Treatment-resistant depression: Therapeutic options when first-line treatments fail

The Cochrane review by Davies et al aimed to address the lack of clarity on the risks and benefits of switching and augmentation strategies in the pharmacological treatment of treatment-resistant depression in adults who did not respond (or partially responded) to at least 4 weeks of antidepressant treatment at a recommended dose. This commentary assesses their review and their conclusion that augmenting the current antidepressant with mianserin or with an antipsychotic improves depressive symptoms over the short-term (8 to 12 weeks). Their results need to be treated with caution owing to the small body of evidence and individual comparisons supported by one, two or three studies, the limited evidence on long-term effects and the significant gaps in the literature (e.g. a lack of studies assessing dose increases).