Skip to main content Accessibility help
×
Home
  • Print publication year: 2014
  • Online publication date: October 2014

Chapter 72 - Methadone and treatment of chronic pain

from Section 7 - Special Topics

Summary

Methadone is familiar to most laypersons as a treatment for heroin addiction, dispensed at special clinics. Methadone is also a powerful, inexpensive, and effective analgesic, but it has many unique and potentially lethal aspects that have to be well understood before using it for pain relief. Addiction treatment with methadone requires a special license, but any provider who can prescribe Schedule II medications can write for methadone for pain. Unfortunately, because no special training is required to prescribe methadone and because poor insurance coverage is leading to the increased use of inexpensive methadone, there has been a tragic dramatic increase in opioid deaths attributed to methadone. This chapter reviews the indications, contraindications, drug interactions, metabolism, genetic issues, ethics, and initial evaluation and treatment for methadone.

References

1. Chen K. Pharmacology of methadone and related compounds. Ann N Y Acad Sci. 1948;51(1):83–97.
2. Substance Abuse Mental Health Services Administration. National survey of substance abuse treatment services (N-SSATS). Data on Substance Abuse Treatment Facilities. Rockville, MD: SAMHSA/Office of Applied Studies. 2008.
3. Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MC. QTc interval screening in methadone treatment. Ann Intern Med. 2009;150(6):387–395.
4. Hughes J, Bickel W, Higgins S. Buprenorphine for pain relief in a patient with drug abuse. Am J Drug Alcohol Abuse. 1991;17(4):451–455.
5. Umbricht A, Hoover D, Tucker M, et al. Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection. Drug Alcohol Depend. 2003;69(3):263–272.
6. Maxwell JC, McCance-Katz EF. Indicators of buprenorphine and methadone use and abuse: what do we know? Am J Addictions. 2010;19(1):73–88.
7. GoodRx. GoodRx Methadone Page. GoodRx.com 2013; http://www.goodrx.com/methadone.
8. Davoli M, Bargagli AM, Perucci CA, et al. Risk of fatal overdose during and after specialist drug treatment: the VEdeTTE study, a national multi-site prospective cohort study. Addiction. 2007;102(12):1954–1959.
9. Kornick CA, Kilborn MJ, Santiago-Palma J, et al. QTc interval prolongation associated with intravenous methadone. Pain. 2003;105(3):499–506.
10. Krantz MJ, Lewkowiez L, Hays H, et al. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002;137(6):501–504.
11. Gil M, Sala M, Anguera I, et al. Qt prolongation and Torsades de Pointes in patients infected with human immunodeficiency virus and treated with methadone. Am J Cardiol. 2003;92(8):995–997.
12. Cruciani RA. Methadone: to ECG or not to ECG…That is still the question. J Pain Symptom Manage. 2008;36(5):545–552.
13. Chugh SS, Socoteanu C, Reinier K, et al. A community-based evaluation of sudden death associated with therapeutic levels of methadone. Am J Med. 2008;121(1):66–71.
14. Piguet V, Desmeules J, Ehret G, Stoller R, Dayer P. QT interval prolongation in patients on methadone with concomitant drugs. J Clin Psychopharmacol. 2004;24(4):446–448.
15. Krantz MJ, Rowan SB, Mehler PS. Cocaine-related torsade de pointes in a methadone maintenance patient. J Addict Dis. 2005;24(1):53–60.
16. Ehret GB, Voide C, Gex-Fabry M, et al. Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors. Arch Intern Med. 2006;166(12):1280.
17. Kapur BM, Hutson JR, Chibber T, Luk A, Selby P. Methadone: a review of drug-drug and pathophysiological interactions. Crit Rev Clin Lab Sci. 2011;48(4):171–195.
18. Benmebarek M, Devaud C, Gex-Fabry M, et al. Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone. Clin Pharmacol Ther. 2004;76(1):55–63.
19. Wynn G, Cozza K, Zapor M, Wortmann G, Armstrong S. Med-psych drug-drug interactions update. Antiretrovirals, part III: antiretrovirals and drugs of abuse. Psychosomatics. 2005;46(1):79–87.
