozac, manufactured by Eli Lilly.

The analysis, prepared by Tarek Hammad of FDA, examined the clinical trials in "different ways, and results differ depending on which drugs are involved, which conditions were being treated in the trial and how Dr. Hammad selected the incidents he was examining," the Journal reports. The analysis found that when all 25 clinical trials were examined with incidents classified as a "suicide attempt," "preparatory actions toward imminent suicidal behavior" or "suicidal ideation," children who took antidepressants were 1.78 times as likely to have incidents as those who took a placebo. The analysis also found that when all 25 clinical trials were examined with a broader category of incidents, children who took antidepressants were 2.06 times as likely to have incidents as those who took a placebo. However, other results of the analysis were less "definitive," and the results were not statistically significant when suicidal behavior and suicidal thoughts were separated as categories or when only clinical trials of SSRIs were examined. In addition, "results varied sharply from drug to drug," and in some cases, multiple clinical trials of the same antidepressant had different results, the Journal reports.

The new analysis likely will "reignite debate" over the potential link between antidepressants and suicidal behavior in children and "intensify pressure on the agency" to address the issue, the Journal reports. An FDA spokesperson said that the agency has not completed a review of the analysis and could not comment before the advisory committee meeting. Mosholder declined to comment on the analysis (Wall Street Journal, 8/5).