Treatment response in depressed adolescents with and without co-morbid attention-deficit/hyperactivity disorder in the Treatment for Adolescents with Depression Study

Abstract

Objective: In the Treatment for Adolescents with Depression Study (TADS), fluoxetine (FLX) and the combination of fluoxetine with cognitive-behavioral therapy (COMB) had superior improvement trajectories compared to pill placebo (PBO), whereas cognitive-behavioral therapy (CBT) was not significantly different from PBO. Because attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) frequently co-exist, we examined whether ADHD moderated these outcomes in TADS.

Method: A total of 439 adolescents with MDD, 12-17 years old, were randomized to FLX, CBT, COMB, or PBO. Random coefficients regression models examined depression improvement in 377 depressed youths without ADHD and 62 with ADHD, including 20 who were treated with a psychostimulant.

Results: Within the ADHD group, the improvement trajectories of the three active treatments were similar, all with rates of improvement greater than PBO. For those without ADHD, only COMB had a rate of improvement that was superior to PBO.

Conclusions: Co-morbid ADHD moderated treatment of MDD. CBT alone or FLX alone may offer benefits similar to COMB in the treatment of MDD in youths with co-morbid MDD and ADHD, whereas monotherapy may not match the benefits of COMB for those without ADHD. The ADHD subgroup analysis presented in this paper is exploratory in nature because of the small number of youths with ADHD in the sample.

Clinical trial registry: www.clinicaltrials.gov Identifier: NCT00006286. The TADS protocol and all of the TADS manuals are available on the Internet at https://trialweb.dcri.duke.edu/tads/index.html .

FIG. 1.

Mean Adjusted CDRS-R Total Scores for the 12-Week Analysis (N = 439)

FIG. 2.

CDRS-R adjusted total scores for youths with and without ADHD across the 36-week analysis. Shown is the profile of treatment-group effects based on the random coefficients regression models completed to compare the outcome of three treatments across 36 weeks. CDRS-R = Children's Depression Rating Scale–Revised; ADHD = attention-deficit/hyperactivity disorder; COMB = combined treatment of cognitive–behavioral therapy and fluoxetine; FLX = fluoxetine; CBT = cognitive–behavioral therapy.