Clinical trials
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By K K Jain MD

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

  • Results: Patients randomized to selegiline did better than those randomized to tocopherol or placebo.
  • Author: (Anonymous 1989)
  • Comments: None

Study #2: Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson disease

  • Results: Mortality in levodopa and selegiline treated patients was higher than those treated by levodopa alone.
  • Author: (Lees 1995)
  • Comments: This study had methodological flaws, and the findings are not accepted universally (Olanow et al 1996). The authors conceded that they have no evidence whether this apparent relationship between selegiline and mortality is a causal one and that this finding is not incompatible with neuroprotection (Lees 1996).

Study #3: Effect of adding selegiline to levodopa in early, mild Parkinson disease

  • Results: Indicated that prior treatment with levodopa did not lead to superior survival with regard to the end point of disability requiring levodopa. It was further concluded that treatment with selegiline or tocopherol did not reduce the occurrence of subsequent levodopa-associated adverse effects in the study’s Parkinson disease patients.
  • Author: (Anonymous 1989)
  • Comments: None

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

  • Results: The early combination of selegiline and levodopa proved to be clearly superior to levodopa alone.
  • Author: (Przuntek et al 1999)
  • Comments: None

Study #5: Supplementary information from the United Kingdom Parkinson Disease Research Group 1995 study

  • Results: The cause-specific mortality rates did not suggest a specific cause for the excess deaths. No significant mortality due to combined treatment with levodopa and selegiline.
  • Author: (Ben-Shlomo et al 1998)
  • Comments: The issue of increased mortality remains unsolved, but no evidence exists that is against use of combined selegiline and levodopa.

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.

  • Results: Patients treated with the combination of selegiline and levodopa developed markedly less severe parkinsonism than patients treated with levodopa and placebo.
  • Author: (Larsen et al 1999)
  • Comments: None

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).