Teens with depression often respond to combination of antidepressant and behavioral therapy


Adolescents with major depressive disorder showed improvement after treatment that combined fluoxetine (an antidepressant medication) and cognitive behavioral therapy (CBT), according to the results of the Treatment for Adolescents with Depression Study (TADS) published in the August 18 issue of JAMA, the Journal of the American Medical Association.

According to background information in the article, major depressive disorder (MDD) is common in adolescence. "…depression in adolescence is a major risk factor for MDD, suicide, and long-term psycho-social impairment in adulthood. Thus, improvements in the treatment of MDD among adolescents should positively affect public health."

John S. March, M.D., M.P.H., from Duke University Medical Center, Durham, N.C., and colleagues from the TADS team, evaluated the effectiveness of four treatments among adolescents with MDD. This study included 439 patients with a primary diagnosis of MDD who ranged in age from 12 to 17 years. They enrolled in the study between spring 2000 and summer 2003 at 13 academic and community clinics across the United States. The participants were randomly assigned to twelve weeks of fluoxetine alone, CBT alone, CBT with fluoxetine, or placebo (sugar pill). "In TADS, CBT is a skills-oriented treatment based on the assumption that depression is caused by or maintained by depressive thought patterns and a lack of active, positively reinforcing behavioral patterns; treatment included 15 sessions, which lasted between 50 and 60 minutes, over the first 12 weeks," the authors describe.

"Compared with fluoxetine alone and CBT alone, treatment [combining] fluoxetine with CBT was superior," the authors report. "Fluoxetine alone is a superior treatment to CBT alone. Rates of response for fluoxetine with CBT were 71 percent; fluoxetine alone, 60.6 percent; CBT alone, 43.2 percent; and placebo, 34.8 percent. … Clinically significant suicidal thinking, which was present in 29 percent of the sample at baseline, improved significantly in all 4 treatment groups. Fluoxetine with CBT showed the greatest reduction. Seven (1.6 percent) of 439 patients attempted suicide; there were no completed suicides." The researchers also found treatment with fluoxetine alone elevated the risk for psychiatric adverse events. "While fluoxetine did not appear to increase suicidal ideation [thoughts], harm-related adverse events may occur more frequently in fluoxetine-treated patients and CBT may protect against these events," the researchers add.

In conclusion the authors write: "First, given the high prevalence, morbidity, and significant mortality associated with MDD, the identification of depressed adolescents and provision of evidence-based treatment should be mandatory in health care systems. Second, despite calls to restrict access to medications, medical management of MDD with fluoxetine, including careful monitoring for adverse events, should be made widely available, not discouraged. Third, given incremental improvement in outcome when CBT is combined with medication and, as importantly, increased protection from suicidality, CBT also should be readily available as part of comprehensive treatment for depressed adolescents."

(JAMA. 2004;292:807-820. Available post-embargo at JAMA.com)

Editor's Note: The research for this article was supported by a contract from the National Institute of Mental Health. Lilly Inc. provided fluoxetine and matching placebo under an independent educational grant to Duke University. Please see JAMA study for authors' financial disclosures.

Editorial: Treatment of Adolescents with Major Depression
In an accompanying editorial, Richard M. Glass, M.D., Deputy Editor, JAMA, and the Department of Psychiatry, University of Chicago, writes, "the publication of the results of the Treatment for Adolescents With Depression Study (TADS) in this issue of JAMA is certainly timely in view of recent and widely publicized controversies regarding treating adolescents with depression.

"…the TADS results raise a mixture of questions and answers regarding the complicated issue of whether antidepressant drug treatment prescribed to treat depression might increase the risk for depression's most dangerous outcome, suicidal behavior. The reduction of suicidal ideation over time is reassuring, but the increased risk for harm-related adverse events observed in the patients receiving fluoxetine suggests that the increase in activation, irritability, or disinhibition sometimes associated with SSRI [selective serotonin reuptake inhibitor] treatment warrants careful monitoring in clinical practice. However, the TADS results leave this as a question rather than a firm answer because those specific symptoms were rare among the patients receiving fluoxetine."

"Probably the most important message from TADS is that carefully assessed, empirically validated treatments are available for adolescents with major depression. A corollary of that message is that depressive illness is a major public health problem with substantial morbidity and mortality for adolescents as well as for adults. The results from this major new trial demonstrate that although treatment of a depressive illness is often successful and gratifying for patients and clinicians, such success typically requires more than a brief visit for prescription of medication. Rather, it requires careful assessment and monitoring in the context of an ongoing patient-physician relationship. Furthermore, the current evidence suggests that the likelihood of a good outcome is enhanced by the combination of appropriate and carefully monitored drug treatment with an empirically validated psychotherapy."

(JAMA. 2004;292:861-863. Available post-embargo at JAMA.com.)

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