Morphine versus  Mexiletine for Treatment of Postamputation Pain

Abstract

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.

Clinical practice guidelines for management of neuropathic pain: Expert panel recommendations for South Africa

“…38,80 In head-tohead comparisons, opioids provided at least as much analgesia as TCAs and gabapentin. 81,82 Despite strong evidence of efficacy, most of the international guidelines reserve opioid analgesics as second-or third-line agents mainly because of risk of long-term side-effects and possible opioid misuse and addiction.…”

Safety of opioid patch initiation in Australian residential aged care

“…Morphine was superior to mexiletine (53% vs 30% pain relief) in treating postamputation pain; the NNT for 50% pain relief was 5.6 (Wu et al, 2008 Level II).…”

“…Clinically significant injury responses can be broadly classified as inflammation, hyperalgesia, hyperglycaemia, protein catabolism, increased free fatty acid levels (lipolysis) and changes in water and electrolyte flux (Liu & Wu, 2008;Carli & Schricker, 2009) (Figure 1.3). In addition, there are cardiovascular effects of increased sympathetic activity and diverse effects on respiration, coagulation and immune function (Liu & Wu, 2008).…”

“…as the magnitude and duration of the response is related to the magnitude and duration of the stimulus, effective pain relief can have a significant impact on the injury response (Liu & Wu, 2008;Carli & Schricker, 2009). …”

Pain Management and Symptom-Oriented Drug Therapy in Palliative Care

“…The effect of opioids alone on neuropathic pain may vary [17,18], a combination with co-analgesics should always be considered. The dosage of strong opioids can be escalated until sufficient alleviation of pain is achieved or side effects limit further increase.…”