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Unipolar depression in adults: Management of highly resistant (refractory) depression

Authors
Michael Thase, MD
K Ryan Connolly, MD, MS
Section Editor
Peter P Roy-Byrne, MD
Deputy Editor
David Solomon, MD

INTRODUCTION

Although numerous treatments are available for unipolar major depression (major depressive disorder), patients may be highly resistant (refractory) to many sequential treatment regimens, including multiple classes of antidepressants and adjunctive drugs, as well as electroconvulsive therapy and psychotherapy [1].

This topic reviews management and treatment of refractory depression. The epidemiology, assessment, prognosis, and treatment of resistant depression are discussed separately, as are the initial treatment of depression and clinical features and diagnosis of depression.

(See "Unipolar treatment resistant depression in adults: Epidemiology, risk factors, assessment, and prognosis".)  

(See "Unipolar depression in adults: Treatment of resistant depression".)

(See "Unipolar major depression in adults: Choosing initial treatment".)

                     

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Literature review current through: Nov 2016. | This topic last updated: Wed Dec 30 00:00:00 GMT 2015.
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References
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  1. Malone DA Jr, Dougherty DD, Rezai AR, et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry 2009; 65:267.
  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
  3. Keller MB. Issues in treatment-resistant depression. J Clin Psychiatry 2005; 66 Suppl 8:5.
  4. Rush AJ, Warden D, Wisniewski SR, et al. STAR*D: revising conventional wisdom. CNS Drugs 2009; 23:627.
  5. Ibrahim L, Diazgranados N, Luckenbaugh DA, et al. Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35:1155.
  6. Lozano AM, Mayberg HS, Giacobbe P, et al. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 2008; 64:461.
  7. Bewernick BH, Hurlemann R, Matusch A, et al. Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry 2010; 67:110.
  8. Christmas D, Eljamel MS, Butler S, et al. Long term outcome of thermal anterior capsulotomy for chronic, treatment refractory depression. J Neurol Neurosurg Psychiatry 2011; 82:594.
  9. Shields DC, Asaad W, Eskandar EN, et al. Prospective assessment of stereotactic ablative surgery for intractable major depression. Biol Psychiatry 2008; 64:449.
  10. Keitner GI, Mansfield AK. Management of treatment-resistant depression. Psychiatr Clin North Am 2012; 35:249.
  11. Ryan CE, Keitner GI, Bishop S. An adjunctive Management of Depression Program for difficult-to-treat depressed patients and their families. Depress Anxiety 2010; 27:27.
  12. Goldberg RW, Dickerson F, Lucksted A, et al. Living well: an intervention to improve self-management of medical illness for individuals with serious mental illness. Psychiatr Serv 2013; 64:51.
  13. Swan J, Sorrell E, MacVicar B, et al. "Coping with depression": an open study of the efficacy of a group psychoeducational intervention in chronic, treatment-refractory depression. J Affect Disord 2004; 82:125.
  14. Wooderson SC, Juruena MF, Fekadu A, et al. Prospective evaluation of specialist inpatient treatment for refractory affective disorders. J Affect Disord 2011; 131:92.
  15. Rush AJ. STAR*D: what have we learned? Am J Psychiatry 2007; 164:201.
  16. Papakostas GI. Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry 2009; 70 Suppl 6:16.
  17. Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 2003; 53:649.
  18. McIntyre RS. When should you move beyond first-line therapy for depression? J Clin Psychiatry 2010; 71 Suppl 1:16.
  19. Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA 1999; 282:1737.
  20. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16:606.
  21. Pampallona S, Bollini P, Tibaldi G, et al. Combined pharmacotherapy and psychological treatment for depression: a systematic review. Arch Gen Psychiatry 2004; 61:714.
  22. Wiles N, Thomas L, Abel A, et al. Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial. Lancet 2013; 381:375.
  23. Shuchman M. Approving the vagus-nerve stimulator for depression. N Engl J Med 2007; 356:1604.
  24. Daban C, Martinez-Aran A, Cruz N, Vieta E. Safety and efficacy of Vagus Nerve Stimulation in treatment-resistant depression. A systematic review. J Affect Disord 2008; 110:1.
  25. Rush AJ, Marangell LB, Sackeim HA, et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry 2005; 58:347.
  26. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, third edition. Am J Psychiatry 2010; 167 (supplement):1.
  27. American Psychiatric Association: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, 2010. http://psychiatryonline.org/guidelines.aspx (Accessed on April 17, 2012).
  28. National Institute for Health and Clinical Excellence (NICE). Vagus nerve stimulation for treatment-resistant depression, IPG330. December, 2009 http://www.nice.org.uk/ (Accessed on December 30, 2012).
  29. Bond DJ, Lim KO. 13C magnetic resonance spectroscopy and glutamate metabolism in mood disorders: Current challenges, potential opportunities. Am J Psychiatry 2014; 171:1240.
  30. Kellner CH, Greenberg RM, Ahle GM, Liebman LS. Electroconvulsive therapy is a standard treatment; ketamine is not (yet). Am J Psychiatry 2014; 171:796.
  31. Newport DJ, Carpenter LL, McDonald WM, et al. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry 2015; 172:950.
  32. Fond G, Loundou A, Rabu C, et al. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl) 2014; 231:3663.
  33. McGirr A, Berlim MT, Bond DJ, et al. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med 2015; 45:693.
  34. Caddy C, Amit BH, McCloud TL, et al. Ketamine and other glutamate receptor modulators for depression in adults. Cochrane Database Syst Rev 2015; :CD011612.
  35. Ghasemi M, Kazemi MH, Yoosefi A, et al. Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Res 2014; 215:355.
  36. Schatzberg AF. A word to the wise about ketamine. Am J Psychiatry 2014; 171:262.
  37. Szymkowicz SM, Finnegan N, Dale RM. A 12-month naturalistic observation of three patients receiving repeat intravenous ketamine infusions for their treatment-resistant depression. J Affect Disord 2013; 147:416.
  38. Mathews DC, Zarate CA Jr. Current status of ketamine and related compounds for depression. J Clin Psychiatry 2013; 74:516.
  39. Aan Het Rot M, Zarate CA Jr, Charney DS, Mathew SJ. Ketamine for depression: where do we go from here? Biol Psychiatry 2012; 72:537.
  40. Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 2013; 170:1134.
  41. Galvez V, O'Keefe E, Cotiga L, et al. Long-lasting effects of a single subcutaneous dose of ketamine for treating melancholic depression: a case report. Biol Psychiatry 2013.
  42. Lapidus KA, Levitch CF, Perez AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry 2014; 76:970.
  43. Price RB, Iosifescu DV, Murrough JW, et al. Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depress Anxiety 2014; 31:335.
  44. Murrough JW, Soleimani L, DeWilde KE, et al. Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. Psychol Med 2015; 45:3571.
  45. Kennedy SH, Milev R, Giacobbe P, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. J Affect Disord 2009; 117 Suppl 1:S44.
  46. Shelton RC, Osuntokun O, Heinloth AN, Corya SA. Therapeutic options for treatment-resistant depression. CNS Drugs 2010; 24:131.