SPECIAL SECTION: TREATMENT FOR ADOLESCENTS WITH DEPRESSION STUDY-TADS
Remission and Residual Symptoms After Short-Term Treatment in the Treatment of Adolescents With Depression Study (TADS)

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ABSTRACT

Objective

To ascertain remission rates in depressed youth participating in the Treatment for Adolescents With Depression Study (TADS), a multisite clinical trial that randomized 439 adolescents with major depressive disorder (MDD) to a 12-week treatment of fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or clinical management with pill placebo (PBO).

Method

Using an end-of-treatment Children's Depression Rating Scale-Revised (CDRS-R) total score of 28 or below as the criterion for remission, rates of remission were examined with logistic regression, controlling for site. Loss of MDD diagnosis and residual symptoms in responders (defined as Clinical Global Impressions-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) were also examined across treatment groups.

Results

After 12 weeks of treatment, 102 (23%) of 439 youths had reached remission. The remission rate was significantly higher in the COMB group (37%) relative to the other treatment groups (FLX, 23%; CBT, 16%; PBO, 17%), with odds ratios of 2.1 for COMB versus FLX, 3.3 for COMB versus CBT, and 3.0 for COMB versus PBO. In addition, 71% of subjects across treatment groups no longer met criteria for MDD at the end of acute treatment. Fifty percent of the youths who responded by CGI-I criteria continued to have residual symptoms, such as sleep or mood disturbances, fatigue, and poor concentration.

Conclusions

The combination of FLX and CBT was superior to both monotherapy and PBO in terms of remission rates, but overall rates of remission remain low and residual symptoms are common at the end of 12 weeks of treatment.

Section snippets

Study Participants

The study sample was composed of 439 adolescents who met DSM-IV criteria for MDD and had a CDRS-R score of ≥45 at study entry. The demographic and clinical characteristics of the TADS sample are described in a prior report (TADS, 2005). Study participants were randomized to one of the four treatment conditions: COMB (n = 107), FLX (n = 109), CBT (n = 111), and PBO (n =112).

Measures

During the acute phase of treatment, participants were assessed by a blinded independent evaluator (IE) at baseline, week

Remission Rates

The rate of remitted subjects at the end of treatment, based on the dichotomized CDRS-R, was 102 of 439, or 23%. There was a significant overall treatment (Wald X2 = 17.08, df = 3, p = .0007) and site (Wald X2 = 21.5, df = 12, p = .04) effect. More specifically, the COMB group with a 37% remission rate was superior to all of the other treatment conditions (FLX: 23%, p = .02; CBT: 16%, p = .0004; PBO: 17%, p = .0009). However, the FLX, CBT, and PBO rates were not statistically different from one

DISCUSSION

In this study of adolescents suffering from moderate to severe MDD, the combination of the antidepressant FLX and CBT was statistically and clinically superior to monotherapy with FLX, CBT, or PBO using a criterion measure of remission. Thirty-seven percent of those treated with COMB achieved remission. Treatment with either monotherapy, although effective in decreasing symptoms, was associated with low remission rates (23% for FLX and 16% for CBT) and neither was statistically different from

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    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).

    Disclosure: Dr. Silva is a consultant to Pfizer. Dr. Kratochvil is a consultant or scientific advisor to Eli Lilly, Shire, Cephalon, Organon, AstraZeneca, Boehringer-Ingelheim, Abbott, and Pfizer; he receives research support from Eli Lilly, McNeil, Cephalon, and Abbott; receives study drug for an NIMH-funded study from Lilly; and is on the Eli Lilly speakers' bureau. Dr. Weller is a consultant to and receives grants from Otsuka, Johnson & Johnson, AstraZeneca, Organon, Pharma, Shire, and GlaxoSmithKline. Dr. Ginsburg has received research support from Pfizer. Dr. Pathak receives research support from Forest Laboratories. Dr. Emslie receives research support from Eli Lilly, Organon, and Forest Laboratories; is a consultant to Eli Lilly, GlaxoSmithKline, Forest Laboratories, Wyeth-Ayerst, and Pfizer; and is on the speakers' bureau for McNeil. Dr. March is a speaker for Pfizer and Eli Lilly and has received researched support from Eli Lilly, Pfizer, and Wyeth. The other authors have no financial relationships to disclose.

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