1932

Abstract

The therapeutic onset of traditional antidepressants is delayed by several weeks and many depressed patients fail to respond to treatment altogether. In contrast, subanesthetic ketamine can rapidly alleviate symptoms of depression within hours of a single administration, even in patients who are considered treatment-resistant. Ketamine is thought to exert these effects by restoring the integrity of neural circuits that are compromised in depression. This hypothesis stems in part from preclinical observations that ketamine can strengthen synaptic connections by increasing glutamate-mediated neurotransmission and promoting rapid neurotrophic factor release. An improved understanding of how ketamine, and other novel rapid-acting antidepressants, give rise to these processes will help foster future therapeutic innovation. Here, we review the history of antidepressant treatment advances that preceded the ketamine discovery, critically examine mechanistic hypotheses for how ketamine may exert its antidepressant effects, and discuss the impact this knowledge has had on ongoing drug discovery efforts.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-clinpsy-072120-014126
2021-05-07
2024-06-17
Loading full text...

Full text loading...

/deliver/fulltext/clinpsy/17/1/annurev-clinpsy-072120-014126.html?itemId=/content/journals/10.1146/annurev-clinpsy-072120-014126&mimeType=html&fmt=ahah

Literature Cited

  1. Abdallah CG, Averill LA, Gueorguieva R, Goktas S, Purohit P et al. 2020. Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Neuropsychopharmacology 45:990–97
    [Google Scholar]
  2. Adaikkan C, Taha E, Barrera I, David O, Rosenblum K. 2018. Calcium/calmodulin-dependent protein kinase II and eukaryotic elongation factor 2 kinase pathways mediate the antidepressant action of ketamine. Biol. Psychiatry 84:65–75
    [Google Scholar]
  3. Aguilar-Valles A, De Gregorio D, Matta-Camacho E, Eslamizade MJ, Khlaifia A et al. 2020. Antidepressant actions of ketamine engage cell-specific translation via eIF4E. Nature https://doi.org/10.1038/s41586-020-03047-0
    [Crossref] [Google Scholar]
  4. Alger B. 2019. Defense of the Scientific Hypothesis: From Reproducibility Crisis to Big Data New York: Oxford Univ. Press
    [Google Scholar]
  5. Alt A, Nisenbaum ES, Bleakman D, Witkin JM. 2006. A role for AMPA receptors in mood disorders. Biochem. Pharmacol. 71:1273–88
    [Google Scholar]
  6. Anis NA, Berry SC, Burton NR, Lodge D. 1983. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br. J. Pharmacol. 79:565–75
    [Google Scholar]
  7. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF et al. 2011. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91–95
    [Google Scholar]
  8. Ayd FJ Jr. 1957. A preliminary report on marsilid. Am. J. Psychiatry 114:459
    [Google Scholar]
  9. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR et al. 2000. Antidepressant effects of ketamine in depressed patients. Biol. Psychiatry 47:351–54
    [Google Scholar]
  10. Brodie BB, Shore PA. 1957. A concept for a role of serotonin and norepinephrine as chemical mediators in the brain. Ann. N.Y. Acad. Sci. 66:631–42
    [Google Scholar]
  11. Bunney WE Jr, Davis JM 1965. Norepinephrine in depressive reactions: a review. Arch. Gen. Psychiatry 13:483–94
    [Google Scholar]
  12. Burgdorf J, Zhang XL, Nicholson KL, Balster RL, Leander JD et al. 2013. GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects. Neuropsychopharmacology 38:729–42
    [Google Scholar]
