Background The available drugs to treat neuropathic pain haveincomplete efficacy and dose-limiting adverse effects. We comparedthe efficacy of a combination of gabapentin and morphine withthat of each as a single agent in patients with painful diabeticneuropathy or postherpetic neuralgia.
Methods In this randomized, double-blind, active placebo–controlled,four-period crossover trial, patients received daily activeplacebo (lorazepam), sustained-release morphine, gabapentin,and a combination of gabapentin and morphine — each givenorally for five weeks. The primary outcome measure was meandaily pain intensity in patients receiving a maximal tolerateddose; secondary outcomes included pain (rated according to theShort-Form McGill Pain Questionnaire), adverse effects, maximaltolerated doses, mood, and quality of life.
Results Of 57 patients who underwent randomization (35 withdiabetic neuropathy and 22 with postherpetic neuralgia), 41completed the trial. Mean daily pain (on a scale from 0 to 10,with higher numbers indicating more severe pain) at a maximaltolerated 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<0.05for the combination vs. placebo, gabapentin, and morphine).Total scores on the Short-Form McGill Pain Questionnaire (ona scale from 0 to 45, with higher numbers indicating more severepain) at a maximal tolerated dose were 14.4 with placebo, 10.7with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin–morphinecombination (P<0.05 for the combination vs. placebo, gabapentin,and morphine). The maximal tolerated doses of morphine and gabapentinwere lower (P<0.05) with the combination than for each drugas single agent. At the maximal tolerated dose, the gabapentin–morphinecombination resulted in a higher frequency of constipation thangabapentin alone (P<0.05) and a higher frequency of dry mouththan morphine alone (P<0.05).
Conclusions Gabapentin and morphine combined achieved betteranalgesia at lower doses of each drug than either as a singleagent, with constipation, sedation, and dry mouth as the mostfrequent adverse effects.
Source Information
From the Departments of Anesthesiology (I.G., J.M.B.) and Pharmacology and Toxicology (I.G.), the Departments of Mathematics and Statistics and Community Health and Epidemiology (D.T.), the Department of Psychology (R.R.H.), and the Department of Medicine (Division of Endocrinology) (R.L.H.), Queen's University, Kingston, Ont.; and the Departments of Medicine (Division of Neurology) and Chemistry (D.F.W.), Dalhousie University, Halifax, N.S. — both in Canada.
Address reprint requests to Dr. Gilron at the Department of Anesthesiology, Queen's University, 76 Stuart St., Kingston, ON K7L 2V7, Canada, or at gilroni{at}post.queensu.ca.
Ziegler, D.
(2009). Painful Diabetic Neuropathy: Advantage of novel drugs over old drugs?. Diabetes Care
32: S414-S419
[Full Text]
Passik, S. D.
(2009). Issues in Long-term Opioid Therapy: Unmet Needs, Risks, and Solutions. Mayo Clin Proc.
84: 593-601
[Abstract][Full Text]
Argoff, C. E., Silvershein, D. I.
(2009). A Comparison of Long- and Short-Acting Opioids for the Treatment of Chronic Noncancer Pain: Tailoring Therapy to Meet Patient Needs. Mayo Clin Proc.
84: 602-612
[Abstract][Full Text]
McQuay, H. J., Poon, K. H., Derry, S., Moore, R. A.
(2008). Acute pain: combination treatments and how we measure their efficacy. Br J Anaesth
101: 69-76
[Abstract][Full Text]
Chattopadhyay, M., Mata, M., Fink, D. J.
(2008). Continuous {delta}-Opioid Receptor Activation Reduces Neuronal Voltage-Gated Sodium Channel (NaV1.7) Levels through Activation of Protein Kinase C in Painful Diabetic Neuropathy. J. Neurosci.
28: 6652-6658
[Abstract][Full Text]
Simpson, D. M., Brown, S., Tobias, J., For the NGX-4010 C107 Study Group,
(2008). Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology
70: 2305-2313
[Abstract][Full Text]
Caraceni, A, Zecca, E, Martini, C, Pigni, A, Bracchi, P
(2008). Letter to the Editor: Gabapentin for breakthrough pain due to bone metastases. Palliat Med
22: 392-393
Siniscalchi, A., Piraccini, E., Miklosova, Z., Taddei, S., Faenza, S., Martinelli, G.
(2008). Opioid-Induced Hyperalgesia and Rapid Opioid Detoxification After Tacrolimus Administration. Anesth. Analg.
106: 645-646
[Abstract][Full Text]
Galluzzi, K. E.
