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Mexiletine did not reduce painful diabetic neuropathy overall but led to improvement in patients who had burning pain, heat sensations, and formication

ACP J Club. 1993 Mar-April;118:39. doi:10.7326/ACPJC-1993-118-2-039

Source Citation

Stracke H, Meyer UE, Schumacher HE, Federlin K. Mexiletine in the treatment of diabetic neuropathy. Diabetes Care. 1992 Nov;15:1550-5.



To compare the efficacy of 3 different doses of mexiletine for patients with painful diabetic neuropathy.


Randomized, double-blind, placebo-controlled trial with 5-week follow-up.


7 clinics in Germany.


Adults ≥ 18 years of age were enrolled if they had pain or malaise from diabetic neuropathy that required treatment and impaired their lifestyle, pain intensity at 25% on the Visual Analog Scale (VAS), and pain for ≥ 4 months. Exclusion criteria were possibility of pregnancy, neuropathy of other origin, substance abuse, vitamin B12 deficiency, renal or cardiac insufficiency, cirrhosis, hepatitis, chronic liver damage, cardiac arrhythmia, or occlusive arterial disease. 95 patients (mean age 57 y, 53 men, 68% insulin dependent, 39% taking oral antidiabetic agents) enrolled in and completed the study.


During a 1-week run-in phase, all patients stopped taking medication for diabetic neuropathy. For the first week all patients received mexiletine, 75 mg 3 times/d, or placebo. This dose could be raised at weekly intervals to 150 mg and 225 mg of mexiletine 3 times/d or corresponding placebo. Paracetamol (acetaminophen) could be used. At study end, 7 patients were taking low-dose mexiletine, and 1 was taking low-dose placebo; 18 were taking medium-dose mexiletine, and 12, medium-dose placebo; and 21 were taking high-dose mexiletine, and 35, high-dose placebo.

Main outcome measures

Patients were examined weekly for neurologic status, blood glucose levels, blood pressure, and adverse effects. They also answered the McGill Pain Questionnaire (MPQ). Patients filled out the VAS for pain twice daily and recorded paracetamol use.

Main results

The groups did not differ for paracetamol use, total MPQ, and VAS pain scores. The Pain Rating Index Scale of the MPQ showed a trend toward improvement (P = 0.06). Subgroup analysis showed that mexiletine decreased complaints of stabbing pain (P = 0.02), heat (P = 0.1), burning (P = 0.01), and formication (P = 0.04). Patients with ≥ 2 of these 4 symptoms reported the greatest improvement with mexiletine (P < 0.03). 11 people taking mexiletine and 6 taking placebo reported adverse effects, but the differences were statistically significant only for patients taking the highest dose. The medium- and high-dose groups did not differ for any benefits.


In a subgroup analysis, mexiletine, when used for 5 weeks, reduced stabbing or burning pain, heat sensations, and formication in adults with painful diabetic neuropathy.

Source of funding: Not stated.

For article reprint: Dr. H. Stracke, Klinikum der Justus-Liebig, Universität Giessen, Medizinische Poliklinik, Rodthohl 6, D-35385 Giessen, Germany. FAX 49-641-994-2796.


Stracke and colleagues have added another drug, mexiletine, to a large group of drugs, most of which are only partially effective in the treatment of painful diabetic neuropathy. In this case, a particular group of symptoms (stabbing, burning, heat, and formication) was improved, although overall quality of life was not. As with phenytoin, carbamazepine, amitriptyline, and capsaicin, mexiletine may be worth trying, but patients should be monitored carefully by documenting the type and extent of symptom response before and during treatment. Adverse effects are important with the use of mexiletine because it is a class I antiarrhythmic and can cause prolongation of the QT interval, torsade, and sudden death. Fortunately, the dose required to relieve pain is lower than the usual antiarrhythmic dose. Still, the QT interval should be monitored before and after treatment when mexiletine is started. If pain relief is minimal, mexiletine should be withdrawn.

Another contribution of this study is that it can help the community of physicians who care for patients with diabetic neuropathy develop treatment algorithms for neuropathy that are more creative. Physicians can use the information from this study to tailor the drug treatment to the patient's symptoms while weighing the potential for drug side effects against the degree of pain relief. Given the limited responses to mexiletine and the potential but low risk for mortality, I can only recommend its use when the rest of the available drugs have failed.

Jacqueline A. Pugh, MD
University of TexasSan Antonio, Texas, USA