Management of Parkinson's disease - Defining the role of entacapone

Parkinson's disease, a movement disorder caused by degeneration of nigrostriatal dopaminergic neurons in the substantia nigra, is characterized by resting tremor, rigidity, bradykinesia and postural instability. For over 30 years levodopa has been considered as the first-line treatment for this condition, but long-term treatment is complicated by the development of motor fluctuations and hyperkinesias. For patients with Parkinson's disease, entacapone reduces the peripheral metabolism of levodopa by inhibiting catechol-O-methyl transferase and, thus, prolonging the bioavailability of levodopa in the CNS. In patients with Parkinson's disease who have motor fluctuations, entacapone significantly increases the duration of "on" time, reduces that of "off" time and reduces mean daily intake of levodopa compared with placebo treatment. Data from the Unified Parkinson's Disease Rating Scale indicate that treatment with entacapone is associated with improved activities of daily living and motor disability scores. In clinical studies, entacapone is not associated with elevation of liver enzymes or changes in other clinical chemistry parameters. Gastrointestinal (such as nausea and diarrhea) or CNS (such as hallucinations and worsening of dyskinesias) adverse events with entacapone are of mild to moderate severity and usually subside with adjustment of the levodopa dosage. Pharmacoeconomic evaluations also suggest that entacapone is a viable treatment option in Parkinson's disease. Two Markov state transition studies suggest that the increased drug costs incurred when entacapone is added to a patients' treatment regimen would be at least partially offset by savings in other healthcare sectors such as inpatient care. Both studies predicted that treatment with entacapone would result in an increase in quality-adjusted life years. The clinical and economic data clearly support the use of entacapone in combination with levodopa in patients with Parkinson's disease. However, a levodopa-sparing strategy is favored by many clinicians in an attempt to offset the development of motor fluctuations in later years and thus dopamine agonists are often employed in monotherapy and in combination with lower dosages of levodopa. The use of COMT inhibitors should lead to an increase in the duration of clinical effect of each individual levodopa dose, a consequent reduction in the frequency of levodopa administration, and ultimately to a potential reduction in the development of motor fluctuations.