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Iadarola ND, Niciu MJ, Richards EM, et al. Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review. Ther Adv Chronic Dis. 2015;6(3):97-114doi: 10.1177/2040622315579059.
Iadarola, N. D., Niciu, M. J., Richards, E. M., Vande Voort, J. L., Ballard, E. D., Lundin, N. B., Nugent, A. C., Machado-Vieira, R., & Zarate, C. A. (2015). Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review. Therapeutic advances in chronic disease, 6(3), 97-114. https://doi.org/10.1177/2040622315579059
Iadarola, Nicolas D, et al. "Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review." Therapeutic advances in chronic disease vol. 6,3 (2015): 97-114. doi: https://doi.org/10.1177/2040622315579059
Iadarola ND, Niciu MJ, Richards EM, Vande Voort JL, Ballard ED, Lundin NB, Nugent AC, Machado-Vieira R, Zarate CA. Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review. Ther Adv Chronic Dis. 2015 May;6(3):97-114. doi: 10.1177/2040622315579059. PMID: 25954495; PMCID: PMC4416968.
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Ther Adv Chronic Dis. 2015 May;6(3):97-114. doi: 10.1177/2040622315579059.

Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review.

Therapeutic advances in chronic disease

Nicolas D Iadarola, Mark J Niciu, Erica M Richards, Jennifer L Vande Voort, Elizabeth D Ballard, Nancy B Lundin, Allison C Nugent, Rodrigo Machado-Vieira, Carlos A Zarate

Affiliations

  1. National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USA.
  2. National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Room 7-5545, Bethesda, MD 20892, USA.

PMID: 25954495 PMCID: PMC4416968 DOI: 10.1177/2040622315579059

Abstract

Current pharmacotherapies for major depressive disorder (MDD) and bipolar depression (BDep) have a distinct lag of onset that can generate great distress and impairment in patients. Furthermore, as demonstrated by several real-world effectiveness trials, their efficacy is limited. All approved antidepressant medications for MDD primarily act through monoaminergic mechanisms, agonists or antagonists with varying affinities for serotonin, norepinephrine and dopamine. The glutamate system has received much attention in recent years as an avenue for developing novel therapeutics. A single subanesthetic dose infusion of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been shown to have rapid and potent antidepressant effects in treatment-resistant MDD and BDep. In a reverse translational framework, ketamine's clinical efficacy has inspired many preclinical studies to explore glutamatergic mechanisms of antidepressant action. These studies have revealed enhanced synaptic plasticity/synaptogenesis via numerous molecular and cellular mechanisms: release of local translational inhibition of brain-derived neurotrophic factor and secretion from dendritic spines, mammalian target of rapamycin activation and glycogen synthase kinase-3 inhibition. Current efforts are focused on extending ketamine's antidepressant efficacy, uncovering the neurobiological mechanisms responsible for ketamine's antidepressant activity in biologically enriched subgroups, and identifying treatment response biomarkers to personalize antidepressant selection. Other NMDA receptor antagonists have been studied both preclinically and clinically, which have revealed relatively modest antidepressant effects compared with ketamine but potentially other favorable characteristics, for example, decreased dissociative or psychotomimetic effects; therefore, there is great interest in developing novel glutamatergic antidepressants with greater target specificity and/or decreased adverse effects.

Keywords: N-methyl-D-aspartate receptor; NR2B; antagonist; bipolar depression; bipolar disorder; glutamate; ketamine; major depressive disorder; treatment-resistant depression

