The Relationship Between Ketamine and Memory Impairment: A Systematic Review

Ghaith Al-badran

doi:10.7197/cmj.1452303

EN TR

The Relationship Between Ketamine and Memory Impairment: A Systematic Review

Abstract

Various studies have reported conflicting results regarding the effect of ketamine on cognitive function, although increasing evidence supports its impact. This study aimed to investigate the potential correlation between Ketamine usage and memory deterioration, which is crucial for informing clinical practice and public health interventions. A systematic review was conducted, and six databases were scanned according to the PRISMA guidelines. As a result, 50 studies were analyzed to investigate the relationship between Ketamine and memory deterioration. It was found that most studies provided evidence for the claim that there is a negative association between Ketamine and cognitive function, specifically in the realm of memory. Some studies emphasized gender differences; however, their results were inconclusive. Studies have also found that the impact of ketamine is not limited to cognitive functions; it extends to other aspects such as depression, suicidal ideation, and neurocognitive functions. In conclusion, it is evident that there is an association between Ketamine and memory deterioration however, this relationship is challenging to develop and further studies are required.

Keywords

Ketamin ve Bellek Bozuklukları Arasındaki İlişki: Bir Sistematik Derleme

Öz

Ketaminin bilişsel işlevleri etkilediğine dair bulgular giderek artsa da çeşitli çalışmalarda farklı görüşler ortaya koyulmuştur. Bu çalışma, klinik uygulamalar ve halk sağlığı müdahaleleri hakkında bilgi vermede çok önemli olan Ketamin kullanımı ile bellek bozuklukları arasındaki potansiyel ilişkiyi araştırmayı amaçlamaktadır. Çalışmada sistematik derleme yöntemi benimsenerek PRISMA kılavuzuna göre altı veri tabanı taranmış, Ketamin ve bellek bozuklukları arasındaki ilişkiyi araştıran 50 çalışma analize dahil edilmiştir. Çoğu çalışma, Ketaminin bilişsel işlevler, özellikle de bellek üzerinde olumsuz bir etkisi olduğunu göstermektedir. Bazı çalışmalar cinsiyet farklılıklarını vurgulamış; ancak bunların sonuçları yetersiz kalmıştır. Çalışmalar ayrıca Ketaminin etkisinin bilişsel işlevlerle sınırlı olmadığını; depresyon, intihar düşüncesi ve nörobilişsel işlevler gibi diğer yönler üzerinde de etkili olduğunu ortaya koymuştur. Sonuç olarak Ketamin ve bellek bozuklukları arasında bir ilişki olduğu açıktır, ancak bu ilişkinin tam anlamıyla açıklanabilmesi için daha fazla çalışmaya ihtiyaç vardır.

Anahtar Kelimeler

Ethical Statement

Ethics committee approval is not required for review articles.

References

1. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: a review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clinical pharmacokinetics. 2016;55:1059-77.
2. Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, et al. Consensus guidelines on the use of intravenous ketamine infusions for acute pain management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia & Pain Medicine. 2018;43(5):456-66.
3. Asim M, Wang B, Hao B, Wang X. Ketamine for post-traumatic stress disorders and it's possible therapeutic mechanism. Neurochemistry International. 2021;146:105044.
4. Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS. Ketamine: a paradigm shift for depression research and treatment. Neuron. 2019;101(5):774-8.
5. Martinotti G, Chiappini S, Pettorruso M, Mosca A, Miuli A, Di Carlo F, et al. Therapeutic potentials of ketamine and esketamine in obsessive–compulsive disorder (OCD), substance use disorders (SUD) and eating disorders (ED): a review of the current literature. Brain Sciences. 2021;11(7):856.
6. Leslie E, Pittman E, Drew B, Walrath B. Ketamine use in operation enduring freedom. Military medicine. 2021;186(7-8):e720-e5.
7. Bloch MH, Wasylink S, Landeros-Weisenberger A, Panza KE, Billingslea E, Leckman JF, et al. Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Biological psychiatry. 2012;72(11):964-70.
8. Pham TH, Gardier AM. Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacology & therapeutics. 2019;199:58-90.

