In the past decade,
dopamine agonists have emerged as important treatment options for patients with
Parkinson's disease. Originally,
dopamine agonists were used only in patients with advanced disease in whom the response to
levodopa had decreased (
levodopa failures). The decreased response to
levodopa, usually associated with diurnal oscillations in performance and the 'wearing-off' and 'on-off' phenomena, is secondary to
disease progression with continued degeneration of the nigrostriatal neurons. In addition, chronic
levodopa treatment itself may contribute to the decreased
drug response and the diurnal oscillations in performance.
Dopamine receptor agonists bypass the degenerating nigrostriatal neurons and directly stimulate the striatal
dopamine receptors.
Dopamine receptor agonists also permit a reduction in the dose of
levodopa. Five
ergoline dopamine agonists--
bromocriptine,
lergotrile,
pergolide,
lisuride,
mesulergine, and the nonergoline agonist,
ciladopa--have undergone clinical trials in
Parkinson's disease. In 10 years, we treated a total of 278 patients with advanced
Parkinson's disease, a declining response to
levodopa, and diurnal oscillations in performance with five
ergoline dopamine agonists (in addition to
levodopa). The mean
duration of treatment was one year (with a range of 1-60 months). Improvement was noted in 140 (50%) of our patients. Adverse effects necessitating discontinuation of the agonist occurred in 131 patients (46%). We compared our results with those of others who, unlike us, began treatment with a
dopamine agonist earlier, using the agonist alone or adding it to
levodopa before the response to
levodopa had decreased. Many of the patients so treated had mild or moderate
Parkinson's disease. A total of 1,599 patients were treated with
ergoline dopamine agonists. Of these patients, 976 (61%) improved, while 407 (25%) experienced adverse effects. We believe that a greater number of these patients improved and fewer experienced adverse effects, in comparison to our patients, because the patients had less advanced disease.