References

  1. Int J Neuropsychopharmacol. 2012 Sep;15(8):1135-48 - PubMed
  2. Pharmacopsychiatry. 2010 Jan;43(1):33-5 - PubMed
  3. Biol Psychiatry. 2008 Feb 15;63(4):349-52 - PubMed
  4. Bipolar Disord. 2012 Feb;14(1):64-70 - PubMed
  5. J Psychopharmacol. 2013 May;27(5):444-50 - PubMed
  6. Pharmacopsychiatry. 2014 Jul;47(4-5):141-4 - PubMed
  7. Biol Psychiatry. 2010 Jan 15;67(2):139-45 - PubMed
  8. Aust N Z J Psychiatry. 2008 Feb;42(2):170 - PubMed
  9. Neuropharmacology. 2012 Jan;62(1):35-41 - PubMed
  10. J Clin Psychiatry. 2014 May;75(5):e417-23 - PubMed
  11. Int J Neuropsychopharmacol. 2013 Oct;16(9):2111-7 - PubMed
  12. J Affect Disord. 2015 Feb 1;172:307-11 - PubMed
  13. CNS Drugs. 2012 Mar 1;26(3):189-204 - PubMed
  14. Anesthesiology. 1980 Mar;52(3):231-9 - PubMed
  15. Bipolar Disord. 2014 Mar;16(2):119-28 - PubMed
  16. J Neurosci. 1997 Apr 15;17(8):2921-7 - PubMed
  17. J Clin Psychopharmacol. 2008 Dec;28(6):631-7 - PubMed
  18. Genes Dev. 2004 Aug 15;18(16):1926-45 - PubMed
  19. Neuroscience. 2011 May 19;182:88-97 - PubMed
  20. J Affect Disord. 2006 Jul;93(1-3):239-43 - PubMed
  21. Neurosci Lett. 2013 Jun 24;546:6-10 - PubMed
  22. Depress Anxiety. 2014 Apr;31(4):335-43 - PubMed
  23. Neuro Endocrinol Lett. 2013;34(4):287-93 - PubMed
  24. Hum Psychopharmacol. 2013 Jan;28(1):87-90 - PubMed
  25. Biol Psychiatry. 2013 Aug 15;74(4):250-6 - PubMed
  26. Biol Psychiatry. 2014 Dec 15;76(12 ):970-6 - PubMed
  27. Pharmacol Biochem Behav. 2012 Feb;100(4):656-64 - PubMed
  28. Biol Psychiatry. 2013 Nov 15;74(10):e23-4 - PubMed
  29. J Psychopharmacol. 2013 Jul;27(7):651-4 - PubMed
  30. Psychol Med. 2008 Sep;38(9):1331-40 - PubMed
  31. Mol Psychiatry. 2011 Nov;16(11):1068-70 - PubMed
  32. Behav Brain Res. 2014 Sep 1;271:111-5 - PubMed
  33. J Psychopharmacol. 2014 Jun;28(6):536-44 - PubMed
  34. Pharmacopsychiatry. 2012 Nov;45(7):269-74 - PubMed
  35. Addiction. 2010 Jan;105(1):121-33 - PubMed
  36. Nat Rev Drug Discov. 2013 Feb;12(2):87-90 - PubMed
  37. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8649-54 - PubMed
  38. J Psychiatr Res. 2013 Jul;47(7):892-9 - PubMed
  39. Addiction. 2009 Jan;104(1):77-87 - PubMed
  40. Mayo Clin Proc. 2012 Sep;87(9):871-8 - PubMed
  41. J Pharmacol Exp Ther. 1999 Jan;288(1):204-10 - PubMed
  42. J Psychopharmacol. 2010 Apr;24(4):585-94 - PubMed
  43. Mol Psychiatry. 2014 Sep;19(9):978-85 - PubMed
  44. Indian J Psychol Med. 2014 Jan;36(1):71-6 - PubMed
  45. Br J Pharmacol. 2014 Apr;171(8):2230-42 - PubMed
  46. Int J Neuropsychopharmacol. 2011 Sep;14(8):1127-31 - PubMed
  47. Nat Rev Drug Discov. 2008 May;7(5):426-37 - PubMed
  48. J Clin Psychiatry. 2009 Dec;70(12):1662-6 - PubMed
  49. Am J Psychiatry. 2012 Aug;169(8):868-9 - PubMed
  50. Biol Psychiatry. 2012 Jun 1;71(11):939-46 - PubMed
  51. Indian J Psychiatry. 2013 Apr;55(2):186-8 - PubMed
