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Morphine, gabapentin, or their combination for neuropathic pain.

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.

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  • Authors+Show Affiliations

    ,

    Department of Anesthesiology, Queen's University, Kingston, Ont, Canada. gilroni@post.queensu.ca

    , , , ,

    Source

    The New England journal of medicine 352:13 2005 Mar 31 pg 1324-34

    MeSH

    Adult
    Aged
    Aged, 80 and over
    Amines
    Analgesics
    Analgesics, Opioid
    Cross-Over Studies
    Cyclohexanecarboxylic Acids
    Double-Blind Method
    Drug Therapy, Combination
    Female
    Gabapentin
    Humans
    Male
    Middle Aged
    Morphine
    Neuralgia
    Pain Measurement
    Treatment Outcome
    gamma-Aminobutyric Acid

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    15800228

    Citation

    Gilron, Ian, et al. "Morphine, Gabapentin, or Their Combination for Neuropathic Pain." The New England Journal of Medicine, vol. 352, no. 13, 2005, pp. 1324-34.
    Gilron I, Bailey JM, Tu D, et al. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352(13):1324-34.
    Gilron, I., Bailey, J. M., Tu, D., Holden, R. R., Weaver, D. F., & Houlden, R. L. (2005). Morphine, gabapentin, or their combination for neuropathic pain. The New England Journal of Medicine, 352(13), pp. 1324-34.
    Gilron I, et al. Morphine, Gabapentin, or Their Combination for Neuropathic Pain. N Engl J Med. 2005 Mar 31;352(13):1324-34. PubMed PMID: 15800228.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Morphine, gabapentin, or their combination for neuropathic pain. AU - Gilron,Ian, AU - Bailey,Joan M, AU - Tu,Dongsheng, AU - Holden,Ronald R, AU - Weaver,Donald F, AU - Houlden,Robyn L, PY - 2005/4/1/pubmed PY - 2005/4/6/medline PY - 2005/4/1/entrez SP - 1324 EP - 34 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 352 IS - 13 N2 - 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. SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/15800228/Morphine_gabapentin_or_their_combination_for_neuropathic_pain_ L2 - https://www.nejm.org/doi/10.1056/NEJMoa042580?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=www.ncbi.nlm.nih.gov DB - PRIME DP - Unbound Medicine ER -