Glutamatergic Modulators in Depression

Harvard Review of Psychiatry

Volumn 26, Issue 6, 2018, Pages 307-319

  Henter, Ioline D ^a   De Sousa, Rafael Teixeira ^a   Zarate, Carlos A ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

Author keywords

AMPA receptor; bipolar disorder; major depressive disorder; NMDA receptor; treatment

Indexed keywords

ANTIDEPRESSANT AGENT; AV 101; AZD 2066; BASIMGLURANT; CYCLOSERINE; DECOGLURANT; DEUDEXTROMETHORPHAN; DEXTROMETHORPHAN; DEXTROMETHORPHAN PLUS QUINIDINE; ESKETAMINE; JNJ 40411813; KETAMINE; LANICEMINE; NITROUS OXIDE; PLACEBO; R 04995819; RAPASTINEL; RISLENEMDAZ; SARCOSINE; TRAXOPRODIL; UNCLASSIFIED DRUG; AMINO ACID RECEPTOR AFFECTING AGENT; METABOTROPIC RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR;

ANTIDEPRESSANT ACTIVITY; ANXIETY DISORDER; BECK DEPRESSION INVENTORY; BIPOLAR DEPRESSION; CLINICAL GLOBAL IMPRESSION SCALE; COGNITIVE DEFECT; CYSTITIS; DEPRESSION; DISSOCIATIVE DISORDER; DIZZINESS; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MEGADOSE; DRUG POTENCY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; ELEVATED BLOOD PRESSURE; GASTROINTESTINAL SYMPTOM; HAMILTON DEPRESSION RATING SCALE; HEADACHE; HUMAN; INSOMNIA; MAINTENANCE THERAPY; MAJOR DEPRESSION; MANIA; MONOTHERAPY; MONTGOMERY ASBERG DEPRESSION RATING SCALE; NAUSEA; NAUSEA AND VOMITING; NEUROTOXICITY; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; PSYCHOSIS; QT PROLONGATION; REMISSION; REVIEW; SEDATION; SEIZURE; SIDE EFFECT; SLEEP DISORDER; SUICIDAL IDEATION; TACHYCARDIA; TINNITUS; TREATMENT RESISTANT DEPRESSION; VERTIGO; VISUAL DISORDER; YOUNG MANIA RATING SCALE; BIPOLAR DISORDER; DRUG EFFECT;

ANTIDEPRESSIVE AGENTS; BIPOLAR DISORDER; DEPRESSIVE DISORDER, MAJOR; EXCITATORY AMINO ACID AGENTS; HUMANS; RECEPTORS, METABOTROPIC GLUTAMATE; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 85052600459     PISSN: 10673229     EISSN: 14657309     Source Type: Journal    
DOI: 10.1097/HRP.0000000000000183     Document Type: Review

References (105)

