Early combination therapy (bromocriptine and levodopa) does not prevent motor fluctuations in Parkinson's disease

Early combination therapy with bromocriptine (Br) and levodopa (LD) is believed to delay or prevent the onset of late treatment complications typically associated with LD monotherapy in Parkinson's disease (PD). Studies recommending this regimen have been uncontrolled. We evaluated this possibility in a 4-year, double-blind, randomized, parallel group trial comparing Br and LD both alone and in combination in 22 PD patients never before treated with dopaminergic medications. In the group receiving Br monotherapy, 17% had motor fluctuations (end-of-dose failure or on-off), 17% chorea, 33% dystonia, and 83% freezing. In the LD group, 33% had motor fluctuations, 56% chorea, 100% dystonia, and 22% freezing. In the combination group, 71% had motor fluctuations, 57% chorea, 71% dystonia, and 57% freezing. The frequency of dystonia was significantly lower with Br monotherapy than in the other two treatment groups. No other significant differences were observed. LD monotherapy appeared to have superior efficacy in the treatment of PD. Mean final doses of LD and Br were similar for the different treatment groups. Early combination therapy does not prevent or delay the onset of motor fluctuations or dyskinesia in PD.