BACKGROUND: The available drugs to treat neuropathic pain have incomp lete efficacy and dose-limiting adverse effects. We compared the efficacy of a combination of gabapentin and morphine with that of each as a single...BACKGROUND: The available drugs to treat neuropathic pain have incomp lete 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 p lacebo-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 outc ome measure was mean daily pain intensity in patients receiving a maximal tolera ted dose; secondary outcomes included pain (rated according to the Short-Form M cGill Pain Questionnaire), adverse effects, maximal tolerated doses, mood, and q uality of life. RESULTS: Of 57 patients who underwent randomization (35 with dia betic neuropathy and 22 with postherpetic neuralgia), 41 completed the trial. Me an daily pain (on a scale from 0 to 10, with higher numbers indicating more seve re pain) at a maximal tolerated dose of the study drug was as follows: 5.72 at b aseline, 4.49 with placebo, 4.15 with gabapentin, 3.70 with morphine, and 3.06 w ith the gabapentin-morphine combination (P < 0.05 for the combination vs. place bo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Quest ionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pa in)-at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 1 0.7 with morphine, and 7.5 with the gabapentin-morphine combination (P < 0.05 f or the combination vs. placebo, gabapentin, and morphine). The maximal tolerated doses of morphine and gabapentin were lower (P < 0.05) with the combination tha n for each drug as single agent. At the maximal tolerated dose, the gabapentin- morphine combination resulted in a higher frequency of constipation than gabapen tin 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, s edation, and dry mouth as the most frequent adverse effects.展开更多
文摘BACKGROUND: The available drugs to treat neuropathic pain have incomp lete 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 p lacebo-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 outc ome measure was mean daily pain intensity in patients receiving a maximal tolera ted dose; secondary outcomes included pain (rated according to the Short-Form M cGill Pain Questionnaire), adverse effects, maximal tolerated doses, mood, and q uality of life. RESULTS: Of 57 patients who underwent randomization (35 with dia betic neuropathy and 22 with postherpetic neuralgia), 41 completed the trial. Me an daily pain (on a scale from 0 to 10, with higher numbers indicating more seve re pain) at a maximal tolerated dose of the study drug was as follows: 5.72 at b aseline, 4.49 with placebo, 4.15 with gabapentin, 3.70 with morphine, and 3.06 w ith the gabapentin-morphine combination (P < 0.05 for the combination vs. place bo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Quest ionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pa in)-at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 1 0.7 with morphine, and 7.5 with the gabapentin-morphine combination (P < 0.05 f or the combination vs. placebo, gabapentin, and morphine). The maximal tolerated doses of morphine and gabapentin were lower (P < 0.05) with the combination tha n for each drug as single agent. At the maximal tolerated dose, the gabapentin- morphine combination resulted in a higher frequency of constipation than gabapen tin 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, s edation, and dry mouth as the most frequent adverse effects.
