FDA Issues Public Health Advisory for New Warnings on Antidepressants
FDA on Monday issued a public health advisory that calls for new warning labels on antidepressants and improved efforts to monitor patients who take such medications, the Wall Street Journal reports. The advisory asks several companies that manufacture 10 different antidepressants to revise the labels of the products to include detailed warnings about the potential risk of suicidal tendencies in patients who take the medications. In addition, the advisory asks physicians, families and caregivers to monitor patients who take such antidepressants for a number of symptoms that could indicate more serious risks. However, FDA officials said that studies have not established a link between suicidal tendencies and such antidepressants, adding that the agency would continue to study the issue (Mathews/Hensley, Wall Street Journal, 3/23). According to the New York Times, the decision by FDA to issue such a "broad warning was a surprise" because of the lack of "clear-cut evidence from well-run clinical trials" that links suicidal tendencies and such antidepressants (Harris, New York Times, 3/23). An FDA advisory committee last month concluded that the agency should issue warnings about a potential link between selective serotonin reuptake inhibitors and suicidal tendencies in children and teenagers. Although Prozac, manufactured by Eli Lilly, is the only SSRI approved by FDA to treat depression in children, many physicians prescribe to children other SSRIs only approved to treat depression in adults. Physicians each year diagnose about 1% of U.S. children with depression and prescribe medication to about half of those children. Concerns about the use of SSRIs in children has increased since the British Medicines and Healthcare Products Regulatory Agency in a December 2003 letter to British physicians recommended against the use of six SSRIs in children because of a potential link to an increased risk of suicide. FDA last October issued a public health advisory that asked U.S. physicians to use caution when they prescribe antidepressants to children and teens (California Healthline, 2/3).
The FDA advisory asks pharmaceutical companies to revise labels on 10 antidepressants: the SSRIs Prozac; Zoloft from Pfizer; Paxil from GlaxoSmithKline; Luvox from Solvay; Clexa and Lexapro from Forest Laboratories; and Effexor from Wyeth; as well as Wellbutrin from GSK, Serzone from Bristol-Myers Squibb and Remeron from Akzo Nobel, which operate differently than SSRIs (Neergaard, AP/Philadelphia Inquirer, 3/23). Although "suicide is already mentioned in a rarely read portion of a sheet included" with the antidepressants, the recommended label revision would place the information in the "warning section, the most important, widely read and prominent section" of the label, the Times reports (New York Times, 3/23). In addition, the label would ask physicians to monitor for "worrisome behavior changes" -- such as agitation, anxiety, irritability and recklessness -- among patients recently prescribed the antidepressants, the AP/Inquirer reports. Physicians who detect such symptoms should recommend that patients take lower doses of or end treatment with the medications (AP/Philadelphia Inquirer, 3/23). The advisory also asks parents to monitor the effect of antidepressants on their children and for patients to consult with their physicians before they end treatment (Wall Street Journal, 3/23). FDA does not have the authority to require the label revisions but can declare medications mislabeled and force their removal from the market in the event that pharmaceutical companies do not comply, the Times reports. In addition, the label revisions would leave no company at a disadvantage because they would appear on every antidepressant introduced in the past 15 years (New York Times, 3/23).
According to the Journal, the FDA advisory could prompt physicians to "become more cautious in how they prescribe antidepressants" for children and teens, as well as cause them to "put greater emphasis on other treatment methods," such as individual psychotherapy and family counseling. "People might wait until they've been in talking therapy a little bit, before trying drugs," Richard Malone, a member of the FDA advisory panel and a child psychiatrist at the Drexel University College of Medicine, said. In addition, the advisory could prompt physicians who prescribe antidepressants to children and teens to "gravitate more toward Prozac," the Journal reports (Wall Street Journal, 3/23). However, the Baltimore Sun reports that the advisory "should have little or no impact on the $12 billion U.S. market" for antidepressants. "This issue has been out in the public domain for quite a long time. It's not going to be that big a deal," Barbara Ryan, managing director of Deutsche Bank Securities, said (Zaneski, Baltimore Sun, 3/23).
"We think this is good advice whether the drugs increase the risk or not," Robert Temple, FDA director of medical policy, said, adding, "There's a reason people are put on therapy -- their depression is worse or somebody's worried about it. Maybe that's what drives it (reports of suicides) or maybe it's the drugs" (AP/Philadelphia Inquirer, 3/23). Thomas Laughren, FDA team leader for psychiatric drug products, said that the suicide rate among teens has decreased as antidepressant use has increased (Vedantam, Washington Post, 3/23). Cynthia Folcarelli, executive vice president of the National Mental Health Association, said that FDA "did a good job of warning doctors and consumers without suggesting that people avoid antidepressants," the Baltimore Sun reports (Bell, Baltimore Sun, 3/23). Although critics of antidepressants called the advisory "a victory," they asked FDA to take additional action, the Post reports. "Doctors are going to be on the line not to prescribe them as if they were pacifiers," Vera Hassner Sharav, president of the patient advocacy group Alliance for Human Research Protection, said (Washington Post, 3/23). However, Bela Sood, chair of pediatric psychiatry at Virginia Commonwealth University, said, "We do a disservice to a population of people who could benefit from these medications" by overreacting. Officials for several of the drug companies said that they were still reviewing the advisory" (AP/Philadelphia Inquirer, 3/23). However, the companies "are almost certain to adopt the agency's proposed changes," the Times reports (New York Times, 3/23).
Several broadcast programs reported on the FDA advisory:
- ABCNews' "World News Tonight": The segment includes comments from Dr. Harold Kopelwicz of New York University School of Medicine and Dr. Thomas Laughren from FDA (McKenzie, "World News Tonight," ABCNews, 3/22).
- CBS' "Evening News": The segment includes comments from Kopelwicz and Laughren (Kaledin, "Evening News," CBS, 3/22). The complete segment is available online in RealPlayer.
- MPR's "Marketplace": The segment includes comments from George Annas, a medical ethicist at Boston University, and Dr. Sidney Wolfe, director of the Health Research Group at Public Citizen (Palmer, "Marketplace," MPR, 3/22). The complete segment is available online in RealPlayer.
- NBC's "Nightly News": The segment includes comments from Dr. Paramjit Joshi of Children's National Medical Center and Dr. Russell Katz, director of the FDA Division of Neuropharmacological Drug Products (Hager, "Nightly News," NBC, 3/22). The complete segment is available online in Windows Media.
- NPR's "All Things Considered": The segment includes comments from Laughren and Dr. Alan Siegel, chief of mental health services at the Massachusetts Institute of Technology (Knox, "All Things Considered," NPR, 3/22). The complete segment is available online in RealPlayer.
- PBS' "NewsHour with Jim Lehrer": The segment includes comments from FDA medical policy chief Dr. Robert Temple ("NewsHour with Jim Lehrer," PBS, 3/22). The complete transcript is available online.