What’s increasingly well known is that Depression often begins early in childhood. What’s hardly known is what to do about it.

“The chronicity, morbidity, and mortality associated with Depression in youths make the current state of knowledge a cause for great concern,” wrote Neal D. Ryan, M.D., in the Sept. 10 issue of The Lancet. “The clinician faced with a depressed child or adolescent cannot in good faith merely suggest waiting for the healing effects of time.”

But evidence for the efficacy of various drugs and psychotherapeutic interventions to counter Depression in kids and teenagers is scant at best, said Dr. Ryan, a psychiatric researcher at the Western Psychiatric Institute and Clinic at the University of Pittsburgh.

In the U.S., an estimated 1% to 2% of children from the ages of six to 12 years, and about twice as many adolescents (13-18 years), suffer from a major depressive disorder. It’s thought that as many as 25% of youngsters will have at least one episode of major Depression before reaching adulthood, Dr. Ryan wrote.

Despite these figures, there are many fewer clinical studies of treatment for childhood depression compared with adult depression, due in part to fewer patients, less funding, and fewer investigators specializing in this area.

When it comes to antidepressant agents used in adults, “because the market for these agents in youth is small and because typically the compounds are tested in youth late (so the compounds have little patent life remaining), there is little incentive to keep trying if early studies are either negative or borderline,” he wrote.

“Therefore, assuming a particular compound works equally well in youth as in adult Depression, the chances of obtaining an FDA indication for Depression in youth are very much less since more than half of adult (and child/adolescent) antidepressant studies done in recent years have not produced a significant effect.”

So what does seem to work in this population?

Cognitive behavioral therapy was shown in one study to be superior to family therapy and supportive psychotherapy at alleviating Depression. But a second study, the Treatment for Adolescents with Depression Study (TADS), found that a combination of Prozac (fluoxetine) and cognitive behavioral therapy was the most effective means of treating teens with depression. In this study, Prozac alone was almost as good as the combination therapy, with cognitive behavioral therapy contributing an additional 10% benefit.

Although tricyclic antidepressants such as Elavil (amitriptyline), selective serotonin reuptake inhibitors such as Prozac and Zoloft (sertraline) and specific norepinephrine reuptake inhibitor (SNRI) such as Strattera (atomoxetine) all appear to work equally well in adults, there is little evidence to support the use of any but the selective serotinin reuptake inhibitors (SSRIs) in kids, Dr. Ryan asserted.

“Although the separate studies are almost all quite small, considered separately or in aggregate there is simply no evidence of efficacy of tricyclic antidepressants for children and very little evidence of efficacy when considered overall in adolescents,” he wrote. “The available aggregate sample size is insufficient to completely rule out meaningful antidepressant effects for tricyclic antidepressants, but is sufficient to suggest less efficacy than is seen in adults and possibly almost no efficacy at all in youth.”

There is also some evidence to support the use of Celexa (citalopram) and Paxil (paroxetine) in this population, although this evidence is weaker than that for Prozac. Serzone (nefazodone), which also appeared to be effective, has been withdrawn from the market.

SSRIs may be helpful for treating anxiety disorders that could lead to co-existing depression or exacerbate it. So it is a treatment strategy that deserves to be explored in controlled studies, Dr. Ryan commented.

The flip side of pharmacotherapy for childhood Depression, however, is the potential for increased suicide risk. In 2004, the FDA and its European counterpart issued warnings that SSRI and SNRI antidepressants increase the risk of suicidal thoughts and behavior in children and adolescents.

Whether there is a net gain from SSRI use in children or an unacceptably high risk is difficult to determine from the data at hand.

“The important clinical question is how to maximize the putative net protective effect by keeping to a minimum any potential component of increased risk,” Dr. Ryan wrote. “Such a model and approach is compatible with suggestions to increase monitoring of suicide-related ideation and behavior in adolescents treated with antidepressants.”

He advocates a strategy focusing on aggressive treatment of anxiety disorders in children and teens to prevent progression to Depression, improved screening and diagnosis, and monitoring patients to ensure treatment compliance and completion.

“Cognitive behavioral therapy and interpersonal therapy are probably effective in the treatment of Depression in youth,” he wrote. “But clinicians trained to deliver these specific treatments are scarce or simply unavailable in many communities. Therefore, psychotherapy for Depression in children and adolescents has a part to play but is not a panacea.”