Augmentation in treatment-resistant depression

Almost one-third of patients with major depressive disorder do not respond to a series of treatments and are considered treatment-resistant. Many pharmacological strategies have been evaluated for the management of treatment-resistant depression, but none have been formally approved for the disorder. There is evidence to support the efficacy of both lithium and thyroid hormone as augmentation agents, although this is mostly based on studies with tricyclic antidepressants. The current review assesses strategies for augmentation with nonantidepressant drugs and evidence based on published studies. Preclinical studies that provide evidence for proposed mechanisms of action have also been included. Strategies with evidence including at least one randomized, controlled trial include augmentation of the primary antidepressant with olanzapine, buspirone, lamotrigine, pindolol or methylphenidate. However, it appears that the choice of augmentation strategy is based largely on clinical preference and therapeutic need in individual patients, rather than on evidence of efficacy from randomized, controlled studies.