  13. Can A, Zanos P, Moaddel R, Kang HJ, Dossou KS et al. 2016. Effects of ketamine and ketamine metabolites on evoked striatal dopamine release, dopamine receptors, and monoamine transporters. J. Pharmacol. Exp. Ther. 359:159–70
    [Google Scholar]
  14. Carlsson A. 1970. Structural specificity for inhibition of [14C]-5-hydroxytryptamine uptake by cerebral slices. J. Pharm. Pharmacol. 22:729–32
    [Google Scholar]
  15. Carlsson A, Corrodi H, Fuxe K, Hökfelt T. 1969. Effect of antidepressant drugs on the depletion of intraneuronal brain 5-hydroxytryptamine stores caused by 4-methyl-alpha-ethyl-meta-tyramine. Eur. J. Pharmacol. 5:357–66
    [Google Scholar]
  16. Carlsson A, Fuxe K, Ungerstedt U. 1968. The effect of imipramine of central 5-hydroxytryptamine neurons. J. Pharm. Pharmacol. 20:150–51
    [Google Scholar]
  17. Cavalleri L, Merlo Pich E, Millan MJ, Chiamulera C, Kunath T et al. 2018. Ketamine enhances structural plasticity in mouse mesencephalic and human iPSC-derived dopaminergic neurons via AMPAR-driven BDNF and mTOR signaling. Mol. Psychiatry 23:812–23
    [Google Scholar]
  18. Chaturvedi HK, Dinesh C, Bapna JS. 1999. Effect of NMDA receptor antagonists in forced swimming test and its modification by antidepressants. Indian J. Pharmacol. 31:104–9
    [Google Scholar]
  19. Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ et al. 2018. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 391:1357–66
    [Google Scholar]
  20. Collo G, Cavalleri L, Chiamulera C, Merlo Pich E 2018. (2R,6R)-Hydroxynorketamine promotes dendrite outgrowth in human inducible pluripotent stem cell-derived neurons through AMPA receptor with timing and exposure compatible with ketamine infusion pharmacokinetics in humans. NeuroReport 29:1425–30
    [Google Scholar]
  21. Coppen A, Shaw D, Farrell J. 1963. Potentiation of the antidepressive effect of a monoamine-oxidase inhibitor by tryptophan. Lancet 281:79–81
    [Google Scholar]
  22. Crane GE. 1957. Iproniazid (marsilid) phosphate, a therapeutic agent for mental disorders and debilitating diseases. Psychiatr. Res. Rep. Am. Psychiatr. Assoc. 8:142–52
    [Google Scholar]
  23. Delgado PL. 2000. Depression: the case for a monoamine deficiency. J. Clin. Psychiatry 61:Suppl. 67–11
    [Google Scholar]
  24. Demyttenaere K, Enzlin P, Dewé W, Boulanger B, De Bie J et al. 2001. Compliance with antidepressants in a primary care setting, 1: beyond lack of efficacy and adverse events. J. Clin. Psychiatry 62:Suppl. 2230–33
    [Google Scholar]
  25. Deyama S, Duman RS. 2020. Neurotrophic mechanisms underlying the rapid and sustained antidepressant actions of ketamine. Pharmacol. Biochem. Behav. 188:172837
    [Google Scholar]
  26. Domino EF. 2010. Taming the ketamine tiger. Anesthesiology 113:678–84
    [Google Scholar]
  27. Domino EF, Chodoff P, Corssen G. 1965. Pharmacologic effects of CI-581, a new dissociative anesthetic, in man. Clin. Pharmacol. Ther. 6:279–91
    [Google Scholar]
  28. Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T et al. 2019. Positive N-methyl-D-aspartate receptor modulation by rapastinel promotes rapid and sustained antidepressant-like effects. Int. J. Neuropsychopharmacol. 22:247–59
    [Google Scholar]
  29. Dravid SM, Erreger K, Yuan H, Nicholson K, Le P et al. 2007. Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block. J. Physiol. 581:107–28
    [Google Scholar]
  30. Duman RS. 1998. Novel therapeutic approaches beyond the serotonin receptor. Biol. Psychiatry 44:324–35
    [Google Scholar]
  31. Duman RS. 2014. Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connections. Dialogues Clin. Neurosci. 16:11–27
