Hostname: page-component-8448b6f56d-tj2md Total loading time: 0 Render date: 2024-04-24T21:01:14.268Z Has data issue: false hasContentIssue false
  • English
  • Français

Methadone in the Management of Intractable Neuropathic Noncancer Pain

Published online by Cambridge University Press:  02 December 2014

D. E. Moulin ,
D. Palma ,
C. Watling  and
V. Schulz
D. E. Moulin*
Affiliation:
Department of Clinical Neurological Sciences, Faculty of Medicine, University of Western Ontario, London, Ontario, Canada
D. Palma
Affiliation:
Department of Clinical Neurological Sciences, Faculty of Medicine, University of Western Ontario, London, Ontario, Canada
C. Watling
Affiliation:
Department of Clinical Neurological Sciences, Faculty of Medicine, University of Western Ontario, London, Ontario, Canada
V. Schulz
Affiliation:
Department of Anesthesia and Perioperative Medicine, Faculty of Medicine, University of Western Ontario, London, Ontario, Canada
*
London Regional Cancer Centre, 790 Commissioners Rd. E., London, Ontario, N6A 4L6, Canada
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective:

To evaluate the role of methadone in the management of intractable neuropathic noncancer pain.

Methods:

A case series of 50 consecutive noncancer pain patients who were seen at a tertiary care centre and treated with oral methadone for a variety of intractable neuropathic pain states.

Results:

The mean age was 52.7 years and the mean duration of follow-up was 13.9 months. Post-discectomy nerve root fibrosis, complex regional pain syndrome, peripheral neuropathy and central spinal cord pain syndromes were the most common diagnoses. Over 90% had been treated with one or more tricyclic antidepressants and anticonvulsants and a similar number had received other adjuvant analgesics. All patients had failed treatment with one or more conventional opioid analgesics (mean 2.8) at a mean maximal morphine dose of 384 mg (or equivalents) per day. Twelve patients had failed spinal cord stimulation. Nineteen patients (38%) did not tolerate initial methadone titration or thought their pain was worse on methadone. Five patients (10%) declared initial benefit but required repetitive dose escalation and eventually became non-responders. Twenty-six patients (52%) reported mild (4), moderate (15), marked (6) or complete (1) pain relief and continued on methadone at a mean maintenance dose of 159.8 mg/day for a mean duration of 21.3 months. Fourteen patients (28%) reported improved function on methadone relative to previous treatments.

Conclusions:

Methadone appears to have unique properties including N-methyl-D-aspartate antagonist activity that may make it especially useful in the management of intractable neuropathic pain. This observation needs to be tested in randomized, controlled trials.

Résumé:

RÉSUMÉ:Objectif:

Évaluer le rôle de la méthadone dans le traitement de la douleur névropathique rebelle d’origine non cancéreuse.

Méthodes:

Nous décrivons un groupe de 50 patients consécutifs référés à un centre de soins tertiaires et traités avec de la méthadone par voie orale pour des douleurs névropathiques rebelles non cancéreuses.

Résultats:

L’âge moyen des patients était de 52,7 ans et la durée moyenne du suivi était de 13,9 mois. Les diagnostics les plus fréquents étaient une fibrose radiculaire postdiscectomie, un syndrome de douleur régionale complexe, une neuropathie périphérique et un syndrome de douleur centrale suite à une lésion de la moelle épinière. Plus de 90% des patients avaient reçu un ou plusieurs antidépresseurs tricycliques et des anticonvulsivants, et autant de patients avaient reçu d’autres adjuvants des analgésiques. Tous les patients n’avaient pas répondu aux analgésiques opioïdes conventionnels (moyenne de 2,8) à une dose moyenne maximale de morphine de 384 mg par jour ou l’équivalent. Chez douze patients, la stimulation spinale avait été inefficace. Dixneuf patients (38%) n’ont pas toléré la dose initiale de méthadone ou ont eu l’impression que leur douleur était pire sous méthadone. Cinq patients (10%) ont éprouvé un bénéfice au début du traitement, mais ont eu besoin de doses de plus en plus élevées et sont éventuellement devenus des non-répondeurs. Vingt-six patients (52%) ont rapporté un soulagement léger (4), modéré (15), important (6) ou complet (1) de la douleur et ont continué le traitement à une dose moyenne de maintien de 159,8 mg/jour, pour une durée moyenne de 21,3 mois. Quatorze patients (28%) ont rapporté une amélioration de leur état fonctionnel sous méthadone par rapport aux traitements antérieurs.

Conclusions:

La méthadone semble posséder des propriétés uniques dont une activité antagoniste du N-méthyl-D-aspartate qui peut s’avérer particulièrement utile dans le traitement de la douleur névropathique rebelle. Cette observation doit être validée par des essais cliniques contrôlés et randomisés.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 32 , Issue 3 , August 2005 , pp. 340 - 343
Copyright
Copyright © The Canadian Journal of Neurological 2005

