Memantine as a Potential Therapy in Subacute Herpetic Neuralgia: A Randomized Clinical Trial
Background: Varicella-Zoster virus (VZV) is the causative agent of herpes zoster, or "shingles." Most cases of acute herpes zoster are self-limiting, although the pain can cause significant suffering, and experience postherpetic neuralgia (PHN), particularly in older adults. Early treatment of herpetic neuralgia in the subacute phase may prevent PHN progression. This study aimed to evaluate the efficacy of memantine in the treatment of subacute neuropathic herpes zoster.
Methods: This randomized clinical trial was performed on sixteen patients aged 18-75 years with subacute herpetic neuralgia. Patients were randomly assigned to the intervention or control group according to the inclusion and exclusion criteria (8 in each group). The duration of the study was eight weeks. Patients in the memantine group received Gabapentin 300 mg per day and memantine 5 mg twice a day. Then, after one week, the memantine dose was tapered up to 10 mg twice a day. In the control group, patients received only Gabapentin from the first week to the end of the study. DN4 questionnaire is used to measure the severity of nerve pain. The patients of both control and intervention groups completed the questionnaire before starting the treatment and it was done again after the end of the treatment period (8 weeks).
Results: The results showed improvement in pain in patients who received Memantine along with Gabapentin in comparison with Gabapentin alone (P =0.001). Moreover, the DN4 questionnaire score evaluation indicated a significant difference only for the intervention group's Q1 variable in within-group analysis (P =0.031).
Conclusion: Co-administration of memantine with Gabapentin reduced the severity of subacute neuropathic herpes. In addition, memantine is expected to be a viable option for treating and relieving subacute and chronic nerve pain in patients.
2. Hope-Simpson RE. The nature of herpes zoster: a long-term study and a new hypothesis. Proc R Soc Med. 1965;58(1):9-20.
3. Patil A, Goldust M, Wollina U. Herpes zoster: A Review of Clinical Manifestations and Management. Viruses. 2022;14(2):192.
4. Dworkin RH, Gnann Jr JW, Oaklander AL, Raja SN, Schmader KE, Whitley RJ. Diagnosis and assessment of pain associated with herpes zoster and postherpetic neuralgia. J Pain. 2008;9(1):37-44.
5. Jeon YH. Herpes Zoster and Postherpetic Neuralgia: Practical Consideration for Prevention and Treatment. Korean J Pain. 2015;28(3):177-84.
6. Dubinsky R, Kabbani H, El-Chami Z, Boutwell C, Ali H. Practice Parameter: Treatment of postherpetic neuralgia: An evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63(6):959-65.
7. Moore RA, Wiffen PJ, Derry S, Rice AS. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2011;(3):CD007938.
8. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-73.
9. Hempenstall K, Nurmikko TJ, Johnson RW, A'Hern RP, Rice AS. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLOS Med. 2005;2(7):e164.
10. Koshy E, Mengting L, Kumar H, Jianbo W. Epidemiology, treatment and prevention of herpes zoster: A comprehensive review. Indian J Dermatol Venereol Leprol. 2018;84(3):251-262.
11. Sang CN, Booher S, Gilron I, Parada S, Max MB. Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials. Anesthesiology. 2002;96(5):1053-61.
12. Garrido-Suárez BB, Garrido G, Bellma-Menéndez A, et al. Combination of low frequency electroacupuncture plus subdissociative doses of ketamine in post-herpetic neuralgia patients. A pilot study. Journal of Pharmacy & Pharmacognosy Research. 2017;5(6):381-93.
13. Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ. A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease. Arch Neurol. 2006;63(1):49-54.
14. Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov. 2006;5(2):160-70.
15. Danysz W, Parsons CG. The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Int J Geriatr Psychiatry. 2003;18(S1):S23-S32.
16. Pickering G, Morel V. Memantine for the treatment of general neuropathic pain: a narrative review. Fundam Clin Pharmacol. 2018;32(1):4-13.
