SELEDO: a 5-year long-term trial on the effect of selegiline in early parkinsonian patients treated with levodopa

The SELEDO (from selegiline plus levodopa) study was carried out as a rando mized, 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's disease. One-hundred-and -sixteen patients were randomized either to selegiline or placebo. Before s tarting the study medication, the levodopa dose was titrated to the individ ual requirements of each patient. The primary study end point (time when le vodopa had to be increased by greater than or equal to 50% of the titrated dose) was reached in 23 of 59 patients in the selegiline group and 26 of 48 patients in the placebo group. At the end of the 5 years' treatment period the rates derived from a Life-table analysis were 50.4% in the selegiline group and 74.1% in the placebo group (P = 0.027, log-rank test). The median time to reach the primary end point was 4.9 years in the selegiline group and 2.6 years in the placebo group. In patients treated with selegiline, th e mean levodopa dose changed only slightly over the 5 years of treatment co mpared to the initially titrated dose, but rose markedly in the placebo gro up, where the dose of levodopa had to be adjusted earlier than in the seleg iline group. At the same time, the lower levodopa dosage in the selegiline group was accompanied by at least equal therapeutic efficacy (which is nece ssary for an unambiguous interpretation). Subgroup analyses showed greater benefit for selegiline treated) patients in the earlier stages. Long-term s ide effects appeared later in the selegiline group, although the difference was not significant. The early combination of selegiline and levodopa prov ed to be clearly superior to levodopa monotherapy. Eur J Neurol 6:141-150 ( C) 1999 Lippincott Williams & Wilkins.