Fourteen Parkinsonian patients with fluctuations in therapeutic response to levodopa completed a double-blind, crossover trial of controlled-release levodopa/carbidopa (Sinemet CR4) vs standard Sinemet 25/100 (STD). Significant increases in mean interdose interval and per cent of the waking day spent "on", as well as reductions in the number of daily medication doses and number of "off" episodes were noted. In the double-blind part of the study, relative to open treatment with STD, ten patients rated themselves as improved while taking CR4, whereas only three considered themselves improved with STD. Difficulties using CR4 included an increased "lag-time" to the onset of antiparkinson effect, a tendency to produce increasingly severe dyskinesia late in the day, and a somewhat lessened predictability of motor response. Nonetheless, since the overall level of motor function through the day was equal to or better than that attained with STD, but with fewer medication administrations, Sinemet CR4 should prove a useful antiparkinsonian agent.
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