title: Pharmacological approaches to the challenge of treatment-resistant depression.
abstract: 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.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Dawn F
authors.initials: DF
authors.lastname: Ionescu
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Jerrold F
authors.initials: JF
authors.lastname: Rosenbaum
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Alpert
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D006801:Humans
chemical_list: D000928:Antidepressive Agents
keywords: augmentation; combination; ketamine; optimization; scopolamine; switch therapy; treatment strategy; treatment-resistant depression