Treatment for Adolescents With Depression Study (TADS) Team: Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: treatment for adolescents with depression study (TADS) randomized controlled trial. JAMA 2004;292(7):807-21.
Glass RM: Treatment of adolescents with major depression: contributions of a major trial. JAMA 2004;292(7):861-63 (editorial).
The TADS study was conducted at 13 sites in the United States, involving 428 patients aged 12 to 17 years with a primary diagnosis of major depression. Participants were randomly assigned to one of four treatments for 12 weeks: 1) fluoxetine (starting dose 10 mg adjusted to 40 mg/day) with clinical management (six 20 to 30 minute physician visits to monitor status and medication effects); 2) pill placebo with clinical management; 3) cognitive-behavioral therapy (CBT) in 15 sessions over 12 weeks; or 4) the combination of fluoxetine with CBT. Suicidal thoughts declined in all groups. A suicide-related event occurred in 6% of the adolescents, without any significant difference among the four treatment groups. A broader measure of harm-related events (any self-harm or harm to another person or property) occurred more often (odds ratio 2.19) for patients receiving fluoxetine compared with those who were not. The combination of CBT and fluoxetine had the best outcome, with a response rate of 71% compared to 61% for fluoxetine alone, 43% for CBT alone, and 35% for placebo. The increased risk of harm-related events in patients receiving fluoxetine requires careful monitoring in clinical practice. The combination of fluoxetine with CBT provided the most favorable tradeoff between benefits and risks for these adolescents with major depressive disorder.