Evidence supporting the efficacy of selegiline was obtained in randomized, controlled clinical trials that compared the effects of added selegiline or placebo in patients receiving levodopa and carbidopa. Selegiline was significantly superior to placebo on all 3 principal outcome measures employed: (1) change from baseline in daily levodopa and carbidopa dose, (2) the amount of "off" time, and (3) patient self-rating of treatment success. Beneficial effects were also observed on other measures of treatment success (eg, measures of reduced end of dose akinesia, decreased tremor and sialorrhea, improved speech and dressing ability, and improved overall disability as assessed by walking and comparison to previous state). Some of the clinical trials are shown in Table 1.
Table 1. Clinical Trials of Selegiline
Study #1: DATATOP--patients randomized to receive selegiline, tocopherol, or placebo
Study #2: Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson disease
Study #3: Effect of adding selegiline to levodopa in early, mild Parkinson disease
Study #4: SELEDO--(selegiline plus levodopa) study: randomized, prospective, placebo-controlled, double-blind, multicenter long-term, 5-year trial to evaluate the possible advantages of combining selegiline and levodopa in the early treatment of Parkinson disease
Study #5: Supplementary information from the United Kingdom Parkinson Disease Research Group 1995 study
Study #6: A Norwegian-Danish 5-year randomized, placebo-controlled, double-blind, parallel group study on 163 patients to determine the effect of selegiline on the progression of Parkinson disease.
Randomized clinical studies have been performed using Zydis selegiline--a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption. It was well tolerated and, unlike conventional selegiline tablets, appeared to retain specificity for inhibition of monoamine oxidase type B because it did not potentiate the pressor response to tyramine (Clarke et al 2003).