Antidepressants for children and adolescents: An update

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Antidepressants for children and adolescents: An update

New research is shedding light on the hotly debated question of whether antidepressant medications developed for and tested mainly on adults can help many depressed children and adolescents — and whether some of these drugs may raise the risk of suicidal impulses and suicide attempts in young patients.

These questions are significant. A 2002 survey found that nearly 4% of American 13- to 19-year-olds and 1.4% of 6- to 12-year-olds were taking antidepressants. In the last few years, though, prescriptions have been declining as concerns about suicide have surfaced and culminated in warnings from the FDA.

A task force from the American College of Neuropsychopharmacology reviewed and analyzed the data from clinical trials of selective serotonin reuptake inhibitors (SSRIs), the most widely used prescription antidepressants. The task force found further evidence for the effectiveness of fluoxetine (Prozac), which was approved for the treatment of childhood depression in 2003. According to the report, fluoxetine may be superior to other SSRIs because it lingers longer in the body and therefore remains effective despite the missed doses that are more likely in youths than in adults. The task force says limitations in the design of studies might account for the reports of small differences in the rate of suicidal thoughts or gestures between patients taking antidepressants and those taking placebos.

In a major survey of American and British studies, teams from the University of Toronto and the University of Texas expressed similar concerns about study methods; for example, some used narrower and others used broader definitions of suicidal thinking and behavior. Up to 19% of children and adolescents in the general population have had thoughts of suicide, and 9% have made suicide attempts. Researchers have not always taken account of that, so there could have been an accidental imbalance in some studies, with more suicidal patients assigned to a drug than to a placebo.

The Treatment for Adolescents with Depression Study (TADS), including 439 adolescents (age 12–17) with a diagnosis of major depression, confirms that fluoxetine, although no magic pill, can be helpful for depressed youths. Patients were divided into four groups that were treated with fluoxetine alone, a placebo, cognitive behavioral therapy (CBT), or a combination of fluoxetine and CBT. Only the combined treatment was superior to the placebo, but fluoxetine alone performed better than CBT alone. The patients receiving the combination therapy had a slightly higher rate of self-harming behavior (although not suicidal thoughts), but there was evidence that more patients with suicidal inclinations had been assigned to that group by chance.

The latest word comes from a large project sponsored by the FDA and encompassing a wide range of antidepressants. The researchers used data from TADS and 23 placebo-controlled clinical trials performed by pharmaceutical companies involving 11 different drugs. Experts assembled by Columbia University searched the records of these trials for words that suggested suicidal tendencies and then looked at the records more closely to identify possibly suicidal actions and distinguish them from accidental injuries and overdoses.

They sorted incidents into various categories, such as suicide attempt, preparation for imminent suicidal behavior, suicidal thinking, and self-injury with unknown intentions. They also tallied suggestions of suicidal thinking in patients' reports of their symptoms before they started taking the drugs.

Of more than 4,500 patients in the 24 trials, none committed suicide. Fewer than 100 (about 2%) showed definite suicidal behavior or thinking and somewhat more than 100 showed possible suicidal behavior or thinking. TADS was the only individual study in which differences between drug and placebo groups were statistically significant. But when all studies were combined, patients taking the drugs showed slightly more suicidal tendencies. There was not enough information for meaningful comparisons among individual drugs.

The suicidal thoughts and behavior observed in people taking SSRIs are sometimes attributed to the drugs' energizing effects, to paradoxical responses, or to the extreme intolerable restlessness (akathisia) that a few patients develop as a side effect. The FDA analysis suggests other explanations. For example, SSRIs are known to reduce social anxiety. Might patients taking them be more willing to share their true feelings?

It can be difficult to tell whether a thought or action is genuinely suicidal, especially when judging from clinical trial records compiled for other purposes, so it's not clear when the small resulting differences are practically, as opposed to statistically, significant. While the use of antidepressants increased in the 1990s, the suicide rate among adolescents declined — coincidentally or not — by 31%. And autopsy studies have shown that adolescents who commit suicide, even when they have a prescription for an antidepressant, are usually not taking the drug at the time of death.

We need a better system for tracking responses to antidepressants and other drugs after they are approved and on the market. Meanwhile, a consensus seems to be emerging that concern about the risk of suicide in children and adolescents taking antidepressants may have been exaggerated. Even for children and adolescents, the risk of leaving depression untreated may be greater than the risk of taking antidepressants. Fluoxetine can probably help at least some of these children, and it does not clearly raise the risk of suicidal behavior. Clinicians eagerly await better evidence to guide their use of other antidepressants. Any increased risk of suicide occurs mainly in the first few weeks or months of treatment, and the best defense is regular consultation with a physician.

Last updated:	September 05, 2008