Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded Clinical Trial in Surgical Patients

Abstract

Background: Neuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life.

Method: A randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0-10) numerical rating scale at three months post-mastectomy.

Results: Data analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported.

Conclusions: This study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy.

Trial registration: Clinicaltrials.gov NCT01536314.

Fig 1. Flowchart of participants during the trial.

Fig 2. Effect of memantine on overall pain evaluated by numerical rating scale.

A significant difference was obtained with the Numerical Rating Scale (NRS) at Month 3 post-mastectomy in the memantine group (n = 20) compared with the placebo group (n = 20) (p = 0.017). No significant difference was reported at Month 6 between the two groups. A significant decrease was also reported at M3 in the memantine group compared with baseline (p = 0.016) but such diminution in the same group was not observed at M6 post-mastectomy.

Fig 3. Effect of memantine on analgesics consumption.

Number of patients n (%) being prescribed neuropathic pain analgesics. A significant increase in analgesics (especially antiepileptics) prescriptions was reported in the placebo group (n = 20) compared with the memantine group (n = 20) at Month 3 and maintained at Month 6 (p = 0.040).Over all time different was significant (p = 0.041).

Fig 4. ffect of memantine on the affective component of pain evaluated by the McGill pain questionnaire.

A significant difference was reported in the memantine group (n = 20) compared with the placebo group (n = 20) at Month 3 (p = 0.032).

Fig 5. Effect of memantine on pain in patients who had chemotherapy.

(A) ΔNRS score is the pain intensity difference between Month 3 or Month 6 and baseline. It is significant in the subgroup of chemotherapy which received memantine (n = 11) compared with placebo (n = 10) at Month 3 (p = 0.01) and at Month 6 (p = 0.01). (B) Neuropathic pain (ΔDN4 score) is the neuropathic pain score difference between Month 3 or Month 6 and baseline. Neuropathic pain score in four questions was significantly diminished in the memantine group at Month 3 (***p = 0.001) and at Month 6 (p = 0.009). (C) Number of patients n (%) who replied positively to question 2 (Q2) of DN4 (dysesthesias and paresthesias). In the memantine group, a decrease of 55% of dysesthesias and paresthesias was reported at Month 3 compared with the day of inclusion (Baseline) (p = 0.01).