Skip to main content

Advertisement

SpringerLink
Log in

Ketamine for Chronic Pain and Mental Health: Regulations, Legalities, and the Growth of Infusion Clinics

  • Hot Topics in Pain and Headache (N Rosen, Section Editor)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

  • 3 Altmetric

Abstract

Purpose of Review

In this article, we will review evidence for ketamine’s role in chronic pain and mental health conditions, its current legal status and abuse potential, and the regulations related to its administration in stand-alone infusion clinics, as well as future considerations.

Recent Findings

In the management of chronic pain, ketamine has shown potential to manage neuropathic pain and complex regional pain syndrome and has been used as a treatment for chronic pain management by clinics across the USA. Analogous to the historic rise of lidocaine clinics, ketamine clinics are demonstrating a similar pattern of unregulated growth.

Summary

Ketamine is an anesthetic and analgesic agent commonly used in the perioperative setting and emergency department for sedation and pain management (Mo et al in West J Emerg Med 21(2):272–281, 2020). It was approved for use by the Federal Drug Administration in the USA in the 1970s as the sole anesthetic agent for short diagnostic and surgical procedures (Coppel et al. in Anaesthesia 28(3):293–296, 1973; Schwenk et al. in Reg Anesth Pain Med 43(5):456–466, 2018). Regarding its rising popularity as a treatment option in mental health, ketamine holds promise as a rapidly acting treatment for suicidal ideation and refractory depression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Mo H, Campbell MJ, Fertel BS, et al. Ketamine safety and use in the emergency department for pain and agitation/delirium: a health system experience. West J Emerg Med. 2020;21(2):272–81.:https://doi.org/10.5811/westjem.2019.10.43067.

  2. Coppel DL, Bovill JG, Dundee JW. The taming of ketamine. Anaesthesia. 1973;28(3):293–96. https://doi.org/10.1111/j.1365-2044.1973.tb00449.x.

    Article  CAS  PubMed  Google Scholar 

  3. Schwenk ES, Viscusi ER, Buvanendran A, 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. Reg Anesth Pain Med. 2018;43(5):456–6. https://doi.org/10.1097/aap.0000000000000806.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lovett S, Reed T, Riggs R, et al. A randomized, noninferiority, controlled trial of two doses of intravenous subdissociative ketamine for analgesia in the emergency department. Acad Emerg Med. 2021;28(6):647–54. https://doi.org/10.1111/acem.14200.

    Article  PubMed  Google Scholar 

  5. • Maher DP, Chen L, Mao J. Intravenous ketamine infusions for neuropathic pain management: a promising therapy in need of optimization. Anesth Analg. 2017;124(2):661–74. https://doi.org/10.1213/ane.0000000000001787. Comprehensive clinical trial demonstrating the benefit of short-term ketamine infusions for treatment of neuropathic pain such as spinal cord injuries, phantom limb pain, peripheral nerve injuries due to trauma, whiplash, fibromyalgia, and CRPS.

  6. Taylor SS, Noor N, Urits I, et al. Complex regional pain syndrome: a comprehensive review. Pain Ther. 2021;10(2):875–92. https://doi.org/10.1007/s40122-021-00279-4.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Jouguelet-Lacoste J, La Colla L, Schilling D, Chelly JE. The use of intravenous infusion or single dose of low-dose ketamine for postoperative analgesia: a review of the current literature. Pain Med. 2015;16(2):383–3. https://doi.org/10.1111/pme.12619.

    Article  PubMed  Google Scholar 

  8. Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. 2014;77(2):357–67. https://doi.org/10.1111/bcp.12094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Israel JE, St Pierre S, Ellis E, et al. Ketamine for the treatment of chronic pain: a comprehensive review. Health Psychol Res. 2021;9(1):25535. https://doi.org/10.52965/001c.25535.

  10. Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine infusions for chronic pain: a systematic review and meta-analysis of randomized controlled trials. Anesth Analg. 2019;129(1):241–4. https://doi.org/10.1213/ane.0000000000004185.

    Article  CAS  PubMed  Google Scholar 

  11. Michelet D, Brasher C, Horlin A-L, et al. Ketamine for chronic non-cancer pain: a meta-analysis and trial sequential analysis of randomized controlled trials. Euro J Pain. 2018;22(4):632–46.https://doi.org/10.1002/ejp.1153.

  12. Amr YM. Multi-day low dose ketamine infusion as adjuvant to oral gabapentin in spinal cord injury related chronic pain: a prospective, randomized, double blind trial. Pain Physician May-Jun. 2010;13(3):245–49.

    Article  Google Scholar 

  13. Pickering G, Pereira B, Morel V, et al. Ketamine and magnesium for refractory neuropathic pain: a randomized, double-blind, crossover trial. Anesthesiology. 2020;133(1):154–64. https://doi.org/10.1097/aln.0000000000003345.

