Combination Cognitive Behavioral Therapy With Fluoxetine Effective for Adolescent Depression

green and white pill
green and white pill
This research suggests that combination therapy not only produces greater proportional response in depression symptoms but that it is also effective in a broader range of individuals.

Study data published in the Journal of Affective Disorders suggest that the combination of cognitive-behavioral therapy (CBT) with fluoxetine (FLX; COMB) is more effective in treating adolescent major depressive disorder than either treatment individually.

Researchers performed a secondary analysis of the Treatment for Adolescents with Depression Study, a randomized controlled trial that compared FLX, CBT, and COMB with placebo in the treatment of adolescents with major depression (n=439). The primary analysis outcome measure was proportional change from baseline to week 12 in the Children’s Depression Rating Scale-Revised. Analyses were adjusted for baseline depression scores, study site, and expectations for each patient’s treatment response.

COMB outperformed both FLX and CBT in magnitude of treatment response. Per quantile regression analyses, COMB also elicited a response across a broader range of patients than either individual therapy. Similar effects were present after adjustments for study site and patient treatment expectations. COMB outperformed both FLX (Cohen d:1.39; 95% CI, 1.33-1.45) and CBT (Cohen d: 4.03; 95% CI, 3.94-4.12) significantly. These Cohen d-values were consistent with “large effect” sizes for COMB over other treatment modes.

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These data suggest that COMB not only produces greater proportional response in depression symptoms, it is also effective in a broader range of individuals. Future research is necessary to confirm the projected efficacy of CBT with FLX in treating adolescent depression. Clinicians may still find these data useful in designing treatment courses for adolescents with a broad range of depression severity.


Foster S, Mohler-Kuo M. Treating a broader range of depressed adolescents with combined therapy. J Affect Disord. 2018;241:417-424.