9. Stone JM, Dietrich C, Edden R, Mehta MA, De Simoni S, Reed LJ, et al. Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology. Molecular psychiatry. 2012;17(7):664-5.
10. Andrade C. Oral ketamine for depression, 2: practical considerations. The Journal of clinical psychiatry. 2019;80(2):13521.
11. Caruso K, Tyler D, Lyden A. Ketamine for pain management: A review of literature and clinical application. Orthopaedic Nursing. 2021;40(3):189-93.
12. Domany Y, Bleich-Cohen M, Tarrasch R, Meidan R, Litvak-Lazar O, Stoppleman N, et al. Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study. The British Journal of Psychiatry. 2019;214(1):20-6.
13. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Annals of emergency medicine. 2011;57(5):449-61.
14. Karlow N, Schlaepfer CH, Stoll CR, Doering M, Carpenter CR, Colditz GA, et al. A systematic review and meta‐analysis of ketamine as an alternative to opioids for acute pain in the emergency department. Academic Emergency Medicine. 2018;25(10):1086-97.
15. Rosenbaum SB, Palacios JL. Ketamine 2019 [12.11.2023]. Available from: https://www. ncbi.nlm.nih.gov/books/NBK470357/.
16. American, Addiction, Center. Ketamine: Short and Long-Term Effects of Ketamine 2023 [cited 08.06.2023].
17. Morgan CJ, Dodds CM, Furby H, Pepper F, Fam J, Freeman TP, et al. Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation. Frontiers in psychiatry. 2014;5:149.
18. 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(1):121-33.
19. Torgerson C. Systematic reviews. Systematic Reviews. 2003:1-114.
20. Moher D, Liberati A, Tetzlaff J, Altman DG, Group* P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine. 2009;151(4):264-9.
21. Guba EG, Lincoln YS. Fourth generation evaluation: Sage; 1989.
22. Hayley A, Green M, Downey L, Keane M, Kostakis P, Shehabi Y. Neurocognitive and behavioural performance of healthy volunteers receiving an increasing analgesic-range infusion of ketamine. Psychopharmacology. 2018;235(4): 1273-82.
23. Hayley AC, Green M, Downey LA, Keane M, Kenneally M, Adams M, et al. Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2019;94.
24. Koffler SP, Hampstead BM, Irani F, Tinker J, Kiefer RT, Rohr P, et al. The neurocognitive effects of 5 day anesthetic ketamine for the treatment of refractory complex regional pain syndrome. Archives of Clinical Neuropsychology. 2007;22(6):719-29.
25. Chen WY, Huang MC, Lin SK. Gender differences in subjective discontinuation symptoms associated with ketamine use. Substance Abuse Treatment Prevention and Policy. 2014;9.
26. Cheng WJ, Chen CH, Chen CK, Huang MC, Pietrzak RH, Krystal JH, et al. Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia. Schizophrenia Research. 2018;199:313-8.
27. D'Souza DC, Ahn K, Bhakta S, Elander J, Singh N, Nadim H, et al. Nicotine Fails to Attenuate Ketamine-Induced Cognitive Deficits and Negative and Positive Symptoms in Humans: Implications for Schizophrenia. Biological Psychiatry. 2012;72(9):785-94.
28. D'Souza DC, Carson RE, Driesen N, Johannesen J, Ranganathan M, Krystal JH, et al. Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects. Biological Psychiatry. 2018;84(6):413-21.
29. Driesen NR, McCarthy G, Bhagwagar Z, Bloch MH, Calhoun VD, D'Souza DC, et al. The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity. Neuropsychopharmacology. 2013;38(13):2613-22.
30. Fernie G, Currie J, Perrin JS, Stewart CA, Anderson V, Bennett DM, et al. Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial. British Journal of Psychiatry. 2017;210(6):422-+.
