Antidepressants safe for children and adolescents - black box warnings questioned

Antidepressants are safe and effective for treating anxiety, obsessive compulsive disorder (OCD) and major depressive disorder in children and adolescents, according to a meta-analysis of 27 major studies.

The findings, published by University of Pittsburgh School of Medicine researchers in this week's Journal of the American Medical Association (JAMA), call into question the controversial "black box" warnings placed on the drugs by the Food and Drug Administration, which say that antidepressant medications pose a small but significantly increased risk of suicidal thoughts and behavior for children and adolescents.

"As clinicians, our first concern is for the health and safety of our patients. When the FDA placed the 'black box' warning on antidepressants, it raised a great deal of concern about how we were to treat our young patients who we thought could possibly benefit from antidepressant therapy. Most clinicians, patients and their families found themselves questioning whether or not they should be using treatments out of fear of the risks," said David A. Brent, M.D., professor of psychiatry, University of Pittsburgh School of Medicine. "By combining data from most of the significant studies of antidepressant use in adolescents and children, we've been able to examine a balance of benefits and risks of these medications.

"Antidepressants are safe and effective for treating disorders like anxiety, OCD and depression in children and adolescents," Dr. Brent continued. "While there is a small, increased risk of suicidal thoughts in those who use antidepressants, it would be much, much riskier to not treat these children and adolescents dealing with these disorders."

For this study, the University of Pittsburgh researchers extracted data on study characteristics, efficacy outcomes and emergent suicidal events from 27 trials of second-generation antidepressants used to treat pediatric major depressive disorder, OCD and anxiety in children and adolescents under the age of 19. Fifteen trials were of major depressive disorder and included a total of 3,430 participants; six trials were of OCD, with 718 participants; and six trials were of anxiety, with 1,162 participants. The drugs used were the selective serotonin reuptake inhibitors (SSRIs) nefazodone, venlafaxine and mirtazapine; all of the studies were randomized and placebo-controlled.

Researchers found that one in 100 participants in the studies included in the meta-analysis had new-onset suicidal ideation, or suicidal thoughts, while on medication. Even fewer acted on these thoughts, and there were no completed suicides.

The results showed that antidepressants were most effective in treating anxiety, moderately effective for OCD and modestly effective for depression. The number needed to treat (NNT) , a statistical term meaning the number of patients a clinician would need to treat to prevent an adverse outcome in one , was 10 for major depressive disorder, six for OCD and four for anxiety. The number needed to harm (NNH) , the number of patients who would need to be treated for one to be harmed , was 112 for major depressive disorder, 200 for OCD and 143 for anxiety. These numbers indicate that the increased risk, while not unimportant, is not enough to outweigh the benefits of taking the medications.

"While I support the FDA's role in monitoring the safety of medications, in this case, the FDA should reconsider the black box warning on these medications," said Dr. Brent. "Our study supports the cautious and well-monitored use of antidepressant medications as a first-line treatment for anxiety, OCD and depression."