Antidepressant Data Review Finds Benefits Trump Risks

The benefits of taking antidepressants for mood and anxiety disorders far outweigh the risk of suicide for children and adolescents, according to findings from a review of more than 27 clinical trials published last month.

The findings, which appear in the April 18 Journal of the American Medical Association, prompted researchers to call on the U.S. Food and Drug Administration (FDA) to modify strict black-box warnings that currently appear on labels for antidepressants indicating an increased risk of suicidal thoughts and behaviors in youth taking them.

“Antidepressants are effective in treating disorders such as anxiety, obsessive-compulsive disorder, and depression,” said David Brent, M.D., one of the study's investigators, in an interview with Psychiatric News. While he said that they found a small risk associated with developing suicidal thoughts or behaviors in children and adolescents, he noted, “it would be much riskier not to treat them with these medications.”

Brent is a professor of psychiatry at the University of Pittsburgh School of Medicine.

He and his colleagues analyzed data from 27 randomized, placebo-controlled trials in which antidepressants were used to treat children and adolescents under the age of 19 for major depressive disorder, obsessive-compulsive disorder (OCD), or anxiety disorder. The 27 clinical trials included seven trials that were not covered in the FDA's 2004 analysis, three of which were not available at the time. Brent and his colleagues used a statistical model that differed from the one used by the FDA.

The trials in the current study took place between 1998 and 2006 and included data on roughly 5,300 patients. Fifteen of the clinical trials tested the effects of antidepressants on 3,430 subjects with depression, six of the trials tested the effects of antidepressants on 718 subjects with OCD, and another six trials tested the effects of antidepressants on 1,162 subjects with anxiety.

Antidepressants used in the trials were nefazodone, venlafa xine, mirtazepine, paroxetine, sertraline, citalopram, escitalopram, fluoxetine, and fluvoxamine.

By pooling the data across the trials, the investigators found that the antidepressants were more effective than placebo in subjects with depression, OCD, and anxiety. The drugs were most effective in children and adolescents with anxiety.

For instance, in depression trials using the Clinical Global Inventory–Improvement Scale and the Children's Depression Rating Scale–Revised, 61 percent of subjects treated with antidepressants and 50 percent of those treated with placebo responded with a 50 percent reduction in symptom severity.

In OCD trials using the Children's Yale-Brown Obsessive Compulsive Scale, 52 percent of subjects treated with antidepressants and 32 percent of those treated with placebo responded with a score reduction of 25 percent or more.

In anxiety disorder trials using the Pediatric Anxiety Rating Scale, 69 percent of subjects treated with antidepressants and 39 percent treated with placebo responded with a 50 percent reduction in scores.

Brent, pointed out, however, that “response is not the same as remission,” and that many children and adolescents with these disorders“ need a combination of psychotherapy and antidepressants.”

By pooling the data for all conditions, the investigators found a small but increased risk of treatment-emergent suicidal ideation/suicide attempts among those receiving antidepressant treatment. The statistical model they used found a smaller risk difference than the FDA found. The authors noted that overall the benefits of antidepressants appeared to be much greater than the risk from suicidal ideation/suicidal attempts.

Brent said that since youngsters with anxiety appeared to have the strongest response to antidepressants, the findings may implicate a need for early identification and treatment of anxiety symptoms, which may be a risk factor for depression.