    [Google Scholar]
  32. Duman RS, Deyama S, Fogaça MV. 2021. Role of BDNF in the pathophysiology and treatment of depression: activity-dependent effects distinguish rapid-acting antidepressants. Eur. J. Neurosci. 53:12639
    [Google Scholar]
  33. Duman RS, Heninger GR, Nestler EJ. 1997. A molecular and cellular theory of depression. Arch. Gen. Psychiatry 54:597–606
    [Google Scholar]
  34. Duman RS, Shinohara R, Fogaça MV, Hare B. 2019. Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function. Mol. Psychiatry 24:1816–32
    [Google Scholar]
  35. Fangmann P, Assion HJ, Juckel G, González CA, López-Muñoz F. 2008. Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part II: tricyclics and tetracyclics. J. Clin. Psychopharmacol. 28:11–4
    [Google Scholar]
  36. Fitzgerald PJ, Watson BO. 2019. In vivo electrophysiological recordings of the effects of antidepressant drugs. Exp. Brain Res. 237:1593–614
    [Google Scholar]
  37. Fornaro M, Anastasia A, Novello S, Fusco A, Pariano R et al. 2019. The emergence of loss of efficacy during antidepressant drug treatment for major depressive disorder: an integrative review of evidence, mechanisms, and clinical implications. Pharmacol. Res. 139:494–502
    [Google Scholar]
  38. Freis ED. 1954. Mental depression in hypertensive patients treated for long periods with large doses of reserpine. N. Engl. J. Med. 251:1006–8
    [Google Scholar]
  39. Fukumoto K, Fogaça MV, Liu RJ, Duman C, Kato T et al. 2019. Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine. PNAS 116:1297–302
    [Google Scholar]
  40. Gaynes BN, Lux L, Gartlehner G, Asher G, Forman-Hoffman V et al. 2020. Defining treatment-resistant depression. Depress. Anxiety 37:134–45
    [Google Scholar]
  41. Gilbert JR, Zarate CA Jr. 2020. Electrophysiological biomarkers of antidepressant response to ketamine in treatment-resistant depression: gamma power and long-term potentiation. Pharmacol. Biochem. Behav. 189:172856
    [Google Scholar]
  42. Glasgow NG, Wilcox MR, Johnson JW. 2018. Effects of Mg2+ on recovery of NMDA receptors from inhibition by memantine and ketamine reveal properties of a second site. Neuropharmacology 137:344–58
    [Google Scholar]
  43. Gould TD, Zarate CA Jr., Thompson SM. 2019. Molecular pharmacology and neurobiology of rapid-acting antidepressants. Annu. Rev. Pharmacol. Toxicol. 59:213–36
    [Google Scholar]
  44. Heninger GR, Delgado PL, Charney DS. 1996. The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans. Pharmacopsychiatry 29:2–11
    [Google Scholar]
  45. Highland JN, Zanos P, Riggs LM, Georgiou P, Clark SM et al. 2021. Hydroxynorketamines: pharmacology and potential therapeutic applications. Pharmacol. Rev. 73:76391
    [Google Scholar]
  46. Hirschfeld RM. 2000. History and evolution of the monoamine hypothesis of depression. J. Clin. Psychiatry 61:Suppl. 64–6
    [Google Scholar]
  47. Homayoun H, Moghaddam B. 2007. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J. Neurosci. 27:11496–500
    [Google Scholar]
  48. Huganir RL, Nicoll RA. 2013. AMPARs and synaptic plasticity: the last 25 years. Neuron 80:704–17
    [Google Scholar]
  49. Hyman SE, Nestler EJ. 1996. Initiation and adaptation: a paradigm for understanding psychotropic drug action. Am. J. Psychiatry 153:151–62
    [Google Scholar]
  50. Jacobsen JP, Medvedev IO, Caron MG. 2012. The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse. Philos. Trans. R. Soc. B 367:2444–59
    [Google Scholar]
