Ketamine: A Promising Rapid-Acting Antidepressant

  • Samuel T. Wilkinson
  • Robert B. Ostroff
  • Rachel B. Katz
  • John H. Krystal
Chapter

Abstract

The monoaminergic deficiency hypothesis of depression has dominated the field of mood disorders research for several decades. This hypothesis has led to many advancements, including the theoretical underpinnings of the mechanism of action of all current oral antidepressants. However, the monoaminergic deficiency hypothesis does not fully explain the neurobiology of mood disorders, including the high rates of non-response and the delayed time between initiation of therapy and improvement in mood and related symptoms. Emerging evidence suggests a strong role for the glutamatergic system in the pathophysiology of mood disorders, which may provide more efficient therapeutic targets in the development of novel antidepressants. Ketamine, which acts directly on a glutamatergic receptor (N-methyl-d-aspartate receptor), has been shown to produce robust and rapid antidepressant effects after just a single dose. The effects of a single-dose have been replicated in several clinical trials of modest size. Less is known about multiple dosing protocols. While ketamine is approved by the Food and Drug Administration and similar agencies as an anesthetic, it is not approved in any country as an antidepressant. Concerns of the long-term effects on cognition and abuse from repeated ketamine exposure motivate the search for relapse prevention strategies that do not involve repeated administration of the drug. Given that a growing number of providers have begun offering ketamine off-label for the treatment of psychiatric disorders, future research is urgently needed to better understand long-term risks as well as evidence-based treatment regimens.

Keywords

Ketamine Major depressive disorder Treatment 

References

  1. Abdallah CG, Jiang L, De Feyter HM, Fasula M, Krystal JH, Rothman DL, Mason GF, Sanacora G. Glutamate metabolism in major depressive disorder. Am J Psychiatry. 2014a;171:1320–7.CrossRefGoogle Scholar
  2. Abdallah CG, Niciu MJ, Fenton LR, Fasula MK, Jiang L, Black A, Rothman DL, Mason GF, Sanacora G. Decreased occipital cortical glutamate levels in response to successful cognitive-behavioral therapy and pharmacotherapy for major depressive disorder. Psychother Psychosom. 2014b;83:298–307.CrossRefGoogle Scholar
  3. Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annu Rev Med. 2015;66:509–23.CrossRefGoogle Scholar
  4. Allain N, Leven C, Falissard B, Allain JS, Batail JM, Polard E, Montastruc F, Drapier D, Naudet F. Manic switches induced by antidepressants: an umbrella review comparing randomized controlled trials and observational studies. Acta Psychiatr Scand. 2017;135:106–16.CrossRefGoogle Scholar
  5. Altamura CA, Mauri MC, Ferrara A, Moro AR, D’Andrea G, Zamberlan F. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993;150:1731–3.CrossRefGoogle Scholar
  6. Amital D, Fostick L, Silberman A, Beckman M, Spivak B. Serious life events among resistant and non-resistant MDD patients. J Affect Disord. 2008;110:260–4.CrossRefGoogle Scholar
  7. Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord. 2000;58:19–36.CrossRefGoogle Scholar
  8. Anderson IM. Meta-analytical studies on new antidepressants. Br Med Bull. 2001;57:161–78.CrossRefGoogle Scholar
  9. Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, Luckenbaugh DA, Brutsche NE, Ameli R, Furey ML, Zarate CA Jr. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. J Psychiatr Res. 2014;58:161–6.CrossRefGoogle Scholar
  10. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47:351–4.CrossRefGoogle Scholar
  11. Bloch MH, Wasylink S, Landeros-Weisenberger A, Panza KE, Billingslea E, Leckman JF, Krystal JH, Bhagwagar Z, Sanacora G, Pittenger C. Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Biol Psychiatry. 2012;72:964–70.CrossRefGoogle Scholar
  12. Bobo WV, Voort JL, Croarkin PE, Leung JG, Tye SJ, Frye MA. Ketamine for treatment-resistant unipolar and bipolar major depression: critical review and implications for clinical practice. Depress Anxiety. 2016;33:698–710.CrossRefGoogle Scholar
