Mexiletine Therapy for Chronic Pain: Survival Analysis Identifies Factors Predicting Clinical Success

Abstract

Mexiletine, a sodium channel blocker, treats neuropathic pain but its clinical value has been questioned due to its significant side effects and limited efficacy. We hypothesized that ongoing therapy with mexiletine would have limited patient acceptance, but that an analgesic response to intravenous (IV) lidocaine (a pharmacologically similar drug) would identify patients most likely to choose ongoing therapy with mexiletine. We identified a cohort of 37 patients with neuropathic pain who underwent IV lidocaine infusions at our institution and were subsequently prescribed mexiletine. Time until discontinuation of mexiletine was used as the primary endpoint. Time until discontinuation is a clinically relevant, discrete, objective endpoint gaining acceptance as a metric for assessing clinical performance of drugs with significant side effects and limited efficacy. We used the techniques of survival analysis to determine factors that predicted continued therapy with mexiletine. Median time to discontinuation of mexiletine was only 43 days. A stronger analgesic response to IV lidocaine significantly predicted continued acceptance of mexiletine therapy. Decreasing age and male gender also predicted continued acceptance of mexiletine therapy. Analyzing time to mexiletine discontinuation uncovers important limitations in mexiletine's clinical performance missed by studies with conventional endpoints, such as change in pain score. Despite claims of efficacy, acceptance of mexiletine therapy is poor overall. Test infusions with lidocaine identify patients most likely to continue mexiletine therapy. Further work is needed to confirm these results and evaluate the relative acceptance of mexiletine vs. other treatments of neuropathic pain.

Understanding Neuropathic Corneal Pain—Gaps and Current Therapeutic Approaches

“…Pharmacotherapy used for pain management may provide significant relief, in particular in patients with a central component of neuropathic pain. 98–104 Data on the use of systemic pharmacotherapy for corneal neuropathic pain is however scarce. Various options are available that include anticonvulsants (e.g., carbamazepine), tricyclic antidepressants (e.g.…”

“…101,103 When the above drugs are ineffective or not well tolerated, Mexiletine can serve as an alternative second line therapy. 104 Mexiletine (225 to 675 mg/day) is an orally active local anesthetic agent, which is structurally related to lidocaine and has been used to alleviate neuropathic pain of various origins. 104 Side effects like nausea, sleep disturbance, headache, shakiness, dizziness and tiredness may however limit its prolonged use.…”

Rufinamide Attenuates Mechanical Allodynia in a Model of Neuropathic Pain in the Mouse and Stabilizes Voltage-gated Sodium Channel Inactivated State

“…10 Mexiletine, a sodium channel blocker and an oral analog of local anesthetics has been used in the treatment of neuropathic pain 11 but its tolerance on long-term therapy raises considerable questions as shown by a median discontinuation of treatment of 43 days in a recent study. 12 Rufinamide is an antiepileptic drug licensed for Lennox-Gastaut syndrome, a refractory type of epilepsy. 13 It is considered to inhibit sodium channels, stabilizing its inactive form, and reducing the firing of sodium-dependent action potentials.…”

Intravenous Lidocaine and Mexiletine in the Management of Trigeminal Autonomic Cephalalgias

“…Although IV lidocaine and mexiletine are closely related medications, it is unclear if patients who respond to treatment with one agent will invariably respond to the other. Effective treatment with IV lidocaine, however, does appear to increase patient acceptance of chronic mexiletine therapy [45].…”