Patients with
essential tremor (ET) may not respond to commonly used drugs.
Clozapine, an atypical
neuroleptic drug, has been reported to improve postural
Parkinson's disease tremor clinically resembling ET. The effects of a single dose of 12.5 mg
clozapine and placebo were evaluated in a randomized, double-blind, crossover study in 15
drug-resistant patients with ET. Patient responders with more than 50% improvement after a single dose of
clozapine subsequently received the
drug (39+/-9 mg up to 50 mg) unblinded for a period of 15.8+/-7.7 months.
Tremor was effectively reduced by a single dose of
clozapine in 13 of 15 patients (p <0.01). Sedation was the only side effect reported during the
clozapine test; however, the time course of sedation and of the antitremor effect were not coincident. A significant reduction of
tremor was reported with chronic
clozapine treatment (p <0.01) with no tolerance to
drug antitremor effect, whereas sedation markedly decreased after 6-7 weeks of
therapy. No
clozapine-induced hematologic side effects were observed in our cohort of patients during long-term treatment. Our results suggest that in selected
drug-resistant ET cases,
clozapine should be considered before resorting to neurosurgical options.