Pharmacological approaches to the challenge of treatment-resistant depression

• Published in: Dialogues in clinical neuroscience Vol. 17; no. 2; pp. 111 - 126
• Main Authors: Ionescu, Dawn F., Rosenbaum, Jerrold F., Alpert, Jonathan E.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.06.2015; Les Laboratoires Servier
• Subjects: Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; augmentation; combination; Depressive Disorder, Treatment-Resistant - drug therapy; Humans; ketamine; optimization; scopolamine; State of the Art; switch therapy; treatment strategy; treatment-resistant depression; treatment-resistant depression; treatment strategy; ketamine; optimization; augmentation; scopolamine; switch therapy; combination
• ISSN: 1958-5969; 1294-8322; 1958-5969
• DOI: 10.31887/DCNS.2015.17.2/dionescu

Although monoaminergic antidepressants revolutionized the treatment of Major Depressive Disorder (MDD) over a half-century ago, approximately one third of depressed patients experience treatment-resistant depression (TRD). Such patients account for a disproportionately large burden of disease, as evidenced by increased disability, cost, human suffering, and suicide. This review addresses the definition, causes, evaluation, and treatment of unipolar TRD, as well as the major treatment strategies, including optimization, augmentation, combination, and switch therapies. Evidence for these options, as outlined in this review, is mainly focused on large-scale trials or meta-analyses. Finally, we briefly review emerging targets for antidepressant drug discovery and the novel effects of rapidly acting antidepressants, with a focus on ketamine.