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Although light therapy (LT) has been shown to be efficient in the treatment of seasonal and non-seasonal depression, it is underused in clinical settings and antidepressant drugs (AD) remain so far the usual first line treatment. The aim of this systematic review and weighted random effect meta-analysis is to examine the randomized controlled trials that compared directly light therapy and antidepressant drugs, as well as their combination (LT + AD). A total of 397 participants were included, with a moderate to severe major depressive episode, from seven independent populations. The median duration of intervention was 5 wks (range 2-8 wks). The superiority (lower depression score) of LT + Placebo compared to AD + Placebo was non-significant (SMD = 0.19 [-0.08-0.45]; p = 0.17). The combination LT + AD was superior to AD + Placebo (SMD = 0.56 [0.24-0.88]; p < 0.001). This superiority was confirmed in the subgroup of patients with non-seasonal depression (SMD = 0.55 [0.16-0.93]; p = 0.005). Meta-analyses showed no or small heterogeneity between studies (I2 = 0%, 18.41%, and 39.23% respectively). No potential publication biases were observed by statistical tests and visual inspection of the funnel plots. No differences were observed between LT and AD, with a clear superiority of the combination, thus both LT monotherapy and combination may be proposed as a first line treatment in seasonal and non-seasonal depression. [ABSTRACT FROM AUTHOR]