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Glutamate system as target for development of novel antidepressants

Published online by Cambridge University Press:  01 February 2013

Mario Catena-Dell'Osso ,
Andrea Fagiolini ,
Francesco Rotella ,
Stefano Baroni  and
Donatella Marazziti
Mario Catena-Dell'Osso*
Affiliation:
Department of Psychiatry, Neurobiology, Farmacology and Biotecnology, University of Pisa, Pisa, Italy
Andrea Fagiolini
Affiliation:
Department of Neuroscience, Division of Psychiatry, University of Siena School of Medicine, Siena, Italy
Francesco Rotella
Affiliation:
Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy
Stefano Baroni
Affiliation:
Department of Psychiatry, Neurobiology, Farmacology and Biotecnology, University of Pisa, Pisa, Italy
Donatella Marazziti
Affiliation:
Department of Psychiatry, Neurobiology, Farmacology and Biotecnology, University of Pisa, Pisa, Italy
*
*Address for correspondence: Dr. Mario Catena Dell'Osso, Department of Psychiatry, Neurobiology, Farmacology and Biotecnology, University of Pisa, via Roma, 67, I-56100 Pisa, Italy. (Email catena.mario@virgilio.it)
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Abstract

Depression is a common psychiatric condition characterized by affective, cognitive, psychomotor, and neurovegetative symptoms that interfere with a person's ability to work, study, deal with interpersonal relationships, and enjoy once-pleasurable activities. After the serendipitous discovery of the first antidepressants, for years the only pharmacodynamic mechanisms explored in the search of novel antidepressants were those related to the 3 main monoamines: serotonin, norepinephrine, and dopamine. New-generation monoaminergic antidepressants, such as selective-serotonin and dual-acting serotonin/norepinephrine reuptake inhibitors, improved treatment and quality of life of depressed patients. Nevertheless, there are still important clinical limitations: the long latency of onset of the antidepressant action; side effects, which can lead to early discontinuation; low rate of response; and high rate of relapse/recurrence. Therefore, in the last several years, the focus of research has moved from monoamines toward other molecular mechanisms, including glutamatergic (Glu) neurotransmission. This review provides a comprehensive overview of the current knowledge on the Glu system and on its relationships with mood disorders. Up to now, N-methyl-D-aspartate (NMDA) receptor antagonists, in particular ketamine, provided the most promising results in preclinical studies and produced a consistent and rapid, although transient, antidepressant effect with a good tolerability profile in humans. Although data are encouraging, more double-blind, randomized, placebo-controlled trials are needed to clarify the real potentiality of ketamine, and of the other Glu modulators, in the treatment of unipolar and bipolar depression.

Keywords

Antidepressantsdepressionglutamate (Glu)ketamineN-methyl-daspartate (NMDA) antagonistsriluzole
Type
Review Articles
Information
CNS Spectrums , Volume 18 , Issue 4 , August 2013 , pp. 188 - 198
Copyright
Copyright © Cambridge University Press 2013 

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References

1.Davidson, JR. Major depressive disorder treatment guidelines in America and Europe. J Clin Psychiatry. 2010; 71: e04.CrossRefGoogle ScholarPubMed
2.Gelenberg, AJ. A review of the current guidelines for depression treatment. J Clin Psychiatry. 2010; 71(7): e15.CrossRefGoogle ScholarPubMed
3.Stahl, MS. Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed.New York: Cambridge University Press; 2008.Google Scholar
4.Kessler, RC, Berglund, P, Demler, O. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003; 289(23): 3095–3105.CrossRefGoogle ScholarPubMed
5.World Health Organization. Data and Statistics. http://www.who.int/research/en. Accessed September 16, 2010.Google Scholar
