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Systematic Review January 4, 2022

The Effects of Ketamine on Cognition in Unipolar and Bipolar Depression: A Systematic Review

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J Clin Psychiatry 2022;83(1):21r13870


ABSTRACT

Objective: To determine the objective neurocognitive effects of (1) single-dose ketamine, (2) repeated-dose ketamine, (3) ketamine adjunct to electroconvulsive therapy (ECT), and (4) ketamine as the anesthetic for ECT in major depressive disorder (MDD) and depression in bipolar disorder (BD).

Data Sources: Cochrane, MEDLINE, Embase, and PsycINFO databases were searched on March 19, 2020 (updated July 2, 2020), using the terms terms major depressive disorder bipolar disorder and ketamine and their synonyms. Clinical trial registries (search date May 4, 2020) and reference sections of included articles were also searched. There was no restriction on language or year of publication.

Study Selection: Of 4,035 identified articles, 17 met inclusion criteria. Controlled and open-label studies of adults who received at least 1 ketamine treatment for a current major depressive episode, as part of MDD or BD, were included. Only studies measuring cognition using at least 1 validated, objective neurocognitive assessment were eligible.

Data Extraction: Results are presented using a narrative review format. Data regarding change in cognitive performance from baseline to end-of-treatment and/or differences in cognition between ketamine and control groups were extracted.

Results: There were no negative effects of single- or repeated-dose intravenous ketamine up to 2 weeks post-treatment in MDD. Limited data were available for BD populations, as well as on other routes of ketamine administration.

Conclusions: Data to definitively answer the question of whether ketamine has substantive or persistent cognitive effects are insufficient; thus, larger controlled trials measuring cognition as the primary outcome are needed. Future research should focus on different routes of ketamine administration, ketamine enantiomers, and BD populations.

