Tolcapone

The Agency for Healthcare Research and Quality has released a new evidence report on Parkinson's disease. "Diagnosis and Treatment of Parkinson's Disease: A Systematic Review of the Literature" is available online at http://www.ahrq.gov/clinic/epcsums/parksum.htm.

The mainstay of pharmacologic treatment for Parkinson's disease is levodopa. Its use, however, is limited by the development of motor fluctuations and drug-induced dyskinesias. Dopamine agonists (DAs) also are used, either alone or in combination with levodopa. DAs act directly on dopamine receptors, mimicking endogenous dopamine. Monoamine oxidase B (MAO-B) inhibitors act by inhibiting dopamine catabolism, increasing dopamine levels in the basal ganglia. Catechol O-methyltransferase (COMT) inhibitors act by inhibiting catabolism of dopamine, thereby extending levodopa's peripheral half-life. Despite the large selection of medications available to treat Parkinson's disease, all patients with Parkinson's disease ultimately require levodopa.

In patients with early Parkinson's disease, the goal of treatment is to alleviate symptoms and maintain independent function. In advanced Parkinson's disease, the focus is aimed toward maximizing "on" time (time when medication is effective), minimizing "off" time (time when medication is not effective), and treating medication-related complications, such as dyskinesias, motor fluctuations, and psychiatric problems.

A comprehensive review of the literature found the following associations in pharmacologic treatment:

* Meta-analysis suggests that in early Parkinson's disease, treatment with DAs plus levodopa may control the symptoms of Parkinson's disease better than treatment with levodopa alone, but this was not a consistent finding.

* In studies in which patients were randomized to levodopa versus levodopa plus DAs, the combination of levodopa plus DAs resulted in better scores on the Unified Parkinson's Disease Rating Scale (UPDRS) than levodopa alone. This was true in both short-and long-term (longer than one year) studies.

* In studies where patients were randomized to levodopa versus DAs, where additional levodopa was discretionary, levodopa alone resulted in better UPDRS sores than DAs (with or without additional levodopa).

* Meta-analysis did not suggest that treatment with selegiline plus levodopa controlled symptoms better than treatment with levodopa alone.

* Meta-analysis showed that in patients with advanced disease, treatment with COMT inhibitors combined with levodopa provided significantly greater symptom control than levodopa alone and was associated with lower levodopa doses. However, long-term (more than seven years) results are lacking, and hepatotoxicity is a rare but potentially lethal side effect that has been associated with tolcapone.

The researchers note that their results should be viewed with caution, because they are based on the small number of randomized control trials that met the inclusion criteria for the systematic review. Due to the small number of studies within each meta-analsysis, these findings are sensitive to possible publication bias in the literature (failure to publish "negative" studies).

COPYRIGHT 2003 American Academy of Family Physicians
COPYRIGHT 2003 Gale Group