6.Vieta, E, Colom, F. Therapeutic options in treatment-resistant depression. Ann Med. 2011; 43(7): 512–530.CrossRefGoogle ScholarPubMed
7.Kintscher, U. Reuptake inhibitors of dopamine, noradrenaline, and serotonin. Handb Exp Pharmacol. 2012; 209: 339–347.CrossRefGoogle Scholar
8.Catena-Dell'Osso, M, Marazziti, D, Rotella, F, Bellantuono, C. Emerging targets for the pharmacological treatment of depression: focus on melatonergic system. Curr Med Chem. 2012; 19(3): 428–437.CrossRefGoogle ScholarPubMed
9.Paschos, KA, Veletza, S, Chatzaki, E. Neuropeptide and sigma receptors as novel therapeutic targets for the pharmacotherapy of depression. CNS Drugs. 2009; 23(9): 755–772.CrossRefGoogle ScholarPubMed
10.Marazziti, D, Catena Dell'Osso, M, Consoli, G, Baroni, S. Second messenger modulation: a novel target of future antidepressants? Curr Med Chem. 2009; 16(35): 4679–4690.CrossRefGoogle ScholarPubMed
11.Catena-Dell'Osso, M, Bellantuono, C, Consoli, G, etal. Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development? Curr Med Chem. 2011; 18(2): 245–255.CrossRefGoogle ScholarPubMed
12.Marazziti, D, Catena-Dell'Osso, M. The role of oxytocin in neuropsychiatric disorders. Curr Med Chem. 2008; 15(7): 698–704.CrossRefGoogle ScholarPubMed
13.Coyle, JT, Leski, ML, Morrison, JH. The diverse roles of L-glutamic acid in brain signal transduction. In: Davis KL, Charney D, Coyle JT, Nemeroff C, eds. Neuropsychopharmacology: The Fifth Generation of Progress. Nashville, TN: American College of Neuropsychopharmacology/Lippincott Williams & Wilkins; 2002: 71–90.Google Scholar
14.Zarate, CA, Machado-Vieira, R, Henter, I, etal. Glutamatergic modulators: the future of treating mood disorders? Harv Rev Psychiatry. 2010; 18(5): 293–303.CrossRefGoogle ScholarPubMed
15.Preskorn, SH, Baker, B, Kolluri, S, etal. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol. 2008; 28(6): 631–637.CrossRefGoogle ScholarPubMed
16.Machado-Vieira, R, Manji, HK, Zarate, CA. The role of the tripartite glutamatergic synapse in the pathophysiology and therapeutics of mood disorders. Neuroscientist. 2009; 15(5): 525–539.CrossRefGoogle ScholarPubMed
17.Manev, H, Favaron, M, Guidotti, A, Costa, E. Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death. Mol Pharmacol. 1989; 36(1): 106–112.Google ScholarPubMed
18.Markowitz, AJ, White, MG, Kolson, DL, Jordan-Sciutto, KL. Cellular interplay between neurons and glia: toward a comprehensive mechanism for excitotoxic neuronal loss in neurodegeneration. Cellscience. 2007; 4(1): 111–146.Google Scholar
19.Dubinsky, JM. Intracellular calcium levels during the period of delayed excitotoxicity. J Neurosci. 1993; 13(2): 623–631.CrossRefGoogle ScholarPubMed
20.Hardingham, GE, Bading, H. The yin and yang of NMDA receptor signalling. Trends Neurosci. 2003; 26(2): 81–89.CrossRefGoogle ScholarPubMed
21.Vanhoutte, P, Bading, H. Opposing roles of synaptic and extrasynaptic NMDA receptors in neuronal calcium signalling and BDNF gene regulation. Curr Opin Neurobiol. 2003; 13(3): 366–371.CrossRefGoogle ScholarPubMed
22.Javitt, DC, Zukin, SR. The role of excitatory amino acids in neuropsychiatric illness. J Neuropsychiatry Clin Neurosci. 1990; 2(1): 44–52.Google ScholarPubMed
23.Machado-Vieira, R, Salvadore, G, Ibrahim, I, Diaz-Granados, N, Zarate, CA. Targeting glutamatergic signaling for the development of novel therapeutics for mood disorders. Curr Pharm Des. 2009; 15(14): 1595–1611.CrossRefGoogle ScholarPubMed
24.Kim, JS, Schmid-Burgk, W, Claus, D, Kornhuber, HH. Increased serum glutamate in depressed patients. Arch Psychiatr Nervenkr. 1982; 232(4): 299–304.CrossRefGoogle ScholarPubMed
25.Altamura, CA, Mauri, MC, Ferrara, A, etal. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993; 150(11): 1731–1733.Google ScholarPubMed
26.Mauri, MC, Ferrara, A, Boscati, L, etal. Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology. 1998; 37(3): 124–129.CrossRefGoogle ScholarPubMed
