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TADS. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA 292, 807–820 (2004)

Duke Clinical Research Institute, Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 09/2004; 292(7):807-20. DOI: 10.1001/jama.292.7.807
Source: PubMed

ABSTRACT 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.
To evaluate the effectiveness of 4 treatments among adolescents with major depressive disorder.
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.
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.
Children's Depression Rating Scale-Revised total score and, for responder analysis, a (dichotomized) Clinical Global Impressions improvement score.
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.
The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder.

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    • "A major obstacle to the treatment of adolescent depression is the lack of response to most pharmacotherapies. Selective-serotonin reuptake inhibitor (SSRI) compounds are effective in treating some subjects with adolescent depression [4] [5] but can have deleterious side effects particularly for growth and development [6] [7]. In addition, the treatment of adolescents with SSRI compounds has been severely limited with the introduction of the FDA Black Box warning in regard to suicidality in adolescents. "
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    • "The same therapists treated adolescents in both conditions, which helps control for therapist effects but creates a higher standard than is seen in most treatment studies. Patients stayed in treatment for more sessions than typically found in other CBT trials for adolescent depression (March et al. 2004; Vitiello et al. 2006; Brent et al. 2008; Kennard et al. 2009; Lewis et al. 2010), and both conditions responded very well to the treatments overall. Also, many AO-CBT parents were receiving therapy, and seven out of eight parents were taking medication for their mood. "
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    • "Similar relationships have been observed in youth where child maltreatment may be associated with poorer treatment response to psychiatric intervention and may predict greater morbidity. For example, in the Treatment for Adolescents with Depression Study (March et al., 2004), adolescents with a history of abuse reported higher baseline suicidality than nontraumatized, depressed adolescents (Lewis et al., 2010). Additionally, in the Treatment of Resistant Depression in Adolescent Study (Brent et al., 2008), youth with histories of physical abuse experienced poorer responses to treatment compared to nonabused adolescents (Shamseddeen et al., 2011). "
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