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The Food and Drug Administration is expected to call for revisions on antidepressant labels to reflect a new agency analysis, which showed evidence of a link between the drugs and suicidal tendencies in young people.
The FDA hasn't developed specific language for the label change and will bring the matter to an advisory committee next month, according to people familiar with the matter. The agency will ask the panel to interpret the results of its new analysis and recommend what the labels should say about the findings. The FDA will also ask whether it should take other regulatory steps.
In March, the agency called on makers of major antidepressant drugs to put general warnings on their labels urging doctors to watch all patients for indications of increasing depression or suicidal thinking. The new label changes would likely be more specific, reflecting the new agency analysis that focused on evidence of suicidal tendencies in clinical trials done with pediatric patients. The updated label information may also be different for each individual drug -- or unnecessary for some of them -- because the FDA analysis had results that varied from medicine to medicine.
Another possibility is that the FDA might call for label language noting that studies of many of the drugs have failed to clearly demonstrate that they are effective in young people.
Still, the agency's ultimate decision is unlikely to end the long-running debate over the drugs' possible risks and the proper government response to them. In fact, the FDA is likely to call for more research into the question.
The new analysis of clinical-trial data by the agency, which will be discussed at the committee meeting, found that young people who took antidepressants were more likely than those taking a placebo to experience suicidal thoughts or actions. But the risk level varied depending on how the data was parsed, as well as between different drugs. No participant in the trials actually committed suicide.
The issue has taken on more urgency as antidepressant prescriptions for young people have grown. According to an analysis by Washington State University researchers, the rate of antidepressant prescriptions for children and adolescents more than tripled in the U.S. from the early 1990s to 2001. In 2002, an estimated 10.8 million prescriptions for the most widely used antidepressants were dispensed for patients younger than 18 years old, according to an FDA analysis released in February.
British regulators have specifically called on doctors not to prescribe several of the antidepressants to depressed children and teens, saying that their balance of risks and benefits is "unfavorable," with the sole exception of Prozac. An internal report written by an FDA staffer, Andrew Mosholder, also endorsed action that would likely have required more than a label change: He argued for a "risk management strategy" to discourage use of antidepressants by young people, except in limited cases approved for mention on their labels. Only Prozac, made by Eli Lilly & Co. and generic manufacturers, has an FDA-approved label indication for pediatric depression patients.
Two congressional committees are examining the FDA's handling of the issue, including its decision not to make public Dr. Mosholder's recommendations at a meeting in February. Capitol Hill investigators are also now asking the FDA about its plans for the upcoming advisory meeting, set for Sept. 13-14. Responding to the microscope trained on every detail of its actions, the FDA took the unusual step of publicly posting the agenda and background information for that meeting today. Typically this information is released closer to the date of the panel.
At the center of the advisers' deliberations will be the new FDA analysis of clinical trials that tested antidepressants in young patients. It's based on data which were re-examined by outside researchers spearheaded by a group at Columbia University in New York. According to a draft version of the new analysis, participants in the trials overall were 1.78 times more likely to have suicidal thoughts or actions if they were taking the drugs, compared with those taking placebo pills. That number was based on lumping together all of the drugs' trials.
The analysis focused on clinical trials of nine antidepressants in young people, including Pfizer Inc.'s Zoloft, Forest Laboratories Inc.'s Celexa, Wyeth's Effexor, GlaxoSmithKline PLC's Wellbutrin and Paxil, and Prozac. Because it found different results for each drug, it isn't clear that a new label change would apply to all of them, or whether each drug might get a different recommendation.
The FDA is expected to ask the committee to weigh the findings of that analysis and ask if the data clearly show a link between the drugs and suicidal tendencies, according to people with knowledge of the matter. The agency is also likely to ask the committee to evaluate whether the risk appears tied to all of the drugs as a class, or just some of them. Most important, the agency is expected to ask the committee how the information should be reflected in the drugs' labels, if the advisers do see a risk attached to the drugs.
According to people with knowledge of the matter, Dr. Mosholder will speak at the meeting, comparing his earlier examination with the new analysis of the clinical-trial data. FDA officials argued that his conclusion was premature, because it was based on data that might be improperly categorized. In an internal FDA memo dated Aug. 16 and reviewed by The Wall Street Journal, Dr. Mosholder found that the new analysis result was "consistent" with his finding of a "statistically significant association of suicidal events with antidepressant drug treatment" in the studies. Dr. Mosholder declined to comment.
A spokeswoman from the British Medicines and Healthcare products Regulatory Agency said a representative "is hoping to attend the meeting" and the specifics of that person's presentation will "depend on whether there is any data available to us which the FDA do not already have."
It is also likely that the meeting will draw testimony from opponents of the drugs, including members of the public who often speak about the deaths of loved ones who had been taking the drugs, plaintiffs' attorneys and advocacy groups.
Write to Anna Wilde Mathews at anna.mathews@wsj.com
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