31. Greer A, Treston G. Factors associated with patient-reported procedural memory following emergency department procedural sedation with ketamine and propofol: A prospective cohort of 563 patients. Emergency Medicine Australasia. 2018;30(2):200-8.
32. Khalili-Mahani N, Niesters M, van Osch MJ, Oitzl M, Veer I, de Rooij M, et al. Ketamine interactions with biomarkers of stress: A randomized placebo-controlled repeated measures resting-state fMRI and PCASL pilot study in healthy men. NeuroImage. 2015;108:396-409.
33. Klausen N-O, JØRGENSEN FW, Chraemmer-Jørgensen B. Psychomimetic reactions after low-dose ketamine infusion: comparison with neuroleptanaesthesia. British Journal of Anaesthesia. 1983;55(4):297-301.
34. Krupitsky EM, Burakov AM, Romanova TN, Grinenko NI, Grinenko AY, Fletcher J, et al. Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: Psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists. Neuropsychopharmacology. 2001;25(6):936-47.
35. Krystal JH, D'Souza DC, Karper LP, Bennett A, Abi-Dargham A, Abi-Saab D, et al. Interactive effects of subanesthetic ketamine and haloperidol in healthy humans. Psychopharmacology. 1999;145(2):193-204.
36. Lapidus KAB, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, et al. A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder. Biological Psychiatry. 2014;76(12):970-6.
37. Levin R, Dor-Abarbanel AE, Edelman S, Durrant AR, Hashimoto K, Javitt DC, et al. Behavioral and cognitive effects of the N-methyl-D-aspartate receptor co-agonist D-serine in healthy humans: Initial findings. Journal of Psychiatric Research. 2015;61:188-95.
38. McDaniel WW, Sahota AK, Vyas BV, Laguerta N, Hategan L, Oswald J. Ketamine appears associated with better word recall than etomidate after a course of 6 electroconvulsive therapies. Journal of ECT. 2006;22(2):103-6.
39. Murrough JW, Wan L-B, Iacoviello B, Collins KA, Solon C, Glicksberg B, et al. Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response. Psychopharmacology. 2014;231:481-8.
40. Ni F, Ke X, Yuping N, Daping W, Xiaoyin K, Yi D, et al. Development of a checklist of short-term and long-term psychological symptoms associated with ketamine use. Shanghai archives of psychiatry. 2015;27(3):186.
41. Pfenninger EG, Durieux ME, Himmelseher S. Cognitive impairment after small-dose ketamine isomers in comparison to equianalgesic racemic ketamine in human volunteers. The Journal of the American Society of Anesthesiologists. 2002;96(2):357-66.
42. Rybakowski JK, Bodnar A, Krzywotulski M, Chlopocka-Wozniak M, Michalak M, Rosada-Kurasinska J, et al. Ketamine Anesthesia, Efficacy of Electroconvulsive Therapy, and Cognitive Functions in Treatment-Resistant Depression. Journal of ECT. 2016;32(3):164-8.
43. Stippl A, Scheidegger M, Aust S, Herrera A, Bajbouj M, Gärtner M, et al. Ketamine specifically reduces cognitive symptoms in depressed patients: An investigation of associated neural activation patterns. Journal of Psychiatric Research. 2021;136:402-8.
44. Tian L, Luan HF, Zhu P, Zhang ZY, Bao HG. A randomized controlled trial for measuring effects on cognitive functions of adding ketamine to propofol during sedation for colonoscopy. Medicine. 2020;99(36).
45. Wang LJ, Chen CK, Lin SK, Chen YC, Xu K, Huang MC. Cognitive profile of ketamine-dependent patients compared with methamphetamine-dependent patients and healthy controls. Psychopharmacology. 2018;235(7):2113-21.
