Table 2.

Clinical trials and retrospective studies evaluating the effect of selegiline combinational therapy in PD

Design, number of patients (study name)	Studied daily dose	Key findings	References
Double-blind RCT, 112 patients	7.5 mg selegiline vs. placebo in combination with levodopa	More improvement after 8 weeks in the selegiline group	Takahashi et al. (1994)
Retrospective, 82 patients	10 mg selegiline in combination with levodopa vs. levodopa alone	No difference in motor scores after 1–5 years Lower levodopa dose needed after 1–3 years in the selegiline group, no difference after 4–5 years	Brannan and Yahr (1995)
Double-blind RCT, 101 patients	10 mg selegiline vs. placebo in combination with levodopa and/or bromocriptine	Less disease deterioration after 1 year in the selegiline group. Benefit was maintained after 2-month washout	Olanow et al. (1995)
Double-blind continuation of Myllyla’s study, 44 patients	10 mg selegiline vs. placebo in combination to levodopa	Lower levodopa dose needed even after 5 years in the selegiline group	Myllyla et al. (1997)
Double-blind RCT, 163 patients	10 mg selegiline vs. placebo in combination with levodopa	Less disease deterioration after 5 years in the selegiline group. Benefit was maintained after 1-month washout	Larsen et al. (1999)
Double-blind RCT, 160 patients	10 mg selegiline vs. placebo in combination with levodopa	About twice longer time to need for 50% increase in levodopa dose in the selegiline group	Przuntek et al. (1999)
Double-blind continuation of DATATOP, 368 patients	10 mg selegiline vs. placebo in combination with levodopa	Less wearing-off, freezing of gait and on–off fluctuation and more dyskinesia in the selegiline group	Shoulson et al. (2002)
Double-blind continuation of Palhagen’s study, 140 patients	10 mg selegiline vs. placebo in combination with levodopa	Improved motor scores with 19% lower levodopa dose after 5 years in the selegiline group	Palhagen et al. (2006)
Retrospective and open label, 691 patients	10 mg selegiline in combination with levodopa started within 5 years of disease onset vs. levodopa alone. 4-month open label selegiline treatment initiated in the levodopa alone group	Improved motor scores after 10 years in the selegiline group. Motor scores were improved after 4-month selegiline addition, the late started selegiline was less effective than the early started one	Mizuno et al. (2010)
Retrospective, 687 patients	Effect on disease progression of various pharmacotherapies with or without selegiline was evaluated	At least 3 years selegiline treatment of early PD patients increased the time to progression (Hoehn–Yahr stage transition)	Zhao et al. (2011)