Antidepressant Combination Strategies for Major Depressive Disorder

Abstract

The majority of patients with major depressive disorder (MDD) fail to remit after initial antidepressant (AD) treatment trials. The results of the Treatment Alternatives to Relieve Depression (STAR*D) trial suggest that most MDD patients require a ‘next-step’ treatment, which include AD combination therapies, as well as various AD augmentation strategies. Antidepressant combination strategies are widely used by clinicians for the management of treatment-resistant depression (TRD). The aim of this chapter was to review current evidence on antidepressant combination strategies for TRD. There are limited evidences to guide even the most widely used combination strategies for TRD. This stands in marked contrast to several augmentation strategies for AD non-responders, including adjunctive ­lithium, thyroid hormone or atypical antipsychotics, for which there are stronger evidences from well designed randomized controlled trials to support efficacy. Recently, a few randomized trials have investigated the efficacy of different antidepressant combination strategies for MDD from treatment initiation. These trials provided discrepant results thus far. Potential clinical advantages of various combination strategies are also discussed (for example, avoidance of discontinuation-emergent symptoms). This chapter deals with pharmacological aspects of TRD and will not cover evidence-based psychotherapeutic and neuromodulatory (for example, electroconvulsive therapy) approaches for TRD. This chapter underscores the need for the design of adequately powered randomized controlled trials to provide a clearer evidence base for this widely employed clinical practice.