  51. Jakobsen JC, Katakam KK, Schou A, Hellmuth SG, Stallknecht SE et al. 2017. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry 17:58
    [Google Scholar]
  52. Jourdi H, Hsu YT, Zhou M, Qin Q, Bi X, Baudry M. 2009. Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J. Neurosci. 29:8688–97
    [Google Scholar]
  53. Kato T, Duman RS. 2020. Rapastinel, a novel glutamatergic agent with ketamine-like antidepressant actions: convergent mechanisms. Pharmacol. Biochem. Behav. 188:172827
    [Google Scholar]
  54. Kato T, Fogaça MV, Deyama S, Li XY, Fukumoto K, Duman RS. 2018. BDNF release and signaling are required for the antidepressant actions of GLYX-13. Mol. Psychiatry 23:2007–17
    [Google Scholar]
  55. Kavalali ET, Monteggia LM. 2020. Targeting homeostatic synaptic plasticity for treatment of mood disorders. Neuron 106:715–26
    [Google Scholar]
  56. Kawamoto EM, Vivar C, Camandola S. 2012. Physiology and pathology of calcium signaling in the brain. Front. Pharmacol. 3:61
    [Google Scholar]
  57. Khorramzadeh E, Lotfy AO. 1973. The use of ketamine in psychiatry. Psychosomatics 14:344–46
    [Google Scholar]
  58. Kishi T, Matsunaga S, Iwata N. 2017. A meta-analysis of memantine for depression. J. Alzheimers Dis. 57:113–21
    [Google Scholar]
  59. Koike H, Chaki S. 2014. Requirement of AMPA receptor stimulation for the sustained antidepressant activity of ketamine and LY341495 during the forced swim test in rats. Behav. Brain Res. 271:111–15
    [Google Scholar]
  60. Kryst J, Kawalec P, Mitoraj AM, Pilc A, Lasoń W, Brzostek T. 2020. Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials. Pharmacol. Rep. 72:543–62
    [Google Scholar]
  61. Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS. 2019. Ketamine: a paradigm shift for depression research and treatment. Neuron 101:774–78
    [Google Scholar]
  62. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R et al. 1994. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch. Gen. Psychiatry 51:199–214
    [Google Scholar]
  63. Kuhn R. 1958. The treatment of depressive states with G 22355 (imipramine hydrochloride). Am. J. Psychiatry 115:459–64
    [Google Scholar]
  64. Lee EH, Han PL. 2019. Reciprocal interactions across and within multiple levels of monoamine and cortico-limbic systems in stress-induced depression: a systematic review. Neurosci. Biobehav. Rev. 101:13–31
    [Google Scholar]
  65. Lehmann HE, Cahn CH, De Verteuil RL. 1958. The treatment of depressive conditions with imipramine (G 22355). Can. Psychiatr. Assoc. J. 3:155–64
    [Google Scholar]
  66. Lener MS, Kadriu B, Zarate CA Jr. 2017. Ketamine and beyond: investigations into the potential of glutamatergic agents to treat depression. Drugs 77:381–401
    [Google Scholar]
  67. Lepack AE, Bang E, Lee B, Dwyer JM, Duman RS. 2016. Fast-acting antidepressants rapidly stimulate ERK signaling and BDNF release in primary neuronal cultures. Neuropharmacology 111:242–52
    [Google Scholar]
  68. Lepack AE, Fuchikami M, Dwyer JM, Banasr M, Duman RS. 2015. BDNF release is required for the behavioral actions of ketamine. Int. J. Neuropsychopharmacol. 18:1pyu033
    [Google Scholar]
  69. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM et al. 2010. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959–64
    [Google Scholar]
  70. Li N, Liu RJ, Dwyer JM, Banasr M, Lee B et al. 2011. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol. Psychiatry 69:754–61
    [Google Scholar]
  71. Lidbrink P, Jonsson G, Fuxe K. 1971. The effect of imipramine-like drugs and antihistamine drugs on uptake mechanisms in the central noradrenaline and 5-hydroxytryptamine neurons. Neuropharmacology 10:521–30
