Rasagiline is used as initial monotherapy or as adjunctive therapy to levodopa for the symptomatic treatment of idiopathic parkinsonian syndrome.
Efficacy of rasagiline as initial monotherapy in the management of parkinsonian syndrome has been established in a randomized, double-blind, placebo-controlled study of up to 26 weeks' duration in patients with early disease who were not receiving dopaminergic antiparkinsonian agents or had not received any antiparkinsonian drug therapy. In this study, 404 patients were randomized to receive rasagiline (1 or 2 mg once daily) or placebo; patients were not permitted to use levodopa, dopamine agonists, selegiline, or amantadine but could receive stable dosages of an anticholinergic agent as needed. The primary efficacy measurement was the change from baseline in the total score (i.e., combined scores from part I [mentation], part II [activities of daily living], and part III [motor function]) of the Unified Parkinson's Disease Rating Scale (UPDRS); a reduction in the total score represented an improvement in mentation, activities of daily living, and/or motor function. Treatment with rasagiline was associated with substantially smaller increases in the UPDRS score (i.e., less functional decline) compared with treatment with placebo; efficacy of rasagiline dosages of 1 or 2 mg daily was comparable.
Efficacy of rasagiline as an adjunct to levodopa in the management of parkinsonian syndrome has been established in 2 multicenter, randomized, double-blind, placebo-controlled studies in patients with more advanced disease who were receiving long-term levodopa therapy (mean duration: 8 years; range: 5 months-32 years) in combination with a decarboxylase inhibitor and were experiencing motor fluctuations (e.g., end-of-dose '' wearing off'', sudden or random ''off'' phenomena). In the first study, 472 patients were randomized to receive rasagiline (0.5 or 1 mg daily) or placebo for 26 weeks; in the second study, 687 patients were randomized to receive rasagiline (1 mg daily), entacapone (200 mg with every levodopa dose), or placebo for 18 weeks. Patients in both studies continued receiving levodopa (average dosage: 700-800 mg daily) and were permitted to receive stable dosages of other antiparkinsonian agents; dopamine agonists were used in approximately 65% of patients in both studies, and entacapone was used in 35% of patients in the first study. The primary efficacy measurement was the change from baseline in the mean number of total daily hours spent in the ''off'' state (period of poor functioning and mobility), as measured by 24-hour home diaries. In these studies, therapy with rasagiline (1 mg daily) or entacapone was more effective than placebo in decreasing total daily ''off'' time; therapy with a lower dosage of rasagiline (0.5 mg daily) also resulted in decreased ''off'' time, but to a lesser extent. Duration of ''off'' time was reduced by a mean of 1.2-1.9, 1.4, 1.2, or 0.4-0.9 hours in patients receiving rasagiline 1 mg, rasagiline 0.5 mg, entacapone, or placebo, respectively. In addition, compared with placebo, treatment with rasagiline or entacapone was associated with substantial improvements in the UPDRS activities of daily living (ADL) score during the ''off'' period and the UPDRS motor function score during the ''on'' period. During the first 6 weeks of therapy, reduction in levodopa dosage was permitted if adverse dopaminergic effects (e.g., dyskinesia, hallucinations) occurred or worsened. In these studies, levodopa dosage was reduced in 9-17 or 6-8% of patients receiving rasagiline or placebo, respectively; levodopa dosage was reduced on average by about 9-13% in patients receiving rasagiline or about 7-13% in those receiving placebo.