Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial

Anesthesiology. 2008 Aug;109(2):289-96. doi: 10.1097/ALN.0b013e31817f4523.


Background: Stump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment. The efficacy of pharmacologic therapies, including opioids and sodium channel blockers, for postamputation pain is uncertain.

Methods: The authors conducted a double-blind, randomized, placebo-controlled, crossover study in adult patients with postamputation pain of 6 months or longer and greater than 3 on a 0-10 numeric pain rating scale. Each of the three treatment periods (morphine, mexiletine, or placebo) included a 1-week drug-free interval followed by 4-week titration, 2-week maintenance, and 2-week drug-taper phases. The primary outcome measure was change in average pain intensity from the drug-free baseline to the last week of maintenance.

Results: Sixty amputees were enrolled; data were analyzed from 56 subjects for one drug period, 45 subjects for two drug periods, and 35 subjects who completed all three drug periods. The mean morphine and mexiletine dosages were 112 and 933 mg, respectively. Morphine treatment provided lower pain scores compared with placebo and mexiletine (P = 0.0003). The mean percent pain relief during treatment with placebo, mexiletine, and morphine was 19, 30, and 53%, respectively (P < 0.0001, morphine vs. placebo and mexiletine). The numbers needed to treat to obtain 50% and 33% decreases in pain intensity with morphine were 5.6 and 4.5, respectively. Treatment with morphine was associated with a higher rate of side effects.

Conclusions: Therapy with morphine, but not mexiletine, resulted in a decrease in intensity of postamputation pain but was associated with a higher rate of side effects and no improvement in self-reported levels of overall functional activity and pain-related interference in daily activities.

Trial registration: NCT00383682.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amputation, Surgical*
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / therapeutic use*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Mexiletine / adverse effects
  • Mexiletine / therapeutic use*
  • Middle Aged
  • Morphine / adverse effects
  • Morphine / therapeutic use*
  • Pain, Postoperative / classification
  • Pain, Postoperative / drug therapy*
  • Phantom Limb / classification
  • Phantom Limb / drug therapy*
  • Phantom Limb / etiology


  • Anti-Arrhythmia Agents
  • Mexiletine
  • Morphine

Associated data