Faculty Bibliography

Ciladopa is a partial dopamine agonist that is effective in patients with advanced Parkinson's disease who are no longer satisfactorily responding to levodopa. Thirty-one patients participated in a double-blind randomized study of ciladopa (added to levodopa) versus placebo. Among 21 patients randomized to treatment with ciladopa and levodopa, there was a 32% decrease in symptoms on the Modified Columbia University Disability Scale. This change was significant, p less than or equal to 0.05. Eight of the 21 patients (38%) improved by at least 50%. The mean number of hours 'on' increased by 20%. This change was significant, p less than or equal to 0.05. Five of the 21 patients (24%) were on for at least 4 hours more than at baseline. Dyskinesias were not increased. The mean dose of ciladopa was 19.5 mg/d. The mean dose of levodopa in Sinemet was decreased by 10%. Studies with ciladopa in humans had to be discontinued because of the occurrence of microscopic testicular tumors in some rodents. Although improvement in patients taking ciladopa was modest, there were few adverse effects. These results are encouraging, because two other partial agonists are now available, and they may be as effective as ciladopa

Brain metastasis from ovarian carcinoma is a relatively rare phenomenon. At NYU Medical Center five patients were treated for this entity from 1982 to 1985. The stage at presentation ranged from stage I to stage III, and all patients had received or were receiving chemotherapy. Two patients had active disease elsewhere at diagnosis of brain metastasis, but three patients were otherwise NED. Three patients had solitary cerebellar disease, and two patients had multiple lesions. All patients were treated with whole brain radiotherapy to 3,000 cGy, with neurological improvement in three of the five patients. The central nervous system may need special consideration for prophylactic treatment in those patients with ovarian cancer who receive adjuvant chemotherapy

The activity of pergolide, a clavine ergolene, and mesulergine, an 8-alpha amino ergoline, were compared in 18 patients with advanced Parkinson's disease. All of the patients were no longer satisfactorily responding to levodopa, and 16 patients had diurnal oscillations in performance. Pergolide, mean dose 2.7 mg, when added to levodopa resulted in a significant (27%) decrease in Parkinson disability and a significant improvement in diurnal oscillations in performance (136% increase in hours 'on'). Twelve of the 18 patients (67%) improved. However, after 2 years pergolide was discontinued in all of the patients because of decreased efficacy, adverse effects, or both. At this time, mesulergine, mean dose 9.3 mg., when added to levodopa resulted in a significant (37%) decrease in Parkinson disability and a significant improvement in diurnal oscillations (61% increase in hours 'on'). Twelve of the 18 patients (67%) improved. Adverse effects (dyskinesias) were less with mesulergine than with pergolide. A declining response to one agonist does not preclude a successful response to another agonist of a different class

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

Experience with bromocriptine in 106 patients treated over nine years was reviewed. Most of the patients were already being treated with levodopa (combined with a peripheral decarboxylase inhibitor). These patients, after having initially achieved a good response to levodopa, were no longer responding satisfactorily. Most of the patients were also experiencing diurnal oscillations in performance: 'wearing off' and 'on-off' phenomena. In these patients previous attempts at changing the dose (increasing or decreasing) or changing the scheduling of levodopa had been unsuccessful. Bromocriptine was added to levodopa beginning at a dose of 5 mg/day, and each week was increased by another 5 mg/day. At a dose of bromocriptine of at least 25 mg/day, there was a decrease in disability in the majority of patients with a decrease in the severity of the diurnal oscillations in performance (especially 'wearing off' phenomena). In most patients, the addition of bromocriptine resulted in an approximately 10% reduction in the dose of levodopa. The majority of patients sustained their improvement at least one year. In some patients improvement was sustained for up to five years. The therapeutic efficacy of bromocriptine was limited in many patients by the occurrence of adverse effects including mental changes, dyskinesias, orthostatic hypotension, and nausea. These adverse effects could often be minimized by reducing the dose of bromocriptine or levodopa. All adverse effects were reversible upon stopping the drug. We have found bromocriptine to be a valuable adjunct in the treatment of these patients