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Mexiletine in treatment-resistant bipolar disorder
A Schaffer1, A J Levitt, R T Joffe
1Department of Psychiatry, Sunnybrook Health Science Center, 2075 Bayview Avenue, Room FG46, University of Toronto, Toronto, Canada.
Background:
The purpose of this study was to evaluate the efficacy and safety of mexiletine, a medication with antiarrhythmic, anticonvulsant and analgesic properties, in treatment-resistant bipolar disorder patients.
Methods:
Twenty subjects with rapid-cycling bipolar disorder who had failed to respond or were intolerant to lithium, valproic acid and carbamazepine were entered into the 6-week, open label study. Subjects were followed on a weekly basis for dosing of mexiletine, blood levels, and completion of the Hamilton 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 41 years (S.D.=7.6), and mean duration of illness 20 years (S.D.=7.7) completed the study. The dose range of mexiletine was 200-1200 mg/day. Full response (>/=50% reduction in BMS) was seen in 46% of the subjects, and a partial response (25-49% reduction in BMS) in 15%. Of note, 5/5 subjects with a mixed or manic state demonstrated a full or partial response.
Limitations:
This study has an open label design, and a small number of subjects.
Conclusions:
Mexiletine may be effective and safe in patients with highly treatment-resistant, chronic bipolar disorder. Randomized, controlled trials are required to confirm the current results.
Insights
Mexiletine shows promise for treatment-resistant bipolar disorder. This study found it effective in reducing mood symptoms in patients who did not respond to other treatments.
Area of Science:
- Psychiatry
- Pharmacology
- Neurology
Background:
- Bipolar disorder is a complex mood disorder often requiring multiple treatment strategies.
- Treatment resistance is a significant challenge in managing chronic bipolar disorder.
- Mexiletine, an antiarrhythmic drug, possesses anticonvulsant and analgesic properties with potential neuropsychiatric applications.
Purpose of the Study:
- To evaluate the efficacy and safety of mexiletine in patients with treatment-resistant bipolar disorder.
- To assess mexiletine's impact on mood symptom severity in a difficult-to-treat population.
Main Methods:
- An open-label study involving 20 subjects with rapid-cycling bipolar disorder.
- Participants had previously failed standard treatments like lithium, valproic acid, and carbamazepine.
- Weekly assessments included mexiletine dosing, blood levels, and the Hamilton Depression Rating Scale (HAM-D) and Manic State Rating Scale (MSRS).
Main Results:
- Thirteen subjects completed the 6-week study, with mexiletine doses ranging from 200-1200 mg/day.
- A significant reduction in the Burden of Mood Symptoms (BMS) was observed: 46% showed a full response (≥50% BMS reduction) and 15% a partial response (25-49% BMS reduction).
- Notably, all 5 subjects experiencing mixed or manic states achieved a full or partial response.
Conclusions:
- Mexiletine may represent a viable and safe therapeutic option for individuals with highly treatment-resistant, chronic bipolar disorder.
- The findings suggest mexiletine's potential utility in managing severe mood episodes in this population.
- Further investigation through randomized, controlled trials is necessary to validate these preliminary results.