Morphine, gabapentin, or their combination for neuropathic pain

N Engl J Med. 2005 Mar 31;352(13):1324-34. doi: 10.1056/NEJMoa042580.

Abstract

Background: The available drugs to treat neuropathic pain have incomplete efficacy and dose-limiting adverse effects. We compared the efficacy of a combination of gabapentin and morphine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia.

Methods: In this randomized, double-blind, active placebo-controlled, four-period crossover trial, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine--each given orally for five weeks. The primary outcome measure was mean daily pain intensity in patients receiving a maximal tolerated dose; secondary outcomes included pain (rated according to the Short-Form McGill Pain Questionnaire), adverse effects, maximal tolerated doses, mood, and quality of life.

Results: Of 57 patients who underwent randomization (35 with diabetic neuropathy and 22 with postherpetic neuralgia), 41 completed the trial. Mean daily pain (on a scale from 0 to 10, with higher numbers indicating more severe pain) at a maximal tolerated dose of the study drug was as follows: 5.72 at baseline, 4.49 with placebo, 4.15 with gabapentin, 3.70 with morphine, and 3.06 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Questionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pain) at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). The maximal tolerated doses of morphine and gabapentin were lower (P<0.05) with the combination than for each drug as single agent. At the maximal tolerated dose, the gabapentin-morphine combination resulted in a higher frequency of constipation than gabapentin alone (P<0.05) and a higher frequency of dry mouth than morphine alone (P<0.05).

Conclusions: Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth as the most frequent adverse effects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amines / adverse effects
  • Amines / therapeutic use*
  • Analgesics / adverse effects
  • Analgesics / therapeutic use*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • Cross-Over Studies
  • Cyclohexanecarboxylic Acids / adverse effects
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Gabapentin
  • Humans
  • Male
  • Middle Aged
  • Morphine / adverse effects
  • Morphine / therapeutic use*
  • Neuralgia / drug therapy*
  • Pain Measurement
  • Treatment Outcome
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Amines
  • Analgesics
  • Analgesics, Opioid
  • Cyclohexanecarboxylic Acids
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Morphine