BACKGROUND: More than 50% of patients with Parkinson's disease develop motor 
response fluctuations (the 'wearing off" phenomenon) after more than five years 
of levodopa therapy. Inhibition of catechol-O-methyltransferase by tolcapone has 
been shown to increase levodopa bioavailability and plasma elimination half 
life, thereby prolonging the efficacy of levodopa.
OBJECTIVES: The primary objective was to evaluate the efficacy of tolcapone in 
reducing "wearing off" in levodopa treated, fluctuating parkinsonian patients. 
Secondary objectives included assessment of reduction in levodopa requirements, 
improvement in patients' clinical status, duration of improvements, and 
tolerability of tolcapone.
METHODS: In this multicentre, randomised, double blind, placebo controlled 
trial, 58 patients received placebo, 60 received 100 mg tolcapone three times 
daily (tid), and 59 received 200 mg tolcapone tid, in addition to 
levodopa/benserazide.
RESULTS: After three months with 200 mg tolcapone tid, "off" time decreased by 
26.2% of the baseline value, "on" time increased by 20.6% (p < 0.01 vs. 
placebo), and the mean total daily levodopa dose decreased by 122 mg from the 
baseline dose of 676 mg (p < 0.01). These responses were maintained up to nine 
months. With 100 mg tolcapone tid, "off" time decreased by 31.5% (p < 0.05), 
"on" time increased by 21.3% (p < 0.01), and the mean total daily levodopa dose 
decreased by 109 mg from the baseline dose of 668 mg (p < 0.05). With 200 mg 
tolcapone tid, unified Parkinson's disease rating scale motor and total scores 
were significantly reduced, and quality of life (sickness impact profile) scores 
were significantly improved. Both dosages were well tolerated. Dyskinesia was 
the most often reported levodopa induced adverse event. Diarrhoea was the most 
often reported non-dopaminergic adverse event and the most frequent reason for 
withdrawal from the study: four patients in the 100 mg tolcapone tid group and 
six in the 200 mg tid group withdrew because of diarrhoea.
CONCLUSION: Tolcapone prolongs "on" time in fluctuating parkinsonian patients 
while allowing a reduction in daily levodopa dosage, thereby improving the 
efficacy of long term levodopa therapy.