Health Psychology Research / HPR / Volume 13 / Issue 1 / DOI: 10.52965/001c.129552
Cite this article
1
Download
10
Citations
16
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
GENERAL

Methadone for Chronic Pain: A Review of Pharmacology, Efficacy, and Safety Concerns

Patrick Brown1 Alexa Ryder2 Kayla Valenti3 Katie Phung4 Jamal Hasoon4
Show Less
1 Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX, USA
2 Department of Physical Medicine and Rehabilitation, University of Texas Health Science Center at Houston, Houston, TX, USA
3 Drexel University College of Medicine, Philadelphia, PA, USA
4 Department of Anesthesiology, University of Texas Health Science Center at Houston, Houston, Texas, USA
Submitted: 21 December 2024 | Accepted: 19 January 2025 |
© 2025 by the Author(s). Licensee Health Psychology Research, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Purpose of Review

Methadone is a synthetic opioid extensively used in opioid use disorder management but is gaining recognition for its unique pharmacological properties that make it a viable alternative for chronic pain management. This review aims to explore methadone’s pharmacokinetics, pharmacodynamics, efficacy, and safety profile to assess its potential role in managing chronic pain conditions.

 

Recent Findings

Methadone’s dual action as a mu-opioid receptor agonist and NMDA receptor antagonist positions it as an effective option for managing both nociceptive and neuropathic pain. It has shown promising results in cancer pain management, refractory pain, and opioid rotation strategies. Despite its therapeutic advantages, concerns regarding its narrow therapeutic window, variable pharmacokinetics, QT interval prolongation, and risk of respiratory depression highlight the need for careful patient selection and monitoring. New evidence also sheds light on its affordability and efficacy in low-resource settings, as well as its controversial role in mitigating opioid-induced hyperalgesia.

 

Summary

Methadone offers a unique therapeutic option in chronic pain management due to its multifaceted pharmacological properties. While it provides significant benefits for patients with complex pain syndromes, clinicians must exercise caution due to its safety concerns and variability in individual metabolism. A personalized approach, combined with rigorous monitoring, is essential to optimize its benefits while minimizing risks. Further research is needed to better define its role in chronic pain treatment and address unresolved safety concerns.

