Full Text (PDF)
Review Article

Ketamine Therapy in Psychiatry: A Comprehensive Review

Asif Khan, Satyaveer null, Shrikant K Nair, Deepali Gaikwad Joseph

Author Information

Licence:

Attribution-Non-commercial 4.0 International (CC BY-NC 4.0)

This license enables reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.


Journal of Psychiatric Nursing 14(1):p 31-36, Jan- April 2025. | DOI: https://doi.org/10.21088/jpn.2277.9035.14125.5

How Cite This Article:

Asif Khan, Satyaveer, Shrikant K Nair, Deeksha Srivastava et. al, Ketamine Therapy in Psychiatry: A Comprehensive Review. J Psychiatr Nurs. 2025; 14(1): 31–36.

Timeline

Received : February 21, 2025         Accepted : March 31, 2025          Published : April 30, 2025

Abstract

Ketamine, traditionally known as an anesthetic agent, has garnered attention for its rapid acting antidepressant properties, particularly in patients with treatment resistant depression (TRD). The compound’s unique pharmacological profile primarily as an NMDA receptor antagonist has enabled its repositioning in psychiatric settings, where conventional antidepressants often fall short. This review delves into the evolving role of ketamine in psychiatry, examining its mechanisms of action, therapeutic applications, clinical efficacy, safety concerns, and emerging trends in the field. While ketamine therapy offers promise, its use raises ethical, regulatory, and long-term safety considerations that require continued research and careful implementation.


References

  • 1.   Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, 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):1905–17.
  • 2.   Domino EF. Taming the ketamine tiger. Anesthesiology. 2010;113(3):678–84.
  • 3.   Paul R, Schaaff N, Padberg F, Möller HJ, Frodl T. Comparison of racemic ketamine and S-ketamine in treatment-resistant major depression: report of two cases. CNS Drugs. 2009;23(12):1057–61.
  • 4.   Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856–64.
  • 5.   Duman RS, Aghajanian GK. Synaptic dysfunction in depression: potential therapeutic targets. Science. 2012;338(6103): 68–72.
  • 6.   Williams NR, Schatzberg AF. NMDA antagonist treatment of depression. CNS Drugs. 2016;30(1):33–44.
  • 7.   Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–4.
  • 8.   Price RB, Nock MK, Charney DS, Mathew SJ. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatmentresistant depression. Am J Psychiatry. 2009;166(4):459–65.
  • 9.   Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. Bipolar Disord. 2010;12(6):702–3.
  • 10.   Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71(6):681–8.
  • 11.   Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-ofconcept. J Clin Psychiatry. 2013;74(9):e982–90.
  • 12.   Short B, Fong J, Galvez V, Shelker W, Loo CK. Side-effects associated with ketamine use in depression: a systematic review. J Affect Disord. 2018;227:576–82.
  • 13.   U.S. Food and Drug Administration. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic. FDA News Release. 2019 [cited 2025 May 2]. Available from: https://www.fda.gov/newsevents/press-announcements
  • 14.   Sakurai H, Gamo NJ, Kolb H, Mattis J, Egervari G, Needham M, et al. Long-lasting efficacy of low-dose oral ketamine for depression in a patient with treatment-resistant bipolar disorder. J Psychopharmacol. 2020;34(1): 109–12.
  • 15.   Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134–42.
  • 16.   Coyle CM, Laws KR. The use of ketamine as an antidepressant: a systematic review and meta-analysis. J Psychopharmacol. 2015;29(4):289–99.
  • 17.   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. 2017;174(7):695–6.
  • 18.   Ballard ED, Wills K, Lally N, Luckenbaugh DA, Richards EM, Machado-Vieira R, et al. Anhedonia as a clinical correlate of suicidal thoughts in major depressive disorder. J Affect Disord. 2017;210:42–9.
  • 19.   Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine selfadministration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study. Addiction. 2010;105(1):121–33.
  • 20.   Bonnet U. Long-term ketamine self-injections in major depressive disorder: focus on tolerance in ketamine’s antidepressant response and the development of ketamine addiction. CNS Neurosci Ther. 2015;21(2):188–90.
  • 21.   Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. BJU Int. 2007;100(6):1141–3.
  • 22.   Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74(4):399–405.
  • 23.   Schatzberg AF. A word to the wise about ketamine. Am J Psychiatry. 2014;171(3):262–4.
  • 24.   Loo CK, Galvez V, O’Keefe E, Mitchell PB, Hadzi-Pavlovic D, Leyden J, et al. Placebocontrolled pilot trial testing ketamine augmentation of ECT for depression. World J Biol Psychiatry. 2016;17(1):47–54.
  • 25.   Andrade C. Ketamine for depression, 2: diagnostic and contextual indications. J Clin Psychiatry. 2017;78(2):e150–3.
  • 26.   Duman RS, Li N, Liu RJ, Duric V, Aghajanian G. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology. 2012;62(1):35–41.
  • 27.   Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatmentresistant depression. JAMA Psychiatry. 2018;75(2):139–48.
  • 28.   Wilkinson ST, Farmer C, Ballard ED, Mathew SJ, Grunebaum MF, Murrough JW, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Psychother Psychosom. 2018;87(1):22–31.
  • 29.   Yaden DB, Griffiths RR. The subjective effects of psychedelics are necessary for their enduring therapeutic effects. JAMA Psychiatry. 2020;77(9):787–8.
  • 30.   Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74(4):399–405.
  • 31.   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. 2017;174(7):695–6.
  • 32.   Short B, Fong J, Galvez V, Shelker W, Loo CK. Side-effects associated with ketamine use in depression: a systematic review. J Affect Disord. 2018;227:576–82.

Data Sharing Statement

There are no additional data available. All raw data and code are available upon request.

Funding

This research received no funding.

Author Contributions

All authors contributed significantly to the work and approve its publication.

Ethics Declaration

This article does not involve any human or animal subjects, and therefore does not require ethics approval.

Acknowledgements

We would like to express our gratitude to the patients, their families, and all those who have contributed to this study.

Conflicts of Interest

No conflicts of interest in this work.


About this article


Cite this article

Asif Khan, Satyaveer, Shrikant K Nair, Deeksha Srivastava et. al, Ketamine Therapy in Psychiatry: A Comprehensive Review. J Psychiatr Nurs. 2025; 14(1): 31–36.


Licence:

Attribution-Non-commercial 4.0 International (CC BY-NC 4.0)

This license enables reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.


Received Accepted Published
February 21, 2025 March 31, 2025 April 30, 2025

DOI: https://doi.org/10.21088/jpn.2277.9035.14125.5

Keywords

KetaminePsychiatryDepressionNMDA receptorAntidepressant Treatment-resistant depressionMental healthSuicidalityGlutamatergic systemNeuroplasticity

Article Level Metrics

Last Updated

Tuesday 28 July 2026, 22:03:30 (IST)


1022

Accesses

14
126
00

Citations


NA
NA
NA

Download citation


Article Keywords


Keyword Highlighting

Highlight selected keywords in the article text.


Timeline


Received February 21, 2025
Accepted March 31, 2025
Published April 30, 2025

licence


Attribution-Non-commercial 4.0 International (CC BY-NC 4.0)

This license enables reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.


Access this article



Share