Advisory on Antidepressants

The Food and Drug Administration (FDA) recently 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 being treated with antidepressant medications.

Dr. Lester M. Crawford, the acting FDA Commissioner, said that the agency is directing manufacturers to add a "black box" warning to the health professional labeling of all antidepressant medications to describe the risk and emphasize the need for close monitoring of patients. The FDA also determined that a Patient Medication Guide (MedGuide) is appropriate and is now in the process of developing one. The MedGuide will be given to patients receiving the drugs to advise them of the risk and precautions that can be taken. Dr. Crawford said that the FDA's conclusions are based on the latest and best science.

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. Until now, only ten drug products approved for children contained a black box warning about their use in children. 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 risk of suicidality for these drugs was identified in a combined analysis of short-term (up to 4 months) placebo-controlled trials of nine antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs) and others, in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. A total of 24 trials involving over 4400 patients were included. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants. The average risk of such events on drug was 4%, twice the placebo risk of 2%. No suicides occurred in these trials. Based on these data, the FDA has determined that the following points are appropriate for inclusion in the boxed warning:

• Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with MDD and other psychiatric disorders.
• Anyone considering the use of an antidepressant in a child or adolescent for any clinical use must balance the risk of increased suicidality with the clinical need.
• Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior.
• Families and caregivers should be advised to closely observe the patient and to communicate with the prescriber.
• A statement regarding whether the particular drug is approved for any pediatric indication(s) and, if so, which one(s).

Among the antidepressants, only Prozac is approved for use in treating MDD in pediatric patients. Prozac®, Zoloft®, Luvox®, and Anafranil® are approved for OCD in pediatric patients. None of the drugs is approved for other psychiatric indications in children.

The FDA's actions are consistent with the recommendations made at the September 2004 joint meeting of the FDA's Psychopharmacologic Drugs Advisory Committee and Pediatric Drugs Advisory Committee.

The FDA warned that health care providers, caregivers, patients, and their families should also be alert for certain behaviors associated with antidepressants, such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, severe restlessness, and mood disorders marked by agitation, excitability, or elation (hypomania and mania). Physicians should be particularly vigilant when treating people who have bipolar disorder.

This site is not authorized by GlaxoSmithKline Corp, the manufacturers of Paxil and is not an official site of Paxil.