Mexiletine in treatment-resistant bipolar disorder

Background: The purpose of this study was to evaluate the efficacy and safe ty of mexiletine, a medication with antiarrhythmic, anticonvulsant and anal gesic properties, in treatment-resistant bipolar disorder patients. Methods : Twenty subjects with rapid-cycling bipolar disorder who had failed to res pond or were intolerant to lithium, valproic acid and carbamazepine were en tered into the 6-week, open label study. Subjects were followed on a weekly basis for dosing of mexiletine, blood levels, and completion of the Hamilt on Depression Rating Scale (HAM-D) and the Manic State Rating Scale (MSRS). "Burden of Mood Symptoms" (BMS) was calculated by combining scores for the HAM-D and MSRS. Results: Thirteen subjects (10 female, 3 male), mean age 4 1 years (S.D. = 7.6), and mean duration of illness 20 years (S.D. = 7.7) co mpleted the study. The dose range of mexiletine was 200-1200 mg/day. Full r esponse ( greater than or equal to 50% reduction in EMS) was seen in 46% of the subjects, and a partial response (25-49% reduction in EMS) in 15%. Of note, 5/5 subjects with a mixed or manic state demonstrated a full or parti al response. Limitations: This study has an open label design, and a small number of subjects. Conclusions: Mexiletine may be effective and safe in pa tients with highly treatment-resistant, chronic bipolar disorder. Randomize d, controlled trials are required to confirm the current results. (C) 2000 Elsevier Science B.V. All rights reserved.