20. Gruber V, McCance-Katz E. Methadone, buprenorphine, and street drug interactions with antiretroviral medications. Curr HIV/AIDS Rep. 2010;7(3):152–160.
21. Kakuda TN, Schöller-Gyüre M, Hoetelmans RM. Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinetics. 2011;50(1):25–39.
22. Kharasch E, Walker A, Whittington D, Hoffer C, Bedynek P. Methadone metabolism and clearance are induced by nelfinavir despite inhibition of cytochrome P4503A (CYP3A) activity. Drug Alcohol Depend. 2009;101(3):158–168.
23. Lüthi B, Huttner A, Speck R, Mueller N. Methadone-induced Torsade de pointes after stopping lopinavir–ritonavir. Eur J Clin Microbiol Infect Dis. 2007;26(5):367–369.
24. McCance-Katz E, Rainey P, Jatlow P, Friedland G. Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262). J Acquir Immune Defic Syndr Hum Retrovirol. 1998;18(5):435–443.
25. Doehring A, von Hentig N, Graff J, et al. Genetic variants altering dopamine D2 receptor expression or function modulate the risk of opiate addiction and the dosage requirements of methadone substitution. Pharmacogenet Genomics. 2009;19(6):407–414.
26. Fonseca F, de la Torre R, Díaz L, et al. Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response. PLoS One. 2011;6(5):e19527.
27. Chen C-H, Wang S-C, Tsou H-H, et al. Genetic polymorphisms in CYP3A4 are associated with withdrawal symptoms and adverse reactions in methadone maintenance patients. Pharmacogenomics. 2011;12(10):1397–1406.
28. Coller JK, Barratt DT, Dahlen K, Loennechen MH, Somogyi AA. ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Clin Pharmacol Ther. 2006;80(6):682–690.
29. Codd EE, Shank RP, Schupsky JJ, Raffa RB. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995;274(3):1263–1270.
30. Sotgiu ML, Valente M, Storchi R, Caramenti G, Biella GE. Cooperative N-methyl-d-aspartate (NMDA) receptor antagonism and μ-opioid receptor agonism mediate the methadone inhibition of the spinal neuron pain-related hyperactivity in a rat model of neuropathic pain. Pharmacol Res. 2009;60(4):284–290.
31. Kristensen K, Blemmer T, Angelo HR, et al. Stereoselective pharmacokinetics of methadone in chronic pain patients. Ther Drug Monitor. 1996;18(3):221–227.
32. Ferrari A, Coccia CPR, Bertolini A, Sternieri E. Methadone: metabolism, pharmacokinetics and interactions. Pharmacol Res. 2004;50(6):551–559.
33. Preston KL, Epstein DH, Davoudzadeh D, Huestis MA. Methadone and metabolite urine concentrations in patients maintained on methadone. J Anal Toxicol. 2003;27(6):332–341.
34. Larue F, Fontaine A, Colleau SM. Underestimation and undertreatment of pain in HIV disease: multicentre study. BMJ. 1997;314(7073):23–28.
35. Tsao J, Dobalian A, Stein J. Illness burden mediates the relationship between pain and illicit drug use in persons living with HIV. Pain. 2005;119(1–3):124–132.
36. Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. 2008;136(3):380–387.
37. Ellis RJ, Rosario D, Clifford DB, et al. Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol. 2010;67(5):552.
38. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118(3):289–305.
39. Moulin D, Palma D, Watling C, Schulz V. Methadone in the management of intractable neuropathic noncancer pain. Can J Neurol Sci. 2005;32(3):340–343.
40. Altier N, Dion D, Boulanger A, Choinière M. Management of chronic neuropathic pain with methadone: a review of 13 cases. Clin J Pain. 2005;21(4):364–369.
41. Fingerhut LA. Increases in poisoning and methadone-related deaths: United States, 1999–2005. National Center for Health Statistics. Health E-Stat. 2008.
42. Hall AJ, Logan JE, Toblin RL, et al. Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA. 2008;300(22):2613–2620.
43. Ballantyne JC, LaForge KS. Opioid dependence and addiction during opioid treatment of chronic pain. Pain. 2007;129(3):235–255.
44. Preskorn SH, Greenblatt DJ, Flockhart D, et al. Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. J Clin Psychopharmacol. 2007;27(1):28–34.
45. Kotlyar M, Brauer LH, Tracy TS, et al. Inhibition of CYP2D6 activity by bupropion. J Clin Psychopharmacol. 2005;25(3):226–229.