Background: Randomized trials with antidepressants are often run under double blind placebo-controlled conditions, whereas those with psychotherapies are mostly unblinded. This can introduce bias in favor of psychotherapy when the treatments are directly compared. In this meta-analysis, we examine this potential source of bias. Methods: We searched Pubmed, PsycInfo, Embase and the Cochrane database (1966 to January 2014) by combining terms indicative of psychological treatment and depression, and limited to randomized trials. We included 35 trials (with 3721 patients) in which psychotherapy and pharmacotherapy for adult depression were directly compared with each other. We calculated effect sizes for each study indicating the difference between psychotherapy and pharmacotherapy at post-test. Then, we examined the difference between studies with a placebo condition and those without in moderator analyses. Results: We did not find a significant difference between the studies with and those without a placebo condition. The studies in which a placebo condition was included indicated no significant difference between psychotherapy and pharmacotherapy (g = -0.07; NNT = 25). Studies in which no placebo condition was included (and patients and clinicians in both conditions were not blinded), resulted in a small, but significant difference between psychotherapy and pharmacotherapy in favor of pharmacotherapy (g = -0.13; NNT = 14). Conclusions: Studies comparing psychotherapy and pharmacotherapy in which both groups of patients (and therapists) are not blinded (no placebo condition is included) result in a very small, but significantly higher effect for pharmacotherapy.