By Rob Stein and Marc Kaufman
Washington Post Staff Writers
Sunday, January 1, 2006
Antidepressants, such as Prozac and similar drugs, help many patients overcome their often disabling psychiatric disease and do not increase the risk for suicide in adults, according to two large studies being published today that counter recent concerns about the popular medications.
The findings from two independent, federally funded studies -- the first of their kind -- spurred some psychiatrists to call for the Food and Drug Administration to reevaluate its warnings about the drugs, which have been blamed for a decline in their use.
"The take-home message from these studies is that we have treatment that is effective and that the risk from depression is far greater than the risk of treatment," said Darrel A. Regier, director of research for the American Psychiatric Association, a group that has been critical of the warnings. "These studies are very important."
Some other medical professionals, however, questioned the results, saying they failed, for example, to show that the drugs were more effective or safer than a placebo.
"The big bulk of the response to antidepressants is the placebo response," said Irving Kirsch, a psychologist at the University of Plymouth in England. "I don't think these studies are very informative."
Critics also said the findings indicate that most patients do not benefit from the drugs. "These pills can be useful pills, but they don't match up to the hype we've had that they really cure the illness," said psychiatrist David Healy of Cardiff University in Wales, who added that the research could not rule out the possibility that the medications increase the risk for suicide among some patients. "As far as the risk for suicide, this sheds very little light on that issue," he said.
One of the new studies, of nearly 3,000 adults suffering from major depression, found that about one-third experienced a full remission within weeks of taking an antidepressant, while another 15 percent experienced some improvement -- meaning nearly half got at least some benefit. The second study, of more than 65,000 patients, found that the risk of suicide for both adults and teenagers drops after treatment begins, with the newest drugs appearing to be the safest.
Regier said the new studies provide strong evidence for the safety and effectiveness of the drugs. And he said he fears that the FDA warnings, which were issued in 2004 and 2005, could lead to an increase in suicides because psychiatrists may be reluctant to prescribe the antidepressants.
"What the FDA initiated was in some ways a natural experiment," Regier said. "This is the kind of rigorous scientific information the FDA should consider in evaluating its decisions."
Robert Temple, the FDA's director of medical policy, called the findings "reassuring" but said they do not settle the issue. The agency was continuing to study the drugs' safety in the hopes of clarifying their safety further, he said.
"There's no question that many psychiatrists are worried that the public fuss about suicidality will lead to the failure of some patients to use antidepressants when appropriate. We are very worried about that, too," Temple said.
After rapidly increasing in use for a decade, the number of prescriptions for antidepressants dropped 2 percent for the first 10 months of 2005, according to IMS Health, a pharmaceutical consulting company.
Antidepressants such as Prozac transformed the treatment of depression because they were considered highly effective and safe, allowing many more patients to use them. As a result, they quickly became among the most widely used prescription medications. The drugs, however, fell under a cloud when reports indicated they increased the risk for suicidal thinking, particularly among teenagers.
Those reports led some critics to press for stronger FDA action, and in 2004 the agency ordered companies to include a "black box" warning saying that antidepressants could increase suicidal thinking in young people. That warning was followed by a July 2005 public advisory that said adults beginning on antidepressants should be closely watched because of preliminary studies suggesting that they, too, could be at greater risk of suicidal thinking and behavior.
The new studies are the first large-scale efforts to independently evaluate the drugs without using data from drug companies' studies. Both were funded by the National Institute of Mental Health and conducted by independent scientists. They are being published in today's issue of the American Psychiatric Association's American Journal of Psychiatry.
In one study, Gregory E. Simon of the Group Health Cooperative, a large, private nonprofit health insurance company based in Seattle, analyzed data from 65,103 patients who took antidepressants between Jan. 1, 1992, and June 30, 2003, comparing the rate of suicide attempts and death from suicide attempts before and after treatment began -- the first such study to track patients over time. Previous studies had examined reports of suicidal thoughts among patients.
The researchers found that the risk of attempted suicide was 60 percent lower in the month after treatment began and that it continued to decline. While the overall risk for suicide was higher for adolescents than adults, the reduction in risk was about the same for both groups. When the researchers specifically examined 10 of the newest antidepressants, such as Prozac -- the ones that have come under the most suspicion -- they found that the risk was even lower.
While some people may react negatively to the drugs, the findings indicate that for most patients the medications do not increase the risk of suicide, Simon and others said.
"There may very well be individuals who are sensitive to these medications, and doctors should monitor their patients carefully," Simon said. "But on average most people are not at higher risk. If anything, they appear to be at lower risk for a serious attempt at suicide or dying of suicide."
The second study involved the first analysis of data from a $35 million ongoing trial known as Star-D, which is designed to provide the first large-scale analysis of various depression treatments in real-life settings.
The analysis involved 2,876 adults around the country who took the antidepressant Celexa at 41 sites representing different types of settings, including clinics, psychiatrists' offices and primary care providers' offices, for up to 14 weeks. Within an average of eight weeks, 28 to 33 percent of patients experienced a complete remission, and 10 to 15 percent experienced some improvement, the researchers found.
Although the response rate in some previous studies has been better, researchers said the findings were encouraging because drugs often fail to perform as well in real-world settings, where many of the patients also have other mental or physical problems and treatment is often more complicated. There was no indication the drugs increased the risk for suicide.
"This is very good news," said psychiatrist John Rush of the University of Texas Southwestern Medical Center at Dallas, who led the study. "We were able to achieve a significant level of remission in a group of patients who are difficult to treat in a real-world setting. That's encouraging."
The study will continue to evaluate how best to treat patients who do not respond, including whether other drugs or a combination of drugs and therapy may be effective. The current FDA review of suicidal thinking in adults taking antidepressants will ultimately analyze much of the existing clinical data on the subject. It is scheduled to be completed this summer.