RESEARCH – February 2009

Effect of bupropion augmentation on escitalopram treatment in patients with resistant depression


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Background. Increasing evidence shows that bupropion, a norepinephrine and dopamine reuptake inhibitor, is one of the most widely chosen and effective augmenting agent for depressive patients with insufficient or partial response toserotonin re-uptake inhibitors. In this study we evaluated the efficacy and tolerability of bupropion augmentation in non-responders to escitalopram monotherapy in order to better understand practical steps to improve treatment resistant depression.

Methods. The study sample consisted of 135 outpatients with Major Depressive Disorder (mean age 31.1 ± 11.6 years, 66.1% female) treated with escitalopram 10–20 mg/day for 12 weeks using an open label naturalistic design. After 12 weeks  non-responders to escitalopram monotherapy were taking a combination of 20 mg of escitalopram and 150–300 mg of bupropion (Wellbutrin SR) for additional 6 weeks. Clinical severity and treatment response were assessed bi-weekly using the Montgomery-Asberg’s Depression Rating Scale, the Hamilton Depression Scale and the Clinical Global Impression Scale. The patients were also asked to evaluate  depressive symptoms and possible side effects using self-rating scales.

Results. At the end of week 12 of treatment with escitalopram, 82 patients (60.7%) were defined as responders and 79 of them (58.5%) achieved remission. Forty-four patients (32.6%) showed insufficient or partial response to treatment and 9 patients (6.7%) discontinued escitalopram treatment due to lack of efficacy or adverse effects. Non-responders to escitalopram monotherapy had significantly higher prevalence of melancholic type of depression than responders (86.4% vs 63.4%, respectively, p = 0.007) and had experienced more adverse events including weakness and fatigue during this stage of the trial. Among the non-responders to escitalopram, 41 patients had received bupropion augmentation. At the end of the augmentation period, 25 (61.0%) patients were defined as responders and 22 of them (53.7%) achieved remission, whereas 13 patients (31.7%) showed insufficient or partial response to combined treatment and 3 patients (7.3%) discontinued this trial due to adverse effects or lack of efficacy.

Conclusions. In agreement with previous studies, we found that bupropion augmentation is generally well tolerated and may successfully facilitate treatment response in a majority of non-responders to monotherapy with serotonin re-uptake inhibitors. We found that the melancholic features of depression were associated with insufficient or partial response to escitalopram. Our results provide additional support to the advantage of bupropion in treatment of melancholic depression.