  13. Bokor G, Anderson PD. Ketamine: an update on its abuse. J Pharm Pract. 2014;27:582–6.CrossRefGoogle Scholar
  14. Brown WA, Rosdolsky M. The clinical discovery of imipramine. Am J Psychiatry. 2015;172:426–9.CrossRefGoogle Scholar
  15. Buchborn T, Schroder H, Hollt V, Grecksch G. Repeated lysergic acid diethylamide in an animal model of depression: normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling. J Psychopharmacol. 2014;28:545–52.CrossRefGoogle Scholar
  16. Calabrese JR, Kasper S, Johnson G, Tajima O, Vieta E, Yatham LN, Young AH. International consensus group on bipolar I depression treatment guidelines. J Clin Psychiatry. 2004;65:571–9.CrossRefGoogle Scholar
  17. Cavanagh JT, Carson AJ, Sharpe M, Lawrie SM. Psychological autopsy studies of suicide: a systematic review. Psychol Med. 2003;33:395–405.CrossRefGoogle Scholar
  18. Chang LC, Rajagopalan S, Mathew SJ. The history of ketamine use and its clinical indications. In: Mathew SJ, Zarate CA, editors. Ketamine for treatment-resistant depression: the first decade of progress. Cham: Adis; 2016.Google Scholar
  19. Conway CR, Gebara MA, Walker MC, Lessov-Schlaggar CN, Janski AM, Chibnall JT, Cristancho P, Sheline YI, Gott BM, Svrakic DM. Clinical characteristics and management of treatment-resistant depression. J Clin Psychiatry. 2015;76:1569–70.CrossRefGoogle Scholar
  20. Crown WH, Finkelstein S, Berndt ER, Ling D, Poret AW, Rush AJ, Russell JM. The impact of treatment-resistant depression on health care utilization and costs. J Clin Psychiatry. 2002;63:963–71.CrossRefGoogle Scholar
  21. Dakwar E, Anerella C, Hart CL, Levin FR, Mathew SJ, Nunes EV. Therapeutic infusions of ketamine: do the psychoactive effects matter? Drug Alcohol Depend. 2014;136:153–7.CrossRefGoogle Scholar
  22. Delgado PL, Miller HL, Salomon RM, Licinio J, Heninger GR, Gelenberg AJ, Charney DS. Monoamines and the mechanism of antidepressant action: effects of catecholamine depletion on mood of patients treated with antidepressants. Psychopharmacol Bull. 1993;29:389–96.PubMedGoogle Scholar
  23. Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA Jr. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry. 2010;67:793–802.CrossRefGoogle Scholar
  24. Domino EF. Taming the ketamine tiger. 1965. Anesthesiology. 2010;113:678–84.PubMedGoogle Scholar
  25. Domino EF, Chodoff P, Corssen G. Pharmacologic effects of CI-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther. 1965;6:279–91.CrossRefGoogle Scholar
  26. Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001;62:869–77.CrossRefGoogle Scholar
  27. Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003;53:649–59.CrossRefGoogle Scholar
  28. Fava M, Davidson KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin N Am. 1996;19:179–200.CrossRefGoogle Scholar
  29. Fava M, Rush AJ, Alpert JE, Balasubramani GK, Wisniewski SR, Carmin CN, Biggs MM, Zisook S, Leuchter A, Howland R, Warden D, Trivedi MH. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry. 2008;165:342–51.CrossRefGoogle Scholar
  30. Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71:681–8.CrossRefGoogle Scholar
  31. Fontana AE, Loschi JA. Antidepressive therapy with C1 581. Acta Psiquiatr Psicol Am Lat. 1974;20:32–9.PubMedGoogle Scholar
  32. Francis PT, Poynton A, Lowe SL, Najlerahim A, Bridges PK, Bartlett JR, Procter AW, Bruton CJ, Bowen DM. Brain amino acid concentrations and Ca2+-dependent release in intractable depression assessed antemortem. Brain Res. 1989;494:315–24.CrossRefGoogle Scholar
  33. Frye MA, Tsai GE, Huggins T, Coyle JT, Post RM. Low cerebrospinal fluid glutamate and glycine in refractory affective disorder. Biol Psychiatry. 2007;61:162–6.CrossRefGoogle Scholar
  34. Gaebel W, Falkai P, Bitter I. Ketamine in psychiatric treatment and research: position statement of the European Psychiatric Association. European Psychiatric Association; 2015.Google Scholar
  35. Gerz HO. A preliminary report on a new benzodiazepine in severe depressions. Am J Psychiatry. 1964;121:495–6.CrossRefGoogle Scholar
  36. Goldberg ME, Domsky R, Scaringe D, Hirsh R, Dotson J, Sharaf I, Torjman MC, Schwartzman RJ. Multi-day low dose ketamine infusion for the treatment of complex regional pain syndrome. Pain Physician. 2005;8:175–9.PubMedGoogle Scholar
