By Shankar Vedantam
Washington Post Staff Writer
Thursday, December 14, 2006
Widely used antidepressants double the risk of suicidal behavior in young adults, from around three cases per thousand to seven cases per thousand, according to a huge federal analysis of hundreds of clinical trials. It marks the first time regulators have acknowledged that the drugs can trigger suicidal behavior among patients older than 18.
Officials at the Food and Drug Administration said yesterday that the higher risk was found in patients 18 to 25 and that the risk faded among older patients. The finding comes two years after the agency ordered a "black box" warning on the drug labels following the discovery of a heightened risk of suicidal behavior among children taking the pills.
After reviewing the latest data, an expert federal panel yesterday recommended that agency officials tell doctors and the public of the risk but also find a way to note that the risk declines with age, and that leaving depression untreated is also risky.
While the studies on the relationship between the drugs and suicide appear contradictory, the experts said one possibility is that the drugs may pose a risk early in treatment but have a protective effect in the long term.
The agency is leaning toward expanding its black box warning, said Thomas Laughren, director of FDA's division of psychiatric drug products. Officials said they will try to write language that would urge clinicians to use the drugs carefully, not abandon them.
The new finding created a dilemma for the regulators. Even as it vindicated some of what critics of drugs such as Prozac, Paxil and Zoloft have said for years, the earlier official warnings about the drugs appear to have led to a drop in their use -- and there are troubling signs that this can lead to an increase in suicides.
After concerns were raised in the Netherlands about the suicide risk, there was a 22 percent drop from 2003 to 2005 in antidepressant prescriptions for patients under 18 and a 50 percent increase in suicides, said Robert Gibbons, a professor of psychiatry at the University of Illinois in Chicago. The number of suicides went from 34 to 51.
'What we are seeing is the early signs of an epidemic of suicide in children who are no longer being treated for their depression," Gibbons said in an interview. U.S. suicide data for 2005 is not yet available, but Gibbons said the FDA's black box warning had caused a similar decline in prescriptions among children here. He predicted dozens more suicides as a result and warned that any expansion of the black box would have a similar impact on adults.
Robert Temple, director of FDA's Office of Medical Policy, said regulators are in a bind. On the one hand, they need to tell physicians about the new results to warn them to monitor patients closely for suicidal behavior, but if that means doctors stop prescribing the drugs altogether, "I don't know what you are supposed to do."
Emotions ran high at the meeting of expert advisers yesterday, with both advocates for the drugs and their critics warning the federal regulators that a wrong move would cost lives.
Critics of the drugs said they were deeply distrustful of both the medical profession and FDA itself because of conflicts of interest with the pharmaceutical industry. Allen Jones, of the consumer advocacy group Alliance for Human Research Protection, said, "the love affair between the pharmaceutical industry and our government institutions has to end."
Gwen Olsen, a former pharmaceutical industry representative, told the panel she had influenced doctors by offering them free food, gifts and gimmicks to get access and then presented them with skillfully manipulated data. Olsen said she had a change of heart after her 20- year-old niece committed suicide following a withdrawal reaction from the antidepressant Paxil. She said her niece first tried to hang herself from a ceiling fan. When the fan broke, Olsen said, she doused herself in oil and set herself alight.
Two experts critical of the drugs, British psychiatrist David Healy and Joseph Glenmullen, a psychiatrist who lectures at Harvard University, said the FDA analysis played down the magnitude of the suicide risk. Information uncovered in lawsuits, they said, suggested that several suicides in industry trials were never disclosed.
"Industry controls the data, and industry with the aid of FDA have miscoded the data so all the articles in all the journals that purport to represent clinical trial data are misleading," Healy said in an interview. His own analysis, published in the British Medical Journal in 2005, found a two-fold increase in risk among all adults taking the drugs.
"The idea you would have a risk in one age group but not another is just wrong," Healy said.
Other medical experts and patient advocates, however, warned that black box warnings could scare patients away from necessary treatment.
Christopher Kratochvil, a psychiatrist who spoke on behalf of the American Academy for Child and Adolescent Psychiatry; John Mann, a Columbia University psychiatrist who spoke on behalf of the American Foundation for Suicide Prevention; and Donna Barnes, president of the National Organization for People of Color Against Suicide, all said additional warnings might harm patients by making them fearful of treatment.
Unlike the case with children, in whom antidepressants have generally failed to show they are superior to sugar pills in short-term trials, the drugs have a track record of working in adults. A recent federal study showed that while the drugs do leave much to be desired, treatment provided in the best care settings helped two-thirds of depressed patients recover.
"I feel I am listening to a chapter from [the novel] 'Animal Farm' saying, 'industry bad, industry bad,' " said Carolyn Robinowitz, president-elect of the American Psychiatric Association, in an interview. "Pharmaceutical research has brought us a lot of good things."