Effects of Perioperative Oral Amantadine on Postoperative Pain and Morphine Consumption in Patients after Radical Prostatectomy: Results of a Preliminary Study

Background: Amantadine is known to be a noncompetitive N-methyl-d-aspartate receptor antagonist and may be useful in preventing postoperative central sensitization, acute opioid tolerance, and opioid-induced hyperalgesia, thereby decreasing pain and analgesic requirements. The aim of this pilot study was to evaluate the effects of perioperative oral amantadine on postoperative pain and analgesic consumption.

Methods: Twenty-four patients scheduled to undergo radical prostatectomy were given oral amantadine before and after surgery in a randomized, double-blind, placebo-controlled manner. After surgery, patients received intravenous patient-controlled analgesia with morphine for 48 h. Wound pain intensity, sensitivity to mechanical pressure around the surgical wound, and incidence of bladder spasm pain were assessed. Blood samples were drawn for analysis of amantadine, morphine, and the morphine metabolites. Adverse effects and patient satisfaction were assessed.

Results: The cumulative morphine consumption was significantly lower in the amantadine group at all time points (except at 48 h), amounting to a 32% reduction over the 48-h period. Forty-eight hours after surgery, visual analog pain scores to pressure applied near the wound were significantly lower in the amantadine group than in the placebo group. In addition, the number of patients reporting bladder spasm pain was significantly lower in the amantadine group. Plasma concentration of morphine-3-glucuronide was significantly lower at the end of surgery in the amantadine group. Pharmacokinetic analyses showed that the plasma clearance of morphine at 22–24 h after surgery was also significantly lower in the amantadine group.

Conclusion: The results suggest that perioperative oral amantadine reduces postoperative opioid consumption by pharmacokinetic mechanisms, although additional pharmacodynamic interactions may also be involved.