The efficacy of pramipexole in the treatment of Parkinson's disease

L-DOPA, administered in conjunction with a peripheral decarboxylase inhibitor, remains the standard treatment for Parkinson's disease, though there is strong evidence that it eventually leads to dyskinesias and diurnal fluctuations in performance, 'wearing-off' and 'on-ofF' phenomena. The initial clinical benefits associated with dopamine agonists based upon ergot structures are not as great or as long-lasting as had been hoped, and their use in combination with L-DOPA has also been associated with dyskinesias and hallucinations. Pramipexole is a non-ergot dopamine D2 subfamily receptor agonist, with preferential effects upon D-3 receptors. It has been shown, in a range of double-blind, placebo-controlled trials, to be effective by itself in treating early Parkinsons's disease, and, combined with L-DOPA, in treating advanced Parkinson's disease. The maintenance dose of pramipexole is achieved by a process of gradual upwards titration over a period of days or weeks, after which clinical benefits have been reported, as assessed using several objective tests, in the severity of parkinsonian symptoms. In particular, pramipexole increases the proportion of 'on' time experienced during waking hours, and improvements are also experienced in motor activities and activities of daily living. It also appears that pramipexole is effective in reducing the extent of tremor, particularly rest tremor, which accompanies Parkinson's disease. Evidence is accumulating, based on long-term extension studies, that the efficacy of pramipexole continues to be manifest in the majority of patients for at least 3 years after treatment initiation. It has now been established that if pramipexole treatment is commenced before L-DOPA therapy, the need for the latter may be significantly delayed and this, in its turn, may entail further benefits in the latency to onset of various L-DOPA-associated adverse events, such as 'wearing-off' and 'on-off' phenomena. It is concluded that pramipexole is an effective therapeutic agent which can be used alone or added to L-DOPA therapy in cases of advanced Parkinson's disease, often permitting the dose of L-DOPA to be reduced, and that it may be appropriate to consider it as first-line treatment for early Parkinson's disease, before L-DOPA therapy is instituted. There appear to be pharmacoeconomic benefits associated with pramipexole treatment; direct cost-effectiveness estimates for treatment of early- and late-stage parkinsonian patients are comparable to estimates for therapeutic interventions for a range of other conditions, and total cost-effectiveness estimates further strengthen the case for the use of pramipexole.