title: Development of dyskinesias in a 5-year trial of ropinirole and L-dopa.
abstract: A 5-year trial of ropinirole and levodopa in early Parkinson's disease showed that ropinirole is associated with reduced incidence of dyskinesias. This post hoc analysis investigated whether the dyskinesia-sparing benefit of ropinirole is lost when levodopa is added to the regimen and evaluated other risk factors for developing dyskinesias. Patients receiving levodopa had a significantly higher risk of dyskinesias than those taking ropinirole monotherapy (hazard ratio [HR], 6.67; 95% confidence interval [CI], 3.23-14.29; P < 0.001). When patients randomized to ropinirole were treated with supplementary levodopa, the development of dyskinesias was not significantly different from that in those receiving levodopa from the start (HR, 0.80; 95% CI, 0.48-1.33; P = 0.39). However, the onset of dyskinesias was delayed by around 3 years compared with levodopa monotherapy. Adjusted analyses taking into account baseline and on-treatment factors that influenced use of supplementary levodopa or the development of dyskinesias produced similar results. In conclusion, the risk of developing dyskinesias during maintained initial ropinirole monotherapy is very low. Only once levodopa is added does the risk substantially change. Early use of ropinirole postpones the onset of dyskinesias, but these benefits decline when levodopa therapy is started, with no evidence of a subsequent rapid "catch-up" or a persisting preventive effect.
authors.affiliation: Clinical Investigation Centre, Department of Pharmacology and INSERM U455, Toulouse Hospital, Toulouse, France. rascol@cict.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Amos D
authors.initials: AD
authors.lastname: Korczyn
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.forename: Carl E
authors.initials: CE
authors.lastname: Clarke
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Mona
authors.initials: M
authors.lastname: Abdalla
mesh_terms: D000978:Antiparkinson Agents / Q000009:adverse effects*; D016001:Confidence Intervals; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000401:mortality; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D007980:Levodopa / Q000009:adverse effects*; D008137:Longitudinal Studies; D010300:Parkinson Disease / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D000978:Antiparkinson Agents; D007211:Indoles; C046649:ropinirole; D007980:Levodopa