References
1.Baldo BA, Rose MA. The anaesthetist, opioid analgesic drugs, and serotonin toxicity: A mechanistic and clinical review. British Journal of Anaesthesia. 2020;124(1):44-62. doi:10.1016/​j.bja.2019.08.010
Google Scholar
2.Hanna V, Senderovich H. Methadone in pain management: A systematic review. The Journal of Pain. 2021;22(3):233-245. doi:10.1016/​j.jpain.2020.04.004
Google Scholar
3.Dydyk A, Conermann T. Chronic Diseases: An Encyclopedia of Causes, Effects, and Treatments. In: Chronic Pain. Vol 2. ; 2024:599-601.
Google Scholar
4.de Barros GAM, Baradelli R, Rodrigues DG, et al. Use of methadone as an alternative to morphine for chronic pain management: A noninferiority retrospective observational study. Pain Reports. 2021;6(4):e979. doi:10.1097/​PR9.0000000000000979
Google ScholarPubMed CentralPubMed
5.Heung Y, Reddy A. How to use methadone in an era of an opioid epidemic. Current Treatment Options in Oncology. 2020;21:1-10. doi:10.1007/​s11864-020-0724-4
Google Scholar
6.Kreutzwiser D, Tawfic QA. Methadone for pain management: A pharmacotherapeutic review. CNS Drugs. 2020;34(8):827-839. doi:10.1007/​s40263-020-00743-3
Google Scholar
7.Drug Fact Sheet: Methadone. Department of Justice/ Drug Enforcement Administration. https:/​/​www.dea.gov/​sites/​default/​files/​2020-06/​Methadone-2020_0.pdf
8.Lai G, Aroke EN, Zhang SJ. Rediscovery of methadone to improve outcomes in pain management. Journal of PeriAnesthesia Nursing. 2022;37(4):425-434. doi:10.1016/​j.jopan.2021.08.011
Google Scholar
9.Ferrari A, Coccia CPR, Bertolini A, Sternieri E. Methadone—Metabolism, pharmacokinetics and interactions. Pharmacological Research. 2004;50(6):551-559. doi:10.1016/​j.phrs.2004.05.002
Google Scholar
10.Koehl A, Hu H, Maeda S, et al. Structure of the µ-opioid receptor–Gi protein complex. Nature. 2018;558(7711):547-552.
Google Scholar
11.Durrani M, Bansal K. Methadone. In: StatPearls [Internet]. StatPearls Publishing; 2024.
Google Scholar
12.Rickli A, Liakoni E, Hoener MC, Liechti ME. Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in vitro: Link to clinical reports of serotonin syndrome. British Journal of Pharmacology. 2018;175(3):532-543. doi:10.1111/​bph.14105
Google ScholarPubMed CentralPubMed
13.Berkowitz BA. The relationship of pharmacokinetics to pharmacological activity: Morphine, methadone and naloxone. Clinical Pharmacokinetics. 1976;1:219-188. doi:10.2165/​00003088-197601030-00004
Google Scholar
14.Tran THH. Methadone Patients in Vietnam: Substance Use Patterns, Reasons for Entering Treatment, and Methadone-Related Attitudes. Published online 2023.
Google Scholar
15.Mercadante S, Bruera E. Methadone as a first-line opioid in cancer pain management: A systematic review. Journal of Pain and Symptom Management. 2018;55(3):998-1003. doi:10.1016/​j.jpainsymman.2017.10.017
Google Scholar
16.Nicholson AB, Watson GR, Derry S, Wiffen PJ. Methadone for cancer pain. Cochrane Database of Systematic Reviews. 2017;(2). doi:10.1002/​14651858.CD003971.pub4
Google ScholarPubMed CentralPubMed
17.Ding H, Song Y, Xin W, et al. Methadone Switching for Refractory Cancer Pain. BMC Palliative Care. 2022;21(1):191-197. doi:10.1186/​s12904-022-01076-2
Google Scholar
18.GoodRx. GoodRx Prescription Prices. GoodRx. Accessed December 2, 2024. https:/​/​www.goodrx.com
19.Gagnon B, Almahrezi A, Schreier G. Methadone in the Treatment of Neuropathic Pain. Pain Research & Management. 2003;8(3):149-154. doi:10.1155/​2003/​236718
Google Scholar
20.Altier N, Dion D, Boulanger A, Choinière M. Management of Chronic Neuropathic Pain with Methadone: A Review of 13 Cases. The Clinical Journal of Pain. 2005;21(4):364-369. doi:10.1097/​01.ajp.0000125247.95213.53
Google Scholar
21.Tompkins DA, Campbell CM. Opioid-Induced Hyperalgesia: Clinically Relevant or Extraneous Research Phenomenon? Current Pain and Headache Reports. 2011;15(2):129-136. doi:10.1007/​s11916-010-0171-1
Google Scholar
22.Vorobeychik Y, Chen L, Bush MC, Mao J. Improved Opioid Analgesic Effect Following Opioid Dose Reduction. Pain Medicine (Malden, Mass). 2008;9(6):724-727. doi:10.1111/​j.1526-4637.2008.00501.x
Google Scholar
23.Chu LF, Angst MS, Clark D. Opioid-Induced Hyperalgesia in Humans: Molecular Mechanisms and Clinical Considerations. The Clinical Journal of Pain. 2008;24(6):479-496. doi:10.1097/​AJP.0b013e31816b2f43
Google Scholar
24.Yi P, Pryzbylkowski P. Opioid Induced Hyperalgesia. Pain Medicine. Published online 2015. doi:10.1111/​pme.12914
Google Scholar
25.Kreek MJ, Borg L, Ducat E, Ray B. Pharmacotherapy in the Treatment of Addiction: Methadone. Journal of Addictive Diseases. 2010;29(2):200-216. doi:10.1080/​10550881003684798
Google Scholar
26.Dole VP, Kreek MJ. Methadone Plasma Level: Sustained by a Reservoir of Drug in Tissue. Proceedings of the National Academy of Sciences - PNAS. 1973;70(1):10-10. doi:10.1073/​pnas.70.1.10
Google Scholar
27.Toombs JD, Kral LA. Methadone Treatment for Pain States. American Family Physician. 2005;71(7):1353.
Google Scholar
28.Repple J, Haessner S, Johnen A, et al. Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments. BMC Neurology. 2021;21:1-6. doi:10.1186/​s12883-021-02108-9
Google ScholarPubMed CentralPubMed
29.Miano TA, Wang L, Leonard CE, et al. Identifying clinically relevant drug–drug interactions with methadone and buprenorphine: A translational approach to signal detection. Clinical Pharmacology & Therapeutics. 2022;112(5):1120-1129. doi:10.1002/​cpt.2717
Google ScholarPubMed CentralPubMed
30.Centers for Disease Control and Prevention (CDC). Vital signs: Risk for overdose from methadone used for pain relief-United States, 1999-2010. MMWR: Morbidity & Mortality Weekly Report. 2012;61(26).
Google Scholar
31.Faul M. Methadone prescribing and overdose and the association with Medicaid preferred drug list policies—United States, 2007–2014. MMWR Morbidity and Mortality Weekly Report. 2017;66. doi:10.15585/​mmwr.mm6612a2
Google ScholarPubMed CentralPubMed
32.Chou R, Cruciani RA, Fiellin DA, et al. Methadone safety: A clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. The Journal of Pain. 2014;15(4):321-337. doi:10.1016/​j.jpain.2014.01.494
Google Scholar
33.Rajan J, Scott-Warren J. The clinical use of methadone in cancer and chronic pain medicine. BJA Education. 2016;16(3):102-106. doi:10.1093/​bjaceaccp/​mkv023
Google Scholar
34.Walsh SL, Strain EC. Pharmacology of methadone. In: The Treatment of Opioid Dependence. ; 2006:59-76.
Google Scholar
35.Nosyk B, Min JE, Homayra F, et al. Buprenorphine/Naloxone vs Methadone for the Treatment of Opioid Use Disorder. JAMA. 2024;332(21):1822-1831. doi:10.1001/​jama.2024.16954
Google Scholar
36.Fipps DC, Oesterle TS, Kolla BP. Opioid Maintenance Therapy: A Review of Methadone, Buprenorphine, and Naltrexone Treatments for Opioid Use Disorder. Seminars in neurology. 2024;44(4):441-451. doi:10.1055/​s-0044-1787571
Google Scholar
37.Vu PD, Bansal V, Chitneni A, et al. Buprenorphine for Chronic Pain Management: a Narrative Review. Current pain and headache reports. 2023;27(12):811-820. doi:10.1007/​s11916-023-01185-4
Google Scholar
38.Dalal S, Chitneni A, Berger AA, et al. Buprenorphine for Chronic Pain: A Safer Alternative to Traditional Opioids. Health psychology research. 2021;9(1):27241. doi:10.52965/​001c.27241
Google Scholar
39.Poliwoda S, Noor N, Jenkins JS, et al. Buprenorphine and its formulations: a comprehensive review. Health psychology research. 2022;10(3):37517. doi:10.52965/​001c.37517
Google Scholar
Share
Back to top
Health Psychology Research, Electronic ISSN: 2420-8124 Published by Health Psychology Research