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The dopamine agonist cabergoline has been most widely studied as an adjuvant to levodopa/carbidopa therapy in patients with advanced Parkinson’s disease experiencing response fluctuations (‘wearing-off’ and ‘on-off’ phenomena) to long term levodopa therapy. Significant improvements in Unified Parkinson’s Disease Rating Scale (UPDRS) scores for motor function and activities of daily living were observed with cabergoline in a placebo-controlled study in this patient group. In addition, cabergoline significantly reduced ‘off’ time compared with placebo after 12 and 24 weeks’ therapy. The requirement for levodopa to control symptoms of Parkinson’s disease is reduced in patients given adjuvant cabergoline; however, the duration of this effect remains unclear. To date, adjuvant cabergoline has been shown to control the symptoms of advanced Parkinson’s disease for periods of up to 3 years in noncomparative studies.
Data indicate that cabergoline is at least as effective as bromocriptine in this patient group. Limited data indicate that it is more effective than pergolide in controlling certain disabilities associated with long term levodopa therapy (specifically nocturnal disabilities and motor function during the ‘off’ period).
In patients with early Parkinson’s disease, de novo therapy with cabergoline was associated with a significantly lower risk of developing motor complications after 5 years than de novo levodopa/carbidopa therapy in a single trial. The incidence of motor complications (≥1) in patients randomised to receive cabergoline (± levodopa/carbidopa as required) was 22.3 versus 33.7% in patients given only levodopa/carbidopa (p < 0.05). After 5 years, 64% of cabergoline recipients required additional levodopa/carbidopa; however, the dosage was significantly lower than that given to patients receiving only levodopa/carbidopa. UPDRS motor function scores were better in the levodopa/carbidopa group.
The tolerability profile of cabergoline appears typical of a dopamine agonist. CNS disturbances (including visual hallucinations, confusion, dizziness/light-headedness, increased libido, increased dyskinesias, insomnia and somnolence) and gastric upset are the most common events, but are rarely severe. Clinical trials indicate that the tolerability of cabergoline is similar to that of bromocriptine, but may be better than pergolide.
Conclusions: Cabergoline is useful for controlling symptoms in patients with advanced Parkinson’s disease experiencing response fluctuations to long term levodopa therapy. Importantly, it appears to be valuable as de novo therapy in patients with early disease in terms of reducing the risk of motor complications. Its long elimination half-life (63 to 68 hours) and long duration of action, which allow once daily administration, may prove advantageous in terms of attaining maximal symptom control.
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