FDA May Call for Revised Antidepressant Labels Based on Evidence of Link With Suicidal Tendencies in Children
FDA officials likely will call for changes to labels on antidepressant medications in light of a new agency analysis that shows "evidence of a link between the drugs and suicidal tendencies in young people," the Wall Street Journal reports. The FDA analysis, led by researchers at Columbia University, is based on a re-examination of data from clinical trials that tested antidepressants in young patients (Wilde Mathews, Wall Street Journal, 8/20). The researchers classified about 400 adverse events as potentially suicide-related, according to the New York Times (Harris, New York Times, 8/20). They found that trial participants taking antidepressants overall were 1.78 times as likely to have suicidal thoughts or actions as those taking placebos.
Researchers examined clinical trial data for nine different antidepressants, including Pfizer's Zoloft, Forest Laboratories' Celexa, Wyeth's Effexor, GlaxoSmithKline's Wellbutrin and Paxil and Eli Lilly's Prozac. According to the Journal, risk of suicide varied for the different drugs. No participant in the clinical trials actually committed suicide (Wall Street Journal, 8/20). FDA could release the results of the analysis to the public as early as next week (New York Times, 8/20).
FDA has appointed an advisory committee to consider the possibility of changing the label for antidepressants based on the new analysis. In March, FDA asked makers of major antidepressant drugs to put general warnings on their labels urging doctors to watch all patients closely for signs of increasing depression or suicidal thinking. However, the new label changes, based on the most recent analysis, likely would be more specific, according to the Journal. People close to the matter say FDA will ask the advisory panel to interpret the results of the analysis, recommend what label changes should be made and consider whether FDA should take additional regulatory steps. Specifically, the agency is expected to ask the committee to confirm whether the analysis shows a clear link between antidepressants and suicidal tendencies in young people and whether that risk is tied to all the drugs as a class or just some of the drugs.
The Journal reports that the panel could recommend different label changes for different drugs and no changes for a certain label. In addition, FDA could call for language on the drugs' labels noting that clinical trials for many of the medications did not clearly demonstrate effectiveness in young people. The advisory panel is set to meet Sept. 13-14, and FDA "will take the unusual step of publicly posting" the meeting agenda and background information as early as Friday, according to the Journal. The meeting will likely include testimony from opponents of the drugs, plaintiffs' attorneys, advocacy groups and FDA officials (Wall Street Journal, 8/20).
In an internal memo dated Aug. 16, FDA medical officer Dr. Andrew Mosholder, who earlier this year released his own analysis of the same clinical trials reviewed by FDA, said the results of the new analysis "matched his own," according to the Times (New York Times, 8/20). The original 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.
FDA officials have raised some concerns about how Mosholder classified suicidal behavior in the report. In April, FDA acknowledged that agency officials 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 in 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 (California Healthline, 8/10).
In his memo in response to FDA's analysis of the clinical trials, Mosholder said that although the two studies used different methods and different numbers, they reached similar conclusions. He also said that FDA's study seemed to show that Paxil and Effexor were even more likely to lead to suicidal behavior in young people than his own analysis did. FDA and GSK did not comment on Mosholder's memo. A spokesperson for Wyeth said that Effexor is not approved for use in children. Sen. Chuck Grassley (R-Iowa), who has pushed for an investigation into how FDA has addressed the issue, said through a spokesperson that Mosholder's memo "underscores what my committee investigation is finding as far as the strength of Dr. Mosholder's original analysis about antidepressants and kids" (New York Times, 8/20). Mosholder declined to comment but is expected to speak before the advisory committee considering the label changes (Wall Street Journal, 8/20).This is part of the California Healthline Daily Edition, a summary of health policy coverage from major news organizations. Sign up for an email subscription.