FDA Adds Young Adults to Black Box Warnings on Antidepressants

The FDA has ordered the addition of a "black box" warning to antidepressant labeling of increased suicide risk in adults aged 18 to 24 years. The labeling will also note that no increased risk has been seen in older adults and that, in fact, the incidence of suicidal thoughts and behavior has been found to decrease during antidepressant therapy in patients 65 years and older.

The agency indicated that it has no intention of ditching its requirement that manufacturers of antidepressants include a black box warning about the possibility of suicidal thoughts in adolescents and children. The FDA strongly suggested-the regulatory equivalent of "requiring"-the latter warning in late 2004 after it was recommended by 2 advisory committees, including the Psychopharmacologic Drugs Advisory Committee (PDAC).

The necessity of maintaining that warning was called into question by a report published in the April issue of the Journal of the American Medical Association (JAMA) that found the risk of suicidal thinking or behavior in children is less than the FDA originally thought. "The JAMA article does not change FDA's views about the suicidality risk or, indeed, about the effectiveness of these drugs in children with depression," said Thomas Laughren, MD, director, division of psychiatry products at the FDA. "At this time, nothing indicates a need for change in the 'black box' warning, which urges attention to patients starting treatment, still good advice, and does not suggest avoiding the drugs."

The JAMA researchers analyzed data on 5310 children and teenagers. They found that for every 100 children treated with antidepressants, about 1 more child experienced worsening suicidal feelings above what would have happened without drug treatment. In contrast, the FDA analysis found an added risk affecting about 2 in 100 patients. The new analysis includes data from 7 studies that were not part of the previous FDA analysis, including 2 large pediatric depression trials that were unavailable 3 years ago. There were no suicides in any of the studies. The antidepressants included fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor), nefazodone (Serzone), and mirtazapine (Remeron).

The results of the new study are important because some separate studies done since the black box warnings went into product inserts show that the incidence of suicide in children is increasing. Some people think that may be because some parents decline to give their children antidepressants because of the fear of suicide.

Laughren declined to comment about the increase in childhood suicides, but said the agency is aware of it. "We believe depression is a serious condition that needs attention and treatment," he said. But Laughren did not back away from the agency's contention that antidepressants have not, with the exception of fluoxetine, been proved effective in children in clinical trials. "We have not at all tried to discourage use of these drugs in depressed children, just reminded people of the care needed and that the data supporting use are not strong," he emphasized.

Both Daniel S. Pine, MD, chair of the PDAC and an expert in child and adolescent psychiatry at NIMH, and Marcia J. Slattery, MD, MHS, another PDAC member and head, division of child and adolescent psychiatry at the University of Wisconsin School of Medicine and Public Health, declined comment on the JAMA study.