Should antidepressants add suicide risk in young adults?

In a unanimous vote, a Food & Drug Administration advisory group has recommended modifying antidepressant labels to include new information on the risk of suicidality in young adults.

In mid-December, the Psychopharmacologic Drugs Advisory Committee convened to discuss new findings from the analysis of 372 placebo-controlled trials in almost 100,000 patients. The committee also voted six to two in favor of modifying the existing black box warning that already exists for children and adolescents.

Strongly opposed to this change is the American Psychiatric Association (APA). According to APA's trustee-at-large, David Fassler, M.D., following the implementation of the black box language for the use of antidepressants in the treatment of children and adolescents, he saw a precipitous reduction in the prescribing of these medications. "As a result, I am very concerned that there are many young people with depression who are not currently receiving appropriate and effective treatment. I think the FDA needs to exercise caution before deciding to extend this warning to adults," he said.

According to FDA's Laughren, however, there was general agreement among committee members that there does appear to be an age-related causal link to suicidality. But there was also a great deal of discussion among the group regarding the need for further research to understand the basis for the relationship. Suicidality, as defined at the meeting, is a combination of suicidal ideation and suicidal behavior (i.e., suicide attempt).

Fassler, who is also a child and adolescent psychiatrist in Burlington, Vt., and a clinical professor at the University of Vermont, debates the results of the 372 trials examined. "None of the studies were designed to answer the questions that we are now trying to ask," he pointed out. Fassler contends that there are numerous studies showing that using antidepressants is actually associated with a significant and encouraging reduction in the suicide rate. He pointed to a large-scale, long-term study in December's issue of Archives of General Psychiatry, in which it was reported that use of selective serotonin reuptake inhibitors (SSRIs) led to a 9% reduction in deaths attributable to suicide and a 61% reduction in death from all causes.

In fact, the FDA does agree that the risk of suicide while taking antidepressants diminishes as one ages. The results presented to the advisory committee included what appears to be a reversal, or protective effect, from suicidal thoughts, beginning once a patient reaches the age of 30.

"If you look at the other end of the age spectrum, you're looking at a reduction in suicidality by virtue of taking the drug," said Robert Temple, M.D., director of FDA's Office of Medical Policy. According to Temple, this becomes especially apparent in the 65 and older population. In this group, "a reduction in six 'events' per 1,000 patients treated" was seen.

"There is clearly a perception that people are frightened into not treating patients who ought to be treated," Temple said of adding the new language. However, "we persist and believe that it's an important enough message that, while we don't discourage appropriate use, we still think it needs prominent warning."

The advisory committee did not vote on the precise wording of the labeling change, or the exact age after which the risk of suicidality substantially diminishes. The final action will be determined by the FDA.