In order to compare efficacy of antidepressant monotherapies and combinations of antidepressants, we reviewed retrospectively chart documents of treatment resistant depressive inpatients treated at least 4 weeks with a new antidepressant. Depressive symptoms were assessed using Montgomery and Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory-Short Form and Clinical Global Impression at the baseline, week 2, and at the end of treatment. We identified 78 patients (27 treated with combinations and 51 with monotherapies) that fulfilled the criteria for analyses. In comparison with patients on monotherapy, the combination group achieved higher reduction of MADRS score (14.6 vs 10.2 pts., p = 0.02) and response rate (≥ 50% reduction of MADRS, 67% vs 39%, p=0.03). Number needed to treat for response was 4. Based on these results, we suggest that combination of antidepressants might be more effective than monotherapy in clinical practice.