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

L-DOPA, administered in conjunction with a peripheral decarboxylase inhibit or, remains the standard treatment for Parkinson's disease, though there is strong evidence that it eventually leads to dyskinesias and diurnal fluctu ations in performance, 'wearing-off' and 'on-ofF' phenomena. The initial cl inical benefits associated with dopamine agonists based upon ergot structur es 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 hallu cinations. Pramipexole is a non-ergot dopamine D2 subfamily receptor agonis t, with preferential effects upon D-3 receptors. It has been shown, in a ra nge of double-blind, placebo-controlled trials, to be effective by itself i n treating early Parkinsons's disease, and, combined with L-DOPA, in treati ng advanced Parkinson's disease. The maintenance dose of pramipexole is ach ieved by a process of gradual upwards titration over a period of days or we eks, after which clinical benefits have been reported, as assessed using se veral objective tests, in the severity of parkinsonian symptoms. In particu lar, pramipexole increases the proportion of 'on' time experienced during w aking hours, and improvements are also experienced in motor activities and activities of daily living. It also appears that pramipexole is effective i n reducing the extent of tremor, particularly rest tremor, which accompanie s Parkinson's disease. Evidence is accumulating, based on long-term extensi on studies, that the efficacy of pramipexole continues to be manifest in th e 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 th is, in its turn, may entail further benefits in the latency to onset of var ious L-DOPA-associated adverse events, such as 'wearing-off' and 'on-off' p henomena. It is concluded that pramipexole is an effective therapeutic agen t which can be used alone or added to L-DOPA therapy in cases of advanced P arkinson'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 parkins onian patients are comparable to estimates for therapeutic interventions fo r a range of other conditions, and total cost-effectiveness estimates furth er strengthen the case for the use of pramipexole.