  37. Greenberg PE, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, Berglund PA, Corey-Lisle PK. The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry. 2003;64:1465–75.CrossRefGoogle Scholar
  38. Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30:1181–97.CrossRefGoogle Scholar
  39. Haile CN, Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Foulkes A, Iqbal S, Mahoney JJ 3rd, De La Garza R 2nd, Charney DS, Newton TF, Mathew SJ. Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. Int J Neuropsychopharmacol. 2014;17:331–6.CrossRefGoogle Scholar
  40. Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: from monoamines to glutamate. Exp Clin Psychopharmacol. 2015;23:1–21.CrossRefGoogle Scholar
  41. Hirschfeld RM. History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry. 2000;61(Suppl 6):4–6.Google Scholar
  42. Hollon SD, Stewart MO, Strunk D. Enduring effects for cognitive behavior therapy in the treatment of depression and anxiety. Annu Rev Psychol. 2006;57:285–315.CrossRefGoogle Scholar
  43. Hood RW Jr. The construction and preliminary validation of a measure of reported mystical experience. J Sci Study Relig. 1975;14:29–41.CrossRefGoogle Scholar
  44. Hu YD, Xiang YT, Fang JX, Zu S, Sha S, Shi H, Ungvari GS, Correll CU, Chiu HF, Xue Y, Tian TF, Wu AS, Ma X, Wang G. Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study. Psychol Med. 2016;46:623–35.CrossRefGoogle Scholar
  45. Ibrahim L, Diazgranados N, Franco-Chaves J, Brutsche N, Henter ID, Kronstein P, Moaddel R, Wainer I, Luckenbaugh DA, Manji HK, Zarate CA Jr. Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study. Neuropsychopharmacology. 2012;37:1526–33.CrossRefGoogle Scholar
  46. Ionescu DF, Luckenbaugh DA, Niciu MJ, Richards EM, Slonena EE, Vande Voort JL, Brutsche NE, Zarate CA Jr. Effect of baseline anxious depression on initial and sustained antidepressant response to ketamine. J Clin Psychiatry. 2014;75:e932–8.CrossRefGoogle Scholar
  47. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:3095–105.CrossRefGoogle Scholar
  48. Kim J, Mierzwinski-Urban M. Ketamine for treatment resistant depression or post-traumatic stress disorder in various settings: a review of clinical effectiveness, safety, and guidelines. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2017.Google Scholar
  49. Kohrs R, Durieux ME. Ketamine: teaching an old drug new tricks. Anesth Analg. 1998;87:1186–93.PubMedGoogle Scholar
  50. Kolp E, Young M, Friedman H, Krupitsky E, Jansen K, O’Connor L. Ketamine-enhanced psychotherapy: preliminary clinical observations on its effects in treating death anxiety. Int J Transpersonal Stud. 2007;26:1–17.CrossRefGoogle Scholar
  51. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994;51:199–214.CrossRefGoogle Scholar
  52. Krystal JHD, Souza DC, Petrakis IL, Belger A, Berman RM, Charney DS, Abi-Saab W, Madonick S. NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies in neuropsychiatric disorders. Harv Rev Psychiatry. 1999;7:125–43.CrossRefGoogle Scholar
  53. Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, Epperson CN, Goddard A, Mason GF. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry. 2002;7(Suppl 1):S71–80.CrossRefGoogle Scholar
  54. Laje G, Lally N, Mathews D, Brutsche N, Chemerinski A, Akula N, Kelmendi B, Simen A, McMahon FJ, Sanacora G, Zarate C Jr. Brain-derived neurotrophic factor Val66Met polymorphism and antidepressant efficacy of ketamine in depressed patients. Biol Psychiatry. 2012;72:e27–8.CrossRefGoogle Scholar
  55. Lapidus KA, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, Feder A, Iosifescu DV, Charney DS, Murrough JW. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry. 2014;76:970–6.CrossRefGoogle Scholar
  56. Lenze EJ, Farber NB, Kharasch E, Schweiger J, Yingling M, Olney J, Newcomer JW. Ninety-six hour ketamine infusion with co-administered clonidine for treatment-resistant depression: a pilot randomised controlled trial. World J Biol Psychiatry. 2016;17:230–8.CrossRefGoogle Scholar
  57. Levine J, Panchalingam K, Rapoport A, Gershon S, McClure RJ, Pettegrew JW. Increased cerebrospinal fluid glutamine levels in depressed patients. Biol Psychiatry. 2000;47:586–93.CrossRefGoogle Scholar
