Clinical Experience with Cabergoline in Patients with Advanced Parkinson’s Disease Treated with Levodopa
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The clinical efficacy of the long-acting dopamine agonist cabergoline as an adjunct to levodopa has been investigated in controlled and uncontrolled studies in >1500 patients with advanced Parkinson’s disease and motor complications. Four of these studies (including 2 comparisons with placebo and 2 with bromo-criptine), which used similar methodology (including study design, blindness, selection criteria, treatment modalities and duration) and measurements of efficacy and safety, are reviewed.
Compared with placebo, cabergoline 2 to 10 mg/day (median 5 mg/day) induced a significantly higher percentage decrease in the number of ‘off’ hours (18 vs 45%) in a preliminary phase II study that included 37 patients with severe motor fluctuations. This was not associated with an increase in dyskinesia in either treatment group. In a subsequent phase III placebo-controlled study (n = 188 patients with motor fluctuations), treatment with cabergoline 0.5 to 5 mg/day (median 3.5 mg/day) achieved a statistically significant decrease in levodopa dosage compared with placebo (18 vs 3%) and improved the Unified Parkinson’s Disease Rating Scale scores for activities of daily living in a greater number of patients (23 vs 4%).
Comparisons of cabergoline with bromocriptine have been conducted in 750 patients stabilised on levodopa therapy; one study was conducted in patients without, and the other in patients with, previous exposure to dopamine agonists. Cabergoline was administered once daily at doses ranging from 0.5 to 6mg, and bromocriptine was given at a dosage of 5 to 40 mg/day divided into 3 administrations. A combined analysis of the response rates obtained in the 2 studies found cabergoline to be at least as effective and well tolerated as bromocriptine, with a trend in favour of cabergoline in terms of response rate and number of ‘off’ hours.
The majority of adverse events in this patient population were those associated with levodopa therapy, as shown by the high frequency of adverse events in the placebo group (68%). Both cabergoline and bromocriptine showed a comparable incidence of adverse events, with CNS and gastrointestinal events being the most common.
Thus, the potential advantages of cabergoline include improved patient compliance as a result of its once-daily administration, and an increased threshold for the development of dyskinesia as a result of the levodopa sparing effect of cabergoline.
KeywordsLevodopa Adis International Limited Bromocriptine Dopamine Agonist Cabergoline
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- 1.Destée A, Caraceni T, Chouza C, et al. Multicentre double-blind study of cabergoline vs bromocriptine in parkinsonian patients with motor complications. Mov Disord. In pressGoogle Scholar
- 4.Schneider E, Gershanik O, Dom R, et al. Efficacy and tolerability of cabergoline compared to bromocriptine in patients suffering from levodopa associated motor complications (on treatment with DA-Agents). Mov Disord 1996; 11 Suppl.: 269Google Scholar
- 5.Fahn S, Elton RL, Members of the UPDRS Development Committee. Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, et al., editors. Recent developments in Parkinson’s disease. Vol. 2. Florham Park, New Jersey: MacMillan Healthcare Information, 1987: 153–63Google Scholar
- 6.Di Salle E, Ornati G, Briatico G. FCE 21336, a new ergoline derivative witha potent and long-lasting lowering effect on prolactin secretion in rats. J Endocrinol Invest 1982; 5 Suppl. 1: 45Google Scholar
- 8.Strolin Benedetti M, Cocchiara G, Battaglia R, et al. Pharmacokinetic and metabolic pattern of cabergoline, a long-acting dopamine agonist in healthy volunteers. Presented at the 10th International Symposium on Parkinson’s Disease: 1991 Oct 19; TokyoGoogle Scholar