Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial.
BACKGROUND
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.


METHODS
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder.
March
John
J
Duke Clinical Research Institute, Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. jsmarch@acpub.duke.edu
Silva
Susan
S
Petrycki
Stephen
S
Curry
John
J
Wells
Karen
K
Fairbank
John
J
Burns
Barbara
B
Domino
Marisa
M
McNulty
Steven
S
Vitiello
Benedetto
B
Severe
Joanne
J
D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000628:therapy*; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012306:Risk; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013405:Suicide
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors