Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 6 (6), CD007938

Gabapentin for Chronic Neuropathic Pain in Adults

Affiliations
Review

Gabapentin for Chronic Neuropathic Pain in Adults

Philip J Wiffen et al. Cochrane Database Syst Rev.

Abstract

Background: Gabapentin is commonly used to treat neuropathic pain (pain due to nerve damage). This review updates a review published in 2014, and previous reviews published in 2011, 2005 and 2000.

Objectives: To assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain in adults.

Search methods: For this update we searched CENTRAL), MEDLINE, and Embase for randomised controlled trials from January 2014 to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trials registries.

Selection criteria: We included randomised, double-blind trials of two weeks' duration or longer, comparing gabapentin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.

Data collection and analysis: Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). We performed a pooled analysis for any substantial or moderate benefit. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables.

Main results: We included four new studies (530 participants), and excluded three previously included studies (126 participants). In all, 37 studies provided information on 5914 participants. Most studies used oral gabapentin or gabapentin encarbil at doses of 1200 mg or more daily in different neuropathic pain conditions, predominantly postherpetic neuralgia and painful diabetic neuropathy. Study duration was typically four to 12 weeks. Not all studies reported important outcomes of interest. High risk of bias occurred mainly due to small size (especially in cross-over studies), and handling of data after study withdrawal.In postherpetic neuralgia, more participants (32%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (17%) (RR 1.8 (95% CI 1.5 to 2.1); NNT 6.7 (5.4 to 8.7); 8 studies, 2260 participants, moderate-quality evidence). More participants (46%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (25%) (RR 1.8 (95% CI 1.6 to 2.0); NNT 4.8 (4.1 to 6.0); 8 studies, 2260 participants, moderate-quality evidence).In painful diabetic neuropathy, more participants (38%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (21%) (RR 1.9 (95% CI 1.5 to 2.3); NNT 5.9 (4.6 to 8.3); 6 studies, 1277 participants, moderate-quality evidence). More participants (52%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (37%) (RR 1.4 (95% CI 1.3 to 1.6); NNT 6.6 (4.9 to 9.9); 7 studies, 1439 participants, moderate-quality evidence).For all conditions combined, adverse event withdrawals were more common with gabapentin (11%) than with placebo (8.2%) (RR 1.4 (95% CI 1.1 to 1.7); NNH 30 (20 to 65); 22 studies, 4346 participants, high-quality evidence). Serious adverse events were no more common with gabapentin (3.2%) than with placebo (2.8%) (RR 1.2 (95% CI 0.8 to 1.7); 19 studies, 3948 participants, moderate-quality evidence); there were eight deaths (very low-quality evidence). Participants experiencing at least one adverse event were more common with gabapentin (63%) than with placebo (49%) (RR 1.3 (95% CI 1.2 to 1.4); NNH 7.5 (6.1 to 9.6); 18 studies, 4279 participants, moderate-quality evidence). Individual adverse events occurred significantly more often with gabapentin. Participants taking gabapentin experienced dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (14%).

Authors' conclusions: Gabapentin at doses of 1800 mg to 3600 mg daily (1200 mg to 3600 mg gabapentin encarbil) can provide good levels of pain relief to some people with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is very limited. The outcome of at least 50% pain intensity reduction is regarded as a useful outcome of treatment by patients, and the achievement of this degree of pain relief is associated with important beneficial effects on sleep interference, fatigue, and depression, as well as quality of life, function, and work. Around 3 or 4 out of 10 participants achieved this degree of pain relief with gabapentin, compared with 1 or 2 out of 10 for placebo. Over half of those treated with gabapentin will not have worthwhile pain relief but may experience adverse events. Conclusions have not changed since the previous update of this review.

Conflict of interest statement

PW: none known

SD: none known

RFB: none known. RFB is a retired specialist pain physician who has managed patients with neuropathic pain.

ASCR: undertakes consultancy and advisory board work for Imperial College Consultants ‐ since June 2013 this has included remunerated work for: Spinifex, Abide, Astellas, Neusentis, Merck, Medivir, Mitsubishi, Aquilas, Asahi Kasei, Relmada, Novartis, and Orion. All consultancy activity relates to consultancy advice on the preclinical/clinical development of drugs for neuropathic pain. Neusentis was a subsidiary of Pfizer. He owned share options in Spinifex Pharmaceuticals which was acquired by Novartis in July 2015. ASCR was a Principal Investigator in the EuroPain consortium. EuroPain has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115007, resources for which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/20072013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies (www.imieuropain.org). Specifically, research funding for ASCR's laboratory has been received by Imperial College from Pfizer (manufacturer of gabapentin) and Astellas ‐ both these grants were for projects related to improving the validity of animal models of neuropathic pain. ASCR is a site investigator for the Neuropain project, funded by Pfizer via Kiel University ‐ Chief Investigator Prof Ralf Baron. He is Vice‐Chair of the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (www.neupsig.org) and serves on the Executive Committee of ACTTION (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks; www.acttion.org).

TRT is a site investigator for the Neuropain project, funded by Pfizer. Since 2014 TRT has consulted with or received lecture fees from pharmaceutical companies related to chronic pain and analgesics: Astellas, Eli Lilly, Grünenthal, Pfizer, and Mundipharma.

TP: none known. TP is a specialist pain physician who has managed patients with neuropathic pain.

