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Original Investigation | Meta-analysis

Baseline Depression Severity as Moderator of Depression Outcomes Between Cognitive Behavioral Therapy vs Pharmacotherapy An Individual Patient Data Meta-analysis

Erica S. Weitz, MA1; Steven D. Hollon, PhD2; Jos Twisk, PhD3; Annemieke van Straten, PhD1; Marcus J. H. Huibers, PhD1; Daniel David, PhD4; Robert J. DeRubeis, PhD5; Sona Dimidjian, PhD6; Boadie W. Dunlop, MD, MS7; Ioana A. Cristea, PhD4; Mahbobeh Faramarzi, PhD8; Ulrich Hegerl, MD, PhD9; Robin B. Jarrett, PhD10; Farzan Kheirkhah, MD11; Sidney H. Kennedy, MD12; Roland Mergl, PhD9; Jeanne Miranda, PhD13; David C. Mohr, PhD14; A. John Rush, MD15; Zindel V. Segal, PhD16; Juned Siddique, DrPH17; Anne D. Simons, PhD18; Jeffrey R. Vittengl, PhD19; Pim Cuijpers, PhD1
[+] Author Affiliations
1Department of Clinical Psychology and EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands
2Department of Psychology, Vanderbilt University, Nashville, Tennessee
3Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands
4Department of Clinical Psychology and Psychotherapy, Babes-Bolyai University, Cluj, Romania
5Department of Psychology, University of Pennsylvania, Philadelphia
6Department of Psychology and Neuroscience, University of Colorado, Boulder
7Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
8Fatemeh Zahra Infertility and Reproductive Health Research Center, Babol University of Medical Sciences, Babol, Iran
9Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany
10Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas
11Department of Psychiatry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
12Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
13Health Services Research Center, Neuropsychiatric Institute, University of California, Los Angeles
14Center for Behavioral Intervention Technologies, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
15Duke–National University of Singapore Graduate Medical School, Singapore
16Department of Psychology, University of Toronto Scarborough, Toronto, Ontario, Canada
17Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
18Department of Psychology, University of Notre Dame, Notre Dame, Indiana
19Department of Psychology, Truman State University, Kirksville, Missouri
JAMA Psychiatry. 2015;72(11):1102-1109. doi:10.1001/jamapsychiatry.2015.1516.
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Importance  Current guidelines recommend treating severe depression with pharmacotherapy. Randomized clinical trials as well as traditional meta-analyses have considerable limitations in testing for moderators of treatment outcomes.

Objectives  To conduct a systematic literature search, collect primary data from trials, and analyze baseline depression severity as a moderator of treatment outcomes between cognitive behavioral therapy (CBT) and antidepressant medication (ADM).

Data Sources  A total of 14 902 abstracts were examined from a comprehensive literature search in PubMed, PsycINFO, EMBASE, and Cochrane Registry of Controlled Trials from 1966 to January 1, 2014.

Study Selection  Randomized clinical trials in which CBT and ADM were compared in patients with a DSM-defined depressive disorder were included.

Data Extraction and Synthesis  Study authors were asked to provide primary data from their trial. Primary data from 16 of 24 identified trials (67%), with 1700 outpatients (794 from the CBT condition and 906 from the ADM condition), were included. Missing data were imputed with multiple imputation methods. Mixed-effects models adjusting for study-level differences were used to examine baseline depression severity as a moderator of treatment outcomes.

Main Outcomes and Measures  Seventeen-item Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI).

Results  There was a main effect of ADM over CBT on the HAM-D (β = −0.88; P = .03) and a nonsignificant trend on the BDI (β = −1.14; P = .08, statistical test for trend), but no significant differences in response (odds ratio [OR], 1.24; P = .12) or remission (OR, 1.18; P = .22). Mixed-effects models using the HAM-D indicated that baseline depression severity does not moderate reductions in depressive symptoms between CBT and ADM at outcome (β = 0.00; P = .96). Similar results were seen using the BDI. Baseline depression severity also did not moderate the likelihood of response (OR, 0.99; P = .77) or remission (OR, 1.00; P = .93) between CBT and ADM.

Conclusions and Relevance  Baseline depression severity did not moderate differences between CBT and ADM on the HAM-D or BDI or in response or remission. This finding cannot be extrapolated to other psychotherapies, to individual ADMs, or to inpatients. However, it offers new and substantial evidence that is of relevance to researchers, physicians and therapists, and patients.

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Figure 1.
Flowchart of Included Trials

ADM indicates antidepressant medication; BDI, Beck Depression Inventory; CBT, cognitive behavioral therapy; and HAM-D, Hamilton Rating Scale for Depression.

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Figure 2.
Direct Comparisons of Cognitive Behavioral Therapy (CBT) and Antidepressant Medication (ADM)

Shown are Hedges g of studies included and not included in the individual patient data meta-analysis.

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Submit a Comment
Psychiatry is more than an antidepressant.
Posted on September 23, 2015
Scott Mendelson, M.D., Ph.D.
URMC Roseburg, Oregon
Conflict of Interest: None Declared
I identify myself as a very biological psychiatrist. Thus, it riles me to read a study that suggests that an antidepressant is the only biological treatment that a psychiatrist can offer to treat severe depression. There are also evaluations of nutritional status; hormonal status, particularly thyroid; sleep; exercise; review of other medications; family patterns of illness; considerations of substance abuse and medical co-morbidities; identification of alternate diagnoses such as BPAD II; and consideration of augmentation strategies too wide ranging to describe in this context. How in God's name did psychiatry become reduced to giving an antidepressant?
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