Effect of early administration of the N-methyl-d-aspartate receptor antagonist amantadine on the development of postmastectomy pain syndrome: a prospective pilot study

J Pain. 2007 Mar;8(3):223-9. doi: 10.1016/j.jpain.2006.08.003. Epub 2006 Sep 22.


Postmastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that might develop after breast surgery. Like many other forms of neuropathic pain, it is relatively resistant to treatment and negatively affects the quality of life. A double-blind, randomized, placebo-controlled pilot trial was conducted to study the analgesic efficacy of perioperative administration of the N-methyl-D-aspatrate (NMDA) receptor antagonist amantadine in preventing PMPS after mastectomy plus axillary lymph node dissection (ALND). In the study group, a regimen of 200 mg/day of amantadine was started 1 day before surgery and continued for 14 days, whereas the control group received a placebo. Patients were required to indicate the exact location of their pain and to record its level at 1, 3, and 6 months after surgery. Neurologic examination and Quantitative Thermal Testing (QTT) were performed 1 and 6 months after surgery. On both the neurologic examination and the QTT, all patients, regardless of the perioperative intervention (amantadine or placebo), presented evidence for nerve injury, manifested primarily by painful hypoesthesia (anesthesia dolorosa) in the axilla or inner arm. PMPS persisted for the entire duration of the study in 82% of the patients who were available for follow-up. The average intensity of the pain was moderate in both groups and tended not to decline over time. No differences between the 2 groups in any of the outcome parameters reached statistical significance. According to the results of the present pilot study, the NMDA antagonist amantadine does not prevent the development of PMPS in patients who undergo breast surgery with ALND.

Perspective: Breast surgery that involves ALND seems to uniformly cause nerve injury, which cannot be prevented by the perioperative administration of 200 mg of amantadine. It is most commonly presented by painful hypoesthesia or anesthesia dolorosa in the axillary/inner arm area, which is moderate in intensity and likely to persist for at least 6 months.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amantadine / therapeutic use*
  • Analgesics, Non-Narcotic / therapeutic use*
  • Analysis of Variance
  • Breast Diseases / surgery
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Mastectomy / adverse effects*
  • Middle Aged
  • Neurologic Examination
  • Pain Measurement
  • Pain, Postoperative / etiology*
  • Pain, Postoperative / prevention & control*
  • Pilot Projects
  • Prospective Studies
  • Retrospective Studies
  • Time Factors


  • Analgesics, Non-Narcotic
  • Amantadine