Faculty Bibliography

Treatment with pergolide was compared with bromocriptine in 25 patients, all of whom were also receiving levodopa and in all of whom the response to levodopa had diminished. All 25 patients had 'on-off' phenomena. At the time bromocriptine was added to levodopa, the mean age of the patients was 61.8 years, mean duration of disease was 9.0 years, and mean duration of levodopa treatment was 6.1 years. For the group as a whole, disability as determined in the 'on' period decreased by 36%, from 28.7 to 18.5; and 11 patients improved at least one stage. Disability as determined in the 'off' period decreased by 25%, from 59.5 to 44.4. The number of hours in which patients were 'on' increased by 62%, from 7.1 to 11.5. All of these changes were significant (p less than or equal to 0.05). Bromocriptine had to be discontinued in nine patients (eight because of mental changes). In the remaining 16 patients, bromocriptine was eventually discontinued because of diminishing efficacy. Mean dose of bromocriptine was 50 mg (range, 10-100 mg), and mean duration of treatment was 23 months (range, 2-65 months). At the time of their treatment with pergolide, the patients were older, 65.5 years, had the disease longer, 12.7 years, and were more disabled. Nonetheless, for the group as a whole, disability score as determined in the 'on' period decreased significantly by 40%, from 43.5 to 26.3, and 14 patients improved at least one stage. Disability as determined in the 'off' period decreased significantly by 21%, from 69.0 to 54.8. The number of hours in which patients were 'on' increased significantly by 224%, from 3.4 to 11.0 hr. The mean dose of pergolide was 2.1 mg (range, 0.1-10.0 mg), and the mean duration of treatment was 6.2 months (range, 0.5-20 months). Pergolide was discontinued in eight patients: three because of asymptomatic tachyarrhythmias of unknown clinical significance (detected only by Holter monitoring); two because of orthostatic hypotension; and two because of mental changes. Although pergolide appears to be more potent than bromocriptine because of its greater effect in a larger number of patients at a more advanced stage of their disease, both drugs are useful, and both enhance our ability to manage patients with PD

The effect of pergolide, a semisynthetic ergot alkaloid, on the cardiovascular system of 40 patients with Parkinson's disease (PD) was evaluated. The mean daily dose of pergolide was 2.4 mg (range, 0.1 to 10 mg). The mean duration of follow-up was 6 months (range, 2 weeks to 20 months). The 40 patients were selected only on the basis of severe PD. All 13 patients in the first part of the study underwent 1 to 5 days of Holter monitoring before starting pergolide. Monitoring was then carried out for an additional period of between 2 and 10 weeks while the patients were on pergolide. Seven of the 13 patients manifested repetitive ventricular rhythms. These were isolated and unassociated with increases in premature ventricular contractions. The dose at which the RVRs occurred was a function of the presence or absence of heart disease. The changes occurred below 3 mg/day in patients with heart disease and above 3 mg/day in patients without heart disease. Pergolide was discontinued in three of the patients with heart disease. It was concluded that pergolide may, in the diseased heart, predispose to RVRs. In the second part of the study, Holter monitoring was carried out only at the discretion of the cardiologist, and five patients were so monitored. None of these patients was rejected from the study. Only one patient (with heart disease) of the 27 patients in the second part of the study experienced an arrhythmia. This consisted of an increase in PVCs on 4 mg/day of pergolide. Pergolide was discontinued. Eight of the 40 patients in these early dose-ranging studies experienced orthostasis, two with syncope, immediately on addition of pergolide (0.1 to 0.4 mg) to levodopa. The orthostasis could be eliminated in all but two patients by reducing or discontinuing levodopa

Pergolide was administered to 56 patients with advanced Parkinson disease who were no longer satisfactorily responding to levodopa. The group included 45 patients with on-off phenomena. Pergolide, when combined with levodopa, resulted in a 44% decrease in disability as assessed in the on period, a 15% decrease in disability as assessed in the off period, and a 148% increase in the number of hours in which patients were on (from 4.6 +/- 0.3 hours to 11.4 +/- 0.6 hours). All these changes were significant at 1%. Forty-one of the 56 patients (59%) improved when pergolide was added to levodopa. Mean dose of pergolide was 2.5 mg (range, 0.2 to 10.0 mg). Mean duration of the study was 13 months (range, 1 day to 34 months). Maximum improvement occurred within 2 months and began to decline, usually after 6 months. The major adverse effects necessitating discontinuing pergolide were the occurrence of an organic confusional syndrome (six patients), increased dyskinesias (four patients), and cardiovascular abnormalities (three patients). Nine patients discontinued pergolide because of a lack of effect or declining effect

