EARLY COMBINATION OF BROMOCRIPTINE AND LEVODOPA IN PARKINSONS-DISEASE- A PROSPECTIVE RANDOMIZED STUDY OF 2 PARALLEL GROUPS OVER A TOTAL FOLLOW-UP PERIOD OF 44 MONTHS INCLUDING AN INITIAL 8-MONTH DOUBLE-BLIND STAGE

To determine if the combination of levodopa (LD) plus bromocriptine (B r) in the early stages of Parkinson's disease (PD) permits reduction o f LD dosage and consequently results in fewer motor fluctuations and d yskinesias, a double-blind, multicenter prospective study in 50 PD pat ients who had responded favorably to LD while under treatment with tha t drug for less than or equal to 6 months was undertaken. Patients wer e randomized into two parallel groups (LD alone and LD plus Pr). Durin g the first placebo-controlled stage of the study lasting 8 months, as sociation of a fixed dose of Br (15 mg/day) in the LD regimen did not allow a significant reduction in the daily LD dose. Still, in patients on combined LD plus Pr, there was a tendency toward smaller daily req uirements of LD as compared with those on LD alone, and the difference in LD dose between the two groups was significantly different (515.4 +/- 240 vs. 725.6 +/- 230 mg/day; p < 0.01) after 44 months of continu ous treatment in the 40 patients still enrolled in the open-label stag e. At that point in time, the mean dose of Br had been increased by 9. 2 mg in the combined treatment group, and the mean dose of LD was 40.7 % lower than in the group receiving LD alone. On subsequent evaluation s, the number of patients with dyskinesias or describing wearing-off f luctuations severe enough to require changes in treatment was lower th an in the group under combined therapy, the differences being signific ant after 20 and 44 months, respectively (36.8 vs. 9.5 and 47.3 vs. 14 .2%). Our results support early combined LD-Br therapy in PD, but no c onclusions can be drawn as to whether this dopamine agonist exerts a p reventive effect on the late side effects of LD or has another mechani sm of action.