27.Levine, J, Panchalingam, K, Rapoport, A, etal. Increased cerebrospinal fluid glutamine levels in depressed patients. Biol Psychiatry. 2000; 47(7): 586–593.CrossRefGoogle ScholarPubMed
28.Mitani, H, Shirayama, Y, Yamada, T, etal. Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30(6): 1155–1158.CrossRefGoogle ScholarPubMed
29.Frye, MA, Tsai, GE, Huggins, T, Coyle, JT, Post, RM. Low cerebrospinal fluid glutamate and glycine in refractory affective disorder. Biol Psychiatry. 2007; 61(2): 162–166.CrossRefGoogle ScholarPubMed
30.Francis, PT, Poynton, A, Lowe, SL, etal. Brain amino acid concentrations and Ca2+-dependent release in intractable depression assessed antemortem. Brain Res. 1989; 494(2): 315–324.CrossRefGoogle ScholarPubMed
31.Maes, M, Verkerk, R, Vandoolaeghe, E, Lin, A, Scharpe, S. Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity. Acta Psychiatr Scand. 1998; 97(4): 302–308.CrossRefGoogle ScholarPubMed
32.Sanacora, G, Gueorguieva, R, Epperson, CN, etal. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry. 2004; 61(7): 705–713.CrossRefGoogle ScholarPubMed
33.Auer, DP, Putz, B, Kraft, E, etal. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000; 47(4): 305–313.CrossRefGoogle Scholar
34.Mirza, Y, Tang, J, Russell, A, etal. Reduced anterior cingulate cortex glutamatergic concentrations in childhood major depression. J Am Acad Child Adolesc Psychiatry. 2004; 43(3): 341–348.CrossRefGoogle ScholarPubMed
35.Hasler, G, van der Veen, JW, Tumonis, T, etal. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 2007; 64(2): 193–200.CrossRefGoogle ScholarPubMed
36.Zarate, CA Jr, Du, J, Quiroz, J, etal. Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system. Ann N Y Acad Sci. 2003; 1003: 273–291.CrossRefGoogle ScholarPubMed
37.Scarr, E, Pavey, G, Sundram, S, MacKinnon, A, Dean, B. Decreased hippocampal NMDA, but not kainate or AMPA receptors in bipolar disorder. Bipolar Disord. 2003; 5(4): 257–264.CrossRefGoogle ScholarPubMed
38.Hashimoto, K, Sawa, A, Iyo, M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry. 2007; 62(11): 1310–1316.CrossRefGoogle ScholarPubMed
39.Beneyto, M, Meador-Woodruff, JH. Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia. Synapse. 2006; 60(8): 585–598.CrossRefGoogle ScholarPubMed
40.Nowak, G, Ordway, GA, Paul, IA. Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims. Brain Res. 1995; 675(1–2): 157–164.CrossRefGoogle ScholarPubMed
41.Nudmamud-Thanoi, S, Reynolds, GP. The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders. Neurosci Lett. 2004; 372(1–2): 173–177.Google ScholarPubMed
42.McCullumsmith, RE, Kristiansen, LV, Beneyto, M, etal. Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder. Brain Res. 2007; 1127(1): 108–118.CrossRefGoogle ScholarPubMed
43.Boyce-Rustay, JM, Holmes, A. Genetic inactivation of the NMDA receptor NR2A subunit has anxiolytic and antidepressant-like effects in mice. Neuropsychopharmacology. 2006; 31(11): 2405–2414.CrossRefGoogle ScholarPubMed
44.Sanacora, G, Zarate, CA, Krystal, JH, Manji, HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008; 7(5): 426–437.CrossRefGoogle ScholarPubMed
45.Choudary, PV, Molnar, M, Evans, SJ, etal. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci U S A. 2005; 102(43): 15653–15658.CrossRefGoogle ScholarPubMed
46.Valentine, GW, Sanacora, G. Targeting glial physiology and glutamate cycling in the treatment of depression. Biochem Pharmacol. 2009; 78(5): 431–439.CrossRefGoogle ScholarPubMed
47.McCullumsmith, RE, Meador-Woodruff, JH. Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. Neuropsychopharmacology. 2002; 26(3): 368–375.CrossRefGoogle ScholarPubMed
48.Rajkowska, G, Miguel-Hidalgo, JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets. 2007; 6(3): 219–233.CrossRefGoogle ScholarPubMed
