The effects of the acute administration of
clozapine on parkinsonian mixed
tremor (i.e., resting and postural
tremors) were evaluated to establish
clozapine's predictive value for long-term response and to determine if there is a difference in the pharmacologic responses of the two
tremors. We also investigated the correlation between reduction of
tremor and induction of sedation after acute and chronic administration of
clozapine.
Clozapine (12.5 mg) or placebo were administered po in a double-blind manner to 17 PD patients with mixed
L-dopa-resistant
tremors. Two patients did not reach 50% improvement and were considered nonresponders. The remaining 15 patients reported moderate to marked reduction of
tremor. Responsive patients in the acute test moved on to a long-term, open
clozapine add-on study receiving an average daily dose +/- SD of 45 +/- 9.6 mg for a period of 15.5 +/- 8.3 months. A significant reduction of both resting (p < 0.05) and postural (p < 0.05)
tremors was observed under
clozapine from the first week of treatment through the entire period of the study. There was no statistically significantly difference between the degree of improvement for resting and postural
tremors after either single or chronic
clozapine administration. Sedation was the only side effect reported after
clozapine; however, the time courses of sedation and
tremor reduction did not coincide in the acute or in the chronic experimental paradigm, where it decreased considerably in a few weeks in all patients. During long-term
clozapine treatment, neither systemic side effects nor worsening of motor disability scores were noted. Thus we wish to propose an acute test or a therapeutic attempt, or both, with
clozapine before defining a case of mixed parkinsonian
tremor as resistant
tremor and therefore resorting to a neurosurgical approach.