Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial.
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.
Wu
Christopher L
CL
Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Agarwal
Shefali
S
Tella
Prabhav K
PK
Klick
Brendan
B
Clark
Michael R
MR
Haythornthwaite
Jennifer A
JA
Max
Mitchell B
MB
Raja
Srinivasa N
SN
D000671:Amputation, Surgical; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D010149:Postoperative Pain / Q000145:classification / Q000188:drug therapy*; D010591:Phantom Limb / Q000145:classification / Q000188:drug therapy* / Q000209:etiology
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D009020:Morphine