N-of-1 Randomized Trials to Assess the Efficacy of Gabapentin for Chronic Neuropathic Pain

Yelland, Michael J., Poulos, Christopher J., Pillans, Peter I., Bashford, Guy M., Nikles, Catherine Jane, Sturtevant, Joanna M., Vine, Norma, Del Mar, Christopher, Schluter, Philip J., Tan, Meng, Chan, Jonathon, Mackenzie, Fraser and Brown, Robyn (2009) N-of-1 Randomized Trials to Assess the Efficacy of Gabapentin for Chronic Neuropathic Pain. Pain Medicine, 10 4: 754-761. doi:10.1111/j.1526-4637.2009.00615.x

Author Yelland, Michael J.
Poulos, Christopher J.
Pillans, Peter I.
Bashford, Guy M.
Nikles, Catherine Jane
Sturtevant, Joanna M.
Vine, Norma
Del Mar, Christopher
Schluter, Philip J.
Tan, Meng
Chan, Jonathon
Mackenzie, Fraser
Brown, Robyn
Title N-of-1 Randomized Trials to Assess the Efficacy of Gabapentin for Chronic Neuropathic Pain
Formatted title
N-of-1 Randomized Trials to Assess the Efficacy of Gabapentin for Chronic Neuropathic Pain
Journal name Pain Medicine   Check publisher's open access policy
ISSN 1526-2375
Publication date 2009-05
Year available 2009
Sub-type Article (original research)
DOI 10.1111/j.1526-4637.2009.00615.x
Volume 10
Issue 4
Start page 754
End page 761
Total pages 8
Place of publication United States
Publisher Wiley-Blackwell Publishing Inc
Collection year 2010
Language eng
Subject C1
111717 Primary Health Care
920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified
Formatted abstract
Objective. The objective of this study was to compare the efficacy of gabapentin with placebo for neuropathic pain at the individual and population levels.

Design. This study used an n-of-1 trial methodology with three double-blind, randomized, crossover comparisons of gabapentin with placebo.

Setting. This study was carried out at specialist outpatient clinics at two Australian hospitals.

Patients. The patients are adults with chronic neuropathic pain.

Interventions. Following a dose-finding period, participants underwent three comparisons of 2-week periods on gabapentin (600–1,800 mg per day) and placebo. The dose-finding period was commenced by 112 patients, of whom 39 had no response so they did not enroll, leaving 73 trial participants. Of these, 48 completed and 7 partially completed their trials, and 18 withdrew.
Outcome Measures. The five outcome measures were the visual analog scale (0–10) of pain, sleep interference and functional limitation; frequency of adverse events and medication preference. The aggregate response was determined by weighting the response to each measure equally.

Results. Of the 55 participants who completed at least one cycle, the aggregate response to gabapentin was better than placebo in 16 (29%), of whom 15 continued gabapentin posttrial. No difference was shown in 38 (69%), and 1 (2%) showed a better response to placebo. Fifteen of these
39 continued gabapentin posttrial. Meta-analysis of the mean scores showed lower mean (standard deviation) scores for gabapentin by 0.8 (0.2) for pain, 0.6 (0.2) for sleep interference, and 0.6 (0.2) for functional limitation.

Conclusions. The response rate and mean reduction in symptoms with gabapentin were small. Gabapentin prescribing posttrial was significantly influenced by the trial results.
Keyword randomised controlled trial
crossover trails
References 1. Mellegers MA, Furlan AD, Mailis A. Gabapentin for neuropathic pain: Systematic review of controlled and uncontrolled literature. Clin J Pain 2001;17(4):284–95. 2. Wiffen PJ, McQuay HJ, Edwards JE, Moore RA. Gabapentin for acute and chronic pain. Cochrane Database Syst Rev 2005;(3):cD005452. DOI: 10.1002/14651858.CD005452. 3. Guyatt GH, Keller JL, Jaeschke R, et al. The n-of-1 randomized controlled trial: Clinical usefulness. Our three-year experience. Ann Intern Med 1990; 112:293–9. 4. Nikles CJ, Clavarino AM, Del Mar CB. Using n-of-1 trials as a clinical tool to improve prescribing. Br J Gen Pract 2005;55:175–80. 5. Zucker DR, Schmid CH, McIntosh MW, et al. Combining single patient [N-of-1] trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol 1997;50:401–10. 6. Cepeda MS, Acevedo JC, Miranda N, Cortes C, Carr DB. An N-of-1 trial as an aid to decisionmaking prior to implanting a permanent spinal cord stimulator. Pain Med 2008;9(2):235–9. 7. Merskey H, Bogduk N. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. Seattle,WA: IASP Press; 1994:212. 8. Daut RL, Cleeland CS, Flanery RC. Development of theWisconsin Brief Pain Questionnaire to assess pain in cancer and other disease. Pain 1983;17:197–210. 9. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833– 40. 10. Stratford PW, Gill C, Westaway M, Binkley J. Assessing disability and change in individual patients: A report of a patient-specific measure. Physiother Can 1995;47:258–63. 11. Ehrich EW, Davies GM,Watson DJ, et al. Minimal perceptible clinical improvement with the Western Ontario and McMaster Universities osteoarthritis index questionnaire and global assessments in patients with osteoarthritis. J Rheumatol 2000; 27(11):2635–41. 12. Zisapel N, Nir T. Determination of the minimal clinically significant difference on a patient visual analog sleep quality scale. J Sleep Res 2003;12(4): 291–8. 13. Chatman AB, Hyams SP, Neel JM, et al. The Patient-Specific Functional Scale: Measurement properties in patients with knee dysfunction. Phys Ther 1997;77:820–9. 14. Yelland MJ, Nikles CJ, McNairn N, et al. Celecoxib compared with sustained-release paracetamol for osteoarthritis: A series of n-of-1 trials. Rheumatology (Oxford) 2007;46(1):135–40. 15. Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: A randomized controlled trial. JAMA 1998;280(21): 1831–6. 16. Rice AS, Maton S. Gabapentin in postherpetic neuralgia: A randomized, double blind, placebo controlled study. Pain 2001;94(2):215–24. 17. Larson EB. N-of-1 clinical trials. A technique for improving medical therapeutics. West J Med 1990; 152:52–6. 18. Pincus T, Koch G, Lei H, et al. Patient preference for placebo, acetaminophen or celecoxib efficacy studies [PACES]: Two randomized placebocontrolled cross-over clinical trials in patients with osteoarthritis of the knee or hip. Ann Rheum Dis 2004;63:931–9. 19. Martin R, Vogtle L, Gilliam F, Faught E. Healthrelated quality of life in senior adults with epilepsy: What we know from randomized clinical trials and suggestions for future research. Epilepsy Behav 2003;4:626–34.
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Nursing, Midwifery and Social Work Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 16 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 26 Aug 2009, 11:03:01 EST by Vicki Percival on behalf of School of Nursing, Midwifery and Social Work