Experts to FDA: Don't Change Antidepressant Labels

Dec. 13, 2006 — -- In the debate over labeling for antidepressant drugs, mental health experts are imploring the Food and Drug Administration to refrain from requiring additional package warnings about the risk of suicide in adults.

Federal health officials are planning to add the additional warnings after determining that the use of the drugs may increase the risk of suicidal thoughts and behaviors in young adults.

However, experts said they fear that the additional labeling could scare off patients from the drugs, putting them at an increased risk of taking their own lives.

The American Psychiatric Association estimates that 16 million Americans are on antidepressants at any given time. Currently, all antidepressants bear a so-called "black-box" warning indicating an increased risk of suicidal thinking and behavior in children and adolescents.

Experts said extending this warning to adults could have unintended consequences.

"Patients will be frightened off appropriate treatment," said Dr. Alex Vuckovic, medical director of The Pavilion at McLean Hospital in Belmont, Mass. "It's already happening to child [psychiatrists] and their patients."

"These drugs save lives -- end of story, no ambiguity," he said.

At an FDA hearing today in Silver Spring, Md., the federal agency heard opinions from both mental health experts -- most of whom opposed the new labeling -- and distraught family members of patients who committed suicide who said they believe antidepressant drugs played a key role.

"There are a tremendous amount of unbelievably heart-wrenching, compelling -- but ultimately anecdotal -- stories," said Kelly Posner, an assistant professor of child psychiatry at Columbia University who was commissioned by the FDA to assess the connection between the medications and suicide risk.

"A bunch of people heading mental health and consumer advocacy groups have been getting up and talking desperately, saying, 'please, don't increase this loss of life that we're already beginning to see,'" she said.

"We're unfortunately at the beginning of a suicide epidemic, perhaps."

Could Labeling Affect Use?

The FDA said in documents released ahead of the meeting that an "elevated risk" exists "for suicidality and suicidal behavior among adults younger than 25 years of age that approaches that seen in the pediatric population."

However, experts said the additional warnings for adolescents, adopted in 2004, have already been shown to deter patients.

"After the original warning, rates of antidepressant treatment among U.S. adolescents fell nearly 25 percent," said Greg Simon, a psychiatrist and researcher with Group Health Cooperative in Seattle.

And Posner said that since the black-box labeling has been applied to the drugs for kids, the rates of completed suicide have begun to climb.

"Untreated depression is what kills," she said.

Previous randomized trials do show that use of antidepressants, compared to placebo, led to a higher risk of suicidal thoughts or behavior in adolescents and young adults, said Simon.

"But those randomized trials are not large enough to examine the problems we care the most about -- serious suicide attempts and suicide deaths," he said. Simon added that rather than actually causing patients to commit suicide, antidepressants may just cause patients to think about suicide.

Moreover, he said, older adults still showed an overall reduced risk of suicide when taking antidepressants.

"Several of those studies show that increasing rates of antidepressant use have been accompanied by stable or declining suicide rates," he said.

"The epidemiologic research is dramatic and consistent," Vuckovic said. "Suicide rates among adolescents and children have dropped dramatically in conjunction with more aggressive use of [antidepressants] in that population."

Physicians Split on Impact on Practice

Some practitioners said additional package warnings could cause their patients to second-guess medications, even if those drugs are recommended by a physician.

"A black-box warning would increase the questions and concerns patients have on the medication," said Dr. Davin Quinn, a clinical fellow in psychiatry at Massachusetts General Hospital. "Black-box warnings may make some patients more concerned about being treated by an antidepressant. Black-box warnings may even cause some patients to decline to be treated by those medications."

However, not all practitioners believe the additional warning will affect their practices.

"There have been black-box warnings on anti-psychotics, and they're still prescribed by clinicians," said Dr. Jennifer Narvaez, another clinical fellow in psychiatry at Massachusetts General Hospital. "I don't think people are going to stop taking antidepressants or anti-psychotics entirely because they are helpful. Having black-box warnings do raise consciousness among physicians and patients."

"In general, I feel that it's good to error on the side of prudence," said Dr. David Mischoulon, assistant professor of psychiatry at Massachusetts General Hospital. "Even when there's a hint of adverse effect, especially serious, it's good to put out the warning, so that doctors and patients have that information.

"The black-box warnings probably will not change my practice."