  58. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329:959–64.CrossRefGoogle Scholar
  59. Li JH, Vicknasingam B, Cheung YW, Zhou W, Nurhidayat AW, Jarlais DC, Schottenfeld R. To use or not to use: an update on licit and illicit ketamine use. Subst Abus Rehabil. 2011;2:11–20.CrossRefGoogle Scholar
  60. Loomer HP, Saunders JC, Kline NS. A clinical and pharmacodynamic evaluation of iproniazid as a psychic energizer. Psychiatr Res Rep. 1957;8:129–41.Google Scholar
  61. 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;13:71–82.CrossRefGoogle Scholar
  62. Mauri MC, Ferrara A, Boscati L, Bravin S, Zamberlan F, Alecci M, Invernizzi G. Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology. 1998;37:124–9.CrossRefGoogle Scholar
  63. Mitani H, Shirayama Y, Yamada T, Maeda K, Ashby CR Jr, Kawahara R. Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2006;30:1155–8.CrossRefGoogle Scholar
  64. Morgan CJ, Mofeez A, Brandner B, Bromley L, Curran HV. Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers. Neuropsychopharmacology. 2004;29:208–18.CrossRefGoogle Scholar
  65. Morgan CJ, Muetzelfeldt L, Curran HV. Ketamine use, cognition and psychological wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and non-using controls. Addiction. 2009;104:77–87.CrossRefGoogle Scholar
  66. Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study. Addiction. 2010;105:121–33.CrossRefGoogle Scholar
  67. Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996–2013. Psychiatr Serv. 2014;65:977–87.CrossRefGoogle Scholar
  68. Muller JC, Pryor WW, Gibbons JE, Orgain ES. Depression and anxiety occurring during Rauwolfia therapy. J Am Med Assoc. 1955;159:836–9.CrossRefGoogle Scholar
  69. Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013a;170:1134–42.CrossRefGoogle Scholar
  70. Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013b;74:250–6.CrossRefGoogle Scholar
  71. Murrough JW, Soleimani L, DeWilde KE, Collins KA, Lapidus KA, Iacoviello BM, Lener M, Kautz M, Kim J, Stern JB, Price RB, Perez AM, Brallier JW, Rodriguez GJ, Goodman WK, Iosifescu DV, Charney DS. Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. Psychol Med. 2015;45:3571–80.CrossRefGoogle Scholar
  72. National Survey on Drug Use and Health. The NSDUH report: use of specific hallucinogens. Substance Abuse and Mental Health Services Administration. 2008.Google Scholar
  73. Nierenberg AA, Ostacher MJ, Calabrese JR, Ketter TA, Marangell LB, Miklowitz DJ, Miyahara S, Bauer MS, Thase ME, Wisniewski SR, Sachs GS. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am J Psychiatry. 2006;163:210–6.CrossRefGoogle Scholar
  74. Pennybaker SJ, Niciu MJ, Luckenbaugh DA, Zarate CA. Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion. J Affect Disord. 2017;208:560–6.CrossRefGoogle Scholar
  75. Pletscher A. The discovery of antidepressants: a winding path. Experientia. 1991;47:4–8.CrossRefGoogle Scholar
  76. Rasmussen KG, Lineberry TW, Galardy CW, Kung S, Lapid MI, Palmer BA, Ritter MJ, Schak KM, Sola CL, Hanson AJ, Frye MA. Serial infusions of low-dose ketamine for major depression. J Psychopharmacol. 2013;27:444–50.CrossRefGoogle Scholar
  77. Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, Flood P, Simpson HB. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38:2475–83.CrossRefGoogle Scholar
  78. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163:1905–17.CrossRefGoogle Scholar
  79. Salomon RM, Miller HL, Delgado PL, Charney D. The use of tryptophan depletion to evaluate central serotonin function in depression and other neuropsychiatric disorders. Int Clin Psychopharmacol. 1993;8(Suppl 2):41–6.CrossRefGoogle Scholar
  80. Sanacora G, Fenton LR, Fasula MK, Rothman DL, Levin Y, Krystal JH, Mason GF. Cortical gamma-aminobutyric acid concentrations in depressed patients receiving cognitive behavioral therapy. Biol Psychiatry. 2006;59:284–6.CrossRefGoogle Scholar
  81. 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;7:426–37.CrossRefGoogle Scholar
  82. Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, Summergrad P, Nemeroff CB. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74:399–405.CrossRefGoogle Scholar
