Cochrane Briefs

Systemic Lidocaine or Mexiletine for Neuropathic Pain


Am Fam Physician. 2006 Jul 1;74(1):79.

Clinical Question

When used systemically, are lidocaine (Xylocaine) and its oral analogue mexiletine (Mexitil) safe and effective for the treatment of neuropathic pain?

Evidence-Based Answer

Intravenous lidocaine and oral mexiletine provide a modest reduction in neuropathic pain with no indication of serious adverse effects. However, safety data are limited because most studies were of relatively short duration and fewer than 400 patients have been studied in total for each drug. Intravenous lidocaine and oral mexiletine should be considered second- or third-line options for the treatment of neuropathic pain and should be given only after a careful discussion with the patient regarding risks and benefits.

Practice Pointers

Case reports from the 1950s suggest that intravenous lidocaine, typically used as a local anesthetic, could provide pain relief in patients with cancer or postoperative pain. Subsequent reports in the 1980s suggested a similar benefit for the oral analogues mexiletine, flecainide (Tambocor), and tocainide (Tonocard). In the past decade, several better-designed clinical trials have been published; this Cochrane review provides an update on the safety and efficacy of lidocaine and its oral analogue mexiletine for the systemic treatment of neuropathic pain.

The authors reviewed randomized, double-blind, controlled studies that involved patients with neuropathic pain, including peripheral neuropathy, regional pain syndromes, spinal cord injury, trigeminal neuralgia, phantom limb pain, and fibromyalgia. Of the 30 studies identified, 12 were of good methodologic quality and all were small (median number of participants 28, range 8 to 87). The amount of intravenous lidocaine typically infused was between 1 and 5 mg per kg.

In 11 studies of lidocaine with a total of 373 patients, the researchers found a mean reduction of 11 mm in a 100-mm visual pain scale (95% confidence interval [CI], −17 to −5). The same benefit (mean difference −11 mm, 95% CI, −16 to −6) was found in nine studies of oral mexiletine (median dosage 600 mg per day for a median of nine weeks) with a total of 377 patients. Results generally were consistent and of similar magnitude among studies. Although statistically significant, an 11-mm improvement on a 100-mm scale generally is felt to be of borderline clinical significance. Adverse events (none serious) were more common in patients receiving lidocaine or mexiletine than in those receiving placebo (35 versus 12 percent, respectively).

A consensus guideline from the Reflex Sympathetic Dystrophy Syndrome Association1 mentions mexiletine as a “somewhat experimental” option for treatment of this condition. A second consensus guideline2 similarly notes that although mexiletine is an option, it is not considered a first- or second-line medication.


Challapalli V, et al. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev. 2005;(4):CD003345.


1. Reflex Sympathetic Dystrophy Syndrome Association. Clinical practice guidelines (second edition) for the diagnosis, treatment, and management of reflex sympathetic dystrophy/complex regional pain syndrome (RSD/CRPS). Milford, Conn.: Reflex Sympathetic Dystrophy Syndrome Association, 2002.

2. Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003;60:1524–34.



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