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  1. World Health Organisation. Fact Sheet: Depression. WHO website. https://www.who.int/en/news-room/fact-sheets/detail/depression. Published 2018. Accessed May 4, 2020.
  2. James SL, Abate D, Abate KH, et al; GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet. 2018;392(10159):1789–1858. PubMed CrossRef
  3. Nemeroff CB. Prevalence and management of treatment-resistant depression.J Clin Psychiatry. 2007;68(suppl 8):17–25. PubMed
  4. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.Am J Psychiatry. 2006;163(11):1905–1917. PubMed CrossRef
  5. Gartlehner G, Hansen RA, Morgan LC, et al. Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis.Ann Intern Med. 2011;155(11):772–785. PubMed CrossRef
  6. Rizvi SJ, Grima E, Tan M, et al. Treatment-resistant depression in primary care across Canada.Can J Psychiatry. 2014;59(7):349–357. PubMed CrossRef
  7. Kurdi MS, Theerth KA, Deva RS. Ketamine: current applications in anesthesia, pain, and critical care.Anesth Essays Res. 2014;8(3):283–290. PubMed CrossRef
  8. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients.Biol Psychiatry. 2000;47(4):351–354. PubMed CrossRef
  9. Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856–864. PubMed CrossRef
  10. Murrough JW, Perez AM, Pillemer S, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013;74(4):250–256. PubMed CrossRef
  11. 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(8):793–802. PubMed CrossRef
  12. 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(11):939–946. PubMed CrossRef
  13. Zheng W, Zhou Y-L, Liu W-J, et al. Rapid and longer-term antidepressant effects of repeated-dose intravenous ketamine for patients with unipolar and bipolar depression. J Psychiatr Res. 2018;106:61–68. PubMed CrossRef
  14. Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. 2018;175(2):150–158. PubMed CrossRef
  15. Reinstatler L, Youssef NA. Ketamine as a potential treatment for suicidal ideation: a systematic review of the literature. Drugs R D. 2015;15(1):37–43. PubMed CrossRef
  16. Andrade C. Ketamine for depression, 4: In what dose, at what rate, by what route, for how long, and at what frequency? J Clin Psychiatry. 2017;78(7):e852–e857. PubMed CrossRef
  17. Swainson J, McGirr A, Blier P, et al. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L’humeur Et De L’anxiété (Canmat) Concernant L’utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur. Can J Psychiatry. 2021;66(2):113–125. PubMed CrossRef
  18. Vaccarino SR, Kennedy SH. Treatment Resistant Depression. In: Vasquez GH, Zarate CA, Brietzke E, eds. Ketamine for Treatment Resistant Depression: Neurobiology and Applications. Academic Press; 2020:33-84.
  19. Phillips JL, Jaworska N, Kamler E, et al; CAN-BIND Investigator Team. A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol. BMC Psychiatry. 2020;20(1):268. PubMed CrossRef
  20. ELEKT-D. Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) - Identifier NCT03113968. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT03113968?term=ketamine+OR+esketamine+OR+s-ketamine+OR+r-ketamine+OR+arketamine&recrs=ab&cond=Major+Depressive+Disorder&cntry=US&draw=3&rank=15. Published 2017. Accessed September 14, 2020.
  21. Vidal S, Gex-Fabry M, Bancila V, et al. Efficacy and safety of a rapid intravenous injection of ketamine 0.5 mg/kg in treatment-resistant major depression: an open 4-week longitudinal study. J Clin Psychopharmacol. 2018;38(6):590–597. PubMed CrossRef
  22. Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134–1142. PubMed CrossRef
  23. Mathew SJ, Murrough JW, aan het Rot M, et al. 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. PubMed CrossRef
  24. Shiroma PR, Johns B, Kuskowski M, et al. Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression. J Affect Disord. 2014;155(1):123–129. PubMed CrossRef
  25. aan het Rot M, Collins KA, Murrough JW, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry. 2010;67(2):139–145. PubMed CrossRef
  26. Phillips JL, Norris S, Talbot J, et al. Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: a randomized controlled trial. Am J Psychiatry. 2019;176(5):401–409. PubMed CrossRef
  27. Bahji A, Vazquez GH, Zarate CA Jr. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. J Affect Disord. 2021;278:542–555. PubMed CrossRef
  28. Ghoneim MM, Hinrichs JV, Mewaldt SP, et al. Ketamine: behavioral effects of subanesthetic doses. J Clin Psychopharmacol. 1985;5(2):70–77. PubMed CrossRef
  29. D’Souza DC, Ahn K, Bhakta S, et al. Nicotine fails to attenuate ketamine-induced cognitive deficits and negative and positive symptoms in humans: implications for schizophrenia. Biol Psychiatry. 2012;72(9):785–794. PubMed CrossRef
