The combination of the antidepressant medication fluoxetine and cognitive behavior therapy appears more effective than either strategy alone for the long-term treatment of adolescents with depression, according to a report in the October issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Major depressive disorder affects approximately 5 percent of adolescents, causing difficulties for patients and their families and increasing the risk for suicide, according to background information in the article. To improve the treatment of depression in teens, the National Institute of Mental Health (NIMH) in 1999 funded the Treatment for Adolescents with Depression Study (TADS). TADS is a randomized controlled trial evaluating short- and long-term effectiveness of three treatments: fluoxetine alone; cognitive behavior therapy, a type of psychotherapy addressing the way individuals currently think and act rather than past events; and a combination of the two.
The TADS team randomly assigned 439 adolescents with depression to one of the three treatments or to placebo pills for 12 weeks. At that point, patients receiving placebo were offered active treatment and the remaining 327 patients (average age 14.6) were asked to continue their assigned therapy through 36 weeks. Fluoxetine was initially prescribed at a dose of 10 milligrams per day; the dosage was increased or decreased at various points during the study based on whether patients responded to treatment or experienced adverse effects. Patients receiving cognitive behavioral therapy had fifteen one-hour sessions during the first 12 weeks, then less frequently, with exact timing dependent on how they responded to treatment.
After 12 weeks, 73 percent of patients receiving combination therapy, 62 percent of those receiving fluoxetine only and 48 percent of those undergoing cognitive behavior therapy only responded to treatment, as measured by two clinical scales. At the end of 36 weeks, 243 (74.3 percent) of the 327 patients remained in the study. Response rates were 86 percent for combination therapy, 81 percent for fluoxetine and 81 percent for cognitive behavioral therapy.
Throughout treatment, researchers monitored patients for suicidal thoughts and behaviors. At the beginning of the study, 42 of 106 (39.6 percent) of those in the combination therapy group, 28 of 107 (26.2 percent) of those in the fluoxetine group and 27 of 107 (25.2 percent) of those in the cognitive behavior therapy group warranted prompt evaluation for suicidal tendencies. By week 12, patients treated with fluoxetine alone reported more clinically significant suicidal thoughts and behaviors than those in either of the groups receiving cognitive behavior therapy. After 36 weeks, two of 79 (2.5 percent) combination therapy patients, 10 of 73 (13.7 percent) taking fluoxetine alone and three of 76 (3.9 percent) receiving cognitive behavior therapy reported experiencing significant suicidal thoughts and behaviors.
Suicidal events--defined as suicidal attempts, thoughts and behaviors or preparatory actions toward suicide--occurred in 10 percent of patients in the study, mostly early in treatment. "Patients treated with fluoxetine alone were twice as likely as patients treated with combination therapy or cognitive behavior therapy to experience a suicidal event, indicating that cognitive behavior therapy may protect against treatment-emergent suicidal events in patients taking fluoxetine," the authors write. "After taking benefit and risk into account, we conclude that the combination of fluoxetine and cognitive behavior therapy appears superior to either monotherapy [single treatment] as a long-term treatment strategy for major depressive disorder in adolescents."
(Arch Gen Psychiatry. 2007;64(10):1132-1144. Available pre-embargo to the media at www.jamamedia.org.)
Editor's Note: The TADS is supported by a contract from the NIMH to Duke University Medical Center. Eli Lilly and Company provided fluoxetine and matching placebo under an independent educational grant to Duke University. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.