46. Zeng H, Su DQ, Jiang X, Zhu L, Ye HS. The similarities and differences in impulsivity and cognitive ability among ketamine, methadone, and non-drug users. Psychiatry Research. 2016;243:109-14.
47. Zhang CX, Xu Y, Zhang B, Hao W, Tang WK. Cognitive impairment in chronic ketamine abusers. Psychiatry Research. 2020;291.
48. Anderson IM, Blamire A, Branton T, Clark R, Downey D, Dunn G, et al. 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):365-77.
49. Albott CS, Lim KO, Erbes C, Thuras P, Wels J, Tye SJ, et al. Neurocognitive effects of repeated ketamine infusions in comorbid posttraumatic stress disorder and major depressive disorder. Journal of Affective Disorders. 2022;308:289-97.
50. Chen XY, Wang MQ, Hu YR, Zhan YN, Zhou YL, Zheng W, et al. Working memory associated with anti-suicidal ideation effect of repeated-dose intravenous ketamine in depressed patients. European Archives of Psychiatry and Clinical Neuroscience. 2021;271(3):431-8.
51. Diamond PR, Farmery AD, Atkinson S, Haldar J, Williams N, Cowen PJ, et al. Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic. Journal of Psychopharmacology. 2014;28(6):536-44.
52. Liu WJ, Zhou YL, Zheng W, Wang CY, Zhan YN, Lan XF, et al. Repeated intravenous infusions of ketamine: Neurocognition in patients with anxious and nonanxious treatment-resistant depression. Journal of Affective Disorders. 2019;259:1-6.
53. Phillips JL, Van Geel A, Burhunduli P, Vasudev D, Batten LA, Norris S, et al. Assessment of Objective and Subjective Cognitive Function in Patients With Treatment-Resistant Depression Undergoing Repeated Ketamine Infusions. International Journal of Neuropsychopharmacology. 2022;25(12):992-1002.
54. Salvadore G, Cornwell BR, Sambataro F, Latov D, Colon-Rosario V, Carver F, et al. Anterior Cingulate Desynchronization and Functional Connectivity with the Amygdala During a Working Memory Task Predict Rapid Antidepressant Response to Ketamine. Neuropsychopharmacology. 2010;35(7):1415-22.
55. Schmidt A, Bachmann R, Kometer M, Csomor PA, Stephan KE, Seifritz E, et al. Mismatch Negativity Encoding of Prediction Errors Predicts S-ketamine-Induced Cognitive Impairments. Neuropsychopharmacology. 2012;37(4):865-75.
56. Shiroma PR, Albott CS, Johns B, Thuras P, Wels J, Lim KO. Neurocognitive performance and serial intravenous subanesthetic ketamine in treatment-resistant depression. International Journal of Neuropsychopharmacology. 2014;17(11):1805-13.
57. Shiroma PR, Thuras P, Wels J, Albott CS, Erbes C, Tye S, et al. Neurocognitive performance of repeated versus single intravenous subanesthetic ketamine in treatment resistant depression. Journal of Affective Disorders. 2020;277:470-7.
58. Yurgelun-Todd DA, Renshaw PF, Goldsmith P, Uz T, Macek TA. A randomized, placebo-controlled, phase 1 study to evaluate the effects of TAK-063 on ketamine-induced changes in fMRI BOLD signal in healthy subjects. Psychopharmacology. 2020;237(2):317-28.
59. Zhou YL, Wang CY, Lan XF, Zheng W, Li HQ, Chao ZY, et al. The potential pro-cognitive effects with intravenous subanesthetic ketamine in adults with treatment-resistant major depressive or bipolar disorders and suicidality. Journal of Psychiatric Research. 2021;144:312-9.
60. Zhou YL, Wang CY, Lan XF, Zheng W, Li HQ, Chao ZY, et al. The effectiveness of repeated intravenous ketamine on subjective and objective psychosocial function in patients with treatment-resistant depression and suicidal ideation. Journal of Affective Disorders. 2022;304:78-84.
