Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-29T02:23:06.988Z Has data issue: false hasContentIssue false
  • English
  • Français

New medications for treatment-resistant depression: a brief review of recent developments

Published online by Cambridge University Press:  19 January 2018

Michael E. Thase
Michael E. Thase*
Affiliation:
Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
*
*Address for correspondence: Michael E. Thase, MD, Perelman School of Medicine, 3535 Market Street, Suite 670, Philadelphia, PA 19104, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

There is a great unmet need for new medications with novel mechanisms of action that can effectively treat patients who do not benefit from standard antidepressant therapies. After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine. This article briefly highlights more recent research on ketamine and other investigational antidepressants.

Keywords

ALKS-5461esketamineinvestigational antidepressantsketaminerapastineltreatment-resistant depressiontherapies
Type
CME Review Article
Information
CNS Spectrums , Volume 22 , Supplement S1: CME SUPPLEMENT , December 2017 , pp. 39 - 48
Copyright
© Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

This activity is supported by an unrestricted educational grant from Alkermes.

References

1. Gelenberg, AJ, Freeman, MP, Markowitz, JC, et al. Practice guidelines for the treatment of patients with major depressive disorder (third edition). Am J Psychiatry. 2010; 167(10): 9–118.Google Scholar
2. Kennedy, SH, Lam, RW, McIntyre, RS, et al; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 3. Pharmacological treatments. Can J Psychiatry. 2016; 61(9): 540–560.Google Scholar
3. Rush, AJ, Trivedi, MH, Wisniewski, SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11): 1905–1917.CrossRefGoogle ScholarPubMed
4. Thase, ME. Antidepressant combinations: widely used, but far from empirically validated. Can J Psychiatry. 2011; 56(6): 317–323.Google Scholar
5. Thase, ME. Adverse effects of second-generation antipsychotics as adjuncts to antidepressants: are the risks worth the benefits? Psychiatr Clin North Am. 2016; 39(3): 477–486.Google Scholar
6. Abdallah, CG, Averill, LA, Krystal, JH. Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Ann N Y Acad Sci. 2015; 1344: 66–77.CrossRefGoogle ScholarPubMed
7. Berman, RM, Cappiello, A, Anand, A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000; 47(4): 351–354.Google Scholar
8. Zarate, CA Jr, Singh, JB, Carlson, PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006; 63(8): 856–864.Google Scholar
9. Diazgranados, N, Ibrahim, L, Brutsche, NE, et al. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry. 2010; 67(8): 793–802.Google Scholar
10. Newport, DJ, Carpenter, LL, McDonald, WM, Potash, JB, Tohen, M, Nemeroff, CB, APA Council of Research Task Force on Novel Biomarkers and Treatments. Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. Am J Psychiatry. 2015; 172(10): 950–966.Google Scholar
11. Han, Y, Chen, J, Zou, D, et al. Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies. Neuropsychiatr Dis Treat. 2016; 12: 2859–2867.CrossRefGoogle ScholarPubMed
12. Wilkinson, ST, Ballard, ED, Bloch, MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. In press. doi: 10.1176/appi.ajp.2017.17040472.Google Scholar
13. Lener, MS, Kadriu, B, Zarate, CA Jr. Ketamine and beyond: investigations into the potential of glutamatergic agents to treat depression. Drugs. 2017; 77(4): 381–401.Google Scholar
14. Malhi, GS, Byrow, Y, Cassidy, F, et al. Ketamine: stimulating antidepressant treatment? BJPsych Open. 2016; 2(3): e5–e9.Google Scholar
15. Sisti, D, Segal, AG, Thase, ME. Proceed with caution: off-label ketamine treatment for major depressive disorder. Curr Psychiatry Rep. 2014; 16(12): 527.Google Scholar
16. Sanacora, G, Schatzberg, AF. Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders? Neuropsychopharmacology. 2015; 40(2): 259–267.Google Scholar
17. Sanacora, G, Frye, MA, McDonald, W, et al; American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017; 74(4): 399–405.CrossRefGoogle ScholarPubMed
18. Abdallah, CG, Averill, CL, Salas, R, et al. Prefrontal connectivity and glutamate transmission: relevance to depression pathophysiology and ketamine treatment. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017; 2(7): 566–574.Google Scholar
