Depressed adolescents respond best to combination treatment

October 01, 2007

A combination of psychotherapy and antidepressant medication appears to be the most effective treatment for adolescents with major depressive disorder--more than medication alone or psychotherapy alone, according to results from a major clinical trial funded by the National Institutes of Health's National Institute of Mental Health (NIMH). The study was published in the October 2007 issue of the Archives of General Psychiatry.

The long-term results of the Treatment for Adolescents with Depression Study (TADS) found that when adolescents received fluoxetine (Prozac) alone or in combination with cognitive behavioral therapy (CBT) over the course of 36 weeks, they recovered faster than those who were receiving CBT alone.

However, taking fluoxetine alone appeared to pose some safety concerns for the teens. During treatment, those taking fluoxetine alone had higher rates of suicidal thinking (15 percent) than those in combination treatment (8 percent) and those in CBT alone (6 percent), particularly in the early stages of treatment. This suggests that while treatment with fluoxetine may speed recovery, adding CBT provides additional safeguards for those vulnerable to suicide, according to the researchers.

"Depression in teens is a serious illness that can and should be treated aggressively," said NIMH Director Thomas R. Insel, M.D. "TADS provides compelling evidence for families and clinicians that the most effective way to treat depression in teens is with a two-pronged approach. It reassures us that antidepressant medication combined with psychotherapy is an effective and safe way to help teens recover from this disabling illness."

Results at 36 weeks of treatment were consistent with those found at 12 weeks in the 439-person study, when NIMH reported that combination treatment produced the greatest improvement in teenagers with major depression. At 18 weeks (results not previously reported), combination treatment still outpaced the other treatments with an 85 percent response rate, compared to 69 percent for fluoxetine alone and 65 percent for CBT alone. By 36 weeks, the response rate to combination treatment still remained the highest (86 percent), while response rates to fluoxetine and CBT essentially caught up, at 81 percent each.

"In the combination approach, the two treatments complemented each other," said John March, M.D, MPH, of Duke University and lead author of the study. "The fluoxetine can help dissipate the physical symptoms of major depression relatively quickly, and CBT can help patients develop new skills to contend with difficult, negative emotions."

Because the trial sample included a mix of younger and older teens, both genders, substantial minority representation and variable socioeconomic status, the TADS results can be applied broadly to the adolescent population.
The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website,

The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

Reference: The TADS Team. The Treatment for Adolescents with Depression Study (TADS): Long-term Effectiveness and Safety Outcomes. Archives of General Psychiatry. Oct 2007; VOL 64(10).

NIH/National Institute of Mental Health

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