1. Trivedi MH, Rush AJ,Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurementbased care in STAR∗D: implications for clinical practice. Am J Psychiatry 2006;163:28-40.
2. Grande I, BerkM, Birmaher B, Vieta E. Bipolar disorder. Lancet 2016;387:1561-72.
3. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007;356:1711-22.
4. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002;59:530-7.
5. Machado-Vieira R, Salvadore G, Diazgranados N, Zarate CAJ. Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther 2009;123:143-50.
6. Yildiz-Yesiloglu A, Ankerst DP. Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: a meta-analysis. Psychiatry Res 2006;147:1-25.
7. Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 2007;64:193-200.
8. Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 2000;47:305-13.
9. Arnone D, Mumuni AN, Jauhar S, Condon B, Cavanagh J. Indirect evidence of selective glial involvement in glutamatebased mechanisms of mood regulation in depression: metaanalysis of absolute prefrontal neuro-metabolic concentrations. Eur Neuropsychopharmacol 2015;25:1109-17.
10. Sanacora G, Gueorguieva R, Epperson CN, et al. Subtypespecific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 2004;61:705-13.
11. Port JD, Unal SS, Mrazek DA, Marcus SM. Metabolic alterations in medication-free patients with bipolar disorder: a 3 T CSF-corrected magnetic resonance spectroscopic imaging study. Psychiatry Res 2008;162:113-21.
12. Kaufman RE,OstacherMJ, Marks EH, et al. Brain GABA levels in patients with bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:427-34.
13. ZanettiMV, OtaduyMC, de Sousa RT, et al. Bimodal effect of lithium plasma levels on hippocampal glutamate concentrations in bipolar II depression: a pilot study. Int J Neuropsychopharmacol 2014;18(6).
14. Chitty KM, Lagopoulos J, Lee RS, Hickie IB, Hermens DF. A systematic review and meta-analysis of proton magnetic resonance spectroscopy and mismatch negativity in bipolar disorder. Eur Neuropsychopharmacol 2013;23:1348-63.
15. GiganteAD, Bond DJ, Lafer B, LamRW, Young LT,YathamLN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. Bipolar Disord 2012;14:478-87.
16. De Sousa RT, Loch AA, Carvalho AF, et al. Genetic studies on the tripartite glutamate synapse in the pathophysiology and therapeutics of mood disorders. Neuropsychopharmacology 2017;42:787-800.
17. 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;67:793-802.
18. Zarate CA, Jr, Brutsche NE, Ibrahim L, et al. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 2012;71:939-46.
19. Kohrs R, Durieux ME. Ketamine: teaching an old drug new tricks. Anesth Analg 1998;87:1186-93.
20. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000;47:351-4.
21. Zarate CA, Jr, Singh JB, Quiroz JA, et al. A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry 2006;163:153-5.
22. 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;6:97-114.
23. aan het RotM, Collins KA, Murrough JW, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatmentresistant depression. Biol Psychiatry 2010;67:139-45.
24. Sanacora G, Johnson M, Khan A, Atkinson S, Riesenberg R, Schronen J. Adjunctive lanicemine (AZD6765) in patientswith major depressive disorder and a history of inadequate response to antidepressants: primary results froma randomized, placebo controlled study (PURSUIT). Paper presented at the 53rdmeeting of the American Society of Clinical Psychiatry, Hollywood, FL, June 2014.
25. Insel TR. The NIMH Research Domain Criteria (RDoC) Project: precision medicine for psychiatry. Am J Psychiatry 2014; 171:395-7.
26. Park M, Niciu MJ, Zarate CA Jr. Novel glutamatergic treatments for severe mood disorders. Curr Behav Neurosci Rep 2015;2:198-208.
27. Niciu MJ, Henter ID, Luckenbaugh DA, Zarate CAJ, Charney DS. Glutamate receptor antagonists as fast-acting therapeutic alternatives for the treatment of depression: ketamine and other compounds. Annu Rev Pharmacol Toxicol 2014;54:119-39.
28. Lener MS, Iosifescu DV. In pursuit of neuroimaging biomarkers to guide treatment selection in major depressive disorder: a review of the literature. Ann N Y Acad Sci 2015; 1344:50-65.
29. Machado-Vieira R, Salvadore G, Luckenbaugh DA,Manji HK, Zarate CAJ. Rapid onset of antidepressant action: a new paradigm in the research and treatment ofmajor depressive disorder. J Clin Psychiatry 2008;69:946-58.