    [Google Scholar]
  72. Liebe T, Li S, Lord A, Colic L, Krause AL et al. 2017. Factors influencing the cardiovascular response to subanesthetic ketamine: a randomized, placebo-controlled trial. Int. J. Neuropsychopharmacol. 20:909–18
    [Google Scholar]
  73. Liu RJ, Duman C, Kato T, Hare B, Lopresto D et al. 2017. GLYX-13 produces rapid antidepressant responses with key synaptic and behavioral effects distinct from ketamine. Neuropsychopharmacology 42:1231–42
    [Google Scholar]
  74. Liu RJ, Lee FS, Li XY, Bambico F, Duman RS, Aghajanian GK. 2012. Brain-derived neurotrophic factor Val66Met allele impairs basal and ketamine-stimulated synaptogenesis in prefrontal cortex. Biol. Psychiatry 71:996–1005
    [Google Scholar]
  75. Lodge D, Anis N, Berry S, Burton N. 1983. Arylcyclohexylamines selectively reduce excitation of mammalian neurons by aspartate-like amino acids. Phencyclidine and Related Arylcyclohexylamines: Present and Future Applications, ed. Kamenka JM, Domino EF, Geneste P595–616 Ann Arbor, MI: NPP Books
    [Google Scholar]
  76. Loomer HP, Saunders JC, Kline NS. 1957. A clinical and pharmacodynamic evaluation of iproniazid as a psychic energizer. Psychiatr. Res. Rep. Am. Psychiatr. Assoc. 8:129–41
    [Google Scholar]
  77. López-Muñoz F, Alamo C, Juckel G, Assion HJ. 2007. Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part I: monoamine oxidase inhibitors. J. Clin. Psychopharmacol. 27:555–59
    [Google Scholar]
  78. Lumsden EW, Troppoli TA, Myers SJ, Zanos P, Aracava Y et al. 2019. Antidepressant-relevant concentrations of the ketamine metabolite (2R,6R)-hydroxynorketamine do not block NMDA receptor function. PNAS 116:5160–69
    [Google Scholar]
  79. Maas JW. 1978. Clinical and biochemical heterogeneity of depressive disorders. Ann. Intern. Med. 88:556–63
    [Google Scholar]
  80. MacDonald JF, Miljkovic Z, Pennefather P. 1987. Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine. J. Neurophysiol. 58:251–66
    [Google Scholar]
  81. Maeng S, Zarate CA Jr., Du J, Schloesser RJ, McCammon J et al. 2008. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol. Psychiatry 63:349–52
    [Google Scholar]
  82. Manji HK, Drevets WC, Charney DS. 2001. The cellular neurobiology of depression. Nat. Med. 7:541–47
    [Google Scholar]
  83. Mantovani M, Pértile R, Calixto JB, Santos AR, Rodrigues AL. 2003. Melatonin exerts an antidepressant-like effect in the tail suspension test in mice: evidence for involvement of N-methyl-d-aspartate receptors and the l-arginine-nitric oxide pathway. Neurosci. Lett. 343:11–4
    [Google Scholar]
  84. Maxwell RA, Eckhardt SB. 1990. Drug Discovery: A Casebook and Analysis New York: Springer
    [Google Scholar]
  85. McMillan R, Muthukumaraswamy SD. 2020. The neurophysiology of ketamine: an integrative review. Rev. Neurosci. 31:457–503
    [Google Scholar]
  86. Mealing G, Lanthorn T, Murray C, Small D, Morley P. 1999. Differences in degree of trapping of low-affinity uncompetitive N-methyl-d-aspartic acid receptor antagonists with similar kinetics of block. J. Pharmacol. Exp. Ther. 288:204–10
    [Google Scholar]
  87. Miletich DJ, Ivankovic AD, Albrecht RF, Zahed B, Ilahi AA. 1973. The effect of ketamine on catecholamine metabolism in the isolated perfused rat heart. Anesthesiology 39:271–77
    [Google Scholar]
  88. Miller OH, Yang L, Wang CC, Hargroder EA, Zhang Y et al. 2014. GluN2B-containing NMDA receptors regulate depression-like behavior and are critical for the rapid antidepressant actions of ketamine. eLife 3:e03581
