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Comparing the use of Memantine with Dextromethorphan and Placebo to Reduce Pain before Orthopedic Surgery

Mehrdad Taheri, Alireza Mirkheshti, Alireza Manafi Rasi, Yalda Adili




Introduction: To compare the use of Memantine with Dextromethorphan and placebo to reduce pain after orthopedic surgery.

Materials and Methods: The present study was a double-blind clinical trial including180 patients undergoing elective orthopedic surgery of the lower limbs. Patients were divided randomly into three groups of 60 patients each. The first group (Group M) received 30 mg Memantine orally, the second group (Group D) received 45 mg of Dextromethorphan and the third group (Group P) received only placebo, two and a half hours before the operation. The intensity of pain (VAS score), sedation score, and nausea and vomiting were recorded postoperatively.

Results: In this study, 60 patients were enrolled in each group. The total VAS (Visual Analogue Scale) score was significantly lower among patients receiving Memantine and the satisfaction was significantly higher compared to the Dextromethorphan and placebo groups (P-value <0.001).

Conclusion: The present study results indicate that Memantine has a relatively better outcome compared to Dextromethorphan or placebo in reducing the post surgical pain among patients undergoing orthopedic surgeries. It also reduced the need for post surgical opioid use and improved the patients’ satisfaction. 



Memantine, Dextromethorphan, Pain , orthopedic surgery, postoperative pain


Steven D. Waldman. Pain Management. 2th ed. Philadelphia, Elsevier Saunders; 2011; pp: 50.

Wu CT, Yu JC, Liu ST. Preincisional dextromethorphan treatment for postoperative pain management after upper abdominal surgery. World J Surg. 2000;24(5): 512-7.

Ong CK, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis. Anesth Analg. 2005;100(3):757-73.

Møiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief.Anesthesiology. 2002;96(3):725-41.

Kew JN, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology.Psychopharmacology (Berl).2005;179(1):4-29.

Flor H, Birbaumer N. Phantom limb pain: cortical plasticity and novel therapeutic approaches. Curr Opin Anaesthesiol.2000;13(5):561-4.

Arnstein PM. The neuroplastic phenomenon: a physiologic link between chronic pain and learning. J NeurosciNurs.1997;29(3):179-86.

EntezarySR, FarshadpourS, Alebouyeh MR, Imani F, Emami Meybodi MK, Yaribeygi H. Effects of Preoperative Use of Oral Dextromethorphan on Postoperative Need for Analgesics in Patients With Knee Arthroscopy. Anesth Pain Med. 2013;3(3):e11187.

Weinbroum AA, Rudick V, Paret G, Ben-Abraham R. The role of dextromethorphan in pain control. Can J Anaesth.2000;47(6):585-96.

Weinbroum AA, Gorodezky A, Niv D, Ben-Abraham R, Rudick V, Szold A. Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia.Can J Anaesth. 2001;48 (2):167-74.

Lipton SA. Failures and successes of NMDA receptor antagonists: molecular basis for the useof open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx. 2004;1 (1):101-10.

Muir KW. Glutamate-based therapeutic approaches: clinical trials with NMDA antagonists. Curr Opin Pharmacol. 2006;6 (1):53-60.

Witt A, Macdonald N, Kirkpatrick P. Memantine hydrochloride. Nat Rev Drug Discov.2004;3 (2):109-10.

Schwartzman RJ, Grothusen J, Kiefer RT, Rohr P. Neuropathic central pain: epidemiology, etiology, and treatment options. Arch Neurol. 2001;58 (10):1547-50.

Johnson JW, Kotermanski SE. Mechanism of action of memantine. Curr Opin Pharmacol.2006;6 (1):61-7.

Maier C, Dertwinkel R, Mansourian N, Hosbach I, Schwenkreis P, Senne I, et al. Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain–results of a randomized double-blinded, placebo-controlled trial. Pain. 2003;103(3):277-83.

Schwenkreis P, Maier C, Pleger B, Mansourian N, Dertwinkel R, Malin JP, et al. NMDA-mediated mechanisms in cortical excitability changes after limb amputation. Acta Neurol Scand. 2003;108(3):179-84.

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.

Sinis N, Birbaumer N, Gustin S, Schwarz A, Bredanger S, Becker ST, et al. Memantine treatment of complex regional pain syndrome: a preliminary report of six cases. Clin J Pain. 2007;23(3):237-43.

Javid MJ, Hajijafari M, Hajipour A, Makarem J, Khzaeipour Z. Eval¬uation of A Low Dose Ketamine in Post Tonsillectomy Pain Relief: A Randomized Trial Comparing Intravenous and Subcutaneous Ketamine in Pediatrics. Anesth Pain. 2012;2(3):107-10.

Georg BE, Youssef D, Jocelyne C, Michela R, Adriana W, Alain F, et al. Influence of CYP2D6 Activity on Pre-emptive Analgesia by the N-Methyl-D-Aspartate Antagonist Dextromethorphan in a Randomized Controlled Trial of Acute Pain. Pain Physician. 2013; 16:45-56.

Woolf CJ, Chong MS. Preemptive analgesia: treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg. 1993;77(2):362-79.

Bern J, Peck R. Dextromethorphan: an overview of safety issues. Drug Saf. 1992;7(3):190-199.

Pan YS, Hu YF, Tian FB, Xu K. Effects of epidural preemptive analgesia on stress reaction in retroperitoneal laparoscopic adrenalectomy surgery: a randomized controlled study. Int J Clin Exp Med. 2015;8(6):9862-8.

Lee SH, Kim SH, Noh YH, Choi BM, Noh GJ, Park WD, et al. Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats. Basic Clin Pharmacol Toxicol. 2016;118(2):122-7.

Koch HJ, Szecsey A, Haen E. NMDA-antagonism (memantine): an alternative pharmacological therapeutic principle in Alzheimer's and vascular dementia. Curr Pharm Des. 2004;10(3):253-9.

Emik U, Unal Y, Arslan M, Demirel CB. The effects of memantine on recovery, cognitive functions, and pain after propofol anesthesia. Braz J Anesthesiol. 2016;66(5):485-91.

Nikolajasen L, Gottrup H, Kristensen AGD, Jensen TS. Memantine (a Nmethyl-

D-aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: a randomized double-blinded, cross-over study. Anesth Analg. 2000;91(4):960-6.

Maier C, Dertwinkel R, Mansourian N, Hosbach I, Schwenkreis P, Senne I, et al. Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain-results of a randomized double-blinded placebo-controlled trial. Pain 2003;103(3): 277-83.

Schley M, Topfer S, Wiech K, Schaller HE, Konrad CJ, Schmelz M, et al. Continuous brachial plexus blockade in combination with NMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees. Eur J Pain 2007;11(3): 299-308.

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.

DOI: https://doi.org/10.22037/jcma.v2i4.18182


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