<p>Dextromethorphan and memantine after ketamine analgesia: a randomized control trial</p>

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.

Managing Chronic Neuropathic Pain: Recent Advances and New Challenges

“…Results collected at one month showed that dextromethorphan-maintained pain relief induced by ketamine while memantine and placebo increased pain intensity scores. Adverse events included drowsiness and nausea in the dextromethorphan group and dizziness, drowsiness, and constipation in the memantine group [ 37 ]. Another study compared the anti-nociceptive effects of dextromethorphan to placebo and concluded that because dextromethorphan had no intrinsic anti-nociceptive effect in acute pain on healthy skin, the N-methyl-D-aspartate receptor may need to be sensitized by pain for dextromethorphan to be effective [ 38 ].…”

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

“…Psychotic symptoms (hallucinations and delusions) are strongly related to AD-associated cognitive dysfunction, gradually progressing in parallel with disease severity [182]. In addition, symptoms of personality changes, paranoia, hallucinations, cravings, agitation, and changes in appetite may represent a prodromal noncognitive phenotype of risk for dementia [183].…”

Efficacy of memantine premedication in alleviating postoperative pain- A systematic review and meta-analysis

“…In an interesting study by Martin et al ,[ 41 ] the authors randomized 60 patients who were treated for chronic neuropathic pain with 0.4–0.5 mg/kg IV ketamine infusion (over 2 hours) into two groups. In one group, patients received 90 mg/day oral dextromethorphan, in another group the patients received 20 mg/day oral memantine, and in the third group, patients received a placebo, all for 12 weeks.…”