61. Zhou YL, Wang CY, Lan XF, Li WC, Chao ZY, Wu K, et al. Cognitive Function Mediates the Anti-suicide Effect of Repeated Intravenous Ketamine in Adult Patients With Suicidal Ideation. Frontiers in Psychiatry. 2022;13.
62. Zhou YL, Zheng W, Liu WJ, Wang CY, Zhan YN, Li HQ, et al. Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression. Journal of Psychopharmacology. 2018;32(10):1118-26.
63. Zou L, Min S, Chen QB, Li X, Ren L. Subanesthetic dose of ketamine for the antidepressant effects and the associated cognitive impairments of electroconvulsive therapy in elderly patients-A randomized, double-blind, controlled clinical study. Brain and Behavior. 2021;11(1).
64. Aubrun FG, C.: Rosenthal, D.: Dupuis, M.: Mottet, P.: Marchetti, F.: Coriat, P.: Riou, B. Effect of a low-dose ketamine regimen on pain, mood, cognitive function and memory after major gynaecological surgery: a randomized, double-blind, placebo-controlled trial. European journal of anaesthesiology. 2008;25(2):97-105.
65. Chen MH, Li CT, Lin WC, Hong CJ, Tu PC, Bai YM, et al. Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion. Journal of Affectıve Dısorders. 2018;241:1-7.
66. Chen XWL, Y. T.: Han, Y.: Huan, Y.: Feng, X. Y.: Chen, C. F. Protective effect of neovibsanin B on spatial cognitive functions of rats with cerebrovascular hypoperfusion. International Journal of Clinical and Experimental Medicine. 2015;8(8):12105-12.
67. Davis MT, DellaGiogia N, Maruff P, Pietrzak RH, Esterlis I. Acute cognitive effects of single-dose intravenous ketamine in major depressive and posttraumatic stress disorder. Translational Psychiatry. 2021;11(1).
68. Grunebaum MF, Ellis SP, Keilp JG, Moitra VK, Cooper TB, Marver JE, et al. Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. Bipolar Disorders. 2017;19(3):176-83.
69. Murrough JW, Burdick KE, Levitch CF, Perez AM, Brallier JW, Chang LC, 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):1084-90.
70. Ochs-Ross R, Daly EJ, Zhang Y, Lane R, Lim P, Morrison RL, et al. Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3. American Journal of Geriatric Psychiatry. 2020;28(2):121-41.
71. Zheng W, Zhou YL, Liu WJ, Wang CY, Zhan YN, Li HQ, et al. Neurocognitive performance and repeated-dose intravenous ketamine in major depressive disorder. Journal of Affective Disorders. 2019;246:241-7.
72. Aubrun F, Gaillat C, Rosenthal D, Dupuis M, Mottet P, Marchetti F, et al. Effect of a low-dose ketamine regimen on pain, mood, cognitive function and memory after major gynaecological surgery: a randomized, double-blind, placebo-controlled trial. European Journal of Anaesthesiology. 2008;25(2):97-105.
73. Chen YC, Wang LJ, Lin SK, Chen CK. Neurocognitive Profiles of Methamphetamine Users: Comparison of Those With or Without Concomitant Ketamine Use. Substance Use & Misuse. 2015;50(14):1778-85.

Details

Primary Language

English

Subjects

Mental Health Services , Health Services and Systems (Other)

Journal Section

Systematic Reviews and Meta Analysis

Authors

Ghaith Al-badran ^*
0000-0002-9388-2078
Iraq

Publication Date

June 29, 2024

Submission Date

March 16, 2024

Acceptance Date

May 21, 2024

Published in Issue

Year 2024 Volume: 46 Number: 2

DOI

https://doi.org/10.7197/cmj.1452303

IZ

https://izlik.org/JA47XR96YU

Cite

RIS / Bibtex

AMA

1.Al-badran G. The Relationship Between Ketamine and Memory Impairment: A Systematic Review. CMJ. 2024;46(2):84-98. doi:10.7197/cmj.1452303