A systematic review and meta‐analysis of memantine for the prevention or treatment of chronic pain

Abstract

Background and Objective N‐methyl‐D‐aspartate (NMDA) receptors are involved in pain signalling and neuroplasticity. Memantine has been shown to have analgesic properties in pre‐clinical and small clinical studies. We conducted a systematic review and meta‐analysis to assess the efficacy of memantine to prevent or reduce chronic pain. Databases and data treatment MEDLINE, EMBASE and CENTRAL databases were searched for comparative trials using memantine, either against placebo or active medications, for chronic pain in adults. Pain relief was considered our primary outcome. Meta‐analyses were conducted if outcomes were reported in two or more studies. Outcomes were reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Quality was assessed using the GRADE approach. Results Among 454 citations, 15 studies were included with populations predominantly consisting of neuropathic conditions and fibromyalgia. Overall, we observed unclear reporting of randomization and allocation methods, apart from potential for publication bias. Among the 11 studies looking at chronic pain treatment, the difference in end pain score with memantine was not significant: MD = −0.58 units (95% CI −1.31, 0.14); I2 = 82% (low quality). In two surgical studies using memantine for pain prevention, memantine decreased pain intensity: MD = −1.02 units (95% CI −1.38, −0.66); I2 = 0%. Dizziness was significantly more common with memantine: RR = 4.90 (95% CI 1.26, 18.99); I2 = 52% (moderate quality). Conclusion The current evidence regarding the use of memantine for chronic pain is limited and uncertain. Despite its potential, pain relief achieved in clinical studies is small and is associated with an increase in dizziness. Significance Despite a sound rationale, the benefit of using memantine for chronic pain is unclear. Our systematic review and meta‐analysis show that memantine may have the potential to decrease pain. However, it can also increase common adverse effects. Considering the small number of studies with potential for bias and inconclusive evidence, there was low to very low certainty. Hence, no clear recommendations can be made about its routine clinical use until larger and more definitive studies are conducted.

<p>N-Methyl-D-Aspartate Antagonists and Steroids for the Prevention of Persisting Post-Surgical Pain After Thoracoscopic Surgeries: A Randomized Controlled, Factorial Design, International, Multicenter Pilot Trial</p>

“…49 Another review and meta-analysis looking at memantine for treating or preventing pain observed considerable variation in the dose and duration of its treatment. 19 The other factors that could potentially affect the outcomes include conversion of VATS to open surgeries and the use of continuous epidural analgesia.…”

“…17 Based on the available evidence, use of ketamine and memantine has the potential to decrease the chances of PPSP. 18,19 Steroids are potent antiinflammatory agents affecting both inflammatory and immune pathways. 20,21 Among the commonly used agents, dexamethasone is nearly five times as potent as methylprednisolone and has a biological half-life of 36-72 hrs.…”

Current and Emerging Pharmacotherapy for Fibromyalgia

“…A double-blind, randomized-controlled trial published in 2014 found memantine to achieve a significant reduction in pain [33], with another hypothesis suggesting the combined use of pregabalin and memantine to concomitantly affect voltage-gated calcium channels and NMDA receptors, as a possible therapeutic approach [82]. A recent meta-analysis of 15 studies regarding the benefit of memantine in treating chronic pain (either neuropathic or FMS) concluded that the current evidence regarding memantine for chronic pain is limited and reported an increase in dizziness as a side effect of the medication [34].…”

Neuropathic Pain in Multiple Sclerosis and Its Animal Models: Focus on Mechanisms, Knowledge Gaps and Future Directions

“…Glutamate receptor antagonists have been assessed in EAE, primarily in the context of neuroprotection, prevention of demyelination, and improvement of motor deficits ( 144 – 148 ). Although glutamate receptor antagonists, including memantine ( 149 – 151 ) or modulators of the glutamatergic system such as ketamine ( 152 , 153 ) have been used for the relief of chronic pain in various diseases or injuries, their effectiveness in the alleviation of neuropathic pain during EAE/MS has not been adequately investigated.…”