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Memantine reduces opioid use but not pain in knee osteoarthritis patients after surgery

Memantine reduces opioid use but not pain in knee osteoarthritis patients after surgery
Photo by Navy Medicine / Unsplash
Key Takeaway
Consider memantine for opioid reduction in knee osteoarthritis surgery, but note no significant pain relief.

This randomized controlled trial evaluated memantine versus placebo in eligible participants over 18 years with ASA grades I or II and knee osteoarthritis. The intervention involved memantine at 20 mg daily preoperatively for three days and 10 mg daily postoperatively for two weeks, compared to placebo, with follow-up over 216.0 months. Primary outcomes measured pain levels using Visual Analog Scale (VAS) scores and Short-Form McGill Pain Questionnaire (SF-MPQ), while secondary outcomes included opioid usage and nocturnal awakening.

Main results showed memantine did not significantly lower pain levels compared to placebo. For VAS scores, the mean difference was 0.138 (CI 95%: -0.468-1.103, P=0.418), and for SF-MPQ, the mean difference was 1.962 (CI 95%: -1.013-4.936, P=0.190). However, opioid usage was significantly reduced in the memantine group, with patients needing analgesia 2.85 ± 0.67 times versus 4.14 ± 1.06 times for placebo (P<0.001). Nocturnal awakening did not differ significantly between groups (P=0.067).

Safety and tolerability data, including adverse events and discontinuations, were not reported. Key limitations were not specified in the input, but the lack of safety information and uncertain pain effects warrant careful interpretation. In practice, these results indicate memantine may have opioid-sparing potential in postoperative knee osteoarthritis care, but its role in pain management remains unproven, and clinicians should weigh benefits against unknown risks.

Study Details

Study typeRct
EvidenceLevel 2
Follow-up216.0 mo
PublishedApr 2026
View Original Abstract ↓
INTRODUCTION: Total knee arthroplasty (TKA) provides significant pain relief and improved function for patients with knee osteoarthritis. Despite its effectiveness, postoperative pain remains a major challenge. Effective management of this acute postoperative pain is critical for enhancing recovery. The study investigates the effectiveness of memantine in reducing postoperative pain in patients undergoing TKA. METHODS: This double-blind, randomized controlled trial aimed to evaluate the efficacy of memantine for managing postoperative pain after TKA. Conducted from April to September 2022, eligible participants over 18 years with ASA grades I or II were recruited. Exclusions included patients with substance abuse histories, chronic opioid use, significant comorbidities, or contraindications to memantine. Participants were randomly assigned to receive either memantine (20 mg daily preoperatively for three days and 10 mg daily postoperatively for two weeks) or a placebo. Both groups received standard analgesics during hospitalization and upon discharge. Pain levels were assessed using Visual Analog Scale (VAS) scores and Short-Form McGill Pain Questionnaire (SF-MPQ) at various time points. Secondary outcomes measured included opioid usage and nocturnal awakening. RESULTS: Memantine did not significantly lower pain levels compared to placebo, as measured by VAS (mean difference: 0.138, CI 95%: - 0.468-1.103, P = 0.418) and SF-MPQ (mean difference: 1.962, CI 95%: - 1.013-4.936, P = 0.190). Patients receiving memantine needed opioid analgesia (2.85 ± 0.67 times) significantly (P < 0.001) less frequently than the Placebo patients (4.14 ± 1.06 times). Nocturnal awakening did not differ significantly between the two groups (Memantine: 3.59 ± 2.15, Placebo: 2.33 ± 2.12, P = 0.067). CONCLUSION: The comparison of pain levels between oral memantine and placebo indicates that memantine does not significantly reduce pain in patients undergoing TKA. However, it significantly lowers the need for opioids postoperatively.
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