49.Soriano, FX, Hardingham, GE. Compartmentalized NMDA receptor signalling to survival and death. J Physiol. 2007; 584(2): 381–387.CrossRefGoogle ScholarPubMed
50.Hardingham, GE. Pro-survival signalling from the NMDA receptor. Biochem Soc Trans. 2006; 34(5): 936–938.CrossRefGoogle ScholarPubMed
51.Paul, IA, Skolnick, P. Glutamate and depression: clinical and preclinical studies. Ann N Y Acad Sci. 2003; 1003: 250–272.CrossRefGoogle ScholarPubMed
52.Owen, RT. Glutamatergic approaches in major depressive disorder: focus on ketamine, memantine and riluzole. Drugs Today (Barc). 2012; 48(7): 469–478.CrossRefGoogle ScholarPubMed
53.Olney, JW, Labruyere, J, Price, MT. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science. 1989; 244(4910): 1360–1362.CrossRefGoogle ScholarPubMed
54.Réus, GZ, Abelaira, HM, Stringari, RB, etal. Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats. Metab Brain Dis. 2012; 27(2): 175–182.CrossRefGoogle ScholarPubMed
55.Réus, GZ, Stringari, RB, Kirsch, TR, etal. Neurochemical and behavioural effects of acute and chronic memantine administration in rats: further support for NMDA as a new pharmacological target for the treatment of depression? Brain Res Bull. 2010; 81(6): 585–589.CrossRefGoogle ScholarPubMed
56.Garcia, LS, Comim, CM, Valvassori, SS, etal. Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(3): 450–455.CrossRefGoogle ScholarPubMed
57.Garcia, LS, Comim, CM, Valvassori, SS, etal. Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32(1): 140–144.CrossRefGoogle ScholarPubMed
58.Réus, GZ, Stringari, RB, Ribeiro, KF, etal. Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain. Behav Brain Res. 2011; 221(1): 166–171.CrossRefGoogle ScholarPubMed
59.Monteggia, LM, Gideons, E, Kavalali, ET. The role of eukaryotic elongation factor 2 kinase in rapid antidepressant action of ketamine. Biol Psychiatry. In press. DOI: 10.1016/j.biopsych.2012.09.006.Google Scholar
60.Palucha, A, Tatarczynska, E, Branski, P, etal. Group III mGlu receptor agonists produce anxiolytic- and antidepressant-like effects after central administration in rats. Neuropharmacology. 2004; 46(2): 151–159.CrossRefGoogle ScholarPubMed
61.Li, X, Need, AB, Baez, M, Witkin, JM. Metabotropic glutamate 5 receptor antagonism is associated with antidepressant-like effects in mice. J Pharmacol Exp Ther. 2006; 319(1): 254–259.CrossRefGoogle ScholarPubMed
62.Yoshimizu, T, Shimazaki, T, Ito, A, Chaki, S. An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats. Psychopharmacology (Berl). 2006; 186(4): 587–593.CrossRefGoogle ScholarPubMed
63.Yoshimizu, T, Chaki, S. Increased cell proliferation in the adult mouse hippocampus following chronic administration of group II metabotropic glutamate receptor antagonist, MGS0039. Biochem Biophys Res Commun. 2004; 315(2): 493–496.CrossRefGoogle ScholarPubMed
64.Chaki, S, Yoshikawa, T, Hirota, S, etal. MGS0039: a potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity. Neuropharmacology. 2004; 46(4): 457–467.CrossRefGoogle ScholarPubMed
65.Koike, H, Fukumoto, K, Iijima, M, Chaki, S. Role of BDNF/TrkB signaling in antidepressant-like effects of a group II metabotropic glutamate receptor antagonist in animal models of depression. Behav Brain Res. 2013; 238: 48–52.CrossRefGoogle ScholarPubMed
66.Black, MD. Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits: a review of preclinical data. Psychopharmacology (Berl). 2005; 179(1): 154–163.CrossRefGoogle ScholarPubMed
67.Bleakman, D, Lodge, D. Neuropharmacology of AMPA and kainate receptors. Neuropharmacology. 1998; 37: 1187–1204.CrossRefGoogle ScholarPubMed
68.Zarate, CA, Singh, JB, Manji, HK. Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol Psychiatry. 2006; 59(11): 1006–1020.CrossRefGoogle ScholarPubMed
69.Berman, RM, Cappiello, A, Anand, A, etal. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000; 47(4): 351–354.CrossRefGoogle ScholarPubMed