  52. Transl Psychiatry. 2014 Oct 14;4:e469 - PubMed
  53. Am J Psychiatry. 2006 Jan;163(1):153-5 - PubMed
  54. Anesthesiology. 2010 Sep;113(3):678-84 - PubMed
  55. CNS Spectr. 2013 Oct;18(5):231-41 - PubMed
  56. J Affect Disord. 2014 Apr;159:56-61 - PubMed
  57. Science. 2010 Aug 20;329(5994):959-64 - PubMed
  58. J ECT. 2012 Sep;28(3):157-61 - PubMed
  59. Biol Psychiatry. 2000 Feb 15;47(4):351-4 - PubMed
  60. J Psychiatr Res. 2014 Nov;58:161-6 - PubMed
  61. Trends Neurosci. 2010 Feb;33(2):67-75 - PubMed
  62. Annu Rev Pharmacol Toxicol. 2014;54:119-39 - PubMed
  63. Sci Transl Med. 2012 Oct 10;4(155):155ps19 - PubMed
  64. Neuropsychopharmacology. 2013 Oct;38(11):2268-77 - PubMed
  65. Psychiatr Pol. 2014 Jan-Feb;48(1):35-47 - PubMed
  66. Int J Neuropsychopharmacol. 2013 Apr;16(3):501-6 - PubMed
  67. J Clin Psychopharmacol. 2012 Aug;32(4):551-7 - PubMed
  68. Psychopharmacology (Berl). 2015 Jan;232(2):399-409 - PubMed
  69. Nature. 2013 Nov 7;503(7474):72-7 - PubMed
  70. Aust N Z J Psychiatry. 2014 Jul;48(7):686 - PubMed
  71. Biol Psychiatry. 2011 Apr 15;69(8):754-61 - PubMed
  72. Psychiatry Res. 2011 Feb 28;191(2):122-7 - PubMed
  73. Biol Psychiatry. 2012 Dec 1;72(11):e27-8 - PubMed
  74. J Psychopharmacol. 2015 May;29(5):591-5 - PubMed
  75. Pharmacopsychiatry. 2013 Sep;46(6):227-8 - PubMed
  76. J ECT. 2013 Sep;29(3):158-61 - PubMed
  77. Biol Psychiatry. 2011 Aug 15;70(4):e9-10; author reply e11-2 - PubMed
  78. Biol Psychiatry. 2012 Jun 1;71(11):1022-5 - PubMed
  79. Psychopharmacology (Berl). 2007 Jun;192(2):253-60 - PubMed
  80. Arch Gen Psychiatry. 2006 Aug;63(8):856-64 - PubMed
  81. Am J Psychiatry. 2013 Oct;170(10):1134-42 - PubMed
  82. J Palliat Med. 2010 Jul;13(7):903-8 - PubMed
  83. Neuroimmunomodulation. 2014;21(4):183-8 - PubMed
  84. Eur J Pharmacol. 1990 Aug 21;185(1):1-10 - PubMed
  85. J Clin Psychiatry. 2014 Sep;75(9):e932-8 - PubMed
  86. Depress Anxiety. 2014 Apr;31(4):297-307 - PubMed
  87. J Clin Psychiatry. 2015 Mar;76(3):247-52 - PubMed
  88. Biol Psychiatry. 2012 Aug 15;72(4):e11-2 - PubMed
  89. J Clin Psychiatry. 2010 Dec;71(12):1605-11 - PubMed
  90. J Palliat Med. 2013 Aug;16(8):958-65 - PubMed
  91. Biol Psychiatry. 2013 Aug 15;74(4):257-64 - PubMed
  92. Brain Res Bull. 2010 Apr 5;81(6):585-9 - PubMed
  93. Int J Neuropsychopharmacol. 2010 Feb;13(1):71-82 - PubMed
  94. Biol Psychiatry. 2009 Sep 1;66(5):522-6 - PubMed
  95. Biol Psychiatry. 2009 Jan 15;65(2):181-4 - PubMed
  96. Int J Neuropsychopharmacol. 2014 Feb;17(2):331-6 - PubMed
  97. Science. 2012 Oct 5;338(6103):68-72 - PubMed
  98. Neuropsychopharmacology. 2012 May;37(6):1526-33 - PubMed
  99. Nat Neurosci. 1999 Jan;2(1):44-9 - PubMed
  100. Arch Gen Psychiatry. 2010 Aug;67(8):793-802 - PubMed
  101. Nature. 2011 Jun 15;475(7354):91-5 - PubMed

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