Rasagiline

Placebo-controlled studies

Rasagiline is associated with improved outcomes in patients with early Parkinson's disease and reduces “off” time in patients with moderate to advanced disease with motor fluctuations. In a multicenter, double-blind, randomized, placebo-controlled, parallel-group study for 12 weeks in 70 patients with Parkinson's disease, rasagiline 0.5, 1, and 2 mg/day as adjunctive therapy to levodopa produced a beneficial clinical effect in patients with motor fluctuations; the beneficial effect was still evident 6 weeks after drug withdrawal [ ].

In a multicenter, 26-week, parallel-group, randomized, double-blind, placebo-controlled clinical trial in 404 patients with early Parkinson's disease who did not require dopaminergic therapy rasagiline mesylate 1 or 2 mg/day was compared with placebo [ ]. Rasagiline was effective and there were no differences in the frequencies of adverse events or premature withdrawals.

In a double-blind, parallel-group, randomized, clinical trial in 371 subjects with early Parkinson's disease, who did not require dopaminergic therapy, rasagiline 1 or 2 mg/day for 1 year was compared with placebo for 6 months followed by rasagiline 2 mg/day for 6 months [ ]. Those who took rasagiline 2 mg/day for 1 year had a 2.29-unit smaller increase in mean adjusted total Unified Parkinson's Disease Rating Scale score than subjects who took placebo for 6 months followed by rasagiline for 6 months. The authors concluded that treatment with rasagiline for 12 months was preferable to delaying treatment for 6 months.

In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study in 472 patients with Parkinson disease with at least 2.5 hours of daily “off” time (poor motor function), despite optimized treatment with other medications, rasagiline 0.5 or 1.0 mg/day was compared with placebo [ ]. The mean adjusted total daily off time fell by 1.85 hours with rasagiline 1.0 mg/day, by 1.41 hours with 0.5 mg/day, and 0.91 hours with placebo.

In an 18-week, double-blind, multicenter study in 687 out-patients randomly assigned to oral rasagiline 1 mg/day (n = 231), entacapone 200 mg with every dose of levodopa (n = 227), or placebo (n = 229), both rasagiline and entacapone reduced mean daily off-time (by 1.18 hours rasagiline and 1.2 hours entacapone, placebo 0.4 hours) and increased daily on-time without troublesome dyskinesias (0.85 hours for both, placebo 0.03 hours) [ ]. The frequency of adverse events was similar with all treatments ( Table 1 ) and 88 did not complete the study (23 rasagiline, 30 entacapone, 35 placebo), mainly because of withdrawal of consent (n = 34) and adverse events (n = 34). The frequency of dopaminergic adverse events with rasagiline was similar to those with placebo and entacapone. The most common cardiovascular-related dopaminergic adverse event in the study, postural hypotension, occurred in nine patients in the rasagiline and entacapone groups. There were serious adverse events in 41 patients (12 rasagiline, 12 entacapone, and 17 placebo).

Systematic reviews

In a systematic review of adverse reactions to rasagiline, the most frequently reported adverse events during monotherapy were headache, dizziness, and insomnia; depression, dizziness, somnolence, and other sleep disorders were reported during combination therapy [ ].