References

1. Schmader, KE. Epidemiology and impact on quality of life ofpostherpetic neuralgia and painful diabetic neuropathy. Clin J Pain 2002;18:350–354.Google Scholar
2. Bowsher, D. The lifetime occurrence of herpes zoster and prevalenceof postherpetic neuralgia: a retrospective survey in an elderly population. Eur J Pain 1999;3:335–342.Google Scholar
3. Bridges, D, Thompson, SWN, Rice, ASC. Mechanisms in neuropathicpain. Br J Anesth 2001;87:12–26.Google Scholar
4. Sindrup, HJ, Jensen, TS. Efficacy of pharmacological treatments ofneuropathic pain: An update and effect related to mechanism ofdrug action. Pain 1999;83:389–400.Google Scholar
5. Carver, A, Foley, K. Facts and an open mind should guide clinicalpractice. Curr Neurol Neurosci Rep 2001;1:97–98.Google Scholar
6. Watson, CPN, Babul, N. Efficacy of oxycodone in neuropathic pain:A randomized trial in postherpetic neuralgia. Neurology 1998;50:1837–1841.Google Scholar
7. Huse, E, Larbig, W, Flor, H, et al. The effect of opioids on phantom limbpain and cortical reorganization. Pain 2001;90:47–55.Google Scholar
8. Raja, SN, Haythornthwaite, JA, Pappagallo, M, et al. Opioids versusantidepressants in postherpetic neuralgia. Neurology 2002;59:1015–1021.Google Scholar
9. Gimbel, JS, Richards, P, Portenoy, RK. Controlled-release oxycodonefor pain in diabetic neuropathy. Neurology 2003;60:927–934.Google Scholar
10. Watson, CPN, Moulin, DE, Watt-Watson, J, Gordon, A, Eisenhoffer, J. Controlled-release oxycodone relieves neuropathic pain: a randomized, controlled trial in painful diabetic neuropathy. Pain 2003;105:71–78.Google Scholar
11. Rowbotham, MC, Twilling, L, Davies, PS, et al. Oral opioid therapyfor chronic peripheral and central neuropathic pain. New Eng J Med 2003;348:1223–1232.Google Scholar
12. Joseph, H, Stancliff, S, Langrod, J. Methadone maintenance treatment(MMT): A review of historical and clinical issues. Mt Sinai J Med 2000;67:347–364.Google Scholar
13. Fishman, SM, Wilsey, B, Mahajan, G, et al. Methadone reincarnated:Novel clinical applications with related concerns. Am Acad PainMed 2002;3:339–348.Google Scholar
14. Codd, EE, Shank, RP, Schupsky, JJ, et al. Serotonin andnorepinephrine uptake inhibiting activity of centrally acting analgesics: Structural determinants and role in antinociception. J Pharmacol Exp Ther 1995;274:1263–1270.Google Scholar
15. Davis, AM, Inturrisi, CE. d-Methadone blocks morphine tolerance andN-methyl-D-aspartate -induced hyperalgesia. J Pharmacol Exp Ther 1999;289:1048–1053.Google Scholar
16. Mercadante, S, Casuccio, A, Fulfaro, F, et al. Switching from morphineto methadone to improve analgesia and tolerability in cancer patients: a prospective study. J Clin Oncology 2001:2898–2904.Google Scholar
17. Bruera, E, Sweeney, C. Methadone use in cancer patients with pain. J Palliative Med 2002;5:127–137.Google Scholar
18. Jovey, RD, Ennis, J, Gardner-Nix, J, et al. Use of opioid analgesics forthe treatment of chronic noncancer pain – A consensus statement and guidelines from the Canadian Pain Society, 2002. Pain Res Manage 2003;8:3A-14A.Google Scholar
19. Levy, MH. Pharmacologic treatment of cancer pain. New Eng J Med 1996;335:1124–1132.CrossRefGoogle ScholarPubMed
20. Hampf, GBC, Kalso, EA. Chronic use of opioids in intractable facialpain. Acta Odontol Scand 1991;49:215–218.Google Scholar
21. Altier, N, Dion, D, Boulanger, A, et al. Successful use of methadone inthe treatment of chronic neuropathic pain arising from burn injuries: A case study. Burns 2001;27:771–775.Google Scholar
22. Bergmans, L, Snijdelaar, DG, Katz, J, et al. Methadone for PhantomLimb Pain. Clin J Pain 2002;18:203–205.Google Scholar
23. Gardner-Nix, JS. Oral methadone for managing chronicnonmalignant pain. J Pain Symptom Manage 1996;11:321–328.Google Scholar
24. Mironer, YE, Haasis, JC III, Chapple, IT, et al. Successful use ofmethadone in neuropathic pain: A multicentre study by the National Forum of Independent Pain Clinicians. Pain Digest 1999;9:191–193.Google Scholar
25. Gagnon, B, Almahrezi, MB, Schreier, G. Methadone in the treatmentof neuropathic pain. Pain Res Manage 2003;8:149–154.Google Scholar
26. Zenz, M, Strumpf, M, Tryba, M. Long-term oral opioid therapy inpatients with chronic nonmalignant pain. J Pain SymptomManage 1992;7:69–77.CrossRefGoogle Scholar
27. Davis, M, Walsh, D. Methadone for the relief of cancer pain: a reviewof pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration. Support Care Cancer 2001;9:73–83.Google Scholar
28. Moulin, DE. Use of methadone for neuropathic pain. Pain Res Manage 2003;8:131–132.Google Scholar
29. Pasternak, GW. Incomplete cross-tolerance and multiple mu opioidpeptide receptors. Trends Pharmacol Sci 2001;22:67–70.Google Scholar
30. Ripamonti, C, Groff, L, Brunelli, C, et al. Switching from morphine tooral methadone in treating cancer pain: What is the equianalgesic dose ratio? Clin Oncol 1998;16:3216–3221.Google Scholar
31. Krantz, MJ, Lewkowiez, L, Hays, H, et al. Torsade de pointesassociated with very high dose methadone. Ann Intern Med 2002;137:142.CrossRefGoogle ScholarPubMed
32. Wood, AJJ. Drug-induced prolongation of the QT interval. N Eng J Med 2004;350:1013–1022.Google Scholar
33. Cunningham, G, Bodley, S, Chaiet, A, et al. Methadone for painguidelines. College of Physicians and Surgeons of Ontario, November 2004 (www.cpso.on.ca).Google Scholar
34. Lynch, ME. A review of the use of methadone for treatment ofchronic non-cancer pain. Pain Res and Manage (in press).Google Scholar