(2007). Managing Neuropathic Pain. JAOA: Journal of the American Osteopathic Association
107: ES39-ES48
[Abstract][Full Text]
Jude, E. B, Schaper, N.
(2007). Treating painful diabetic polyneuropathy. BMJ
335: 57-58
[Full Text]
Bloomgarden, Z. T.
(2007). Diabetic Retinopathy and Diabetic Neuropathy. Diabetes Care
30: 760-765
[Full Text]
Hix, M. D.
(2007). Pain Management in Elderly Patients. Journal of Pharmacy Practice
20: 49-63
[Abstract]
Martell, B. A., O'Connor, P. G., Kerns, R. D., Becker, W. C., Morales, K. H., Kosten, T. R., Fiellin, D. A.
(2007). Systematic Review: Opioid Treatment for Chronic Back Pain: Prevalence, Efficacy, and Association with Addiction. ANN INTERN MED
146: 116-127
[Abstract][Full Text]
Turan, A., White, P. F., Karamanlioglu, B., Pamukcu, Z.
(2007). Premedication with Gabapentin: The Effect on Tourniquet Pain and Quality of Intravenous Regional Anesthesia. Anesth. Analg.
104: 97-101
[Abstract][Full Text]
Jensen, T. S, Backonja, M.-M., Jimenez, S. H., Tesfaye, S., Valensi, P., Ziegler, D.
(2006). New perspectives on the management of diabetic peripheral neuropathic pain. Diabetes and Vascular Disease Research
3: 108-119
[Abstract]
Gilron, I., Watson, C. P. N., Cahill, C. M., Moulin, D. E.
(2006). Neuropathic pain: a practical guide for the clinician.. CMAJ
175: 265-275
[Abstract][Full Text]
Somers, D. L, Clemente, F R.
(2006). Transcutaneous Electrical Nerve Stimulation for the Management of Neuropathic Pain: The Effects of Frequency and Electrode Position on Prevention of Allodynia in a Rat Model of Complex Regional Pain Syndrome Type II. ptjournal
86: 698-709
[Abstract][Full Text]
Deshpande, M. A., Holden, R. R., Gilron, I.
(2006). The impact of therapy on quality of life and mood in neuropathic pain: what is the effect of pain reduction?. Anesth. Analg.
102: 1473-1479
[Abstract][Full Text]
Argoff, C. E., Backonja, M.-M., Belgrade, M. J., Bennett, G. J., Clark, M. R., Cole, B. E., Fishbain, D. A., Irving, G. A., McCarberg, B. H., McLean, M. J.
(2006). Consensus Guidelines: Treatment Planning and Options. Mayo Clin Proc.
81: S12-S25
[Abstract][Full Text]
Dworkin, R. H., Farrar, J. T.
(2005). Research design issues in pain clinical trials. Neurology
65: S1-S2
[Full Text]
Haythornthwaite, J. A.
(2005). Clinical trials studying pharmacotherapy and psychological treatments alone and together. Neurology
65: S20-S31
[Abstract][Full Text]
Max, M. B.
(2005). Afterword: Five steps to increase the payoff of chronic pain trials. Neurology
65: S74-S77
[Full Text]
Galluzzi, K. E.
(2005). Management of Neuropathic Pain. JAOA: Journal of the American Osteopathic Association
105: S12-S19
[Abstract][Full Text]
(2005). Treating Neuropathic Pain with Combined Morphine and Gabapentin Therapy. JWatch Psychiatry
2005: 10-10
[Full Text]
Curran, N, Brandner, B
(2005). Chronic pain following trauma. Trauma
7: 123-131
[Abstract]
Baillie, J. K., Power, I., Tesfaye, S., Selvarajah, D., Gilron, I., Weaver, D. F.
(2005). Morphine, Gabapentin, or Their Combination for Neuropathic Pain. NEJM
352: 2650-2651
[Full Text]
(2005). Treating Neuropathic Pain with Combined Morphine and Gabapentin Therapy. JWatch Neurology
2005: 3-3
[Full Text]
(2005). Combined Morphine and Gabapentin for Painful Neuropathy. JWatch General
2005: 6-6
[Full Text]
Martyn, C.
(2005). What's new in the other general journals. BMJ
330: 811-811
[Full Text]
Raja, S. N., Haythornthwaite, J. A.
(2005). Combination Therapy for Neuropathic Pain -- Which Drugs, Which Combination, Which Patients?. NEJM
352: 1373-1375
[Full Text]
Previous