30. Newport DJ, Carpenter LL, McDonald WM, et al. Ketamine and otherNMDA antagonists: early clinical trials and possible mechanisms in depression. Am J Psychiatry 2015;172:950-66.
31. Kishimoto T, Chawla JM, Hagi K, et al. Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a metaanalysis of efficacy, safety and time trajectories. Psychol Med 2016;46:1459-72.
32. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 1989; 36:186-97.
33. Green SM, Rothrock SG, Harris T, Hopkins GA, Garrett W, Sherwin T. Intravenous ketamine for pediatric sedation in the emergency department: safety profile with 156 cases. Acad Emerg Med 1998;5:971-6.
34. Green SM, Rothrock SG, Lynch EL, et al. Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases. Ann Emerg Med 1998;31: 688-97.
35. Ionescu DF, Luckenbaugh DA, Niciu MJ, Richards EM, Zarate CA, Jr. A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar Disord 2015;17:438-43.
36. Murrough JW, Wan LB, Iacoviello B, et al. Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response. Psychopharmacology (Berl) 2013;Sep 11 [Epub ahead of print].
37. Sos P, Klirova M, Novak T, Kohutova B, Horacek J, Palenicek T. Relationship of ketamine's antidepressant and psychotomimetic effects in unipolar depression. Neuro Endocrinol Lett 2013;34:287-93.
38. DiazGranados N, Ibrahim LA, Brutsche NE, et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatmentresistant major depressive disorder. J Clin Psychiatry 2010;71: 1605-11.
39. Lally N, Nugent AC, Luckenbaugh D, Niciu MJ, Roiser JP, Zarate CA. Neural correlates of change in anhedonia following ketamine in major depressive disorder. J Psychopharmacol 2015;29:596-607.
40. Lally N, Nugent AC, Luckenbaugh DA, Ameli R, Roiser JP, Zarate CA. Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Transl Psychiatry 2014;4:e469.
41. Saligan LN, Luckenbaugh D, Slonena EE, Machado-Vieira R, ZarateCA, Jr. An assessment of anti-fatigue effects of ketamine from a double-blind, placebo-controlled, crossover study in bipolar disorder. J Affect Disord 2016;194:115-9.
42. Parsaik AK, Singh B, Khosh-Chashm D, Mascarenhas SS. Efficacy of ketamine in bipolar depression: systematic review and meta-analysis. J Psychiatr Pract 2015;21:427-35.
43. Permoda-Osip A, Kisielewski J, Bartkowska-Sniatkowska A, Rybakowski JK. Single ketamine infusion and neurocognitive performance in bipolar depression. Pharmacopsychiatry 2015; 48:78-9.
44. Kantrowitz JT, Halberstam B, Gangwisch J. Single-dose ketamine followed by daily D-cycloserine in treatment-resistant bipolar depression. J Clin Psychiatry 2015;76:737-8.
45. Niciu MJ, Luckenbaugh DA, Ionescu DF, Mathews DC, Richards EM, Zarate CA Jr. Subanesthetic dose ketamine does not induce an affective switch in three independent samples of treatment-resistant major depression. Biol Psychiatry 2013;74: e23-4.
46. Price RB, Nock MK, Charney DS, Mathew SJ. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry 2009;66:522-6.
47. 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;31:335-43.
48. Murrough JW, Soleimani L, DeWilde KE, et al. Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. Psychol Med 2015;45:3571-80.
49. Ballard ED, Ionescu DF, Vande Voort JL, et al. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. J Psychiatr Res 2014;58: 161-6.
50. Xu Y, Hackett M, Carter G, et al. Effects of low-dose and very low-dose ketamine among patients with major depression: a systematic review and meta-analysis. Int J Neuropsychopharmacol 2016;19(4).
51. Vande Voort JL, Ballard ED, Luckenbaugh D, et al. Antisuicidal response following ketamine infusion is associated with decreased nighttime wakefulness in major depressive disorder and bipolar disorder. J Clin Psychiatry 2017;78: 1068-74.
52. Lapidus KA, Levitch CF, Perez AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry 2014;76:970-6.
53. Chilukuri H, Reddy NP, Pathapati RM, Manu AN, Jollu S, Shaik AB. Acute antidepressant effects of intramuscular versus intravenous ketamine. Indian J Psychol Med 2014;36:71-6.
54. Glue P,Gulati A, LeNedelec M, Duffull S.Dose- and exposureresponse to ketamine in depression. Biol Psychiatry 2011;70: e9-10; author reply e11-2.
55. Irwin SA, Iglewicz A. Oral ketamine for the rapid treatment of depression and anxiety in patients receiving hospice care. J Palliat Med 2010;13:903-8.