  83. Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M. A review of ketamine abuse and diversion. Depress Anxiety. 2016;33:718–27.CrossRefGoogle Scholar
  84. Schak KM, Vande Voort JL, Johnson EK, Kung S, Leung JG, Rasmussen KG, Palmer BA, Frye MA. Potential risks of poorly monitored ketamine use in depression treatment. Am J Psychiatry. 2016;173:215–8.CrossRefGoogle Scholar
  85. Shiroma PR, Johns B, Kuskowski M, Wels J, Thuras P, Albott CS, Lim KO. Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression. J Affect Disord. 2014;155:123–9.CrossRefGoogle Scholar
  86. Singh JB, Fedgchin M, Daly EJ, De Boer P, Cooper K, Lim P, Pinter C, Murrough JW, Sanacora G, Shelton RC, Kurian B, Winokur A, Fava M, Manji H, Drevets WC, Van Nueten L. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry. 2016;173:816–26.CrossRefGoogle Scholar
  87. 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.PubMedGoogle Scholar
  88. Steffens DC, Krishnan KR, Helms MJ. Are SSRIs better than TCAs? Comparison of SSRIs and TCAs: a meta-analysis. Depress Anxiety. 1997;6:10–8.CrossRefGoogle Scholar
  89. Stewart WF, Ricci JA, Chee E, Hahn SR, Morganstein D. Cost of lost productive work time among US workers with depression. JAMA. 2003;289:3135–44.CrossRefGoogle Scholar
  90. Suppes T, Dennehy EB, Hirschfeld RM, Altshuler LL, Bowden CL, Calabrese JR, Crismon ML, Ketter TA, Sachs GS, Swann AC. The Texas implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005;66:870–86.CrossRefGoogle Scholar
  91. Tundo A, Calabrese JR, Proietti L, de Filippis R. Short-term antidepressant treatment of bipolar depression: are ISBD recommendations useful in clinical practice? J Affect Disord. 2015;171:155–60.CrossRefGoogle Scholar
  92. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358:252–60.CrossRefGoogle Scholar
  93. Vande Voort JL, Morgan RJ, Kung S, Rasmussen KG, Rico J, Palmer BA, Schak KM, Tye SJ, Ritter MJ, Frye MA, Bobo WV. Continuation phase intravenous ketamine in adults with treatment-resistant depression. J Affect Disord. 2016;206:300–4.CrossRefGoogle Scholar
  94. Vollenweider FX, Leenders KL, Scharfetter C, Antonini A, Maguire P, Missimer J, Angst J. Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). Eur Neuropsychopharmacol. 1997;7:9–24.CrossRefGoogle Scholar
  95. Walker AJ, Foley BM, Sutor SL, McGillivray JA, Frye MA, Tye SJ. Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance. Behav Brain Res. 2015;293:198–202.CrossRefGoogle Scholar
  96. Wilkinson ST, Sanacora G. Ketamine: a potential rapid-acting antisuicidal agent? Depress Anxiety. 2016;33:711–7.CrossRefGoogle Scholar
  97. Wilkinson ST, Toprak M, Turner MS, Levine SP, Katz RB, Sanacora G. A survey of the clinical, off-label use of ketamine as a treatment for psychiatric disorders. Am J Psychiatry. 2017a;174:695–6.CrossRefGoogle Scholar
  98. Wilkinson ST, Wright D, Fasula M, Fenton L, Griepp M, Ostroff RB, Sanacora G. Cognitive behavior therapy may sustain antidepressant effects of intravenous ketamine in treatment-resistant depression. Psychother Psychosom. 2017b;86:162–7.CrossRefGoogle Scholar
  99. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jonsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21:655–79.CrossRefGoogle Scholar
  100. World Health Organization, website 2017.Google Scholar
  101. Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, Alkondon M, Yuan P, Pribut HJ, Singh NS, Dossou KS, Fang Y, Huang XP, Mayo CL, Wainer IW, Albuquerque EX, Thompson SM, Thomas CJ, Zarate CA Jr, Gould TD. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533:481–6.CrossRefGoogle Scholar
  102. Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856–64.CrossRefGoogle Scholar
  103. Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA. Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012;71:939–46.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Samuel T. Wilkinson
    • 1
    • 2
  • Robert B. Ostroff
    • 2
  • Rachel B. Katz
    • 2
  • John H. Krystal
    • 1
    • 2
  1. 1.Yale Depression Research ProgramYale School of MedicineNew HavenUSA
  2. 2.Interventional Psychiatric ServiceYale-New Haven HospitalNew HavenUSA

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