Fluoxetine, cognitive-behavioral therapy, and their combination for adolescences with depression: Treatment for Adolescents with Depression Study (TADS) randomized controlled trial.
Treatment for Adolescents With Depression Study (TADS) Stage 1 was a randomized clinical trial comparing fluoxetine, cognitive behavioral therapy (CBT), their combination, and placebo. Fluoxetine plus CBT showed the greatest improvement in symptoms. All four treatment groups (including placebo) showed significant improvement in suicidal thinking.
- N=439 adolescents, ages 12-17, with DSM-IV major depressive disorder, randomized to 12 weeks of:
- Fluoxetine alone
- CBT alone
- Fluoxetine + CBT
- Setting: 13 US academic and community clinics, 2000-2003.
- Placebo and fluoxetine were double-blinded, while CBT and CBT + fluoxetine were unblinded.
- Fluoxetine dose ranged from 10-40 mg/day.
- CBT was administered in 15 sessions lasting 50-60 minutes, over 12 weeks.
- Primary outcomes: Children’s Depression Rating Scale-Revised (CDRS-R) total score. For responder analysis: Clinical Global Impressions (CGI) improvement score.
- Additional outcomes: The Suicidal Ideation Questionnaire-Junior High School Version (SIQ-Jr) was used to measure suicidal ideations.
- Based on CDRS-R scores at 12 weeks, combination fluoxetine with CBT was superior to:
- Placebo (P=0.001)
- Fluoxetine alone (P=0.02)
- CBT alone (P=0.01)
- Fluoxetine alone was superior to CBT alone (P=0.01), but not to placebo (based on CDRS-R).
- Response rates (CGI based):
- 71.0% for fluoxetine plus CBT
- 60.6% for fluoxetine alone
- 43.2% for CBT alone
- 34.8% for placebo
- Suicidal thinking improved significantly in all 4 groups, with fluoxetine plus CBT showing the greatest reduction. At baseline, 29% of subjects showed a level of suicidality requiring prompt clinical attention, based on SIQ-Jr. This had decreased to 10.3% after 12 weeks of treatment.
- Harm-related adverse events were statistically significantly greater in subjects receiving fluoxetine compared to those not (odds ratio: 2.19; 95% CI: 1.03-4.62). The same trend was observed for suicide-related events, but did not achieve statistical significance.
- Suicide was attempted by 7 participants (6 of whom were taking fluoxetine), with no completed suicides. This number was too small for statistical comparison, and their lethality was characterized as low to moderate. The authors note that 6 of these 7 participants met SIQ-Jr criteria for clinically significant suicidal ideation at baseline (86%; compared to 29% of all subjects who met those criteria), suggesting the risk for suicide at baseline may not have been evenly balanced across treatment groups.
March J, Silva S, Petrycki S, et al. 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):807–820. doi:10.1001/jama.292.7.807.