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FDA May Expand Antidepressant Warning

Dec. 13, 2006 — The FDA said Wednesday it planned to expand warnings on up to a dozen antidepressant medications following studies suggesting the drugs raise the risk of suicidal behavior in a wider range of patients than previously thought.

In 2004, the agency ordered “black box” warnings to be added to antidepressant packaging alerting doctors of evidence that the drugs increase the risk of suicidal thoughts and attempts in children and teens under the age of 18. Officials said Wednesday they would now move to expand the warning to include young adults up to age 25.

The warnings apply to selective serotonin reuptake inhibitors (SSRIs) such as Prozac and Paxil, in addition to related drugs including Effexor and Wellbutrin. Officials said the warnings would also likely be included in medication guides distributed to patients

Antidepressants and Young People

Adult antidepressant studies have suggested that adults, up to the age of 24, who take antidepressants are more than twice as likely to think about or attempt suicide as adults taking a placebo.

An analysis of 372 studies performed by the FDA showed no evidence of any completed suicides that can be blamed on the drug. The analysis also showed that suicidal ideas and behaviors remain relatively rare.

The regulators pointed to a consistent trend, which is highest in children and then tapers off through early adulthood.

“There’s nothing magical about 25. It’s not like this goes away the day you turn 25,” said Marc B. Stone, MD, a medical reviewer in the FDA’s division of psychiatric products. “But the risk seems fairly flat in the 25 to 64 range and pretty steep in the 18 to 24 range,” he told an advisory panel called to review the warnings. “We can’t ignore it.”

The FDA estimated in 2004 that antidepressants cause suicidal thoughts and behaviors in an additional 14 children for every 1,000 who take them. The agency concluded Wednesday that less than a third as many young adults may face that additional risk.

Elusive Explanation of Risk

But officials and other researchers acknowledged that any biological explanation for the increased risk is elusive. Widespread use of antidepressants is credited with helping to lower the risk of suicide attempts or completion in the population at large.

Experts at the meeting said it is possible that the drugs spur suicidal behavior at the beginning of treatment in younger patients, only to help stave it off later as depression or other mental disorder symptoms wane. They add that a greater proclivity toward impulsiveness in younger people could be to blame.

On the other hand, antidepressants may merely make young patients more communicative, making it more likely that they relate suicidal thoughts to a parent or doctor.

“We don’t know enough to be surprised or not surprised,” said Robert Temple, MD, director of FDA’s office of drug evaluations.

Outside experts convened by the FDA said they agreed that studies clearly signal an increased danger of suicidal ideas and actions with antidepressant use.

“The data are really pretty clear to me and to all the committee members that we need to look at the issue pretty carefully and the public needs to know more,” said Daniel S. Pine, MD, chief of child and adolescent research at the National Institute of Mental Health and the panel’s chairman.

But in a public hearing, a coalition of mental health and psychiatry groups warned that doctors have already shied away from prescribing antidepressants since the FDA and British regulators first began addressing potential suicide risk in 2003.

Impact of Warnings on Antidepressant Use

Some experts fear that increased warnings may lead to less antidepressant use and, therefore, more suicides.

“Introducing the black box warning has led directly in our opinion to … the increase in suicide rates,” said John Mann, MD, a professor at the New York State Psychiatric Institute.

Drugmakers joined in those warnings. John R Hayes, MD, vice president for research at Prozac-maker Eli Lilly and Co., said that new safety warnings are having an unintended negative impact on mental health treatment.

“We urge you to be clear about the infrequent occurrence of any events under discussion,” he said.

Some panelists said they were hesitant to endorse expanding “black box” warnings to include young adults because it could undermine needed drug treatment for depressionand other disorders.

“I don’t think any of us want the black box warning to preclude the proper use of these medications,” said Jean Bronstein, the committee’s consumer representative.

“The problem is, I’m equally uncomfortable doing nothing,” said Pine.

Emotional Testimony

About 70 members of the public addressed the committee during an emotional open hearing. Witnesses were roughly divided between opponents of new warnings and relatives and friends of patients who committed suicide while taking antidepressants.

Ellen Hanson, whose 43-year-old husband, Scott, committed suicide in 2004 after taking Paxil for three weeks, said she strongly believed the drug caused his death because it was only prescribed to treat mild anxiety.

“It was completely impulsive and bizarre. Even two years later I feel his death was an accident. A medical accident,” she said. “There was no hint that he’d become suicidal.”

Nada Stotland, MD, vice president of the American Psychiatric Association, warned that prescribing doctors, most of whom are primary care physicians, should be encouraged to increase their treatment of depression.

“It is untreated depression that deserves a black box label,” she said.

Posted by: Dr.Health

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