    Article  CAS  PubMed  Google Scholar 

  14. Rigo FK, Trevisan G, Godoy MC, et al. Management of neuropathic chronic pain with methadone combined with ketamine: a randomized, double blind, active-controlled clinical trial. Pain Phys. 2017;20(3):207–15.

    PubMed  Google Scholar 

  15. Corriger A, Voute M, Lambert C, Pereira B, Pickering G. Ketamine for refractory chronic pain: a 1-year follow-up study. Pain. 2022;163(4):690–1. https://doi.org/10.1097/j.pain.0000000000002403.

    Article  CAS  PubMed  Google Scholar 

  16. Noppers I, Niesters M, Swartjes M, et al. Absence of long-term analgesic effect from a short-term S-ketamine infusion on fibromyalgia pain: a randomized, prospective, double blind, active placebo-controlled trial. Euro J Pain. 2011;15(9):942–49. https://doi.org/10.1016/j.ejpain.2011.03.008.

    Article  CAS  Google Scholar 

  17. Bell RF, Eccleston C, Kalso E. Ketamine as adjuvant to opioids for cancer pain. a qualitative systematic review. J Pain Symp Manag 2003;26(3):867–75. https://doi.org/10.1016/S0885-3924(03)00311-7.

  18. • Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–54. https://doi.org/10.1016/s0006-3223(99)00230-9. First published positive response that ketamine can rapidly reduce symptoms of depression.

  19. Fond G, Loundou A, Rabu C, et al. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology. 2014;231(18):3663–76. https://doi.org/10.1007/s00213-014-3664-5.

    Article  CAS  PubMed  Google Scholar 

  20. Rush AJ, Fava M, Wisniewski SR, et al. Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design. Contr Clin Trials. 2004;25(1):119–42. https://doi.org/10.1016/s0197-2456(03)00112-0.

    Article  PubMed  Google Scholar 

  21. Mandal S, Sinha VK, Goyal N. Efficacy of ketamine therapy in the treatment of depression. Indian J Psychiatry. 2019;61(5):480–85. https://doi.org/10.4103/psychiatry.IndianJPsychiatry_484_18.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ghasemi M, Kazemi MH, Yoosefi A, et al. Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Res. 2014;215(2):355–61. https://doi.org/10.1016/j.psychres.2013.12.008.

    Article  CAS  PubMed  Google Scholar 

  23. Ekstrand J, Fattah C, Persson M, et al. Racemic ketamine as an alternative to electroconvulsive therapy for unipolar depression: a randomized, open-label, non-inferiority trial (KetECT). Int J Neuropsychopharmacol. 2022;25(5):339–49. https://doi.org/10.1093/ijnp/pyab088.

    Article  CAS  PubMed  Google Scholar 

  24. 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):150–58. https://doi.org/10.1176/appi.ajp.2017.17040472.

    Article  PubMed  Google Scholar 

  25. Liriano F, Hatten C, Schwartz TL. Ketamine as treatment for post-traumatic stress disorder: a review. Drugs Context. 2019;8:212305. https://doi.org/10.7573/dic.212305.

  26. Ross C, Jain R, Bonnett CJ, Wolfson P. High-dose ketamine infusion for the treatment of posttraumatic stress disorder in combat veterans. Ann Clin Psychiatry. 2019;31(4):271–79.

    PubMed  Google Scholar 

  27. Abdallah CG, Roache JD, Gueorguieva R, et al. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology. 2022;47(8):1574–81. https://doi.org/10.1038/s41386-022-01266-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nikayin S, Murphy E, Krystal JH, Wilkinson ST. Long-term safety of ketamine and esketamine in treatment of depression. Expert Opin Drug Saf. 2022;21(6):777–87. https://doi.org/10.1080/14740338.2022.2066651.

  29. Naughton M, Clarke G, O’Leary OF, Cryan JF, Dinan TG. A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action. J Affect Disord. 2014;156:24–35. https://doi.org/10.1016/j.jad.2013.11.014.

    Article  CAS  PubMed  Google Scholar 

  30. 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;155:123–29. https://doi.org/10.1016/j.jad.2013.10.036.

    Article  CAS  PubMed  Google Scholar 

  31. Wan LB, Levitch CF, Perez AM, et al. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015;76(3):247–52. https://doi.org/10.4088/JCP.13m08852.

