FDA calls for stronger antidepressant warning

Labeling should cite data on suicidality, and state that untreated depression is linked to suicide risk. The warnings of an increased risk for suicidality in pediatric patients that appear on the labels of antidepressants should be expanded to include young adults aged 18-24 years, but should include a statement saying that depression also is associated with an increased risk of suicide, according to a proposal by the Food and Drug Administration. The FDA announced May 2 that the agency was asking manufacturers of all available antidepressants to revise the warning language on antidepressant labels, which includes the black box warning, to include a new warning about an increased risk of suicidality — suicidal behavior and thinking — during initial treatment with antidepressants to young adults. Initial treatment generally is considered to cover the first 1-2 months of treatment. Language that warns about the increased risk for suicidality in children and adolescents was added to the labels in 2005.

The proposal reflects recommendations made at a December 2006 meeting held by the FDA’s Psychopharmacologic Drugs Advisory Committee. At that meeting, the panel agreed that the warning on the increased risk of suicidality associated with SSRIs and other antidepressants in children and adolescents be extended up to age 25, based on data presented by the FDA at that time. But the revised warning also will note that the FDA’s data did not show an increase in risk beyond age 24 and actually showed a decreased risk of suicidal thinking and behavior in people aged 65 years and older. The revised label also will “emphasize that depression and certain other psychiatric disorders that are treated with these drugs are themselves the most important causes of suicide”. The important message for prescribers is that these drugs do have value across the age spectrum, but their use requires certain precaution. Any patients being treated with these drugs, whatever their age, should be monitored appropriately for worsening or unusual changes in behavior, especially early in treatment.

The proposed labeling changes apply to the entire category of antidepressants, including the older tricyclics. The proposed revisions include a table quantifying the risks, in terms of the number of excess cases of suicidality to be expected, compared with placebo, according to clinical trial data. The differences in risk in adults were estimated, based on pooled analyses of placebo-controlled trials in adults with major depressive disorder or other psychiatric disorders, which included 295 short-term trials, with a median duration of 2 months, of 11 antidepressant drugs in more than 77,000 patients. For patients aged 18-24 years, five additional cases of suicidality per 1,000 patients treated with an antidepressant would be expected, compared with those on placebo. The rate then drops, so that between ages 25 to 64, one fewer case per 1,000 patients treated would be expected, dropping to six fewer cases per 1,000 patients treated for those ages 65 and older. (For those under age 18, the table says there would be 14 additional cases per 1,000 patients treated, which is based on pooled analyses of placebo-controlled clinical trials of nine antidepressants in more than 4,400 patients.)

The proposed changes are similar to those made in 2005, when the black box label was added to the labels of all antidepressants, with the warning about the suicidality risk in children and adolescents treated with antidepressants. President-elect of the American Psychiatric Association, said in a statement that the organization is pleased that the FDA is changing the label on antidepressants “to acknowledge, for the first time, that it is untreated depression that puts people at the greater risk for suicide. This change in labeling is supported by the science. We believe the new label reminds physicians and patients that antidepressants save lives.”