56. PaslakisG, Gilles M, Meyer-Lindenberg A, DeuschleM.Oral administration of the NMDA receptor antagonist S-ketamine as add-on therapy of depression: a case series. Pharmacopsychiatry 2010;43:33-5.
57. Irwin SA, Iglewicz A,Nelesen RA, et al. Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial. J Palliat Med 2013;16:958-65.
58. De Gioannis A, De Leo D. Oral ketamine augmentation for chronic suicidality in treatment-resistant depression. Aust N Z J Psychiatry 2014;48:686.
59. Lara DR, Bisol LW, Munari LR. Antidepressant, mood stabilizing and procognitive effects of very lowdose sublingual ketamine in refractory unipolar and bipolar depression. Int J Neuropsychopharmacol 2013;16:2111-7.
60. Sanacora G,Heimer H,Hartman D, et al. Balancing the promise and risks of ketamine treatment formood disorders.Neuropsychopharmacology 2017;42:1179-81.
61. Morgan CJ, Curran HV; Independent Scientific Committee on Drugs. Ketamine use: a review. Addiction 2012;107:27-38.
62. Zanos P, Moaddel R, Morris PJ, et al. NMDAR inhibition-independent antidepressant actions of a ketamine metabolite. Nature 2016;533:481-6.
63. Domino EF. Taming the ketamine tiger. 1965. Anesthesiology 2010;113:678-84.
64. Oye I, Paulsen O, Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors. J Pharmacol Exp Ther 1992;260:1209-13.
65. Singh JB, FedgchinM, Daly E, et al. Intravenous esketamine in adult treatment-resistant depression: a double-blind, doublerandomization, placebo-controlled study. Biol Psychiatry 2016;80:424-31.
66. Daly EJ, Singh JB, FedgchinM, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry 2017;Dec 27 [Epub ahead of print].
67. Canuso CM, Singh J, Fedgchin M, et al. PeRSEVERe: a study of esketamine for the rapid reduction of the symptoms ofmajor depressive disorder, including suicidal ideation, in patients assessed to be at imminent risk for suicide. Paper presented at the annual meeting of the American Society of Clinical Psychopharmacology, Scottsdale, AZ, May-June 2016.
68. Esketamine receives breakthrough therapy designation from food and drug administration for major depressive disorder with imminent risk for suicide. 2016. http://www.jnj.com/ news/all/Esketamine-Receives-Breakthrough-Therapy-Designation-from-US-Food-and-Drug-Administration-for-Major-Depressive-Disorder-with-Imminent-Risk-for-Suicide
69. Lauterbach EC. Dextromethorphan as a potential rapid-acting antidepressant. Med Hypotheses 2011;76:717-9.
70. Lauterbach EC. An extension of hypotheses regarding rapidacting, treatment-refractory, and conventional antidepressant activity of dextromethorphan and dextrorphan.Med Hypotheses 2012;78:693-702.
71. Lee SY, Chen SL, Chang YH, et al. The DRD2/ANKK1 gene is associated with response to add-on dextromethorphan treatment in bipolar disorder. J Affect Disord 2012;138: 295-300.
72. Kelly TF, Lieberman DZ. The utility of the combination of dextromethorphan and quinidine in the treatment of bipolar II and bipolar NOS. J Affect Disord 2014;167:333-5.
73. Messias E, Everett B.Dextromethorphan and quinidine combination in emotional lability associated with depression: a case report. Prim Care Companion CNS Disord 2012;14(5).
74. Murrough JW, Wade E, Sayed S, et al. Dextromethorphan/ quinidine pharmacotherapy in patients with treatment resistant depression: a proof of concept clinical trial. J Affect Disord 2017;218:277-83.
75. Nagele P, Duma A, Kopec M, et al. Nitrous oxide for treatment-resistant major depression: a proof-of-concept trial. Biol Psychiatry 2015;78:10-8.
76. Zarate CA, MathewsD, IbrahimL, et al. A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression. Biol Psychiatry 2013;74:257-64.
77. Sanacora G, Schatzberg AF. Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders? Neuropsychopharmacology 2015;40:259-67.
78. Drug profile: AZD 6765. 2017. http://adisinsight.springer. com/drugs/800026805.
79. Preskorn SH, Baker B, Kolluri S, Menniti FS, Krams M, Landen JW. 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;28:631-7.
80. Ibrahim L, Diazgranados N, Jolkovsky L, et al. A randomized, placebo-controlled, crossover pilot trial of the oral selective NR2B antagonist MK-0657 in patients with treatmentresistant major depressive disorder. J Clin Psychopharmacol 2012;32:551-7.
