OBJECTIVE: Phototherapy, ie, bright light therapy, is an effective and safe treatment of major depressive disorder (MDD). It exerts rapid mood-elevating activity, similar to antidepressant medications, most likely mediated through both monoaminergic and circadian system melatonergic mechanisms. We assessed the efficiency of bright light therapy as an adjuvant treatment to antidepressant pharmacotherapy in patients with severe MDD randomized by Hamilton Depression Rating Scale (HDRS) score to either (1) 150 mg venlafaxine hydrochloride daily at 7:00 AM or (2) 150 mg venlafaxine plus 60-minute light of 7000 lux the initial week of clinical management (venlafaxine + bright light therapy) daily at 7:00 AM. METHOD: 50 inpatients with severe MDD at the Psychiatry Clinic of Yüzüncü Yıl University Training and Education Hospital participated. The study, which was conducted from January 2013 through June 2014, entailed patients diagnosed with severe MDD based on DSM-IV-TR for the first time. Mood states were assessed by the HDRS, Profile of Mood States (POMS), and Beck Depression Inventory (BDI) before treatment and at 1, 2, 4, and 8 weeks of treatment. RESULTS: On the basis of the HDRS score as the primary outcome variable, both strategies significantly improved depression and negative mood states already at the first treatment week (P < .001). Differences in therapeutic effects by treatment strategy were remarkable at the second and fourth weeks of clinical management (P = .018 and P = .011, respectively), with beneficial effects continuing until trial conclusion. Those treated with venlafaxine + bright light therapy evidenced significantly lower HDRS depression scores (P < .05) as well as BDI scores (P < .05) and POMS negative mood states scores (depression-dejection, tension-anxiety, anger-hostility, fatigue-inertia, and confusion-bewilderment subscales; all P < .05) after the second week. At week 4 of the trial, 19 (76%) of the 25 venlafaxine + bright light therapy patients versus just 11 (44%) of the 25 venlafaxine patients (P < .05) attained the target goal of treatment, a HDRS score ≤ 13, indicative of mild depression, and, although not statistically significant in our small sample study (P = .36), at week 8, 76% of venlafaxine + bright light therapy patients (n = 19) versus just 64% of the venlafaxine patients (n = 16) experienced complete remission of depression (HDRS score ≤ 7). CONCLUSIONS: Both venlafaxine and venlafaxine + bright light therapy treatment strategies significantly reversed the depressive mood of patients with severe MDD; however, the latter induced significantly stronger and more rapid beneficial effects. Future longer-term studies with large sample sizes, nonetheless, are required to confirm and generalize these results to patients of diverse ethnicities and cultures with both severe and mild MDD. TRIAL REGISTRATION: ANZCTR.org.au registration number: ACTRN12614001061628.