Immediate-release and controlled-release carbidopa/levodopa in PD - A 5-year randomized multicenter study

Objective: To compare effects of immediate-release (IR) and sustained-relea se (CR) carbidopa/levodopa in levodopa-naive PD patients. Background: It wa s hypothesized that the long-acting preparation would be associated with fe wer long-term complications. Methods: A total of 618 patients were studied in 36 centers worldwide in a blinded, randomized parallel study. Measures o f efficacy and adverse reactions were recorded at 3-month intervals for 5 y ears. Motor fluctuations and dyskinesias were evaluated by a patient diary and a physician-recorded questionnaire. The Nottingham Health Profile (NHP) was used to evaluate quality of life. Results: Approximately 60% of patien ts completed the trial. After 5 years, the mean dose of IR was 426 mg/day, and the bioavailable dose of CR was 510 mg/day (mean dose, 736 mg/day). Aft er 5 years, 20.6% of the IR group and 21.8% of the CR group had motor fluct uations or dyskinesia. Sixteen percent of both groups had changes in motor response by the questionnaire's definition. There was no significant differ ence between the two treatment groups. Disability scores and the motor scor e of the Unified Parkinson Disease Rating Scale (UPDRS) were highest at bas eline, improved with therapy, and thereafter worsened over time to reach ba seline scoring at the end of 5 years. The CR group was superior to IR for t he Activities of Daily Living subsection of the UPDRS for all 5 years and f or emotional reactivity and social isolation on the NHP; however, this may have resulted from higher doses of CR that were used. Conclusion: Despite t he progressive nature of PD, both the immediate-release and sustained-relea se carbidopa/levodopa formulations maintained a similar level of control in PD after 5 years compared with baseline. Additionally, the low incidence o f motor fluctuations or dyskinesia was not significantly different between the treatment groups and may be partly attributed to the relatively low dos es of levodopa used throughout the 5-year study.