Hostname: page-component-5cf477f64f-pw477 Total loading time: 0 Render date: 2025-03-31T04:38:59.020Z Has data issue: false hasContentIssue false
  • English
  • Français

Ketamine for unipolar major depression: critical examination of antidepressant effects

Part of: BJPsych Advances Cochrane Corner and Round the Corner Collection

Published online by Cambridge University Press:  18 March 2025

Aditya Patel Open the ORCID record for Aditya Patel [Opens in a new window]
Aditya Patel*
Affiliation:
Foundation doctor with Oxford University Hospitals NHS Foundation Trust, based in the Department of Psychiatry, John Radcliffe Hospital, Oxford, UK.
*
Correspondence Dr Aditya Patel. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

This critical appraisal of a Cochrane Review assesses the efficacy of ketamine for treating unipolar major depressive disorder. The review included 31 randomised controlled trials involving ketamine. Results indicate that intravenous (i.v.) ketamine significantly improves antidepressant response compared with i.v. saline and, to a lesser extent, i.v. midazolam within 24–72 h. However, the evidence is constrained by performance bias owing to masking (‘blinding’) concerns and study heterogeneity, necessitating further robust research to confirm ketamine's clinical potential.

Keywords

Electroconvulsive therapydepressive disordersantidepressantssystematic reviewgeneral adult psychiatry
Type
Round the corner
Information
BJPsych Advances , First View , pp. 1 - 6
Check for updates
Copyright
Copyright © The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

Commentary on… Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder (Cochrane Corner). See this issue.

References

Anand, A, Mathew, SJ, Sanacora, G, et al (2023) Ketamine versus ECT for nonpsychotic treatment-resistant major depression. New England Journal of Medicine, 388: 2315–25.CrossRefGoogle ScholarPubMed
Anderson, IM, Blamire, A, Branton, T, et al (2017) 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, 4: 365–77.CrossRefGoogle ScholarPubMed
Andrade, C (2017) Ketamine for depression, 4: in what dose, at what rate, by what route, for how long, and at what frequency? Journal of Clinical Psychiatry, 78: e852–57.CrossRefGoogle ScholarPubMed
Arabzadeh, S, Hakkikazazi, E, Shahmansouri, N, et al (2018) Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial. Journal of Affective Disorders, 235: 236–41.CrossRefGoogle ScholarPubMed
Atkins, D, Best, D, Briss, PA, et al (2004) Grading quality of evidence and strength of recommendations. BMJ, 328: 1490.Google ScholarPubMed
Chen, Q, Min, S, Hao, X, et al (2017) Effect of low dose of ketamine on learning memory function in patients undergoing electroconvulsive therapy – a randomized, double-blind, controlled clinical study. Journal of ECT, 33: 89–95.CrossRefGoogle ScholarPubMed
Corriger, A, Pickering, G (2019) Ketamine and depression: a narrative review. Drug Design, Development and Therapy, 13: 3051–67.CrossRefGoogle ScholarPubMed
Dean, RL, Hurducas, C, Hawton, K, et al (2021) Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database of Systematic Reviews, 9: CD011612 (https://doi.org/10.1002/14651858.CD011612.pub3).Google ScholarPubMed
Ekstrand, J, Fattah, C, Persson, M, et al (2022) Racemic ketamine as an alternative to electroconvulsive therapy for unipolar depression: a randomized, open-label, non-inferiority trial (KetECT). International Journal of Neuropsychopharmacology, 25: 339–49.CrossRefGoogle Scholar
Fava, M, Freeman, MP, Flynn, M, et al (2020) Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment- resistant depression (TRD). Molecular Psychiatry, 25: 1592–603.Google ScholarPubMed
Fond, G, Loundou, A, Rabu, C, et al (2014) Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology, 231: 3663–76.CrossRefGoogle ScholarPubMed
Gálvez, V, Huggins, C, Glue, P, et al (2018) Repeated intranasal ketamine for treatment-resistant depression - the way to go? Results from a pilot randomised controlled trial. Journal of Psychopharmacology, 32: 397–407.CrossRefGoogle ScholarPubMed
Ghasemi, M, Kazemi, MH, Yoosefi, A, et al (2013) Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Research, 215: 355–61.CrossRefGoogle ScholarPubMed
Hirota, K, Lambert, DG (2018) Ketamine and depression. British Journal of Anaesthesia, 121: 1198–202.CrossRefGoogle ScholarPubMed
Ionescu, DF, Bentley, KH, Eikermann, M, et al (2019) Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: a randomized, double blind, placebo controlled trial. Journal of Affective Disorders, 243: 516–24.CrossRefGoogle ScholarPubMed
Kalsi, SS, Wood, DM, Dargan, PI (2011) The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use. Emerging Health Threats Journal, 4(1): 7107.CrossRefGoogle ScholarPubMed
Lapidus, KA, Levitch, CF, Perez, AM, et al (2014) A randomized controlled trial of intranasal ketamine in major depressive disorder. Biological Psychiatry, 76: 970–6.CrossRefGoogle ScholarPubMed
Loo, CK, Katalinic, N, Garfield, JB, et al (2012) Neuropsychological and mood effects of ketamine in electroconvulsive therapy: a randomised controlled trial. Journal of Affective Disorders, 142: 233–40.CrossRefGoogle ScholarPubMed
Murrough, JW, Iosifescu DV, Chang LC, et al (2013) Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. American Journal of Psychiatry,170: 1134–2.CrossRefGoogle Scholar
National Institute for Health and Care Excellence (2024) Depression: Scenario: New or Initial Management. CKS/NICE (https://cks.nice.org.uk/topics/depression/management/initial-management/). Accessed 14 Jul 2024.Google Scholar
Nemeroff, CB (2007) Prevalence and management of treatment-resistant depression. Journal of Clinical Psychiatry, 68(suppl 8): 17–25.Google ScholarPubMed
Phillips, JL, Norris, S, Talbot, J, et al (2019) Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: a randomized controlled trial. American Journal of Psychiatry, 176: 401–9.CrossRefGoogle ScholarPubMed
Rhee, TG, Shim, SR, Forester, BP, et al (2022) Efficacy and safety of ketamine vs electroconvulsive therapy among patients with major depressive episode: a systematic review and meta-analysis. JAMA Psychiatry, 79: 1162–72.CrossRefGoogle ScholarPubMed
Romeo, B, Choucha, W, Fossati, P, et al (2015) Meta-analysis of short-and mid-term efficacy of ketamine in unipolar and bipolar depression. Psychiatry Research, 230: 682–8.CrossRefGoogle ScholarPubMed
Sassano-Higgins, S, Baron, D, Juarez, G, et al (2016) A review of ketamine abuse and diversion. Depression and Anxiety, 33: 718–27.CrossRefGoogle Scholar
Shiroma, PR, Thuas, P, Wels, J, et al (2020) A randomized, double-blind, active placebo-controlled study of efficacy, safety and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression. Translational Psychiatry, 10(1): 206.CrossRefGoogle ScholarPubMed
UK ECT Review Group (2003) Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet, 361: 799–808.CrossRefGoogle Scholar
Wilkinson, ST, Farmer, C, Ballard, ED, et al (2019) Impact of midazolam vs. saline on effect size estimates in controlled trials of ketamine as a rapid-acting antidepressant. Neuropsychopharmacology, 44: 1233–8.CrossRefGoogle ScholarPubMed
Xu, Y, Hackett, M, Carter, G, et al (2016) Effects of low-dose and very low-dose ketamine among patients with major depression: a systematic review and meta-analysis. International Journal of Neuropsychopharmacology, 19(4): pyv124.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.