COMB was effective in improving functioning, global health, and quality of life in adolescents with MDD. FLX alone improved functioning. CBT alone was not statistically different in effect from the placebo on any of the measures. Most patients, however, regardless of treatment condition, continued to show signs of significant functional impairment after 12 weeks of treatment. This indicates the need for either longer or more intensive treatment that targets the various impairments associated with major depression in adolescence. Treatment effects were mediated by improvement in depressive symptoms measured on the Child Depression Rating Scale-Revised. Functioning was measured with the Children's Global Assessment Scale, and global health was measured with the Health of the Nation Outcome Scales for Children and Adolescents. Quality of life was assessed with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire. Random-effects regression models were applied to the data. 2 tables, 1 figure, and 27 references