RAM has received grant support from Grünenthal relating to individual participant‐level analyses of trial data regarding tapentadol in osteoarthritis and back pain (2015) and from Novartis for network meta‐analyses in acute pain. He has received honoraria for attending boards with Menarini concerning methods of analgesic trial design (2014), with Novartis (2014) about the design of network meta‐analyses, and RB on understanding pharmacokinetics of drug uptake (2015). He has received honoraria from Omega Pharma (2016) and Futura Pharma (2016) for providing advice on trial and data analysis methods.

This review was identified in a 2019 audit as not meeting the current definition of the Cochrane Commercial Sponsorship policy. At the time of its publication it was compliant with the interpretation of the existing policy. As with all reviews, new and updated, at update this review will be revised according to 2020 policy update.

Figures

1
1
Study flow diagram
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Forest plot of comparison: 1 All placebo‐controlled studies, outcome: 1.1 At least 50% pain reduction over baseline.
4
4
Forest plot of comparison: 1 All placebo‐controlled studies, outcome: 1.2 Very much improved.
5
5
Forest plot of comparison: 1 All placebo‐controlled studies, outcome: 1.3 Much or very much improved.
6
6
Forest plot of comparison: 1 All placebo‐controlled studies, outcome: 1.4 IMMPACT outcome of substantial improvement.
7
7
Forest plot of comparison: 1 All placebo‐controlled studies, outcome: 1.5 IMMPACT outcome of at least moderate improvement.
8
8
Postherpetic neuralgia: percentage of participants achieving at least 50% pain intensity reduction (PIR) over baseline with gabapentin 1200 mg‐3600 mg daily, or placebo
9
9
Painful diabetic neuropathy: percentage of participants achieving at least 50% pain intensity reduction (PIR) over baseline with gabapentin 1200‐3600 mg daily, or placebo
1.1
1.1. Analysis
Comparison 1 Efficacy ‐ placebo‐controlled studies, Outcome 1 At least 50% pain reduction over baseline.
1.2
1.2. Analysis
Comparison 1 Efficacy ‐ placebo‐controlled studies, Outcome 2 Very much improved.
1.3
1.3. Analysis
Comparison 1 Efficacy ‐ placebo‐controlled studies, Outcome 3 Much or very much improved.
1.4
1.4. Analysis
Comparison 1 Efficacy ‐ placebo‐controlled studies, Outcome 4 IMMPACT outcome of substantial improvement.
1.5
1.5. Analysis
Comparison 1 Efficacy ‐ placebo‐controlled studies, Outcome 5 IMMPACT outcome of at least moderate improvement.
2.1
2.1. Analysis
Comparison 2 Withdrawals ‐ placebo‐controlled studies, Outcome 1 All‐cause withdrawal.
2.2
2.2. Analysis
Comparison 2 Withdrawals ‐ placebo‐controlled studies, Outcome 2 Adverse event withdrawal.
2.3
2.3. Analysis
Comparison 2 Withdrawals ‐ placebo‐controlled studies, Outcome 3 Lack of efficacy withdrawal.
3.1
3.1. Analysis
Comparison 3 Adverse events, Outcome 1 At least one adverse event.
3.2
3.2. Analysis
Comparison 3 Adverse events, Outcome 2 Serious adverse events.
3.3
3.3. Analysis
Comparison 3 Adverse events, Outcome 3 Somnolence.
3.4
3.4. Analysis
Comparison 3 Adverse events, Outcome 4 Dizziness.
3.5
3.5. Analysis
Comparison 3 Adverse events, Outcome 5 Peripheral oedema.
3.6
3.6. Analysis
Comparison 3 Adverse events, Outcome 6 Ataxia or gait disturbance.

Update of

Similar articles

  • Gabapentin for chronic neuropathic pain and fibromyalgia in adults.
    Moore RA, Wiffen PJ, Derry S, Toelle T, Rice AS. Moore RA, et al. Cochrane Database Syst Rev. 2014 Apr 27;2014(4):CD007938. doi: 10.1002/14651858.CD007938.pub3. Cochrane Database Syst Rev. 2014. PMID: 24771480 Free PMC article. Updated. Review.
  • Pregabalin for neuropathic pain in adults.
    Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA. Derry S, et al. Cochrane Database Syst Rev. 2019 Jan 23;1(1):CD007076. doi: 10.1002/14651858.CD007076.pub3. Cochrane Database Syst Rev. 2019. PMID: 30673120 Free PMC article.
  • Topical capsaicin (high concentration) for chronic neuropathic pain in adults.
    Derry S, Rice AS, Cole P, Tan T, Moore RA. Derry S, et al. Cochrane Database Syst Rev. 2017 Jan 13;1(1):CD007393. doi: 10.1002/14651858.CD007393.pub4. Cochrane Database Syst Rev. 2017. PMID: 28085183 Free PMC article. Review.
  • Tramadol for neuropathic pain in adults.
    Duehmke RM, Derry S, Wiffen PJ, Bell RF, Aldington D, Moore RA. Duehmke RM, et al. Cochrane Database Syst Rev. 2017 Jun 15;6(6):CD003726. doi: 10.1002/14651858.CD003726.pub4. Cochrane Database Syst Rev. 2017. PMID: 28616956 Free PMC article. Review.
  • Morphine for chronic neuropathic pain in adults.
    Cooper TE, Chen J, Wiffen PJ, Derry S, Carr DB, Aldington D, Cole P, Moore RA. Cooper TE, et al. Cochrane Database Syst Rev. 2017 May 22;5(5):CD011669. doi: 10.1002/14651858.CD011669.pub2. Cochrane Database Syst Rev. 2017. PMID: 28530786 Free PMC article. Review.
See all similar articles

Cited by 42 articles

See all "Cited by" articles

MeSH terms

Feedback