Traditional statistical analyses of clinical trials encompass the central tendency of outcomes and, hence, are restricted to a treatment's average effectiveness. Our aim was to get a more complete picture of the effectiveness of standard treatment options for adolescent depression, by analyzing treatment effects across low, middle, and high levels of response.
Secondary data analysis was performed of the Treatment for Adolescents with Depression Study (TADS, ClinicalTrials.gov, NCT00006286), a randomized controlled trial comparing fluoxetine (FLX), cognitive-behavioral therapy (CBT), and their combination (COMB) against placebo treating adolescents with major depression (n = 439). The proportional change from baseline to week 12 in the Children's Depression Rating Scale-Revised was used as an index of response. Response levels were analyzed via quantile regression models, thereby estimating treatment effects across the entire response level distribution, adjusted for baseline depression, study site, and patients' treatment expectancies.
Whereas CBT was no more effective than placebo across response levels, COMB was more effective than FLX in that its quantile treatment effects were both larger in magnitude and spread out across a broader range of response levels, including the low end of the response level distribution. Cohen's d of the difference was 1.39 (95% confidence interval 1.33-1.45).
Ad-hoc analysis using data from a trial that was not originally designed to accommodate such analysis.
The combination of cognitive-behavioral therapy and fluoxetine was more effective than either treatment used alone, not just in average effectiveness, but in the breadth of patients in whom it was effective.