17. Collins S, Sigtermans MJ, Dahan A, Zuurmond WW, Perez RS. NMDA receptor antagonists for the treatment of neuropathic pain. Pain Med. 2010;11(11):1726-42.
18. Johnson JW, Kotermanski SE. Mechanism of action of memantine. Curr Opin Pharmacol. 2006;6(1):61-7.
19. Rice AS, Smith BH, Blyth FM. Pain and the global burden of disease. Pain. 2016;157(4):791-6.
20. Van Hecke O, Austin SK, Khan RA, Smith B, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654-62.
21. Pereira V, Goudet C. Emerging Trends in Pain Modulation by Metabotropic Glutamate Receptors. Front Mol Neurosci. 2019;11:464.
22. Bennett GJ. Update on the neurophysiology of pain transmission and modulation: focus on the NMDA-receptor. J Pain Symptom Manage. 2000;19(1 Suppl):S2-6.
23. Rahimzadeh P, Faiz S. Role of memantin, NMDA antagonist, in management of acute and chronic pain. Anesthesiology and Pain. 2013;4(2):193-5.
24. Alexander JK, DeVries AC, Kigerl KA, Dahlman JM, Popovich PG. Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation. Brain Behav Immun. 2009;23(6):851-60.
25. Morel V, Etienne M, Wattiez A-S, et al. Memantine, a promising drug for the prevention of neuropathic pain in rat. Europ J Pharmacol. 2013;721(1-3):382-90.
26. Chaplan SR, Malmberg AB, Yaksh TL. Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat. J Pharmacol Exp Ther. 1997;280(2):829-38.
27. Park BY, Park SH, Kim WM, Yoon MH, Lee HG. Antinociceptive Effect of Memantine and Morphine on Vincristine-induced Peripheral Neuropathy in Rats. Korean J Pain. 2010;23(3):179-85.
28. Schley M, Topfner S, Wiech K, et al. Continuous brachial plexus blockade in combination with the NMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees. Europ J Pain. 2007;11(3):299-308.
29. Sinis N, Birbaumer N, Gustin S, et al. Memantine treatment of complex regional pain syndrome: a preliminary report of six cases. Clin J Pain. 2007;23(3):237-43.
30. Ahmad-Sabry M-H, Shareghi G. Effects of memantine on pain in patients with complex regional pain syndrome--a retrospective study. Middle East J Anaesthesiol. 2015;23(1):51-4.
31. Hackworth RJ, Tokarz KA, Fowler IM, Wallace SC, Stedje-Larsen ET. Profound pain reduction after induction of memantine treatment in two patients with severe phantom limb pain. Anesth Analg. 2008;107(4):1377-9.
32. Olivan-Blázquez B, Herrera-Mercadal P, Puebla-Guedea M, et al. Efficacy of memantine in the treatment of fibromyalgia: a double-blind, randomised, controlled trial with 6-month follow-up. Pain. 2014;155(12):2517-25.
33. Schifitto G, Yiannoutsos CT, Simpson DM, et al. A placebo-controlled study of memantine for the treatment of human immunodeficiency virus–associated sensory neuropathy. J Neurovirology. 2006;12(4):328-31.
34. Mohammadzadeh P, Shaseb E, Sanaat Z, et al. Prophylactic effect of memantine in docetaxel induced neuropathy in patients with breast cancer. Preprint; 2021.
35. Chen S-R, Samoriski G, Pan HL. Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain. Neuropharmacol. 2009;57(2):121-6.
36. Eisenberg E, Kleiser A, Dortort A, Haim T, Yarnitsky D. The NMDA (N‐methyl‐D‐aspartate) receptor antagonist memantine in the treatment of postherpetic neuralgia: a double‐blind, placebo‐controlled study. Europ J Pain. 1998;2(4):321-7.
|Issue||Vol 10, No 4 (Autumn 2022)|
|Herpes Zoster ; Neuropathy Neuralgia Memantine|
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