    [Google Scholar]
  89. Moda-Sava RN, Murdock MH, Parekh PK, Fetcho RN, Huang BS et al. 2019. Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation. Science 364:6436eaat8078
    [Google Scholar]
  90. Moghaddam B, Adams B, Verma A, Daly D. 1997. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J. Neurosci. 17:2921–27
    [Google Scholar]
  91. Molloy BB, Wong DT, Fuller RW. 1994. The discovery of fluoxetine. Pharm. News 1:6–10
    [Google Scholar]
  92. Moskal JR, Burch R, Burgdorf JS, Kroes RA, Stanton PK et al. 2014. GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists. Expert Opin. Investig. Drugs 23:243–54
    [Google Scholar]
  93. Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE et al. 2013. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am. J. Psychiatry 170:1134–42
    [Google Scholar]
  94. Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB. 2015. Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. Am. J. Psychiatry 172:950–66
    [Google Scholar]
  95. Nolen WA, van de Putte JJ, Dijken WA, Kamp JS, Blansjaar BA et al. 1988. Treatment strategy in depression. I. Non-tricyclic and selective reuptake inhibitors in resistant depression: a double-blind partial crossover study on the effects of oxaprotiline and fluvoxamine. Acta Psychiatr. Scand. 78:668–75
    [Google Scholar]
  96. Nyström C, Hällström T. 1987. Comparison between a serotonin and a noradrenaline reuptake blocker in the treatment of depressed outpatients: a cross-over study. Acta Psychiatr. Scand. 75:377–82
    [Google Scholar]
  97. Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A et al. 2016. Major depressive disorder. Nat. Rev. Dis. Primers 2:16065
    [Google Scholar]
  98. Papakostas GI. 2008. Tolerability of modern antidepressants. J. Clin. Psychiatry 69:Suppl. E18–13
    [Google Scholar]
  99. Pham TH, Defaix C, Xu X, Deng SX, Fabresse N et al. 2018. Common neurotransmission recruited in (R,S)-ketamine and (2R,6R)-hydroxynorketamine–induced sustained antidepressant-like effects. Biol. Psychiatry 84:1E3–6
    [Google Scholar]
  100. Porsolt RD, Bertin A, Jalfre M. 1977. Behavioral despair in mice: a primary screening test for antidepressants. Arch. Int. Pharmacodyn. Ther. 229:327–36
    [Google Scholar]
  101. Preskorn S, Macaluso M, Mehra DO, Zammit G, Moskal JR, Burch RM. 2015. 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. 21:140–49
    [Google Scholar]
  102. Protti M, Mandrioli R, Marasca C, Cavalli A, Serretti A, Mercolini L. 2020. New-generation, non-SSRI antidepressants: drug-drug interactions and therapeutic drug monitoring. Part 2: NaSSAs, NRIs, SNDRIs, MASSAs, NDRIs, and others. Med. Res. Rev. 40:1794–832
    [Google Scholar]
  103. Redmond L, Ghosh A. 2005. Regulation of dendritic development by calcium signaling. Cell Calcium 37:411–16
    [Google Scholar]
  104. Riggs LM, Aracava Y, Zanos P, Fischell J, Albuquerque EX et al. 2020. (2R,6R)-hydroxynorketamine rapidly potentiates hippocampal glutamatergic transmission through a synapse-specific presynaptic mechanism. Neuropsychopharmacology 45:426–36
    [Google Scholar]
  105. Salzer HM, Lurie ML. 1953. Anxiety and depressive states treated with isonicotinyl hydrazide (isoniazid). AMA Arch. Neurol. Psychiatry 70:317–24
    [Google Scholar]
  106. Schildkraut JJ. 1965. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am. J. Psychiatry 122:509–22
    [Google Scholar]
  107. Sheppard H, Zimmerman JH. 1960. Reserpine and the levels of serotonin and norepinephrine in the brain. Nature 185:41–42
