CLOZAPINE IN PARKINSONS-DISEASE TREMOR - EFFECTS OF ACUTE AND CHRONICADMINISTRATION

The effects of the acute administration of clozapine on parkinsonian m ixed tremor (i.e., resting and postural tremors) were evaluated to est ablish clozapine's predictive value for long-term response and to dete rmine if there is a difference in the pharmacologic responses of the t wo tremors. We also investigated the correlation between reduction of tremor and induction of sedation after acute and chronic administratio n 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 t remors. 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 d ose +/-SD of 45 +/- 9.6 mg for a period of 15.5 +/- 8.3 months. A sign ificant reduction of both resting (p < 0.05) and postural (p < 0.05) t remors was observed under clozapine from the first week of treatment t hrough the entire period of the study. There was no statistically sign ificant difference between the degree of improvement for resting and p ostural tremors after either single or chronic clozapine administratio n. Sedation was the only side effect reported after clozapine; however , the time courses of sedation and tremor reduction did not coincide i n the acute or in the chronic experimental paradigm, where it decrease d considerably in a few weeks in all patients. During long-term clozap ine treatment, neither systemic side effects nor worsening of motor di sability scores were noted. Thus we wish to propose an acute test or a therapeutic attempt, or both, with clozapine before defining a case o f mixed parkinsonian tremor as resistant tremor and therefore resortin g to a neurosurgical approach.