Risk and Benefit Assessment for Tolcapone in the Treatment of Parkinson's Disease

Abstract

Objectives: To assess the evidence for the effectiveness and tolerability of tolcapone in the treatment of Parkinson’s disease. Methods: The literature from 1990 to 2003 was searched systematically to identify randomised trials of tolcapone. Search methods included the Roche intranet to find the most up to date safety issues, the electronic database including Medline, PubMed and Web of Science as recommended by Cochrane Collaboration and also a manual search of the major journals in the field. Eligible patients for the present study were those with fluctuating PD who were being treated with peripheral dopa-decarboxylase inhibitor (DDC-I) L-dopa / beserazide or L-dopa/ carbidopa. Results: Thirteen randomised trials were identified but ultimately only 5 studies met all the criteria for the present study. The efficacy of tolcapone 200 mg three times daily as adjunct therapy to Ldopa/DDC-I was examined. All outcomes of “on” time, “off” time, changes in daily L-dopa dose and Parkinson’s disease rating scale showed favourable results for toleapone compared to placebo, and meta-analysis was able to identify significant improvement from the baseline with reduction in the L-dopa daily dose. In the present study, fixed effects were used when the Q statistic showed no significance. With “on” time increase (hours), the pooled weighted mean difference (WMD) = 1.92(95% CI = 1.40, 2.45) (fixed effects) (6 week assessment). With “off” time decrease(hours), the pooled (WMD) = -1.83 (95% CI = -2.34, -1.32) (fixed effects) (6 week assessment), the pooled (WMD) = -1.38 (95% CI = -2.05, -0.71) (fixed effects) (12 week assessment). With L-dopa daily dose, random effects was used as the Q statistic was significant, and the pooled weighted mean difference = -168.90 (95% CI = -204.57, -133.24) (random effects) (6 week assessment). More dopaminergic side effects were reported in the patients randomised to the tolcapone group. Hepatotoxicity appeared after marketing but none of the studies included in the present study considered the results of the liver function test to be significant. Conclusion: Systematic review provides the most reliable available current evidence from randomised clinical trials. The present study to assess tolcapone demonstrates the hypothesis that the currently most used L-dopa treatment combined with tolcapone prolongs L-dopa efficacy. Most adverse events reported in the studies were managed by reducing the dose of L-dopa. A patient’s quality of life is very poor indeed with advanced Parkinson’s disease. The cause of hepatoxicity is not clear, but if there is no other effective treatment, it maybe worth using tolcapone for the benefits in spite of this risk. However it is essential to keep patients under careful observation when tolcapone is used concomitantly.