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Dextromethorphan and memantine after ketamine analgesia: a randomized control trial

Authors Martin E, Sorel M, Morel V, Marcaillou F, Picard P, Delage N, Tiberghien F, Crosmary MC, Najjar M, Colamarino R, Créach C, Lietar B, Brumauld de Montgazon G, Margot-Duclot A, Loriot MA, Narjoz C, Lambert C, Pereira B, Pickering G

Received 2 March 2019

Accepted for publication 5 June 2019

Published 2 August 2019 Volume 2019:13 Pages 2677—2688


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Georgios D. Panos

Elodie Martin,1 Marc Sorel,2 Véronique Morel,3 Fabienne Marcaillou,4 Pascale Picard,4 Noémie Delage,4 Florence Tiberghien,5 Marie-Christine Crosmary,6 Mitra Najjar,6 Renato Colamarino,6 Christelle Créach,7,8 Béatrice Lietar,7 Géraldine Brumauld de Montgazon,9 Anne Margot-Duclot,10 Marie-Anne Loriot,11,12 Céline Narjoz,11,12 Céline Lambert,13 Bruno Pereira,13 Gisèle Pickering1,3

1Université Clermont Auvergne, Pharmacologie Fondamentale Et Clinique de la Douleur, Neuro-Dol, Inserm 1107, F-63000 Clermont-Ferrand, France; 2Centre D’evaluation et de Traitement de la Douleur/soins Palliatifs, Nemours, France; 3CHU Clermont-Ferrand, Centre de Pharmacologie Clinique/Centre d’investigation Clinique Inserm 1405, F-63003 Clermont-Ferrand cedex, France; 4Centre d’Evaluation et de Traitement de la Douleur, CHU de Clermont-Ferrand, France; 5Centre d’evaluation et de Traitement de la Douleur/soins Palliatifs, CHU Jean Minjoz, Besançon, France; 6Centre d’evaluation et de Traitement de la Douleur, CH Jacques Lacarin Vichy, France; 7Centre d’evaluation et de Traitement de la Douleur, CHU de Saint-etienne, France; 8Inserm U1028 & Umr 5292, Centre de Neurosciences de Lyon, Université Lyon & Jean-monnet De Saint-etienne, France; 9Centre d’evaluation et de Traitement de la Douleur/soins Palliatifs, CH La Rochelle, France; 10Centre d’evaluation et de Traitement de la Douleur, Fondation A de Rothschild, Paris, France; 11Service de biochimie, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France; 12Inserm UMR-S 1147, Université Paris Descartes, Paris, France; 13CHU Clermont-Ferrand, Délégation Recherche Clinique & Innovation - Villa annexe IFSI, 58 Rue Montalembert, F-63003 Clermont-Ferrand cedex, France

Purpose: Intravenous ketamine is often prescribed in severe neuropathic pain. Oral N-methyl-D-aspartate receptor (NMDAR) antagonists might prolong pain relief, reducing the frequency of ketamine infusions and hospital admissions. This clinical trial aimed at assessing whether oral dextromethorphan or memantine might prolong pain relief after intravenous ketamine.
Patients and methods: A multicenter randomized controlled clinical trial included 60 patients after ketamine infusion for refractory neuropathic pain. Dextromethorphan (90 mg/day), memantine (20 mg/day) or placebo was given for 12 weeks (n=20 each) after ketamine infusion. The primary endpoint was pain intensity at one month. Secondary endpoints included pain, sleep, anxiety, depression, cognitive function and quality of life evaluations up to 12 weeks.
Results: At 1 month, dextromethorphan maintained ketamine pain relief (Numeric Pain Scale: 4.01±1.87 to 4.05±2.61, p=0.53) and diminished pain paroxysms (p=0.03) while pain intensity increased significantly with memantine and placebo (p=0.04). At 3 months, pain remained lower than at inclusion (p=0.001) and was not significantly different in the three groups. Significant benefits were observed on cognitive-affective domains and quality of life for dextromethorphan and memantine (p<0.05).
Conclusions: Oral dextromethorphan given after ketamine infusion extends pain relief during one month and could help patients to better cope with pain. Future studies should include larger populations stratified on pharmacogenetics screening. Optimization of an oral drug that could extend ketamine antihyperalgesia, with fewer hospital admissions, remains a prime challenge in refractory neuropathic pain.

Keywords: N-methyl-D-aspartate antagonists, peripheral neuropathic pain, drug relay, cognitive-affective status, health-related quality of life

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