Strategy to Strengthen Safeguards for Children Treated with Antidepressants

The U.S. Food and Drug Administration (FDA) has issued a public health advisory announcing a multi-pronged strategy to warn the public about the increased risk of suicidal thoughts and behavior (“suicidality”) in children and adolescents taking antidepressants. The advisory is available online athttp://www.fda.gov/cder/drug/antidepressants/SSRIPHA200410.htm.

The FDA is directing antidepressant manufacturers to add a “black box” warning to the health professional labeling of all antidepressants to describe this risk and emphasize the need for close monitoring of patients started on these medications.

This direction is based on a pooled analysis of 24 studies of antidepressants (selective serotonin reuptake inhibitors [SSRIs] and others) in more than 4,400 children and adolescents with major depression, obsessive-compulsive disorder, and other psychiatric disorders. These studies found a 4 percent risk of suicidal thinking or behavior in patients taking antidepressants compared with a 2 percent risk in patients taking placebo (number needed to treat for one to four months: 50).

The black box warning also notes what uses the anti-depressants have been approved or not approved for in these patients. The FDA also has addressed other labeling changes designed to include additional information about studies of these drugs in children. These labeling changes are applicable to the entire category of antidepressant medications because the currently available data are not adequate to exclude any single medication from the increased risk of suicidality.

Fluoxetine (Prozac) is the only medication approved to treat depression in children and adolescents. The analyses of the placebo-controlled trials in children and adolescents summarized in the revised labeling are based on studies of five SSRIs (citalopram [Celexa], fluvoxamine [Luvox], paroxetine [Paxil], fluoxetine, and sertraline [Zoloft]) and four “atypical” antidepressants (bupropion [Wellbutrin], mirtazapine [Remeron], nefazodone [Serzone], and venlafaxine [Effexor]). In these studies, there was no reported suicide.

A black box warning is the most serious warning placed in the labeling of a prescription medication. Advertisements that serve to remind health care professionals of a product’s availability (so-called “reminder ads”) are not allowed for products with black box warnings. The new warning language does not prohibit the use of antidepressants in children and adolescents. Rather, it warns of the risk of suicidality and encourages prescribers to balance this risk with clinical need.

The FDA recognizes that depression and other psychiatric disorders in children and adolescents can have significant consequences if not appropriately treated. The new warning language recognizes this need but advises close monitoring of patients as a way of managing the suicidality risk.

The FDA is developing a Patient Medication Guide which needs to be given by pharmacists to patients taking antidepressants to advise them of the suicidality risk and precautions that can be taken. In addition, the FDA intends to work with manufacturers to implement “Unit-of-Use” packaging for all antidepressants as a means of ensuring that patients receive a medication guide with every prescription or refill. Unit-of-use packaging is a method of preparing a medication in an original container, sealed and labeled by the manufacturer, and containing sufficient medication for one normal course of therapy.