  30. Harborne GC, Watson FL, Healy DT, et al. The effects of sub-anaesthetic doses of ketamine on memory, cognitive performance and subjective experience in healthy J Psychopharmacol. 1996;10(2):134–140. PubMed CrossRef
  31. Malhotra AK, Pinals DA, Weingartner H, et al. NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology. 1996;14(5):301–307. PubMed CrossRef
  32. Zhang C, Xu Y, Zhang B, et al. Cognitive impairment in chronic ketamine abusers. Psychiatry Res. 2020;291:113206. PubMed CrossRef
  33. Ke X, Ding Y, Xu K, et al. The profile of cognitive impairments in chronic ketamine users. Psychiatry Res. 2018;266:124–131. PubMed CrossRef
  34. Chan KWS, Lee TMC, Siu AMH, et al. Effects of chronic ketamine use on frontal and medial temporal cognition. Addict Behav. 2013;38(5):2128–2132. PubMed CrossRef
  35. Morgan CJA, Curran HV. Acute and chronic effects of ketamine upon human memory: a review. Psychopharmacology (Berl). 2006;188(4):408–424. PubMed CrossRef
  36. Rock PL, Roiser JP, Riedel WJ, et al. Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med. 2014;44(10):2029–2040. PubMed CrossRef
  37. Martínez-Arán A, Vieta E, Reinares M, et al. Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. Am J Psychiatry. 2004;161(2):262–270. PubMed CrossRef
  38. McGirr A, Berlim MT, Bond DJ, et al. Adjunctive ketamine in electroconvulsive therapy: updated systematic review and meta-analysis. Br J Psychiatry. 2017;210(6):403–407. PubMed CrossRef
  39. MacPherson RD, Loo CK. Cognitive impairment following electroconvulsive therapy–does the choice of anesthetic agent make a difference? J ECT. 2008;24(1):52–56. PubMed CrossRef
  40. Short B, Fong J, Galvez V, et al. Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry. 2018;5(1):65–78. PubMed CrossRef
  41. Crisanti C, Enrico P, Fiorentini A, et al. Neurocognitive impact of ketamine treatment in major depressive disorder: A review on human and animal studies. J Affect Disord. 2020;276:1109–1118. PubMed CrossRef
  42. Guyatt GH, Oxman AD, Schünemann HJ, et al. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64(4):380–382. PubMed CrossRef
  43. Meader N, King K, Llewellyn A, et al. A checklist designed to aid consistency and reproducibility of GRADE assessments: development and pilot validation. Syst Rev. 2014;3(1):82. PubMed CrossRef
  44. McDaniel WW, Sahota AK, Vyas BV, et al. Ketamine appears associated with better word recall than etomidate after a course of 6 electroconvulsive therapies. J ECT. 2006;22(2):103–106. PubMed CrossRef
  45. Rybakowski JK, Bodnar A, Krzywotulski M, et al. Ketamine anesthesia, efficacy of electroconvulsive therapy, and cognitive functions in treatment-resistant depression. J ECT. 2016;32(3):164–168. PubMed CrossRef
  46. Zhong X, He H, Zhang C, et al. Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression. J Affect Disord. 2016;201:124–130. PubMed CrossRef
  47. Permoda-Osip A, Kisielewski J, Bartkowska-Sniatkowska A, et al. Single ketamine infusion and neurocognitive performance in bipolar depression. Pharmacopsychiatry. 2015;48(2):78–79. PubMed CrossRef
  48. Murrough JW, Burdick KE, Levitch CF, et al. Neurocognitive effects of ketamine and association with antidepressant response in individuals with treatment-resistant depression: a randomized controlled trial. Neuropsychopharmacology. 2015;40(5):1084–1090. PubMed CrossRef
  49. Chen M-H, Li C-T, Lin W-C, et al. Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion. J Affect Disord. 2018;241(201):1–7. PubMed CrossRef
  50. Grunebaum MF, Ellis SP, Keilp JG, et al. Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. Bipolar Disord. 2017;19(3):176–183. PubMed CrossRef
  51. Zhou Y, Zheng W, Liu W, et al. Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression. J Psychopharmacol. 2018;32(10):1118–1126. PubMed CrossRef
  52. Shiroma PR, Albott CS, Johns B, et al. Neurocognitive performance and serial intravenous subanesthetic ketamine in treatment-resistant depression. Int J Neuropsychopharmacol. 2014;17(11):1805–1813. PubMed CrossRef
  53. Zheng W, Zhou Y-L, Liu W-J, et al. Neurocognitive performance and repeated-dose intravenous ketamine in major depressive disorder. J Affect Disord. 2019;246:241–247. PubMed CrossRef
  54. Liu W, Zhou Y, Zheng W, et al. Repeated intravenous infusions of ketamine: Neurocognition in patients with anxious and nonanxious treatment-resistant depression. J Affect Disord. 2019;259:1–6. PubMed CrossRef
  55. Wajs E, Aluisio L, Holder R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label Study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891. PubMed CrossRef
  56. Anderson IM, Blamire A, Branton T, et al; Ketamine-ECT Study team. Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial. Lancet Psychiatry. 2017;4(5):365–377. PubMed CrossRef
