FDA Releases Documents Related to Antidepressant Risk Analysis
FDA on Friday "took the unusual step" of posting on its Web site "numerous documents" to be considered by an advisory panel next month that are related to the agency's latest analysis of the risk of increased suicidal tendencies in children who take antidepressants, the Newark Star-Ledger reports. Normally, such information would be released a day or two before the advisory panel convenes, according to the Star-Ledger (Silverman, Newark Star-Ledger, 8/21). For the analysis, researchers examined 25 studies of 4,250 pediatric psychiatric patients nationwide (Vrazo, Philadelphia Inquirer, 8/21).
The clinical trials involved nine different antidepressants, including Pfizer's Zoloft, Forest Laboratories' Celexa, Wyeth's Effexor, GlaxoSmithKline's Wellbutrin and Paxil and Eli Lilly's Prozac. When the data from the studies were combined, researchers found that trial participants taking antidepressants overall were 1.78 times more likely to have suicidal thoughts or actions than those taking placebos (California Healthline, 8/20). Risk "varied widely from drug to drug and among studies of the same drug," but risk was particularly high in patients who took Effexor or who had histories of suicide attempt or behavior, according to FDA, the AP/Birmingham News reports (Neergaard, AP/Birmingham News, 8/21). Because of the inconsistencies in results for different drugs and different studies, "an overall interpretation of these findings represents a substantial challenge," FDA said in a "talk paper." Only Prozac is approved for use in children, although doctors are believed to frequently prescribe other antidepressants off-label to patients under age 18 (Kaufman, Washington Post, 8/21).
The documents released by FDA include an Aug. 16 memo by Andrew Mosholder, the FDA medical examiner who in February was prevented from publicly discussing his findings that children in nearly two dozen studies were about two times as likely to have suicidal thoughts as those given placebos. Mosholder's memo said the new agency analysis confirms his conclusions, the Star-Ledger reports (Newark Star-Ledger, 8/21).
The release of Mosholder's second report represents "a dramatic change for the agency," the Post reports. Critics, including Sen. Chuck Grassley (R-Iowa), have complained that FDA has been "moving too slowly on the issue of children and antidepressants and was not sharing potentially important information with the public," according to the Post (Washington Post, 8/21).
As a result of the new analysis, federal health officials are preparing stronger warnings for some antidepressants prescribed to children, but the FDA documents said the agency has not determined which drugs will bear the warnings, how strong the warnings will be or whether any of the drugs will have specific prohibitions for use in children, the AP/News reports (AP/Birmingham News, 8/21). FDA officials will ask the advisory panel, which convenes Sept. 13, to make recommendations on the language for the new warning labels and on additional research to be conducted. Some FDA officials disagree over what the studies' data mean, partly because of questions about the statistical confidence of the relatively small clinical trials and about the trial designs (Bell, Baltimore Sun, 8/21). "While there remains a signal of risk ... for some drugs in some trials, it is important to note that the data are not black and white in providing a clear and definitive answer," Dr. Thomas Laughren, chief of psychiatric drugs for FDA, wrote to the advisory panel last week (AP/Birmingham News, 8/21).
Steven Hyman, provost of Harvard University and former chief of the National Institute of Mental Health, said that the data are not clear, but the "biggest danger is that people will stop treating children for major depression" because of the issue (Philadelphia Inquirer, 8/21). The information released by FDA is available online. NPR's "All Things Considered" on Friday reported on the FDA analysis. The segment includes comments from Hyman (Baron, "All Things Considered," NPR, 8/20). The complete segment is available online in RealPlayer. Expanded NPR coverage is available online.
In related news, the New York Times on Monday examined the homicide case against 15-year-old Christopher Pittman, which is among "the first to arise amid a national debate over the safety of antidepressant use in children and teenagers." At age 12, Pittman in 2001 allegedly killed his grandparents in their home in Chester, S.C., shortly after beginning treatment with Zoloft.
Defense attorneys for Pittman say the killings were initiated by a psychotic reaction to the medication. According to the Times, "Such defenses ... have rarely succeeded. And most medical experts do not believe there is a link between antidepressants and acts of extreme violence." The trial is scheduled to begin this fall (Meier, New York Times, 8/23).