Many patients with major depressive disorder fail to achieve remission with standard antidepressant therapy. Current options for the management of treatment resistant depression (TRD) comprise dose optimization, switching within or between drug classes, augmenting with other drugs and combination strategies. However, the application of combination treatment may be limited by adverse side effects.

From February 2010 to February 2011, twelve inpatients with TRD were retrospectively identified as being treated with a combination of agomelatine and bupropion after discontinuation of former antidepressant treatment. Mean doses of agomelatine at the end of treatment were 47.9 ± 7.2 mg/d, and bupropion 325 ± 86.6 mg/d. Intensity of depressive symptoms was routinely assessed using Beck's Depression Inventory-2. Response was defined as decrease of BDI sum score by 50%, and remission as BDI sum score below 13. Metabolic parameters and adverse side effects were routinely measured. Statistical analysis was performed using paired t-test and repeated measurements ANOVA with degree of TRD as covariate, and unpaired t-test for gender comparisons.

Eight patients showed response, and seven reached remission after 6–8 weeks of inpatient treatment. This effect was independent of the degree of TRD.

How to continue antidepressive treatment after an initially unsuccessful trial is a vital question. However, guidance as to which option is to be favoured remains limited. In particular, the use of antidepressant combinations to address TRD is understudied. We have shown that combination treatment with agomelatine/bupropion in TRD may lead to significant symptom relief. Future randomized controlled trials are needed to confirm our results.