Robert A Hauser1, Theresa A Zesiewicz. 1. Department of Neurology, Parkinson's Disease and Movement Disorders Center, University of South Florida and Tampa General Healthcare, Tampa, Florida 33606, USA. rhauser@hsc.usf.edu
Abstract
BACKGROUND: Levodopa, in combination with a dopa decarboxylase inhibitor, provides the greatest symptomatic benefit with the fewest short-term side effects in the treatment of Parkinson disease (PD). However, the disease continues to progress, and the long-term use of levodopa is associated with the development of motor fluctuations and dyskinesias. REVIEW SUMMARY: Alternatives to the use of levodopa in early PD include monoamine oxidase B (MAO-B) inhibitors, dopamine agonists, and amantadine. Although no medication has been proven to slow the progression of Parkinson disease, preclinical studies have demonstrated neuroprotective effects of MAO-B inhibitors, and a recent study of rasagiline found that PD patients treated with rasagiline for 12 months experienced less progression of symptoms than patients treated with placebo for 6 months followed by rasagiline for 6 months. Several clinical trials have demonstrated that the initial use of a dopamine agonist to which levodopa can be added is associated with fewer motor complications than treatment with levodopa alone. In addition, preclinical studies suggest that adjunctive use of the catechol-O-methyltransferase (COMT) inhibitor entacapone when levodopa is first introduced may be associated with fewer motor complications than treatment with levodopa alone. CONCLUSION: Treatment of early PD with an MAO-B inhibitor, dopamine agonist, or amantadine, may provide useful alternatives to treatment with levodopa. Adding entacapone at the initiation of levodopa therapy may reduce the development of motor complications. Long-term studies are required to evaluate the potential long-term benefits of these treatment strategies.
BACKGROUND:Levodopa, in combination with a dopa decarboxylase inhibitor, provides the greatest symptomatic benefit with the fewest short-term side effects in the treatment of Parkinson disease (PD). However, the disease continues to progress, and the long-term use of levodopa is associated with the development of motor fluctuations and dyskinesias. REVIEW SUMMARY: Alternatives to the use of levodopa in early PD include monoamine oxidase B (MAO-B) inhibitors, dopamine agonists, and amantadine. Although no medication has been proven to slow the progression of Parkinson disease, preclinical studies have demonstrated neuroprotective effects of MAO-B inhibitors, and a recent study of rasagiline found that PDpatients treated with rasagiline for 12 months experienced less progression of symptoms than patients treated with placebo for 6 months followed by rasagiline for 6 months. Several clinical trials have demonstrated that the initial use of a dopamine agonist to which levodopa can be added is associated with fewer motor complications than treatment with levodopa alone. In addition, preclinical studies suggest that adjunctive use of the catechol-O-methyltransferase (COMT) inhibitor entacapone when levodopa is first introduced may be associated with fewer motor complications than treatment with levodopa alone. CONCLUSION: Treatment of early PD with an MAO-B inhibitor, dopamine agonist, or amantadine, may provide useful alternatives to treatment with levodopa. Adding entacapone at the initiation of levodopa therapy may reduce the development of motor complications. Long-term studies are required to evaluate the potential long-term benefits of these treatment strategies.