Augmentation strategies in patients with refractory depression

Charles B. Nemeroff

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


In the evaluation of treatment-resistant or treatment-refractory depression (TRD), true resistance to antidepressant therapy must be distinguished from inadequate dose, duration, or compliance with past antidepressant therapy. Reassessment of the diagnosis may reveal psychiatric comorbidity, the presence of depressive subtypes, or the possibility of a medical etiology. Management of TRD should consider patient-specific factors; drug therapy may be directed by depressive subtype or the presence of psychiatric comorbidity. Increasing the dose or duration of current antidepressant therapy is appropriate for patients who have received inadequate therapy in the past. Augmentation of tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI) therapy with thyroid hormone (T3) or lithium has been shown to be effective in open and controlled trials. Efficacy of other strategies such as higher-dose antidepressant treatment, venlafaxine therapy, combined antidepressant therapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or augmentation with pindolol or buspirone has been less well established, but emerging data from open studies and case reports are encouraging.

Original languageEnglish (US)
Pages (from-to)169-181
Number of pages13
JournalDepression and anxiety
Issue number4
StatePublished - 1996
Externally publishedYes


  • augmentation
  • combination therapy
  • lithium
  • refractory depression
  • resistant depression
  • selective serotonin reuptake inhibitors
  • thyroid hormone
  • tricyclic antidepressants

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Psychology(all)
  • Clinical Psychology


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