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Abstract
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.
Acknowledgments
This study was financed by a Regional Hospital grant (PHRC interregional 2011) and by “Fondation de France”. We thank these institutions for their financial support.
Availability of data and materials
All available data are in the manuscript and no other document will be made available.
Supplementary materials
Table S1 Effect of ketamine on the Numeric Pain Scale (NPS), Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory (BPI), McGill Pain questionnaire, Hospital Anxiety and Depression Scale (HADS) and Leeds Sleep Evaluation Questionnaire (LSEQ) between preK and postK
Table S2 Pharmacogenetic characteristics of patients in the dextromethorphan and memantine groups
Author contributions
Conceived and designed the experiments: GP, MS, FM, FT, PP, ND, M-CC, MN, RC, CC, BL, GBM, AMD. Performed the experiments: GP, EM, VM, MS, FM, FT, PP, ND, M-CC, MN, RC, CC, BL, GBM, AMD. All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.