Background: Lidocaine is a local anaesthetic that is sometimes used on the skin to treat neuropathic pain.
Objectives: To assess the analgesic efficacy of topical lidocaine for chronic neuropathic pain in adults, and to assess the associated adverse events.
Search methods: We searched CENTRAL, MEDLINE, and EMBASE from inception to 1 July 2014, together with the reference lists of retrieved papers and other reviews. We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal to identify additional published or unpublished data.
Selection criteria: We included randomised, double-blind studies of at least two weeks' duration comparing any formulation of topical lidocaine with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 and over. We included only full journal publication articles.
Data collection and analysis: Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. 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, 8 to 12 weeks' duration, parallel design); second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison; and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both.
Main results: We included 12 studies (508 participants) in comparisons with placebo or an active control. Six studies enrolled participants with moderate or severe postherpetic neuralgia, and the remaining studies enrolled different, or mixed, neuropathic pain conditions, including trigeminal neuralgia and postsurgical or post-traumatic neuralgia. Four different formulations were used: 5% medicated patch, 5% cream, 5% gel, and 8% spray. Most studies used a cross-over design, and two used a parallel-group design. Two studies used enriched enrolment with randomised withdrawal. Seven studies used multiple doses, with one to four-week treatment periods, and five used single applications. We judged all of the studies at high risk of bias because of small size or incomplete outcome assessment, or both.There was no first or second tier evidence, and no pooling of data was possible for efficacy outcomes. Only one multiple-dose study reported our primary outcome of participants with ≥ 50% or ≥ 30% pain intensity reduction. Three single-dose studies reported participants who were pain-free at a particular time point, or had a 2-point (of 10) reduction in pain intensity. The two enriched enrolment, randomised withdrawal studies reported time to loss of efficacy. In all but one study, third tier (very low quality) evidence indicated that lidocaine was better than placebo for some measure of pain relief. Pooling multiple-dose studies across conditions demonstrated no clear evidence of an effect of lidocaine on the incidence of adverse events or withdrawals, but there were few events and the withdrawal phase of enriched enrolment designs is not suitable to assess the true impact of adverse events (very low quality evidence).
Authors' conclusions: This review found no evidence from good quality randomised controlled studies to support the use of topical lidocaine to treat neuropathic pain, although individual studies indicated that it was effective for relief of pain. Clinical experience also supports efficacy in some patients. Several large ongoing studies, of adequate duration, with clinically useful outcomes should provide more robust conclusions about both efficacy and harm.