Yael Waknine

March 22, 2004 — The U.S. Food and Drug Administration (FDA) has asked manufacturers of the several antidepressant drugs to include in their labeling a warning statement that recommends close observation of adult and pediatric patients treated with their agents for worsening depression or the emergence of suicidality

The antidepressant drugs are fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), bupropion (Wellbutrin), venlafaxine (Effexor), nefazodone (Serzone), and mirtazapine (Remeron).

Several of these drugs are approved for the treatment of obsessive-compulsive disorder in pediatric patients (sertraline, fluoxetine, fluvoxamine). Only fluoxetine is approved for use in children with major depressive disorder. None of these drugs are approved as monotherapy in treating bipolar depression, either in adults or children, and fluvoxamine is not approved as an antidepressant in the U.S.

The FDA has been closely reviewing the results of antidepressant studies in children since June 2003, after an initial report appeared to suggest increased risk of suicidal thoughts and actions in the pediatric population, according to today's advisory.

Although it is unclear whether antidepressants contribute to the emergence of suicidal thinking and behavior, these interim actions are intended to draw more attention to the need for careful monitoring of patients being treated with these drugs, especially at the beginning of therapy and during dose changes.

Discontinuation of medication may be appropriate in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms. Therapy changes should be made under the guidance of a physician, as certain medications should be tapered rather than stopped abruptly.

The warning also alerts physicians, patients, and caregivers to symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania in patients being treated with antidepressants for major depressive disorder as well as other indications. According to the FDA, there is concern that patients who experience one or more of these symptoms may be at increased risk for worsening depression or suicidality.

Because antidepressants are believed to have the potential for inducing manic episodes in patients with bipolar disorder, the FDA recommends that physicians be particularly vigilant in screening and monitoring patients who may be at risk.

The FDA is continuing to review available clinical trial data for pediatric patients with depression and other psychiatric disorders to determine whether there is evidence that some or all antidepressants increase the risk of suicidality in children.

Later this summer, the FDA plans to update the Psychopharmacological Drugs Advisory Committee (PDAC) and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee (Peds AC) about the results of this review.

In the interim, the FDA plans to work closely with each of the nine manufacturers of the antidepressants involved to optimize safe drug use and implement proposed labeling changes and other safety communications in a timely manner.

Reviewed by Gary D. Vogin, MD

Yael Waknine is a freelance writer for Medscape.