Treating depression in children and adolescents is a delicate business. It can involve counseling, cognitive behavioral therapy, the administration of antidepressant medications, or a combination of those therapies. If one type of medication doesn't work, the clinician may switch to another. But it may be weeks before an antidepressant shows any effect.

Disorder: Recently, Dartmouth child psychiatrist Craig Donnelly, M.D., led the first study to explore certain differences in how an antidepressant affects children versus adolescents with major depressive disorder. He reported, in the October 2006 issue of the Journal of the American Academy of Child and Adolescent Psychiatry, that preteens respond more quickly to sertraline (Zoloft) than adolescents do.

"I think the value of this study was to show that preteens were perhaps more sensitive to the effect of medicine," says Donnelly. He was not surprised by the results, however. "I think that child clinicians have for years assumed that

younger children and children with other kinds of neurological issues—like mental retardation or autistic spectrum disorders or neurological syndromes—have more sensitive brains, more sensitive central nervous systems."

The 10-week, randomized, double-blind, placebo-controlled study included 177 children aged 6 to 11 and 199 adolescents aged 12 to 17. The children had an initial response to sertraline after about two weeks and a persistent response after four weeks; the adolescents had an initial response after about three weeks and a persistent response after 4.5 weeks. The findings will be useful for clinicians, parents, and patients, Donnelly feels. "If you're three or four weeks in with a preteen using this medicine and you're not seeing any beneficial effect, then it may be time to think about switching out or to adding in cognitive behavioral therapy or altering your treatment plan."

Some 7 million to 12 million children in the United States suffer from mental health disorders, according to the U.S.

Department of Health and Human Services. As many as one in 33 children —and one in eight adolescents—may have clinical depression.

Risk: Yet many people fear using antidepressants in this population because they are associated with a risk of suicide. "But not treating major depression has huge risks," says Donnelly. Twenty percent of people with untreated major depression die by their own hand, he points out, and the increased use of antidepressants has resulted in a drop in the number of suicides. "What I tell parents is that the mortality and morbidity risk of major depression in childhood and adolescents far outweighs the risk the medication induces."

Donnelly also studied another antidepressant, in what he says is the largest federally funded, multisite autism treatment trial ever conducted in the U.S. He expects the results to be published within the next year. Funding for the sertraline trials was provided by Pfizer, Inc., the manufacturer of Zoloft.