Pergolide Therapy Research Articles

BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.

BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.

Pergolide dosing compliance and factors affecting the laboratory control of equine pituitary pars intermedia dysfunction.

Equine pituitary pars intermedia dysfunction (PPID) is treated with daily pergolide therapy. Owner compliance and its effect on PPID control have not been previously investigated. Clinical records were searched to identify the sample of animals with PPID treated with pergolide from 2016 to 2019. The signalment was noted and the dose of pergolide received calculated. Animals were classified as compliant (receiving ≥90% of the veterinarian recommended dose of pergolide) or non-compliant, and as controlled (follow-up basal adrenocorticotrophic hormone concentrations within the reference range) or not. In total, 110 animals were included. The majority (85%) were ≥16 years (mean ± SD 19.8 ± 4.4 years); the most common breeds were Cob (18%), Thoroughbred (16%) and Welsh (15%); 37% were female and 63% male. Overall, 48% were compliant and 52% non-compliant. There was no significant effect of compliance on laboratory control. Of those that were compliant, 74% were controlled, while 67% of non-compliant animals were controlled. Univariable analysis revealed a significant (p < 0.001) effect of age and breed on compliance and control, and of sex on control. On multivariable analysis, only age (compliance) and breed (compliance and control) were retained in the final model. Only half of animals received the recommended pergolide dose; however, this did not affect laboratory control of PPID.

Does pergolide therapy prevent laminitis in horses diagnosed with pituitary pars intermedia dysfunction?

Does pergolide therapy prevent laminitis in horses diagnosed with pituitary pars intermedia dysfunction?

Equine Cushing’s Syndrome: Long-term effect of Pergolide therapy

Equine Cushing’s Syndrome: Long-term effect of Pergolide therapy

Sclerosing mesenteritis: An ergot‐related complication of pergolide therapy in Parkinson's disease?

Sclerosing mesenteritis: An ergot‐related complication of pergolide therapy in Parkinson's disease?

Pleuropulmonary Fibrosis After Long-term Treatment With the Dopamine Agonist Pergolide for Parkinson Disease

Dopamine agonists are increasingly used in the treatment of Parkinson disease, but they may cause serious adverse effects. In December 1983, symptoms of Parkinson disease developed in a 55-year-old man with no history of pulmonary disease, smoking, or asbestos exposure. He began treatment with dopamine agonists bromocriptine mesylate (in 1984) and pergolide mesylate (in 1989). In late 2000, pulmonary symptoms developed. Chest radiographs and computed tomographic findings showed a mass in the right upper lobe and effusion. A biopsy specimen showed pleural and parenchymal fibrosis. This syndrome resolved after cessation of pergolide therapy and a switch to pramipexole dihydrochloride. This case draws attention to the association of long-term ergot dopamine agonist therapy with pleuropulmonary fibrosis, which can develop as late as 11 years after the initiation of therapy. We also review evidence that the risk of this complication is substantially lower with the newer nonergot dopamine agonists.

A patient with tremors and breathlessness

We describe a patient with Parkinson's disease who developed bilateral pleural effusions and pleural fibrosis associated with pergolide therapy. Pergolide is an ergot-derived dopamine agonist used in the treatment of Parkinson's disease. This case report illustrates that physicians should have a high index of suspicion and consider drug-induced adverse effects in any differential diagnosis.

PERGOLIDE‐INDUCED RETROPERITONEAL FIBROSIS

SUMMARYRetroperitoneal fibrosis is a rare complication of pergolide therapy. This complication can be easily missed, so it is essential to have a high index of suspicion. We describe a case of well controlled Parkinson's disease who presented with shortness of breath and oedema. (Int J Clin Pract 2000; 54(6): 403)

Pergolide as primary therapy for macroprolactinomas.

