• Philip J Wiffen, Sheena Derry, MooreR AndrewRA, and Eija A Kalso.
• Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.
• Cochrane Db Syst Rev. 2014 Apr 10 (4): CD005451.

BackgroundThis is an update of a Cochrane review entitled 'Carbamazepine for acute and chronic pain in adults' published in Issue 1, 2011. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This updated review considers the treatment of chronic neuropathic pain and fibromyalgia only, and adds no new studies. The update uses higher standards of evidence than the earlier review, which results in the exclusion of five studies that were previously included.ObjectivesTo assess the analgesic efficacy of carbamazepine in the treatment of chronic neuropathic pain and fibromyalgia, and to evaluate adverse events reported in the studies.Search MethodsWe searched for relevant studies in MEDLINE, EMBASE and CENTRAL up to February 2014. Additional studies were sought from clinical trials databases, and the reference list of retrieved articles and reviews.Selection CriteriaRandomised, double blind, active or placebo controlled trials (RCTs) investigating the use of carbamazepine (any dose, by any route, and for at least two weeks' duration) for the treatment of chronic neuropathic pain or fibromyalgia, with at least 10 participants per treatment group. Participants were adults aged 18 and over.Data Collection And AnalysisTwo study authors independently extracted data on efficacy, adverse events, and withdrawals, and examined issues of study quality. Numbers needed to treat for an additional beneficial effect (NNT) or harmful effect (NNH) with 95% confidence intervals (CIs) were calculated from dichotomous data.We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts, at least 200 participants in the comparison, at least 8 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both.Main ResultsTen included studies (11 publications) enrolled 480 participants with trigeminal neuralgia, diabetic neuropathy, and post stroke pain. Nine studies used a cross-over design, and one a parallel group design. Most of the studies were of short duration, lasting four weeks or less.No study provided first or second tier evidence for an efficacy outcome. Using third tier evidence, carbamazepine generally provided better pain relief than placebo in the three conditions studied, with some indication of pain improvement over mainly the short term, but with poorly defined outcomes, incomplete reporting, and in small numbers of participants. There were too few data in studies comparing carbamazepine with active comparators to draw any conclusions.In four studies 65% (113/173) of participants experienced at least one adverse event with carbamazepine, and 27% (47/173) with placebo; for every five participants treated, two experienced an adverse event who would not have done so with placebo. In eight studies 3% (8/268) of participants withdrew due to adverse events with carbamazepine, and none (0/255) with placebo. Serious adverse events were not reported consistently; rashes were associated with carbamazepine. Four deaths occurred in patients on carbamazepine, with no obvious drug association.Authors' ConclusionsCarbamazepine is probably effective in some people with chronic neuropathic pain, but with caveats. No trial was longer than four weeks, had good reporting quality, nor used outcomes equivalent to substantial clinical benefit. In these circumstances, caution is needed in interpretation, and meaningful comparison with other interventions is not possible.

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