A pilot efficacy and tolerability trial of memantine for essential tremor.

Objective: We studied the potential efficacy and tolerance of memantine for essential tremor in an open-treatment trial.

Methods: Participants with upper-limb tremor were titrated to no more than 40 mg/d memantine, as monotherapy or as adjunct to stable antitremor medication, followed by a 12-week extension phase. Tremor was assessed in study 1 with accelerometry and in study 2 by blinded ratings of videotaped Washington Heights Inwood Genetic Essential Tremor (WHIGET) rating scale items. Subjects also rated their tremor treatment response and tremor-associated impairment on the Functional Disabilities scale.

Results: In study 1, average accelerometry-measured tremor at last titration visit (average dose, 30.3 mg/d) did not change from baseline, but 2 of 9 subjects, taking 40 mg/d, had greater than 70% accelerometry tremor reduction. In study 2, 13 of 16 provided evaluable data. Average blinded rater-evaluated WHIGET scores were significantly different from baseline scores among those taking 20 mg/d (-12.7%; P < 0.05), but not at last titration visit (-8.4%; average dose, 30.4 mg/d), 40 mg/d (-14.1%), or at end-of-extension visit (-18.2%). Raters judged WHIGET scores as greater than 30% improved in 2 subjects. Unblinded subjects rated Functional Disabilities significantly improved at 30 to 40 but not at 10 to 20 mg/d, and tremor treatment response was positive at all doses. Adverse events were more common at higher doses and included dizziness, somnolence, and poor energy.

Conclusions: These pilot results with small samples indicate that the average effect of memantine on tremor is mild or not significant. However, in a small subset of patients, memantine may confer meaningful tremor benefit.