No network meta-analysis has examined the relative effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression, while this is a very important clinical issue. We conducted systematic searches in bibliographical databases to identify randomized trials in which a psychotherapy and a pharmacotherapy for the acute or long-term treatment of depression were compared with each other, or in which the combination of a psychotherapy and a pharmacotherapy was compared with either one alone. The main outcome was treatment response (50% improvement between baseline and endpoint). Remission and acceptability (defined as study drop-out for any reason) were also examined. Possible moderators that were assessed included chronic and treatment-resistant depression and baseline severity of depression. Data were pooled as relative risk (RR) using a random-effects model. A total of 101 studies with 11,910 patients were included. Depression in most studies was moderate to severe. In the network meta-analysis, combined treatment was more effective than psychotherapy alone (RR=1.27; 95% CI: 1.14-1.39) and pharmacotherapy alone (RR=1.25; 95% CI: 1.14-1.37) in achieving response at the end of treatment. No significant difference was found between psychotherapy alone and pharmacotherapy alone (RR=0.99; 95% CI: 0.92-1.08). Similar results were found for remission. Combined treatment (RR=1.23; 95% CI: 1.05-1.45) and psychotherapy alone (RR=1.17; 95% CI: 1.02-1.32) were more acceptable than pharmacotherapy. Results were similar for chronic and treatment-resistant depression. The combination of psychotherapy and pharmacotherapy seems to be the best choice for patients with moderate depression. More research is needed on long-term effects of treatments (including cost-effectiveness), on the impact of specific pharmacological and non-pharmacological approaches, and on the effects in specific populations of patients.