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Early introduction of dopamine agonists in the long-term treatment of Parkinson's disease

From the Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Okayama, Japan.

Address correspondence and reprint requests to Dr. Norio Ogawa, Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, 2-5-1 Shikatacho, Okayama 700-8558, Japan.

Abstract.

Recent efforts in treatment of Parkinson's disease (PD) have focused on the development of agents or strategies that suppress or delay disease progression and levodopa-induced adverse reactions. In the past decade, many reports have demonstrated advantages of the early introduction of a dopamine(DA) agonist or early combination therapy with a DA agonist and levodopa. In the search for available clinical information, most long-term studies of early treatment with a DA agonist have used bromocriptine. Although DA agonist monotherapy is effective for a majority of patients for a year or less, only a small proportion of patients (10%) obtain benefits for as long as 4-5 years. Those patients on long-term monotherapy with a DA agonist exhibited a few or no adverse reactions, such as the wearing-off phenomenon or dyskinesia. DA agonist monotherapy may avoid unnecessary levodopa administration to the special subpopulation of PD patients who have very slowly progressing disease and who can be maintained for the long-term on DA agonist monotherapy. In contrast to the high incidence of adverse reactions in patients receiving high-dose levodopa monotherapy, many trials have demonstrated that early combination therapy for PD using partial substitution of levodopa by bromocriptine can inhibit the development of motor fluctuations and/or dyskinesia. In these trials, good symptomatic effects with few adverse reactions were achieved by >25% substitution of levodopa by bromocriptine. In addition, in patients receiving bromocriptine plus levodopa therapy, disease progression appeared to be slowed for a few years. Although the mechanism by which the action of DA agonists combined with levodopa remains to be clarified, the lower incidence of levodopa-related adverse reactions in patients receiving early combination therapy suggests that continued use of a DA agonist is beneficial for patients with PD. In summary, because levodopa-induced adverse reactions can be reduced by combined use of a DA agonist with low-dose levodopa, introduction of a DA agonist at an early stage of PD, or with restricted use of additional levodopa, may be useful for long-term treatment of PD.