Mexiletine Usage in a Chronic Pain Clinic: Indications, Tolerability, and Side Effects

Abstract

Background: Background: Intravenous lidocaine has multiple applications in the management of acute and chronic pain. Mexiletine, an oral lidocaine analogue, has been used in a number of chronic pain conditions although its use is not well characterized. Objectives: To report our experience using mexiletine in a chronic pain population, specifically looking at tolerability, side effects, and EKG changes. Study Design: Retrospective, cohort study. Setting: Multiple pain clinic locations in an integrated multispecialty health system. Methods: All patients who had a mexiletine prescription between August 2015 and August 2016 were queried via the electronic medical record. Each chart was examined for demographics, QTc changes on EKG, length of use, and reasons for stoppage. Results:There were 74 total patients identified in the chronic pain management clinics as receiving at least 1 mexiletine prescription over the 1-year time period. Twice as many women as men received mexiletine prescriptions. Neuropathic pain was the most common primary diagnosis (64%) which included diabetic neuropathy, radiculopathy, and others. Fibromyalgia was the next most common primary diagnosis (28%). A QTc change on the EKG showed a mean decrease of 0.1 ms and median increase of 1.5 ms. At 6 months (180 days), approximately 30% of the patients remained on mexiletine therapy, and 28% remained on the therapy at 1 year (360 days). Median duration of use was 60 days and the mean was 288 days. Neurologic and gastrointestinal side effects were the most commons reason for stoppage. All side effects were mild and resolved with stoppage. After side effects, lack of response, or loss of efficacy, were the next most common reasons for stoppage. Limitations: Pain relief and outcomes were not specifically examined due to confounding factors including interventional treatments and multiple treatment modalities. This was a retrospective, cohort study limited to our specific clinic population with a relatively high loss to follow-up rate. Conclusion:Mexiletine is rarely a first line option for chronic pain management and is often used when multiple other modalities have failed. By reporting our experience, we hope other clinicians may have more familiarity with the drug’s use in a chronic pain practice. It appears reasonably tolerable, may not require frequent EKG monitoring, and can be an appropriate adjunct in the chronic pain population. More research is needed regarding efficacy and dose titration for mexiletine in chronic pain. Key Words: Chronic pain, mexiletine, IV lidocaine, pain, neuropathic pain, neuropathy, fibromyalgia, QTc, tolerability

Dose-dependent analgesic activity of mexiletine on thermally induced pain in rats

“…All these side effects were mild and resolved with stoppage of mexiletine. 12 A phase II trial conducted to evaluate the safety and tolerability of mexiletine with doses of 300mg per day and 900mg per day showed that mexiletine was safe at both the doses but was well tolerated only at 300mg per day dose. Adverse effects noted at doses of 900mg per day led to a higher rate of discontinuation.…”

“…Mexiletine also has a role in peripheral neuropathy and chronic pain. [11][12][13] Recently, it has been used in the treatment of sporadic amyotrophic lateral sclerosis. 14 Mexiletine has been used off-label for various painful conditions of chronic nature.…”

Treatment Updates for Neuromuscular Channelopathies

“…Dyspepsia was the most common symptom but adjunctive treatment with proton pump inhibitors ameliorated this in most. Other adverse events were headache, palpitations, nausea and syncope but there were no serious adverse events and all side effects resolved when medication was discontinued [34,35]. ECG parameters between baseline and highest mexiletine dose levels did not change significantly and overall frequent ECG monitoring when on a stable dose of mexiletine was not deemed necessary.…”