Pharmacological approaches to the challenge of treatment-resistant depression

Dawn F. Ionescu, Jerrold F. Rosenbaum, Jonathan E. Alpert

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)111-126
Number of pages16
JournalDialogues in Clinical Neuroscience
Issue number2
StatePublished - Jan 1 2015
Externally publishedYes


  • Augmentation
  • Combination
  • Ketamine
  • Optimization
  • Scopolamine
  • Switch therapy
  • Treatment strategy
  • Treatment-resistant depression

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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