FDA Official Admits Agency Withheld Report on Antidepressants and Suicide in Children
Dr. Robert Temple, associate director of medical policy at FDA, on Thursday admitted that agency managers did not allow medical officer Dr. Andrew Mosholder to testify at a February public hearing about a report that found antidepressants may lead to suicidal behavior in children because they "viewed his findings as alarmist and premature," the New York Times reports. Temple said in an interview, "It would have been entirely inappropriate to present as an FDA conclusion an analysis of data that were not ripe," adding, "This is a very serious matter. If you get it wrong and over-discourage the use of these medicines, people could die" (Harris, New York Times, 4/16). House and Senate Republican leaders at a hearing at the end of last month launched investigations into whether FDA managers prevented the release of the report to an agency advisory committee at a meeting in February. 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. After the meeting, the advisory committee recommended that FDA issue stronger warnings to physicians about the potential link between SSRIs and suicidal behavior in children. FDA in March issued a public health advisory that calls for new warning labels on 10 different antidepressants -- which included both SSRIs and other antidepressants -- to include detailed warnings about the potential risk of suicidal behavior in patients who take the medications (California Healthline, 4/6).
The report from Mosholder, 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 (New York Times, 4/16). The report found that Effexor and Paxil almost tripled the risk of suicidal behavior, that Zoloft more than doubled the risk and that Prozac increased the risk the least. In the 33-page report, Mosholder wrote, "Given the strength of the association shown by the present data, the clinical importance of the apparent effect, and the fact that the additional analyses are likely to take several more months to complete while considerable numbers of pediatric patients are being exposed to these drugs, I favor an interim risk management plan" (Waters, San Francisco Chronicle, 4/16). However, FDA said that managers were not "sure what to make of the data" because "companies classified the data in different ways, with some labeling any incident of self-harm as possibly suicide-related -- including a girl slapping her own face -- while other events were labeled accidental though they might have been suicide attempts," the Baltimore Sun reports (Bell, Baltimore Sun, 4/16). Temple said that "Mosholder had failed to treat with appropriate skepticism some reports of suicidal behavior," the Times reports (New York Times, 4/16). Temple also said that FDA researchers often disagree on issues, adding, "We thought the investment of a few more months was worth it to get it right" (Neergaard, AP/Las Vegas Sun, 4/16). FDA has commissioned researchers at Columbia University to perform a new study of the data to determine which behaviors the agency should consider suicidal (Mathews/Lueck, Wall Street Journal, 4/16).
In a letter sent to House Energy and Commerce Committee Chair Joe Barton (R-Texas) on Wednesday, Amit Sachdev, acting FDA commissioner for legislation, "defended the agency's decision to keep Mosholder from presenting his report," the Chronicle reports. The letter said that FDA officials "decided that having Dr. Mosholder present his conclusion to the Advisory Committee, with the appearance that it was an agency determination, would be potentially harmful to public health as it might lead patients who were actually benefiting from the use of these drugs to inappropriately discontinue therapy" (San Francisco Chronicle, 4/16). The letter added that some FDA researchers disagreed with the report and sought to conduct additional research on the issue (Wall Street Journal, 4/16). Barton and Senate Finance Committee Chair Chuck Grassley (R-Iowa) have said that they plan to investigate whether the FDA "inappropriately suppressed crucial findings," the Times reports (New York Times, 4/16). In a statement, Barton said information that the House committee has found to date raises "troubling questions of whether FDA supervisors inappropriately suppressed significant information that would have been of consequence to their own advisory committee, not to mention the public." He also said that the committee may hold a hearing on the issue (Wall Street Journal, 4/16). According to the Chronicle, an unnamed congressional source predicted that Congress likely will hold such a hearing, adding, "There's no way to put a good face on this decision not to allow Dr. Mosholder to present his conclusions to the advisory committee."
Vera Sharav, president of the Alliance for Human Research Protection, a patient advocacy group, said, "It's astounding that FDA officials actively blocked vital, possibly life-saving information about the suicide risks to children" caused by antidepressants, adding, "Every day that doctors and parents are not informed about the risks, children are at risk of dying." Joseph Glenmullen, a Harvard University clinical instructor in psychiatry, said that the "agency's withholding of the Mosholder report and its failure to take stronger action was an example of the FDA's failure to protect the public from the dangerous side effects of antidepressants," adding, "They have mishandled this issue for 15 years" and "have not adequately protected American children" (San Francisco Chronicle, 4/16). Glenmullen said that he supports congressional hearings on the issue. According to the Sun, "there is widespread skepticism" about whether the new Columbia study will resolve the issue. Dr. Herbert Meltzer, a Vanderbilt University psychiatry and pharmacology professor, said, "It's virtually impossible to design an actual trial that would tell you whether the illness or a medicine is making a patient suicidal" (Baltimore Sun, 4/16). ABCNews' "World News Tonight" Thursday reported on the decision by FDA to withhold the report. The segment includes comments from Glenmullen, Grassley and Temple (Stark, "World News Tonight," ABCNews, 4/15). A video excerpt of the segment is available online in RealPlayer.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.