COMT inhibitors may boost levodopa/carbidopa’s effects
A randomized double-blinded trial followed 423 patients for 39 weeks to compare the combination of the catechol-O-methyltransferase (COMT) inhibitor entacapone and levodopa/carbidopa (LCE) with levodopa/carbidopa alone (LC).6 The researchers found statistically significant improvements with LCE in UPDRS scores for activities of daily living (mean change from baseline=3.0 for LCE vs 2.3 for LC on a 52-point scale; P=.025) but not mentation or motor symptoms.
Dyskinesia and wearing-off symptoms (motor fluctuations) didn’t differ significantly between the 2 groups. LCE was associated with a higher incidence of adverse effects than LC, and involved mostly nausea (26.6% vs 13.5%) and diarrhea (8.7% vs 2.8%).
Anticholinergics may help, but cause adverse mental effects
Another Cochrane review compared anticholinergic agents with placebo or no treatment in 9 studies that included 221 patients.7 Meta-analysis wasn’t possible because of heterogeneity in patient populations, outcomes, and measurements and incomplete reporting. Compared with placebo, anticholinergic agents may improve Parkinson’s-related motor symptoms but have significant mental adverse effects, including confusion, memory problems, restlessness, and hallucinations.
Recommendations
The most recent guidelines (2002) from the American Academy of Neurology recommend levodopa and dopamine agonists as first-line therapies.8 Levodopa is more effective at improving the motor symptoms of Parkinson’s disease but is associated with a higher risk of dyskinesia than dopamine agonists. No compelling evidence suggests a difference in efficacy between long- and short-acting levodopa.