  57. Loo CK, Katalinic N, Garfield JBB, et al. Neuropsychological and mood effects of ketamine in electroconvulsive therapy: a randomised controlled trial. J Affect Disord. 2012;142(1-3):233–240. PubMed CrossRef
  58. Altinay M, Karne H, Anand A. Administration of sub-anesthetic dose of ketamine and electroconvulsive treatment on alternate week days in patients with treatment resistant depression: a double blind placebo controlled trial. Psychopharmacol Bull. 2019;49(1):8–16. PubMed
  59. Chen Q, Min S, Hao X, et al. Effect of low dose of ketamine on learning memory function in patients undergoing electroconvulsive therapy-a randomized, double-blind, controlled clinical study. J ECT. 2017;33(2):89–95. PubMed CrossRef
  60. Jagtiani A, Khurana H, Malhotra N. Comparison of efficacy of ketamine versus thiopentone-assisted modified electroconvulsive therapy in major Indian J Psychiatry. 2019;61(3):258–264. PubMed CrossRef
  61. Carspecken CW, Borisovskaya A, Lan S-T, et al. Ketamine anesthesia does not improve depression scores in electroconvulsive therapy: a randomized clinical trial. J Neurosurg Anesthesiol. 2018;30(4):305–313. PubMed CrossRef
  62. Yoosefi A, Sepehri AS, Kargar M, et al. Comparing effects of ketamine and thiopental administration during electroconvulsive therapy in patients with major depressive disorder: a randomized, double-blind study. J ECT. 2014;30(1):15–21. PubMed CrossRef
  63. Sackeim HA, Prudic J, Fuller R, et al. The cognitive effects of electroconvulsive therapy in community settings. Neuropsychopharmacology. 2007;32(1):244–254. PubMed CrossRef
  64. Lisanby SH, Maddox JH, Prudic J, et al. The effects of electroconvulsive therapy on memory of autobiographical and public events. Arch Gen Psychiatry. 2000;57(6):581–590. PubMed CrossRef
  65. Fraser LM, O’Carroll RE, Ebmeier KP. The effect of electroconvulsive therapy on autobiographical memory: a systematic review. J ECT. 2008;24(1):10–17. PubMed CrossRef
  66. Olney JW, Farber NB. NMDA antagonists as neurotherapeutic drugs, psychotogens, neurotoxins, and research tools for studying schizophrenia. Neuropsychopharmacology. 1995;13(4):335–345. PubMed CrossRef
  67. Olney JW, Labruyere J, Price MT. Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science. 1989;244(4910):1360–1362. PubMed CrossRef
  68. Brunamonti E, Mione V, Di Bello F, et al. The NMDAr antagonist ketamine interferes with manipulation of information for transitive inference reasoning in non-human primates. J Psychopharmacol. 2014;28(9):881–887. PubMed CrossRef
  69. Blackman RK, Macdonald AW 3rd, Chafee MV. Effects of ketamine on context-processing performance in monkeys: a new animal model of cognitive deficits in schizophrenia. Neuropsychopharmacology. 2013;38(11):2090–2100. PubMed CrossRef
  70. Kos T, Nikiforuk A, Rafa D, et al. The effects of NMDA receptor antagonists on attentional set-shifting task performance in mice. Psychopharmacology (Berl). 2011;214(4):911–921. PubMed CrossRef
  71. Nikiforuk A, Hołuj M, Kos T, et al. The effects of a 5-HT5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia. Neuropharmacology. 2016;105:351–360. PubMed CrossRef
  72. Patton MS, Lodge DJ, Morilak DA, et al. Ketamine corrects stress-induced cognitive dysfunction through JAK2/STAT3 signaling in the orbitofrontal cortex. Neuropsychopharmacology. 2017;42(6):1220–1230. PubMed CrossRef
  73. Papp M, Gruca P, Lason-Tyburkiewicz M, et al. Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression. Behav Pharmacol. 2017;28(1):1–8. PubMed CrossRef
  74. Jett JD, Boley AM, Girotti M, et al. Antidepressant-like cognitive and behavioral effects of acute ketamine administration associated with plasticity in the ventral hippocampus to medial prefrontal cortex pathway. Psychopharmacology (Berl). 2015;232(17):3123–3133. PubMed CrossRef
  75. Gass N, Becker R, Reinwald J, et al. Differences between ketamine’s short-term and long-term effects on brain circuitry in depression. Transl Psychiatry. 2019;9(1):172. PubMed CrossRef
  76. Lee Y, Syeda K, Maruschak NA, et al. A new perspective on the anti-suicide effects with ketamine treatment: a procognitive effect. J Clin Psychopharmacol. 2016;36(1):50–56. PubMed CrossRef
  77. Zhang MWB, Ho RCM. Controversies of the effect of ketamine on cognition. Front Psychiatry. 2016;7:47. PubMed CrossRef
  78. Koffler SP, Hampstead BM, Irani F, et al. The neurocognitive effects of 5 day anesthetic ketamine for the treatment of refractory complex regional pain syndrome. Arch Clin Neuropsychol. 2007;22(6):719–729. PubMed CrossRef
  79. Kim M, Cho S, Lee J-H. The effects of long-term ketamine treatment on cognitive function in complex regional pain syndrome: a preliminary study. Pain Med. 2016;17(8):1447–1451. PubMed CrossRef