    [Google Scholar]
  108. Shore PA, Brodie BB. 1958. Effect of iproniazid on brain levels of norepinephrine and serotonin. Science 127:704
    [Google Scholar]
  109. Shore PA, Pletscher A, Tomich EG, Carlsson A, Kuntzman R, Brodie BB. 1957. Role of brain serotonin in reserpine action. Ann. N.Y. Acad. Sci. 66:609–15
    [Google Scholar]
  110. Sim K, Lau WK, Sim J, Sum MY, Baldessarini RJ. 2016. Prevention of relapse and recurrence in adults with major depressive disorder: systematic review and meta-analyses of controlled trials. Int. J. Neuropsychopharmacol. 19:2pyv076
    [Google Scholar]
  111. Sinyor M, Schaffer A, Levitt A. 2010. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial: a review. Can. J. Psychiatry 55:126–35
    [Google Scholar]
  112. Smith JA. 1953. The use of the isopropyl derivative of isonicotinylhydrazine (marsilid) in the treatment of mental disease; a preliminary report. Am. Pract. Dig. Treat. 4:519–20
    [Google Scholar]
  113. Smith TE, Weissbach H, Udenfriend S. 1963. Studies on monoamine oxidase: the mechanism of inhibition of monoamine oxidase by iproniazid. Biochemistry 2:746–51
    [Google Scholar]
  114. Sofia RD, Harakal JJ. 1975. Evaluation of ketamine HCl for anti-depressant activity. Arch. Int. Pharmacodyn. Ther. 214:68–74
    [Google Scholar]
  115. Steru L, Chermat R, Thierry B, Simon P. 1985. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–70
    [Google Scholar]
  116. Stitzel RE. 1976. The biological fate of reserpine. Pharmacol. Rev. 28:179–208
    [Google Scholar]
  117. Thompson SM, Kallarackal AJ, Kvarta MD, Van Dyke AM, LeGates TA, Cai X. 2015. An excitatory synapse hypothesis of depression. Trends Neurosci 38:279–94
    [Google Scholar]
  118. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM et al. 2010. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol. Rev. 62:405–96
    [Google Scholar]
  119. Trevino K, McClintock SM, McDonald Fischer N, Vora A, Husain MM 2014. Defining treatment-resistant depression: a comprehensive review of the literature. Ann. Clin. Psychiatry 26:222–32
    [Google Scholar]
  120. Trullas R, Skolnick P. 1990. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur. J. Pharmacol. 185:11–10
    [Google Scholar]
  121. Twarog BM, Page IH. 1953. Serotonin content of some mammalian tissues and urine and a method for its determination. Am. J. Physiol. 175:157–61
    [Google Scholar]
  122. Udenfriend S, Weissbach H, Bogdanski DF. 1957. Effect of iproniazid on serotonin metabolism in vivo. J. Pharmacol. Exp. Ther. 120:255–60
    [Google Scholar]
  123. Vos T, Abajobir AA, Abbafati C, Abbas KM, Abate KH et al. 2017. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390:1211–59
    [Google Scholar]
  124. Weil-Malherbe H, Szara SI. 1971. The Biochemistry of Functional and Experimental Psychoses Springfield, IL: Thomas
    [Google Scholar]
  125. Whitaker-Azmitia PM. 1999. The discovery of serotonin and its role in neuroscience. Neuropsychopharmacology 21:2s–8s
    [Google Scholar]
  126. WHO (World Health Organ.) 2017. Depression and Other Common Mental Disorders: Global Health Estimates Geneva: WHO
    [Google Scholar]
  127. Widman AJ, McMahon LL 2018. Disinhibition of CA1 pyramidal cells by low-dose ketamine and other antagonists with rapid antidepressant efficacy. PNAS 115:E3007–16
    [Google Scholar]
  128. Wilkinson ST, Toprak M, Turner MS, Levine SP, Katz RB, Sanacora G. 2017. A survey of the clinical, off-label use of ketamine as a treatment for psychiatric disorders. Am. J. Psychiatry 174:695–96