81. CERC-301: an NR2B-specific NMDA antagonist that may provide a rapid onset of action. 2017. http://www.cerecor. com/pipeline/cerc-301.php
82. MacDougall Biomedical Communications. Cerecor provides update on CERC-301 development in major depressive disorder. 2015. https://www.businesswire.com/news/home/ 20150320005079/en/Cerecor-Update-CERC-301-Development-Major-Depressive-Disorder
83. Paterson B, Fraser H, Wang C, Marcus R. A randomized, double-blind, placebo-controlled, sequential parallel study of CERC-301 in the adjunctive treatment of subjects with severe depression and recent active suicidal ideation despite antidepressant treatment. Paper presented at the National Network of Depression Centers annual conference, Ann Arbor, MI, November 2015.
84. Millan MJ. N-methyl-D-aspartate receptor-coupled glycineB receptors in the pathogenesis and treatment of schizophrenia: a critical review. Curr Drug Targets CNS Neurol Disord 2002;1:191-213.
85. Viu E, Zapata A, Capdevila JL, Fossom LH, Skolnick P, Trullas R. Glycine site antagonists and partial agonists inhibit N-methyl-D-aspartate receptor-mediated [3H]arachidonic acid release in cerebellar granule cells. J Pharmacol Exp Ther 1998;285:527-32.
86. Heresco-Levy U, Javitt DC, Gelfin Y, et al. Controlled trial of D-cycloserine adjuvant therapy for treatment-resistant major depressive disorder. J Affect Disord 2006;93:239-43.
87. Heresco-Levy U,GelfinG, Bloch B, et al.A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression. Int J Neuropsychopharmacol 2013;16:501-6.
88. Nathanson E, Gupta R, Huamani P, et al. Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative. Int J Tuberc Lung Dis 2004;8: 1382-4.
89. Moskal JR, Burch R, Burgdorf JS, et al. 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 2014;23:243-54.
90. Preskorn S,MacalusoM,MehraDO, et al. 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;21:140-9.
91. Allergan's rapastinel receives FDA breakthrough therapy designation for adjunctive treatment of major depressive disorder (MDD). 2016. https://www.allergan.com/news/news/thomsonreuters/ allergan-s-rapastinel-receives-fda-breakthrough-th
92. Huang C-C, HuaWei I, Huang C-L, et al. Inhibition of glycine transporter-I as a novelmechanismfor the treatment of depression. Biol Psychiatry 2013;74:734-41.
93. Salituro FG, Tomlinson RC, Baron BM, et al. Enzymeactivated antagonists of the strychnine-insensitive glycine/ NMDA receptor. J Med Chem 1994;37:334-6.
94. Zanos P, Piantadosi SC, Wu HQ, et al. The prodrug 4-chlorokynurenine causes ketamine-like antidepressant effects, but not side effects, by NMDA/glycineB-site inhibition. J Pharmacol Exp Ther 2015;355:76-85.
95. Lujan R, Roberts JD, ShigemotoR,OhishiH, Somogyi P. Differential plasma membrane distribution ofmetabotropic glutamate receptors mGluR1 alpha,mGluR2 and mGluR5, relative to neurotransmitter release sites. J Chem Neuroanat 1997;13:219-41.
96. Kuwajima M, Hall RA, Aiba A, Smith Y. Subcellular and subsynaptic localization of group I metabotropic glutamate receptors in the monkey subthalamic nucleus. J Comp Neurol 2004;474:589-602.
97. Shigemoto R, Kinoshita A, Wada E, et al. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci 1997;17:7503-22.
98. Aronica E, Gorter JA, Ijlst-Keizers H, et al. Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Eur J Neurosci 2003;17:2106-18.
99. Quiroz JA, Tamburri P, Deptula D, et al. Efficacy and safety of basimglurant as adjunctive therapy for major depression: a randomized clinical trial. JAMA Psychiatry 2016;73:675-84.
100. Kent JM, Daly E, Kezic I, et al. Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/ SNRI in anxious depression. Prog Neuropsychopharmacol Biol Psychiatry 2016;67:66-73.
101. Javelot H. [Psychopharmacology of anxiety and depression: historical aspects, current treatment and perspectives]. Ann Pharm Fr 2016;74:93-118.
102. Roche. 2014 results. 2015. https://www.roche.com/irp150128.pdf
103. Sanacora G, Frye MA,McDonaldW, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry 2017;74:399-405.
104. Zarate CA, Jr, Mathews DC, Furey ML. Human biomarkers of rapid antidepressant effects. Biol Psychiatry 2014; 73:1142-55.
105. Niciu MJ, Mathews DC, Nugent AC, et al. Developing biomarkers in mood disorders research through the use of rapidacting antidepressants. Depress Anxiety 2014;31:297-307.