Copyright @ 2006 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited. Predictors and Moderators of Acute Outcome in the Treatment for Adolescents With Depression Study (TADS) JOHN CURRY, PH.D., PAUL ROHDE, PH.D., ANNE SIMONS, PH.D., SUSAN SILVA, PH.D., BENEDETTO VITIELLO, M.D., CHRISTOPHER KRATOCHVIL, M.D., MARK REINECKE, PH.D., NORAH FEENY, PH.D., KAREN WELLS, PH.D., SANJEEV PATHAK, M.D., ELIZABETH WELLER, M.D., DAVID ROSENBERG, M.D., BETSY KENNARD, PSY.D., MICHELE ROBINS, PH.D., GOLDA GINSBURG, PH.D., JOHN MARCH, M.D., AND THE TADS TEAM ABSTRACT Objective: To identify predictors and moderators of response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive-behavioral therapy (CBT), both fluoxetine and CBT, or clinical management with pill placebo in the Treatment for Adolescents With Depression Study (TADS). Method: Potential baseline predictors and moderators were identified by a literature review. The outcome measure was a week 12 predicted score derived from the Children`s Depression Rating Scale-Revised (CDRS-R). For each candidate moderator or predictor, a general linear model was conducted to examine main and interactive effects of treatment and the candidate variable on the CDRS-R predicted scores. Results: Adolescents who were younger, less chronically depressed, higher functioning, and less hopeless with less suicidal ideation, fewer melancholic features or comorbid diagnoses, and greater expectations for improvement were more likely to benefit acutely than their counterparts. Combined treatment, under no condition less effective than monotherapy, was more effective than fluoxetine for mild to moderate depression and for depression with high levels of cognitive distortion, but not for severe depression or depression with low levels of cognitive distortion. Adolescents from high-income families were as likely to benefit from CBT alone as from combined treatment. Conclusions: Younger and less severely impaired adolescents are likely to respond better to acute treatment than older, more impaired, or multiply comorbid adolescents. Family income level, cognitive distortions, and severity of depression may help clinicians to choose among acute interventions, but combined treatment proved robust in the presence of moderators. J. Am. Acad. Child Adolesc. Psychiatry, 2006;45(12):1427Y1439. Key Words: major depression, moderators, predictors, fluoxetine, cognitive-behavioral therapy. Accepted March 21, 2006. See end of text for author affiliations. National Institute of Mental Health (NIMH) Program Staff participated in the design and implementation of the TADS, analysis of the data, and in authoring this article. Lilly, Inc. provided fluoxetine and matching placebo under an independent educational grant to Duke University but otherwise had no role in the design or implementation of the study, data analysis, or in authoring this manuscript. The authors are indebted to the TADS scientific advisors (Susan Essock, Ph.D., Mount Sinai School of Medicine; Barbara Geller, M.D., Washington University in St. Louis; Joel Greenhouse, Ph.D., Carnegie Mellon University; Robert Johnson, M.D., New Jersey Medical School; James Leckman, M.D., Yale University; Lydia Lewis, Depression and Bipolar Support Alliance; Sue Marcus, Ph.D., Mount Sinai School of Medicine; Kevin Stark, Ph.D., University of Texas at Austin) for their contributions to the design and methods of the study; to our cognitive-behavioral therapy consultants, David Brent, M.D., and Greg Clarke, Ph.D.; to the Columbia Suicidality Classification Group led by Kelly Posner, Ph.D., including Maria Oquendo, M.D., Madelyn Gould, Ph.D., M.P.H., and Barbara Stanley, Ph.D.; and to the members of the NIMH Data and Safety Monitoring Board for monitoring the progress of the study. The protocol and manuals used in this study can be found on the web at https://trialweb.dcri.duke. edu/tads/manuals.html. The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the NIMH, the National Institutes of Health, or the Department of Health and Human Services. TADS is supported by contract RFP-NIH-NIMH 98-DS-0008 from NIMH to Duke University Medical Center (John March, principal investigator). Correspondence to Dr. John Curry, Duke Child and Family Study Center, 718 Rutherford Street, Durham, NC 27705; e-mail: curry005@mc.duke.edu. 0890-8567/06/4512-1427Ó2006 by the American Academy of Child and Adolescent Psychiatry. DOI: 10.1097/01.chi.0000240838.78984.e2 SPECIAL SECTION 1427 J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 45:12, DECEMBER 2006