Antidepressant Suicidality Black-Box Warning for Young Adults: FDA Recommendation

SILVER SPRING, Md., Dec. 14 -- FDA advisers have recommended that a suicidality-risk black box warning on antidepressant drugs be extended from children and adolescents to cover adults in their middle 20s.

The advisory panel voted six to two in favor of extending the black box warning about suicide risk to cover young adults up to their middle 20s, Thomas P. Laughren, M.D., director of FDA's division of psychiatry products, said at a press briefing.

However, the FDA said it might reword the current warning in an effort to ensure that "physicians are not frightened into not treating patients who should be treated."

Although there was much discussion about age 25, the advisers felt they could not be that precise. However, the committee agreed that antidepressant drugs appear to have a risk through patients' middle 20s and a protective effect against suicidality (suicidal thinking and behavior) in those 30 and older, particularly for those 65 and older, Dr. Laughren said.

The committee's evaluated an FDA analysis of 372 randomized, placebo-controlled antidepressant trials involving nearly 100,000 adult patients. The adult analysis was a follow-up to a 2004 study of 24 antidepressant trials involving more than 4,400 children and adolescents, Dr. Laughren said.

The pediatric analysis found an increased risk of suicidal thinking and behavior during early treatment and spurred the black box warning on antidepressant drugs.

In the adult analysis, "What we are seeing is an extension of the suicidality risk that we found in pediatric patients in young adults up to age 25," Dr. Laughren said. "However, the signal did not appear to extend beyond that age. In fact, we are seeing a reversal of that phenomenon after about age 30."

More specifically, the study found that in those ages 18 to 24, antidepressant use was associated with an increase of four events of suicidal ideation per 1,000 patients treated, Dr. Laughren said.

However, in adults 65 and over, antidepressant use was linked to a reduction of six suicidal ideation events per 1,000 patients treated, he said.

While the age of 25 was a somewhat arbitrary cutoff point, the data clearly show a reversal of suicide risk with antidepressants appearing at about age 30, increasing steadily with age, and peaking in adults 65 and older, he said.

As to the mechanisms that may underlie these findings, "we don't know," Dr. Laughren said.

However, the introduction to the FDA analysis of adult antidepressant trials said that "the occurrence of suicidality in the context of treating patients with depression and other psychiatric illnesses has been a concern and a topic of interest and debate for decades."

"In fact, as early as medical school, many physicians learn of this concern," the report continued, "and it has been part of medical lore for many decades that antidepressants may have an early activating effect that perhaps gives depressed patients the energy to follow through in suicidal impulses before the mood improvement associated with antidepressant treatment takes effect."

However, this so-called "roll back" phenomenon is only one of many proposed mechanisms, the report said.

A coalition of mental health organizations has been critical of the FDA black box antidepressant warnings. The coalition, which includes the American Psychiatric Association (APA) and the American Academy of Child & Adolescent Psychiatry (AACAP), says the warnings could frighten depressed individuals away from seeking treatment.

"The AACAP is supportive of the FDA's practice of approving safe and effective treatment for individuals with mental illnesses," the organization said in a statement. "However, while protecting and informing the public, the AACAP urges the FDA to balance the impact of stronger warnings on current practice and the demonstrated effectiveness of antidepressants to treat individuals with depression."

The advisory committee considered such criticism in its deliberations, Dr. Laughren said. "We continue to feel antidepressants are a useful class of drugs, and we are not in any way trying to discourage the use of these products," he said.

But the bottom line is that "we still feel it's good advice for clinicians to carefully observe all patients of all ages who are being treated with antidepressants for emergence of suicidality," Dr. Laughren said.

The FDA is not bound to follow advisory committee recommendations, but it usually does.