Topical lidocaine for neuropathic pain in adults Stable (no update expected for reasons given in 'What's new')
Lidocaine is a local anaesthetic that is sometimes used on the skin to treat neuropathic pain.
To assess the analgesic efficacy of topical lidocaine for chronic neuropathic pain in adults, and to assess the associated adverse events.
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(WHO) International Clinical Trials Registry Platform (ICTRP) search portal to identify additional published or unpublished data.
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.
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).
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.
Sheena Derry, Philip J Wiffen, R Andrew Moore, Jane Quinlan
Plain language summary
Topical lidocaine for neuropathic pain in adults
Neuropathic pain is pain coming from damaged nerves. It differs from pain messages carried along healthy nerves from damaged tissue (a fall, or cut, or arthritic knee). Neuropathic pain is treated by different medicines than pain from damaged tissue. Medicines like paracetamol or ibuprofen are usually not effective in neuropathic pain, while medicines that are sometimes used to treat epilepsy or depression can be very effective in some people with neuropathic pain. Other possible treatments include the use of local anaesthetic applied to the skin.
Lidocaine is a local anaesthetic. It is available in plasters (or patches), sprays, and creams, as topical lidocaine. These contain high concentrations of lidocaine because it crosses the skin poorly. Treatment with plasters usually involves applying one, two, or three plasters for up to 12 hours a day.
In July 2014 we performed searches to look for clinical trials where topical lidocaine was used to treat neuropathic pain. We found 12 small studies of modest quality that tested topical lidocaine against topical placebo for a number of weeks. One study also tested a cream containing amitriptyline, which is an antidepressant. The 508 people in the studies had different types of neuropathic pain, with pain after herpes zoster infection the most common.
There was some indication that topical lidocaine was beneficial in these studies (very low quality evidence). There was no clear evidence of an effect of lidocaine on the incidence of adverse events or withdrawals (very low quality evidence).
A number of studies of topical lidocaine in neuropathic pain are ongoing. Several are large and of long duration. They will be of great help in working out the benefits of topical lidocaine when they are completed and results can be incorporated in this review.
Sheena Derry, Philip J Wiffen, R Andrew Moore, Jane Quinlan
Implications for practice
Limited information from single studies, mainly in postherpetic neuralgia, indicates that topical lidocaine 5% plaster may be effective in treating neuropathic pain in a small number of patients, and is well tolerated, at least in the short term.
Implications for research
With limited numbers of trials and participants, there is a clear need for large, good quality, long duration randomised studies in different neuropathic pain conditions. Several such trials are apparently being conducted and it would not be sensible to embark on a new clinical trial programme without knowledge of their results. An update of this review will be done when ongoing studies present data.
Lidocaine 8% spray may be useful for treating breakthrough pain, due to its apparent rapid onset and limited duration of action. This also represents a potentially useful research area.
Clinical practice indicates that lidocaine plasters can be helpful to carefully chosen patients with neuropathic pain limited to a defined area of superficial allodynia or hyperalgesia. For patients like this a study protocol could be generated to evaluate lidocaine plasters in individual patients. It would need to be designed carefully, with specified measurements, outcomes, and timing, and be part of a nationwide or regional assessment. There are exemplars for this in chronic pain, for example the successful assessment of tumour necrosis factor (TNF)‐antagonists for rheumatoid arthritis in clinical practice in the south of Sweden (Geborek 2002).