Management of Levodopa Failures

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.