19. Correia-Melo, FS, Argolo, FC, Araújo-de-Freitas, L, et al. Rapid infusion of esketamine for unipolar and bipolar depression: a retrospective chart review. Neuropsychiatr Dis Treat. 2017; 13: 1627–1632.Google Scholar
20. Singh, JB, Fedgchin, M, Daly, E, et al. Intravenous esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biol Psychiatry. 2016; 80(6): 424–431.CrossRefGoogle ScholarPubMed
21. van de Loo, AJAE, Bervoets, AC, Mooren, L, et al. The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance: a double-blind, placebo-controlled study. Psychopharmacology (Berl). 2017; 234(21): 3175–3183.Google Scholar
22. Moskal, JR, Burgdorf, JS, Stanton, PK, et al. The development of rapastinel (formerly GLYX-13); a rapid acting and long lasting antidepressant. Curr Neuropharmacol. 2017; 15(1): 47–56.Google Scholar
23. Preskorn, S, Macaluso, M, Mehra, DO, Zammit, G, Moskal, JR, Burch, RM, GLYX-13 Clinical Study Group. Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent. J Psychiatr Pract. 2015; 21(2): 140–149.Google Scholar
24. Sanacora, G, Smith, MA, Pathak, S, et al. Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects. Mol Psychiatry. 2014; 19(9): 978–985.Google Scholar
25. Sanacora, G, Johnson, MR, Khan, A, et al. Adjunctive lanicemine (AZD6765) in patients with major depressive disorder and history of inadequate response to antidepressants: a randomized, placebo-controlled study. Neuropsychopharmacology. 2017; 42(4): 844–853.Google Scholar
26. Panksepp, J, Yovell, Y. Preclinical modeling of primal emotional affects (seeking, panic and play): gateways to the development of new treatments for depression. Psychopathology. 2014; 47(6): 383–393.CrossRefGoogle Scholar
27. Rantala, MJ, Luoto, S, Krams, I, Karlsson, H. Depression subtyping based on evolutionary psychiatry: proximate mechanisms and ultimate functions. Brain Behav Immun. 2017. In press. doi: 10.1016/j.bbi.2017.10.012.Google Scholar
28. Peciña, M, Bohnert, AS, Sikora, M, et al. Association between placebo-activated neural systems and antidepressant responses: neurochemistry of placebo effects in major depression. JAMA Psychiatry. 2015; 72(11): 1087–1094.Google Scholar
29. Ehrich, E, Turncliff, R, Du, Y, et al. Evaluation of opioid modulation in major depressive disorder. Neuropsychopharmacology. 2015; 40(6): 1448–1455.Google Scholar
30. Karp, JF, Butters, MA, Begley, AE, et al. Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults. J Clin Psychiatry. 2014; 75(8): e785–e793.CrossRefGoogle ScholarPubMed
31. Stanciu, CN, Glass, OM, Penders, TM. Use of buprenorphine in treatment of refractory depression—a review of current literature. Asian J Psychiatr. 2017; 26: 94–98.Google Scholar
32. Fava, M, Memisoglu, A, Thase, ME, et al. Opioid modulation with buprenorphine/samidorphan as adjunctive treatment for inadequate response to antidepressants: a randomized double-blind placebo-controlled trial. Am J Psychiatry. 2016; 173(5): 499–508.Google Scholar
33. Nagele, P, Duma, A, Kopec, M, et al. Nitrous oxide for treatment-resistant major depression: a proof-of-concept trial. Biol Psychiatry. 2015; 78(1): 10–18.Google Scholar
34. Griffiths, RR, Johnson, MW, Carducci, MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016; 30(12): 1181–1197.CrossRefGoogle Scholar
35. Ross, S, Bossis, A, Guss, J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016; 30(12): 1165–1180.CrossRefGoogle ScholarPubMed
36. Köhler, CA, Freitas, TH, Maes, M, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017; 135(5): 373–387.CrossRefGoogle ScholarPubMed
37. Miller, AH, Raison, CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol. 2016; 16(1): 22–34.Google Scholar
38. Köhler, O, Benros, ME, Nordentoft, M, et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2014; 71(12): 1381–1391.Google Scholar
39. Uher, R, Tansey, KE, Dew, T, et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry. 2014; 171(12): 1278–1286.Google Scholar
40. Jha, MK, Minhajuddin, A, Gadad, BS, et al. Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial. Psychoneuroendocrinology. 2017; 78: 105–113.Google Scholar
41. Raison, CL, Rutherford, RE, Woolwine, BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013; 70(1): 31–36.Google Scholar