    [Google Scholar]
  129. Wong DT, Horng JS, Bymaster FP, Hauser KL, Molloy BB. 1974. A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p-trifluoromethylphenoxy)-n-methyl-3-phenylpropylamine. Life Sci 15:471–79
    [Google Scholar]
  130. Wong DT, Perry KW, Bymaster FP. 2005. Case history: the discovery of fluoxetine hydrochloride (Prozac). Nat. Rev. Drug Discov. 4:764–74
    [Google Scholar]
  131. Woolley DW, Shaw E 1954. A biochemical and pharmacological suggestion about certain mental disorders. PNAS 40:228–31
    [Google Scholar]
  132. Yamada J, Jinno S. 2019. Potential link between antidepressant-like effects of ketamine and promotion of adult neurogenesis in the ventral hippocampus of mice. Neuropharmacology 158:107710
    [Google Scholar]
  133. Yang Y, Cui Y, Sang K, Dong Y, Ni Z et al. 2018. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature 554:317–22
    [Google Scholar]
  134. Zanos P, Highland JN, Liu X, Troppoli TA, Georgiou P et al. 2019a. (R)-Ketamine exerts antidepressant actions partly via conversion to (2R,6R)-hydroxynorketamine, while causing adverse effects at sub-anaesthetic doses. Br. J. Pharmacol. 176:2573–92
    [Google Scholar]
  135. Zanos P, Highland JN, Stewart BW, Georgiou P, Jenne CE et al. 2019b. (2R,6R)-Hydroxynorketamine exerts mGlu2 receptor-dependent antidepressant actions. PNAS 116:6441–50
    [Google Scholar]
  136. Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J et al. 2016. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 533:481–86
    [Google Scholar]
  137. Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN et al. 2018a. Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms. Pharmacol. Rev. 70:621–60
    [Google Scholar]
  138. Zanos P, Thompson SM, Duman RS, Zarate CA Jr., Gould TD. 2018b. Convergent mechanisms underlying rapid antidepressant action. CNS Drugs 32:197–227
    [Google Scholar]
  139. Zarate CA Jr., Singh JB, Carlson PJ, Brutsche NE, Ameli R et al. 2006a. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch. Gen. Psychiatry 63:856–64
    [Google Scholar]
  140. Zarate CA Jr., Singh JB, Quiroz JA, De Jesus G, Denicoff KK et al. 2006b. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am. J. Psychiatry 163:153–55
    [Google Scholar]
  141. Zeller EA, Barsky J. 1952. In vivo inhibition of liver and brain monoamine oxidase by 1-isonicotinyl-2-isopropyl hydrazine. Proc. Soc. Exp. Biol. Med. 81:459–61
    [Google Scholar]
  142. Zeller EA, Barsky J, Fouts JR, Lazanas JC. 1955. Structural requirements for the inhibition of amine oxidases. Biochem. J. 60:v
    [Google Scholar]
  143. Zhang XL, Sullivan JA, Moskal JR, Stanton PK. 2008. A NMDA receptor glycine site partial agonist, GLYX-13, simultaneously enhances LTP and reduces LTD at Schaffer collateral-CA1 synapses in hippocampus. Neuropharmacology 55:1238–50
    [Google Scholar]
  144. Zhang Y, Lipton P. 1999. Cytosolic Ca2+ changes during in vitro ischemia in rat hippocampal slices: major roles for glutamate and Na+-dependent Ca2+ release from mitochondria. J. Neurosci. 19:3307–15
    [Google Scholar]
  145. Zheng W, Cai DB, Xiang YQ, Zheng W, Jiang WL et al. 2020. Adjunctive intranasal esketamine for major depressive disorder: a systematic review of randomized double-blind controlled-placebo studies. J. Affect. Disord. 265:63–70
    [Google Scholar]
/content/journals/10.1146/annurev-clinpsy-072120-014126
Loading
/content/journals/10.1146/annurev-clinpsy-072120-014126
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error