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

<div><p>Background</p><p>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.</p><p>Method</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p><p>Trial Registration</p><p>Clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01536314" target="_blank">NCT01536314</a></p></div

Effect of memantine on cognition.

<p>Effect of memantine on cognition.</p

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

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

Demographics and clinical characteristics.

<p>Demographics and clinical characteristics.</p

Effect of memantine on analgesics consumption.

<p>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).</p

Effect of memantine on pain in patients who had chemotherapy.

<p>(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).</p

Effect of memantine on quality of sleep with Leeds sleep questionnaire.

<p>Effect of memantine on quality of sleep with Leeds sleep questionnaire.</p

Effect of memantine on neuropathic pain induced by mastectomy.

<p>Effect of memantine on neuropathic pain induced by mastectomy.</p

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

<p>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.</p

Detail of analgesics consumption after mastectomy.

<p>Detail of analgesics consumption after mastectomy.</p