Zonisamide for Essential Tremor

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Abstract
The pharmacological therapy for essential tremor (ET) is inadequate, and many patients resort to surgical procedures. Zonisamide is an antiepileptic with several potential mechanisms of action. We evaluated zonisamide for ET in an open-label pilot trial. The primary efficacy point was the change in the Tremor Study Group rating scale (TSGRS) scores. Twenty-two subjects were enrolled (male, 9; mean age +/- SD, 65.0 +/- 12.6 years; mean duration of ET +/- SD, 25.6 +/- 17.1 years). Six subjects dropped because of either (1) adverse events (AEs) and lack of effect (n = 4) or (2) lack of effect (n = 2). Two were lost to follow-up. Fourteen subjects returned for their complete postmedication evaluation. After 3 months (mean +/- SD, 88 +/- 34 days), the final dose was 200 mg (n = 11), 150 mg (n = 1), 100mg (n = 1), and 12.5 mg (n = 1). The mean Tremor Study Group rating scale scores improved from a mean of 28.9 (SD, +/-9.2) to a mean of 21.1 (SD, +/-6.5) (P = 0.02, unpaired t test). Seven subjects (50%) had at least a 25% improvement. Subjectively, however, only 4 reported marked or moderate improvement, 3 reported mild improvement, and 7 reported no change. Adverse events included decreased concentration/cognition (n = 2), constipation (n = 1), nocturia (n = 1), abdominal pain/diarrhea (n = 1), and sedation (n = 1). Zonisamide significantly (albeit modestly) improved the TSGRS scores in this small group of medically refractory subjects who completed the evaluation. However, clinical impressions did not improve, and the study was complicated by a large dropout rate caused by subjective lack of efficacy and by AEs.