FRIDAY, July 1, 2005 (HealthDayNews) -- The U.S. Food and Drug Administration on Friday issued a second warning that people taking antidepressant drugs be monitored for signs of suicidal thoughts and deepening depression.
The new advisory follows concern about a link between antidepressant use and suicide among children. And it also follows action taken in March 2004, when the FDA said there was a small, but real increased risk of suicidal behavior in adults and children taking these drugs. It then ordered manufacturers to place a warning on the labels of all antidepressants detailing those heightened risks.
Those revised labels applied to both pediatric and adult usage of bupropion (Wellbutrin), citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), mirtazapine (Remeron), nefazodone (Serzone), paroxetine (Paxil), sertraline (Zoloft), escitalopram (Lexapro), and venlafaxine (Effexor). Prozac is the only drug approved for use in children with major depressive disorder, yet doctors are at liberty to -- and do -- prescribe many others for pediatric use.
The FDA said Friday's warning was in response to recent studies that point to the possibility of an increased risk of suicidal behavior in adults taking antidepressants. The agency said it was in the process of reviewing data from drug manufacturers to determine the extent and seriousness of the risk, a review it said could take more than a year.
In the meantime, the agency recommended the following:
- Adults being treated with antidepressant medicines, particularly those being treated for depression, should be watched closely for worsening of depression and for increased suicidal thinking or behavior.
- Close observation of adults may be especially important when antidepressant medications are started for the first time or when doses for the specific drugs prescribed have been changed.
- Adults whose symptoms worsen while being treated with antidepressants, including an increase in suicidal thinking or behavior, should be evaluated by their health care professional.
In its statement Friday, the FDA did not cite the published studies that the agency said prompted the renewed warning about antidepressant use among adults.
In February, the British Medical Journal published three studies that came to conflicting conclusions about the risks of suicidal behavior associated with antidepressants that are part of a class of drugs called selective serotonin reuptake inhibitors (SSRIs).
The three new studies approached the issue of SSRI use and suicidal behavior from different angles. The largest, conducted at the Medicines and Healthcare Products Regulatory Agency in London, England, looked at data on more than 146,000 people taking either SSRIs or older tricyclic antidepressants in the United Kingdom.
That study found "no evidence that the risk of suicide or non-fatal self-harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants," the authors wrote. But they did note "some weak evidence" of such behavior in SSRI users aged 18 or younger.
A second study looked at data on more than 40,000 people taking part in 477 controlled trials. "We found no evidence that SSRIs increased the risk of suicide, but important protective or hazardous effects cannot be excluded," wrote the researchers, from the University of Bristol in England. They, too, said they detected "weak" evidence of an increased risk of self-harm.
"Larger trials with longer follow-up are required to assess the balance of risks and benefits fully," they concluded.
The third study, amassed data on close to 88,000 participants enrolled in 702 clinical trials. It found a "significant increase in the odds of suicide attempts," which were found to be twice as likely in people taking SSRIs than in those taking a placebo.
"The clinical implications are that we have good evidence that there is a rare but serious risk associated with SSRIs," said study author Dean Fergusson, a scientist at the Ottawa Health Research Institute in Ontario, Canada. "This information needs to be relayed to physicians and patients."
In addition, the FDA also updated its Web site with a report that a "higher-than-expected rate of suicide attempts was observed" in research with the nation's newest antidepressant, Eli Lilly's Cymbalta. The controlled studies involved women trying Cymbalta as an incontinence treatment; it was never approved for that use.
The suicide link was not seen in controlled trials of Cymbalta for treatment of depression or diabetic neuropathic pain, both of which it was approved for, the agency notice said.
But the FDA is now evaluating additional data on Cymbalta to determine if there is a link to suicidality.
Dr. C. Barr Taylor, director of the Laboratory for the Study of Behavioral Medicine at Stanford University Medical Center, called the issue of antidepressant use and suicidal behavior "a very complicated problem. You are treating people who are depressed with antidepressants, and that obviously is a confounding factor."
Another problem, Taylor noted, is that antidepressants are often prescribed by health-care providers who are not qualified to monitor depression. "You don't really know who has been giving these drugs, at what doses, or for how long and why," he said.
Taylor said he was glad the FDA was looking into the issue.
"In many ways we should be happy about this, because it shows the complexity of depression, and this cavalier giving of antidepressants to people may not be the best thing," he said.
More information
The American Academy of Family Physicians can tell you more about antidepressants.
