Benztropine vs. Clozapine for Tremor in Parkinson’s

Source: Friedman JH, et al. Benztropine versus clozapine for the treatment of tremor in Parkinson’s disease. Neurology 1997;48:1077-1081.

Tremor represents the bugbear in the treatment of Parkinson’s disease. Clozapine is often prescribed but frequently either fails to bring sufficient amelioration or brings unwanted side effects. This recent trial tested benztropine against clozapine, using a double-blind cross-over paradigm. Nineteen patients (mean age, 67.6 years) made up the study group. Baseline tremor scores were equally poor in either group. Benztropine doses started at 0.75 mg/d and increased weekly by 0.75 mg on a bid program. Clozapine began at 12.5 mg/d and increased daily on a bid program. Maximal doses were 4.5 mg/d for benztropine and 75 mg/d for clozapine, with each individual drug trial lasting up to six weeks, as tolerated. Following a two-week washout, the treatment was reversed.

Three persons dropped out of the study, two because of adverse drug effects. Both drugs improved tremor to approximately the same degree as judged by blind appraisal. At the end of the study, five patients chose to continue benztropine, and four selected clozapine. No serious leukopenia affected any patient, but benztropine induced more unwanted side effects, including dry mouth in 12 patients, confusion in six, and memory impairment in five. Clozapine, by contrast, induced only dry mouth in three, constipation in three, and sedation in three. The authors cautiously conclude that despite its bad reputation for occasionally precipitating agranulocytosis, clozapine deserves a trial in patients whose tremor fails to respond to L-dopa anticholinergics or beta-blockers. —fp