Dust-up over treating childhood depression

July 1, 2004

Two and a half years ago, when

Two and a half years ago, when Contemporary Pediatrics last explored the subject of treating childhood depression, the articlea listed the following continuing medical education learning objectives:

• Diagnose major depression in children and adolescents

• Recognize the importance of a multimodal team approach to treatment

• Identify antidepressants that have demonstrated positive results in placebo-controlled trials with children and adolescents

• Understand that prescribing medications to treat depression in children and adolescents is an off-label use (Contemporary Pediatrics 2002;19(1):70).

To judge by the current uproar, those lessons have still to be learned. To recap, briefly:

Last June, British drug regulators, worried by reports of a link between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts among teenagers, banned all such drugs except fluoxetine (Prozac) in patients younger than 18 years of age. (Prozac is the only SSRI approved by the Food and Drug Administration [FDA] for the treatment of major depressive disorder in patients 8 years of age and older.) The FDA, reacting to the same reports, then issued a warning that patients taking an antidepressant should be watched closely for signs of suicidal or other harmful behavior in the first weeks of therapy.

The reports that touched off the warnings were contained in drug trials conducted by the manufacturers, filed with the FDA but not published in peer-reviewed journals. To quell the uproar, the FDA held public hearings, then cancelled the appearance of one of their own experts who has concluded that antidepressant drugs do sometimes cause children to become suicidal. Not long after, Eliot Spitzer, Attorney General of New York, followed up by suing GlaxoSmithKline, the manufacturer of the SSRI paroxetine (Paxil), for "persistent fraud" by failing to tell doctors that some studies of Paxil showed the drug did not work in adolescents and might even lead to suicidal thoughts. GlaxoSmithKline immediately responded by promising to make full study reports of the safety and efficacy data for clinical studies of paroxetine in adolescent and pediatric patients available on their corporate Web site ( www.gsk.com ).

At about the same time, results of a large (439 children between the ages of 12 and 17), government-funded study were released showing that a combination of Prozac and cognitive behavioral therapy was the most effective therapy, with positive results in 71% of adolescent subjects who received it. Treatment with Prozac alone came in second, talk therapy alone third, and placebo alone last. Five participants who received Prozac attempted suicide, compared with one participant among those who got no medication.

The bottom line? Pediatricians confronted with youthful patients with symptoms of depression would do well to take the learning objectives we began with to heart. Depression is a serious disorder that can lead to suicide if untreated, multimodal treatment is the best bet, and off-label prescription must be approached with caution. Or, as a perspective by Benedetto Vitiello, MD, and Susan Swedo, MD, put it: "While we search for answers to the questions raised about the safety of SSRIs, we must not ignore the documented link between depression and suicide . . . The recognition and appropriate treatment of children with depressive disorder remain vitally important. Unfortunately . . . physicians may sometimes be forced to choose a treatment that has proven efficacy in adults with depression but has not yet been tested in children" (N Engl J Med 2004;350:15).