70.Zarate, CA, Singh, JB, Carlson, PJ, etal. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006; 63(8): 856–864.CrossRefGoogle ScholarPubMed
71.aan het Rot, M, Collins, KA, Murrough, JW, etal. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry. 2010; 67(2): 139–145.CrossRefGoogle ScholarPubMed
72.Diazgranados, N, Ibrahim, L, Brutsche, NE, etal. 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.CrossRefGoogle ScholarPubMed
73.Zarate, CA Jr, Brutsche, NE, Ibrahim, L, etal. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012; 71(11): 939–946.CrossRefGoogle ScholarPubMed
74.Rybakowski, JK, Permoda-Osip, A, Skibinska, M, Adamski, R, Bartkowska-Sniatkowska, A. Single ketamine infusion in bipolar depression resistant to antidepressants: are neurotrophins involved? Hum Psychopharmacol. In press. DOI: 10.1002/hup.2271.Google Scholar
75.Cusin, C, Hilton, GQ, Nierenberg, AA, Fava, M. Long-term maintenance with intramuscular ketamine for treatment-resistant bipolar II depression. Am J Psychiatry. 2012; 169(8): 868–869.CrossRefGoogle ScholarPubMed
76.DiazGranados, N, Ibrahim, LA, Brutsche, NE, etal. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010; 71(12): 1605–1611.CrossRefGoogle ScholarPubMed
77.Okamoto, N, Nakai, T, Sakamoto, K, etal. Rapid antidepressant effect of ketamine anesthesia during electroconvulsive therapy of treatment-resistant depression: comparing ketamine and propofol anesthesia. J ECT. 2010; 26(3): 223–227.CrossRefGoogle ScholarPubMed
78.Wang, X, Chen, Y, Zhou, X, etal. Effects of propofol and ketamine as combined anesthesia for electroconvulsive therapy in patients with depressive disorder. J ECT. 2012; 28(2): 128–132.CrossRefGoogle ScholarPubMed
79.Duncan, WC Jr, Selter, J, Brutsche, N, Sarasso, S, Zarate, CA Jr. Baseline delta sleep ratio predicts acute ketamine mood response in major depressive disorder. J Affect Disord. In press. DOI: 10.1016/j.jad.2012.05.042.Google Scholar
80.Zarate, CA, Singh, JB, Quiroz, JA, etal. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry. 2006; 163(1): 153–155.CrossRefGoogle ScholarPubMed
81.Zarate, CA, Payne, JL, Quiroz, J, etal. An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry. 2004; 161(1): 171–174.CrossRefGoogle ScholarPubMed
82.Sanacora, G, Kendell, SF, Levin, Y, etal. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry. 2007; 61(6): 822–825.CrossRefGoogle ScholarPubMed
83.Zarate, CA, Payne, JL, Singh, J, etal. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry. 2004; 56(1): 54–60.CrossRefGoogle ScholarPubMed
84.Zarate, CA, Quiroz, JA, Singh, JB, etal. An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol Psychiatry. 2005; 57(4): 430–432.CrossRefGoogle ScholarPubMed
85.Mathew, SJ, Murrough, JW, aan het Rot, M, Collins, KA, Reich, DL, Charney, DS. Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial. Int J Neuropsychopharmacol. 2010; 13(1): 71–82.CrossRefGoogle ScholarPubMed
86.Duman, RS, Aghajanian, GK. Synaptic dysfunction in depression: potential therapeutic targets. Science. 2012; 338(6103): 68–72.CrossRefGoogle ScholarPubMed
87.Liebrenz, M, Stohler, R, Borgeat, A. Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression. World J Biol Psychiatry. 2009; 10(4 pt 2): 640–643.CrossRefGoogle Scholar
88.Messer, M, Haller, IV, Larson, P, Pattison-Crisostomo, J, Gessert, CE. The use of a series of ketamine infusions in two patients with treatment-resistant depression. J Neuropsychiatry Clin Neurosci. 2010; 22(4): 442–444.CrossRefGoogle ScholarPubMed
89.Zarate, CA, Charney, DS, Manji, HK. Searching for rational anti-N-methyl-D-asparte treatment for depression. Arch Gen Psychiatry. 2007; 64(9): 1100–1101.CrossRefGoogle Scholar
90.Maeng, S, Zarate, CA, Du, J, etal. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2007; 63(4): 349–352.CrossRefGoogle ScholarPubMed
91.Ibrahim, L, Diazgranados, N, Luckenbaugh, DA, etal. Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35(4): 1155–1159.CrossRefGoogle ScholarPubMed