New research
Anhedonia Predicts Poorer Recovery Among Youth With Selective Serotonin Reuptake Inhibitor Treatment–Resistant Depression

https://doi.org/10.1016/j.jaac.2012.01.011Get rights and content

Objective

To identify symptom dimensions of depression that predict recovery among selective serotonin reuptake inhibitor (SSRI) treatment–resistant adolescents undergoing second-step treatment.

Method

The Treatment of Resistant Depression in Adolescents (TORDIA) trial included 334 SSRI treatment–resistant youth randomized to a medication switch, or a medication switch plus CBT. This study examined five established symptom dimensions (Child Depression Rating Scale—Revised) at baseline as they predicted recovery over 24 weeks of acute and continuation treatment. The two indices of recovery that were evaluated were time to remission and number of depression-free days.

Results

Multivariate analyses examining all five depression symptom dimensions simultaneously indicated that anhedonia was the only dimension to predict a longer time to remission, and also the only dimension to predict fewer depression-free days. In addition, when anhedonia and CDRS-total score were evaluated simultaneously, anhedonia continued to uniquely predict longer time to remission and fewer depression-free days.

Conclusions

Anhedonia may represent an important negative prognostic indicator among treatment-resistant depressed adolescents. Further research is needed to elucidate neurobehavioral underpinnings of anhedonia, and to test treatments that target anhedonia in the context of overall treatment of depression.

Clinical trial registration information—Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902

Section snippets

Study Overview

A brief description of method, study design, and sample as relevant to the current study is presented below, and further details are provided elsewhere.3 The study was approved by internal review boards local to the six research sites. All participants gave informed consent/assent (as appropriate), and parents gave informed consent.

Study Participants

Participants were 334 adolescents aged 12 through 18 years who were in active treatment with an SSRI for major depressive disorder (by DSM-IV criteria), and

Baseline Dimension Scores and Remission Through Continuation Treatment

Through 24 weeks, 130 youth (38.9%) achieved remission. For univariate models, higher levels of Reported Depressed Mood, Anhedonia, and Somatic Symptoms, but not Morbid Thoughts or Observed Depression, predicted a longer time until remission (Table 2). In the multivariate model, only higher levels of anhedonia continued to predict a longer time until remission (Table 2).

Baseline Dimension Scores and Number of Depression-Free Days Through Continuation Treatment

In the univariate models, all depression symptom dimensions were significant predictors of a fewer number of depression-free

Discussion

This study examined how symptom dimensions of depression may predict indices of recovery among SSRI-resistant adolescents enrolled in second-step treatment as part of the TORDIA trial. Anhedonia emerged as a key dimension predicting recovery. Anhedonia predicted a longer time to remission when all five symptom dimensions of depression were included simultaneously in a predictive model. Moreover, anhedonia continued to predict time to remission when examined simultaneous to total CDRS-R score.

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  • Cited by (309)

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    Funded by National Institute of Mental Health grants MH61835 (Pittsburgh); MH61856 (Galveston); MH61864 (University of California–Los Angeles); MH61869 (Portland); MH61958 (Dallas); and MH62014 (Brown), T32MH018951 (D.L.M., T.M.O., D.A.B); and the Advanced Center for Early-Onset Mood and Anxiety Disorders (MH66371, D.A.B.).

    The statistical experts for this study were Thomas M. Olino, Ph.D., and Giovanna Porta, M.S.

    The authors thank the youth, families, staff, and colleagues who made this project possible. 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 Department of Health and Human Services, the National Institutes of Health, or the National Institute of Mental Health.

    Disclosure: Dr. Asarnow has received research support from the National Institute of Mental Health (NIMH). She has received honoraria from the California Institute of Mental Health, Hathaways-Sycamores, Casa Pacifica, and the Melissa Institute. Dr. Brent has received research support from NIMH. He has received royalties from Guilford Press and has served as Editor for UpToDate Psychiatry. Dr. Emslie has received research support from Eli Lilly and Co., Forest, GlaxoSmithKline, and Somerset. He has served as a consultant for Biobehavioral Diagnostics, Eli Lilly and Co., GlaxoSmithKline, INC Research, Lundbeck, Pfizer, Seaside Therapeutics, Shire, Valeant, and Wyeth. He has served on the speakers' bureau for Forest. Dr. Keller has served as a consultant to or received honoraria from Abbott, CENEREX, Cephalon, Cypress Bioscience, Cyberonics, Forest, Janssen, JDS, Medtronic, Organon, Novartis, Pfizer, Solvay, Wyeth, and Sierra Neuropharmaceuticals. He has received research support from Pfizer. He has served on the advisory boards for Abbott, Bristol-Myers Squibb, CENEREX, Cyberonics, Cypress Bioscience, Forest, Janssen, Neuronetics, Novartis, Organon, and Pfizer. Dr. Wagner has received honoraria from the American Psychiatric Association, Physicians Postgraduate Press, CMP Medica, the American Academy of Child and Adolescent Psychiatry, the National Institutes of Health, the Mexican Psychiatric Association, Contemporary Forums, Doctors Hospital in Renaissance, UBM Medica, Quantia Communications, CME LLC, Nevada Psychiatric Association, Slack Inc, Mercy, and Hospital Universitario Ramón y Cajal. Dr. Birmaher has received research support from NIMH. He has served as a consultant for Schering Plough. He has received or will receive royalties from Random House and Lippincott Williams and Wilkins. Dr. Lynch has received research support from NIMH. Drs. McMakin, Olino, Dietz, Ryan, Spirito, Shamseddeen, Clarke, and Kennard, and Ms. Porta, Ms. Mayes, and Mr. Dickerson report no biomedical financial interests or potential conflicts of interest.

    This article is discussed in an editorial by Dr. David H. Rubin on page 353.

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