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.
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).
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.
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).
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.