    Article  PubMed  Google Scholar 

  32. Li Y, Shi J, Yang BF, et al. Ketamine-induced ventricular structural, sympathetic and electrophysiological remodelling: pathological consequences and protective effects of metoprolol. Br J Pharmacol. 2012;165(6):1748–56. https://doi.org/10.1111/j.1476-5381.2011.01635.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhu X, Kohan LR, Goldstein RB. Substantial elevation of liver enzymes during ketamine infusion: a case report. A A Pract. 2020;14(8):e01239. https://doi.org/10.1213/xaa.0000000000001239.

  34. Detsch O, Kochs E. Effects of ketamine on CNS-function. Anaesthesist. 1997;46 Suppl 1:S20–9. Effekte von Ketamin auf die ZNS-Funktion. https://doi.org/10.1007/pl00002460.

  35. Parikh SV, Lopez D, Vande Voort JL, et al. Developing an IV ketamine clinic for treatment-resistant depression: a primer. Psychopharmacol Bull. 2021;51(3):109–24.

    PubMed  PubMed Central  Google Scholar 

  36. FDA alerts health care professionals of potential risks associated with compounded ketamine nasal spray. U.S. Food Drug Admin. https://www.fda.gov/drugs/human-drug-compounding/fda-alerts-health-care-professionals-potential-risks-associated-compounded-ketamine-nasal-spray. Accessed 1 Mar 2023.

  37. Schak KM, Vande Voort JL, Johnson EK, et al. Potential risks of poorly monitored ketamine use in depression treatment. Am J Psychiatry. 2016;173(3):215–18. https://doi.org/10.1176/appi.ajp.2015.15081082.

    Article  PubMed  Google Scholar 

  38. Bricken H. The ketamine clinic craze: legalities and possibilities. Psych Law Blog. 2020. https://harrisbricken.com/psychlawblog/the-ketamine-clinic-craze-legalities-and-possibilities/#page=1.

  39. Ketamine Treatment Centers and Compound Pharmacies. Ketamine Clin Direct. https://ketamineclinicsdirectory.com/. Accessed 5 Mar 2023.

  40. Dodge D. The ketamine cure. The New York Times. https://www.nytimes.com/2021/11/04/well/ketamine-therapy-depression.html?login=email&auth=login-email. Accessed 5 Mar 2023.

  41. Pricing. Ketamine Wellness Institute. https://ketwell.com/pricing/. Accessed 5 Mar 2023.

  42. Projects - what we’ve achieved. Ketamine Taskforce. 2023. https://www.ketaminetaskforce.org/projects. Accessed 2 Mar 2023.

  43. Sanacora G, Frye MA, McDonald W, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiat. 2017;74(4):399–5. https://doi.org/10.1001/jamapsychiatry.2017.0080.

    Article  Google Scholar 

  44. • Cohen SP, Bhatia A, Buvanendran A, et al. Consensusguidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018;43(5):521–46. https://doi.org/10.1097/aap.0000000000000808. Provided evidence base guidelines for the use of IV ketamine infusions for chronic pain.

  45. Ketamine Infusion Therapy Checklist. Am Assoc Nurse Anesthesiol. 2023. https://www.aana.com/docs/default-source/practice-aana-com-web-documents-(all)/ketamine-infusion-therapy-checklistf8fb24731dff6ddbb37cff0000940c19.pdf?sfvrsn=cc0549b1_12. Accessed 2 Mar 2023.

  46. Ketamine Infusion Therapy Treatment Considerations. Am Psych Nurse Assoc. 2023. https://www.apna.org/ketamine-infusion-therapy/. Accessed  2 Mar 2023.

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA

    Andrew Bloomfield

  2. Anesthesiology Service, Durham VA Medical Center, Durham, NC, USA

    Srinivas Pyati

  3. Psychiatry Service, Durham VA Medical Center, Durham, NC, USA

    Leah Fryml

  4. Duke University School of Medicine, Durham, NC, USA

    Norine Chan

  5. Department of Emergency Medicine, Duke University Medical Center, Durham, NC, USA

    Reuben Horace

Authors
  1. Andrew Bloomfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norine Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leah Fryml
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reuben Horace
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Srinivas Pyati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Srinivas Pyati.

Ethics declarations

Conflict of Interest

Dr. Bloomfield, Ms. Norine Chan, Dr. Fryml, Dr. Horrace, and Dr. Pyati declare no conflicts of interest. The views described in the articles do not reflect the views of the Department of Veterans Affairs and it is solely based on the literature review and clinical experience of the authors.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors. Ethics committee approval was not necessary for this article and data presented were all from the literature review. Informed consent was not necessary for this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bloomfield, A., Chan, N., Fryml, L. et al. Ketamine for Chronic Pain and Mental Health: Regulations, Legalities, and the Growth of Infusion Clinics. Curr Pain Headache Rep 27, 579–585 (2023). https://doi.org/10.1007/s11916-023-01150-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-023-01150-1

Keywords

Search

Navigation