The "Treatment for Adolescents with Depression Study" (TADS), reported in this week's Journal of the American Medical Association, is the first multi-center, randomized clinical effectiveness trial to review a combination of treatments for the types of adolescent depression likely to be treated in routine community-based practice settings.
Previous studies typically have examined one method of therapy against a placebo and have involved only adolescents who have depression with no co-occurring disorders.
The Duke investigators examined the individual and combined effectiveness of the antidepressant fluoxetine, also known as Prozac, and cognitive- behavioral therapy (CBT) in 439 adolescents, ages 12-17, who have been diagnosed with major depressive disorder (MDD). The project was funded by the federal National Institute of Mental Health (NIMH).
Seventy-one percent of the depressed adolescent patients in the study responded positively to the combination treatment therapy-a rate double the 35 percent response rate for patients on a placebo. Among study participants who were prescribed fluoxetine alone, the response rate was 60.6 percent, and among those who received only cognitive-behavioral therapy, the response rate was 43.2 percent rate. Response to treatment was rated by independent evaluators at the beginning of the study, at the 6 week mark, and at 12 weeks, using standardized clinical rating instruments.
"This is a landmark study, comparable to the NIMH Treatment of Depression Collaborative study for adults in the mid-1980s, which set the standard for comparing medications, psychotherapy, and placebo," said Darrel A. Regier, M.D., M.P.H., Executive Director, APA's Institute for Research and Education.
"It was designed to compare response rates to different treatment modalities, both individually and in combination, to include adolescents with co-occurring disorders such as attention-deficit/hyperactivity disorder (ADHD). Unlike standard clinical treatment trials, the TADS incorporated significant flexibility based on the clinical response and the needs of the patient. These decisions make it much easier to extrapolate the findings to actual clinical practice," Dr. Regier continued.
"The TADS study has provided clear and convincing evidence that fluoxetine, especially when combined with cognitive behavioral therapy, can be an effective treatment for adolescents who suffer from moderate to severe forms of major depression," said David Fassler, M.D., a trustee of the American Psychiatric Association. "Most physicians believe that medication can be extremely helpful for adolescents who suffer from depression, but that medication is most effective when it's utilized as a component of a comprehensive treatment plan which will often include additional interventions such as psychotherapy," he added.
Regulatory agencies in the United States and the United Kingdom have raised concerns about the use of certain antidepressants when treating children and adolescents, due to reported increases in suicidal ideation with some of these medications. The U.S. Food and Drug Administration continues to study this issue and will release further findings during a hearing next month. Dr. Regier noted that suicidal ideation and attempts are an integral part of clinical depression. This study showed that 29 percent of all subjects had clinically significant suicidal thinking before treatment-a rate that declined to 10 percent after 12 weeks of treatment. Suicidal ideation declined most for those on the combined fluoxetine and CBT treatment regimen, while the decline for the fluoxetine alone and CBT alone were not significantly different from placebo. Although there were no completed suicides in this study, it will be important to examine the 5.5 percent of subjects who had suicide-related events sometime during the course of the study. Such events and their timing need to be related in future analyses to exposure to medications as well as to other medical conditions that could increase impulsivity, such as ADHD, and significant factors such as substance abuse and adverse life events.
Recent statistics indicate that an estimated 5 percent of the U.S. adolescent population is affected by clinical depression at any given time. It is important for physicians and parents to have access to as much information as possible when making decisions about adolescent treatment. The TAD study is one more credible source for such information.