  80. Ersek M, Cherrier MM, Overman SS, et al. The cognitive effects of opioids. Pain Manag Nurs. 2004;5(2):75–93. PubMed CrossRef
  81. Al-Sukhni M, Maruschak NA, McIntyre RS. Vortioxetine: a review of efficacy, safety and tolerability with a focus on cognitive symptoms in major depressive disorder. Expert Opin Drug Saf. 2015;14(8):1291–1304. PubMed CrossRef
  82. Hasselbalch BJ, Knorr U, Hasselbalch SG, et al. The cumulative load of depressive illness is associated with cognitive function in the remitted state of unipolar depressive disorder. Eur Psychiatry. 2013;28(6):349–355. PubMed CrossRef
  83. Murrough JW, Iacoviello B, Neumeister A, et al. Cognitive dysfunction in depression: neurocircuitry and new therapeutic strategies. Neurobiol Learn Mem. 2011;96(4):553–563. PubMed CrossRef
  84. Bhalla RK, Butters MA, Mulsant BH, et al. Persistence of neuropsychologic deficits in the remitted state of late-life depression. Am J Geriatr Psychiatry. 2006;14(5):419–427. PubMed CrossRef
  85. Fernie G, Currie J, Perrin JS, et al. Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial. Br J Psychiatry. 2017;210(6):422–428. PubMed CrossRef
  86. Loo CK, Gálvez V, O’Keefe E, et al. Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression. Acta Psychiatr Scand. 2016;134(1):48–56. PubMed CrossRef
  87. Rasmussen KG, Kung S, Lapid MI, et al. A randomized comparison of ketamine versus methohexital anesthesia in electroconvulsive therapy. Psychiatry Res. 2014;215(2):362–365. PubMed CrossRef
  88. Ray-Griffith SL, Eads LA, Han X, et al. A randomized pilot study comparing ketamine and methohexital anesthesia for electroconvulsive therapy in patients with depression. J ECT. 2017;33(4):268–271. PubMed CrossRef
  89. Dong J, Min S, Qiu H, et al. Intermittent administration of low dose ketamine can shorten the course of electroconvulsive therapy for depression and reduce complications: A randomized controlled trial. Psychiatry Res. 2019;281:112573. PubMed CrossRef
  90. Zhang M, Rosenheck R, Lin X, et al. A randomized clinical trial of adjunctive ketamine anesthesia in electro-convulsive therapy for depression. J Affect Disord. 2018;227:372–378. PubMed CrossRef
  91. Basso L, Bönke L, Aust S, et al. Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients. J Psychiatr Res. 2020;123:1–8. PubMed CrossRef
  92. Wilkinson ST, Katz RB, Toprak M, et al. Acute and longer-term outcomes using ketamine as a clinical treatment at the Yale Psychiatric J Clin Psychiatry. 2018;79(4):17m11731. PubMed CrossRef
  93. Murrough JW, Wan L-B, Iacoviello B, et al. Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response. Psychopharmacology (Berl). 2013;231(3):481–488. PubMed CrossRef
  94. Otto MW, Fava M, Penava SJ, et al. Life event, mood, and cognitive predictors of perceived stress before and after treatment for major depression. Cognit Ther Res. 1997;21(4):409–420. CrossRef
  95. Antikainen R, Hänninen T, Honkalampi K, et al. Mood improvement reduces memory complaints in depressed patients. Eur Arch Psychiatry Clin Neurosci. 2001;251(1):6–11. PubMed CrossRef
  96. Pan Z, Park C, Brietzke E, et al. Cognitive impairment in major depressive disorder. CNS Spectr. 2019;24(1):22–29. PubMed CrossRef
  97. Fleming SK, Blasey C, Schatzberg AF. Neuropsychological correlates of psychotic features in major depressive disorders: a review and meta-analysi J Psychiatr Res. 2004;38(1):27–35. PubMed CrossRef
  98. Gomez RG, Fleming SH, Keller J, et al. The neuropsychological profile of psychotic major depression and its relation to cortisol. Biol Psychiatry. 2006;60(5):472–478. PubMed CrossRef
  99. Ebert B, Mikkelsen S, Thorkildsen C, et al. Norketamine, the main metabolite of ketamine, is a non-competitive NMDA receptor antagonist in the rat cortex and spinal cord. Eur J Pharmacol. 1997;333(1):99–104. PubMed CrossRef
  100. Vollenweider FX, Leenders KL, Øye I, et al. Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET). Eur Neuropsychopharmacol. 1997;7(1):25–38. PubMed CrossRef
  101. Pfenninger EG, Durieux ME, Himmelseher S. Cognitive impairment after small-dose ketamine isomers in comparison to equianalgesic racemic ketamine in human volunteers. Anesthesiology. 2002;96(2):357–366. PubMed CrossRef
  102. Kolp E, Friedman HL, Krupitsky E, et al. Ketamine psychedelic psychotherapy: focus on its pharmacology, phenomenology, and clinical applications. Int J Transpers Stud. 2014;33(2):84–140. CrossRef
  103. Dore J, Turnipseed B, Dwyer S, et al. Ketamine assisted psychotherapy (kap): patient demographics, clinical data and outcomes in three large practices administering ketamine with psychotherapy. J Psychoactive Drugs. 2019;51(2):189–198. PubMed CrossRef
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