title: 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.
authors.affiliation: Stanford Pain Management Center, Stanford University Medical Center, Palo Alto, CA 94304-1573, USA. irc39@pain.stanford.edu
authors.forename: Ian R
authors.initials: IR
authors.lastname: Carroll
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Kaplan
authors.forename: Sean C
authors.initials: SC
authors.lastname: Mackey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000779:Anesthetics, Local / Q000008:administration & dosage; D002755:Choice Behavior; D002908:Chronic Disease; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008012:Lidocaine / Q000008:administration & dosage; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage*; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D026941:Sodium Channel Blockers / Q000008:administration & dosage*
chemical_list: D000779:Anesthetics, Local; D026941:Sodium Channel Blockers; D008801:Mexiletine; D008012:Lidocaine