Context Initial treatment of major depressive disorder in adolescents may include
cognitive-behavioral therapy (CBT) or a selective serotonin reuptake inhibitor
(SSRI). However, little is known about their relative or combined effectiveness.
Objective To evaluate the effectiveness of 4 treatments among adolescents with
major depressive disorder.
Design, Setting, and Participants Randomized controlled trial of a volunteer sample of 439 patients between
the ages of 12 to 17 years with a primary Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of
major depressive disorder. The trial was conducted at 13 US academic and community
clinics between spring 2000 and summer 2003.
Interventions Twelve weeks of (1) fluoxetine alone (10 to 40 mg/d), (2) CBT alone,
(3) CBT with fluoxetine (10 to 40 mg/d), or (4) placebo (equivalent to 10
to 40 mg/d). Placebo and fluoxetine alone were administered double-blind;
CBT alone and CBT with fluoxetine were administered unblinded.
Main Outcome Measures Children's Depression Rating Scale-Revised total score and, for responder
analysis, a (dichotomized) Clinical Global Impressions improvement score.
Results Compared with placebo, the combination of fluoxetine with CBT was statistically
significant (P = .001) on the Children's Depression
Rating Scale-Revised. Compared with fluoxetine alone (P = .02) and CBT alone (P = .01), treatment
of fluoxetine with CBT was superior. Fluoxetine alone is a superior treatment
to CBT alone (P = .01). Rates of response for fluoxetine
with CBT were 71.0% (95% confidence interval [CI], 62%-80%); fluoxetine alone,
60.6% (95% CI, 51%-70%); CBT alone, 43.2% (95% CI, 34%-52%); and placebo,
34.8% (95% CI, 26%-44%). On the Clinical Global Impressions improvement responder
analysis, the 2 fluoxetine-containing conditions were statistically superior
to CBT and to placebo. Clinically significant suicidal thinking, which was
present in 29% of the sample at baseline, improved significantly in all 4
treatment groups. Fluoxetine with CBT showed the greatest reduction (P = .02). Seven (1.6%) of 439 patients attempted suicide;
there were no completed suicides.
Conclusion The combination of fluoxetine with CBT offered the most favorable tradeoff
between benefit and risk for adolescents with major depressive disorder.