Aug. 17, 2004 — Treating depressed teenagers with a combination of antidepressants and psychotherapy is better than either treatment approach alone, according to a major new study.

The results also suggest that combining antidepressant treatment with talk therapy may help alleviate some of the potentially harmful or suicidal behaviors that may be associated with antidepressant use.

Researchers found more teenagers with major depression got relief and were effectively treated for their condition with a combination of Prozac, one of a class of commonly used antidepressants known as SSRIs, and cognitive behavioral therapy than with antidepressants, psychotherapy, or placebo alone.

The study also showed that the combination of Prozac and cognitive behavioral therapy produced the greatest reduction in suicidal thinking among the different treatment approaches. However, researchers found an increase in harm-related adverse events associated with antidepressant use that may be tempered by behavioral therapy.

“The greatest benefit at the lowest risk is not to use medication alone but to use it in combination with cognitive behavioral therapy,” says researcher John March, MD, MPH, of Duke University Medical Center.

Earlier this year, the FDA warned parents and health care providers that children and adolescents taking antidepressants should be closely monitored for worsening depression and suicidal thinking, especially at the start of treatment. FDA officials are currently reviewing data on a possible link between antidepressant use and suicide risk in children and is expected to discuss their findings at a meeting next month.

Comparing Teen Depression Treatments

Researchers say antidepressants are widely used in treating children and adolescents with depression, but previous studies have produced mixed results on the benefits vs. risks associated with these medications.

In this study, published in the Aug. 18 issue of The Journal of the American Medical Association, researchers compared the effectiveness of four different treatment approaches in 439 children and teens aged 12-17 with major depression. The children were randomly assigned to receive a combination of Prozac and behavioral therapy, behavioral therapy alone, Prozac alone, or a placebo (sugar pill) for 12 weeks.

The cognitive behavioral therapy (CBT) used in the study was a skills-oriented treatment that is based on changing negative thought patterns and increasing active, positive behaviors. The treatment consisted of 15, 50-60 minute sessions.

At the end of the treatment period, researchers found 71% of the patients responded to the combination depression treatment compared with 61% of those on Prozac alone, 43% of those who received behavioral therapy, and 35% of those on placebo.

“The take-home message is that the initial treatment of choice for kids with major depression should be the combination of [Prozac] and cognitive behavioral therapy,” March tells WebMD.

Antidepressants and Suicide Risk

Last year, the FDA and health officials in the U.K. issued safety warnings regarding another SSRI, Paxil, after a study showed an increased risk of suicidal thinking and attempts among children taking the drug. But officials say it is not yet clear whether antidepressants increase the risk of suicidal thinking and behavior in depressed persons who inherently face a higher risk of suicide without adequate treatment.

Researchers say it’s important to note that suicidal thinking among the adolescents studied decreased significantly among all four treatment groups from 29% overall to about 10%, and no completed suicides were reported.

However, while antidepressants did not appear to have an effect on suicidal thinking, researchers did find a slightly increased risk of harmful behavior or actions among those taking Prozac.

“Although the rates were low, kids who got [Prozac] either alone or in combination with CBT had a slightly increased rate of engaging in a harm-related adverse event,” says March. “But adding CBT to the mix seems to buffer whatever that effect of [Prozac] has on proclivity to do something dumb, to engage in a harm-related impulsive behavior.”

Study Provides Some Answers

Experts say the results of this study should provide some reassuring answers to parents and health-care providers about the relationship between antidepressants and suicide risk among adolescents, but several questions still remain.

In an editorial that accompanies the study, Richard M. Glass, MD, professor of psychiatry at the University of Chicago, says the biggest answer the study provides is that a combination of antidepressant and behavioral therapy is best for treating adolescents with major depression.

“In treating depression in general and in particular for adolescents, physicians can’t just prescribe medication and then not see the patient for a long period of time; they really need to be carefully monitored,” Glass tells WebMD.

Glass says the study also shows that it’s important for both parents and health-care providers to be on the lookout for potentially dangerous side effects of antidepressant treatment, such as increases in irritability or suicidal thinking, which may emerge after treatment begins. He says more studies are needed to determine whether this is a temporary or lasting side effect of antidepressant use.

It’s also unclear whether the results of this study apply to other SSRI antidepressants. Prozac is the only antidepressant approved to treat adolescents.

Glass says Prozac is unique in that it is long lasting, but its other effects on depression are similar to that found with other SSRIs.

“The weight of evidence right now would be that it is probably the right SSRI antidepressant to use for an adolescent who has a major depression because it had the approval and it has the studies that back up effectiveness,” says Glass. “But whether that’s going to hold up over time, I think that remains to be seen.”

The study was supported by a grant from the National Institute of Mental Health and Eli Lilly and Co., which provided Prozac and a placebo under an educational grant to Duke University. Lilly is a WebMD sponsor.