Pergolide, a semisynthetic ergoline and a potent long-acting adenylcyclase-linked dopamine agonist, was given to 40 patients with advanced Parkinson's disease whose response to levodopa had diminished considerably. The group included 31 patients with marked diurnal oscillations in performance ('wearing off' and/or 'on-off' phenomena). Pergolide alone (7 patients) or combined with levodopa (33 patients), resulted in a reduction in disability (P less than or equal to 0.01) as assessed in both the patients' 'on' and 'off' periods. Pergolide also resulted in an increase (P less than or equal to 0.001) in the number of hours in which patients were on from 3.8 (+/-0.4) to 11.9 (+/-0.9). The mean daily dose of pergolide was 2.4 mg (range 0.1 to 10.0). The mean duration of the study was 12 mo (range 1 to 24). Pergolide is effective in Parkinson's disease and will change the management of patients whose response to levodopa has diminished

Seven patients with progressive supranuclear palsy were treated with lisuride. Mean age was 62 years (range, 52 to 68 years), and duration of disease was 4.4 years (range, 1 to 7 years). All seven had been treated with levodopa/carbidopa and three with bromocriptine; four had, at one time, shown a partial response to levodopa. One patient had also shown a partial response to bromocriptine. Lisuride was used alone in four patients, and combined with levodopa/carbidopa in three patients. Mean dose of lisuride was 2.5 mg (range, 1.5 to 5.0 mg). Mean duration of treatment was 4 months (range, 1 to 10 months). While two patients showed a reduction in rigidity, one in tremor and two in bradykinesia, in only one of them was there an overall improvement. It is postulated that the relative lack of response to lisuride may be due to a loss of both the dopaminergic and serotonergic receptors in progressive supranuclear palsy

We examined the effect of pergolide, a semisynthetic ergot alkaloid, alone or combined with carbidopa and levodopa (Sinemet), on the cardiac rhythm of 12 patients with Parkinson's disease. The patients were selected on the basis of severe Parkinson's disease and stable cardiac rhythm as determined by 1 to 5 days of Holter monitoring. Monitoring was then carried out for an additional period of between 2 and 10 wk while the patients were on pergolide. Seven of the 12 patients had repetitive ventricular rhythms (RVRs). These were isolated, infrequent, and not associated with increases in premature ventricular contractions. The dose at which the RVRs occurred may be a function of the presence or absence of heart disease, but the significance of RVRs remains to be determined

Lisuride, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was combined with levodopa in 20 patients with advanced Parkinson disease who were no longer responding satisfactorily to levodopa, including 14 patients with 'on-off' phenomena. Every patient who completed the 8-week trial improved significantly (p greater than or equal to 0.01), with a decrease in all symptoms. The mean dose of lisuride was 2.4 mg per day. The dose of levodopa (mg of levodopa in Sinemet) was reduced from 1030 to 920 mg. Among the patients with 'on-off' phenomena, there was a significant increase in the time in which they were 'on' (mobile) from 4.6 to 9.6 hours. In 5 of 10 patients who have been on lisuride for at least 1 year, there has been no decline in efficacy

Lisuride hydrogen maleate, a semisynthetic ergoline and potent central dopamine and serotonin agonist, was tested in 10 patients with moderate to marked Parkinson disease whose response to levodopa had diminished. In the group of 10 patients, there was a significant reduction (p less than or equal to 0.05) in bradykinesia, gait disorder, and total Parkinson disease disability score when levodopa was replaced with lisuride. The mean dose of lisuride was 3.6 mg per day. Among the 10 patients, 5 were better on lisuride than on levodopa, and 4 continue on lisuride 1 year later. A decline in efficacy was noted in all four after a mean of 45 months. Adverse effects necessitating discontinuing the drug were mental changes in three patients and nausea in one patient. Lisuride, when used alone, has definite antiparkinsonian activity and is a promising new drug