The aim of the study was to compare the efficacy and tolerability of the combination of reboxetine and sertraline to venlafaxine XR (extended release) in major depressive disorder (MDD). The study consisted of 40 patients with MDD, aged 18-65 years. Patients were evaluated six times during a 10-week period. Treatment was started as venlafaxine XR 75 mg/day once a day (od) or reboxetine 4 mg/day twice a day (bid)+ sertraline 50 mg/day od. In the second week, venlafaxine XR was increased to 150 mg/day od and reboxetine 8 mg/day bid while sertraline was kept at the same dose. The Hamilton Depression Rating Scale (HDRS), Montgomery and Asberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness and Clinical Global Impression s-Global Improvement Scale were applied on each visit. Beginning from the second visit, both groups showed significant declines in each scale. There were no significant differences between treatment response rates. Remission rates defined as HDRS <= 10 were significantly higher in the venlafaxine XR group at visit 4 only. However, when remission was accepted as HDRS <= 7, no significant difference was observed. Side effect frequency was similar between the treatment groups. We may suggest that the reboxetine+ sertraline combination is not superior to venlafaxine treatment. (c) 2006 Elsevier Inc. All rights reserved.