The objective of this study is to determine whether pergolide therapy is an effective modality for the de novo treatment of patients with macroprolactinomas. Twenty-two consecutive patients with macroprolactinomas were included in the study and followed prospectively. These included 16 men and 6 women in whom pregnancy was not of concern. Pergolide was administered once or twice a day depending on the patient's preference. Ten patients received 0.1 mg daily as a maintenance regimen and in the others the daily dose ranged from 0.05 to 0.5 mg. Eight patients reported minor but tolerable side effects. One patient had to be switched to cabergoline because of intolerable nausea. After a mean of 12 months (range, 3-36), mean PRL levels declined from 3,135 ng/ml (range, 126-31,513) to 50 ng/ml (3-573), representing a mean PRL suppression of 88% (range, 0-99). PRL levels became normal in 15 patients and decreased to 25-40 ng/ml in 3 others. The mean tumor volume shrinkage was 25% or greater in 19 patients (86%), 50% or greater in 17 patients (77%), and 75% or greater in 10 patients (45%). Visual abnormalities were reversible after pergolide therapy in all but 1 of 12 patients with initially abnormal formal visual testing. Two out of 4 premenopausal women did not normalize PRL levels and had persistent oligomenorrhea. Testosterone was low in 14 men at presentation and normalized in 3 with pergolide therapy. We conclude that pergolide is a safe, inexpensive, and generally well-tolerated dopamine agonist for the treatment of macroprolactinomas in men and women in whom pregnancy is not of concern. In these specific populations, pergolide may become the first-line therapy for treatment of macroprolactinomas.

Iliocaval Venous Obstruction in Pergolide-Induced Retroperitoneal Fibrosis

Design: Case report. Setting: BMI Priory Hospital, Birmingham, UK. Patient: A 67-year-old man presenting with unilateral lower limb oedema. Past history included ipsilateral lower limb melanoma and Parkinson's disease, treated by pergolide. Intervention: Laparotomy to confirm a diagnosis of retroperitoneal fibrosis (RPF) causing iliac vein obstruction. Conclusion: RPF is a rare complication of pergolide therapy for Parkinson's disease. Previous reports have also described iliocaval obstruction and there may be an association between pergolide-induced RPF and venous complications.

Pergolide versus bromocriptine for levodopa-induced motor complications in Parkinson's disease.

To compare the efficacy and safety of adjunct pergolide therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering the long-term complications of therapy. Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Eli Lilly Company and Sandoz Limited. Randomised controlled trials of pergolide versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. Data was abstracted independently by each author and differences settled by discussion. Three short-term trials fulfilled the inclusion criteria for the review. Pergolide was superior to bromocriptine regarding UPDRS and NYPDS motor and NYPDS ADL scores in two trials. More patients recorded a 'marked' or 'moderate improvement' in clinician's global impression score with pergolide than bromocriptine in two studies. Insufficient evidence on fluctuations and dyskinesia was available to draw any conclusions. No significant differences between the agonists were seen in levodopa dose reduction, drop outs or adverse events. Although pergolide is superior to bromocriptine in reducing motor impairments and disability, no firm conclusions regarding levodopa-induced motor complications can be reached. Levodopa dose reduction, adverse events and withdrawals from treatment are similar for the two agonists. The small advantage of pergolide in efficacy does not take into account its additional cost compared with bromocriptine.

Pergolide for levodopa-induced complications in Parkinson's disease.

To compare the efficacy and safety of adjunct pergolide therapy versus placebo in patients with Parkinson's disease suffering from the complications of levodopa therapy. Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Eli Lilly and Company Limited. Randomised controlled trials of pergolide versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. Data was abstracted independently by each author and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of drop outs and adverse events. A large number of small RCTs were identified, but these were part of a large multicentre trial which was eventually published in full. The final publication was used as the only subject for this review. The time patients spent 'off' was reduced by 1.8 hours with pergolide compared with 0.2 hours with placebo (p < 0.001). Dyskinesia developed or deteriorated in 62% of pergolide-treated compared with 25% placebo-treated patients (p < 0. 05). The excess in dyskinesia prevalence and severity resolved by the end of the study with levodopa reduction. Levodopa dose was reduced more in those receiving pergolide (235 mg v 51 mg; p < 0. 001). Pergolide produced significant improvement in Hoehn and Yahr stage (p < 0.05) and both the motor and activities of daily living parts of a modified Columbia rating scale (both p < 0.001). Significantly more patients suffered nausea (24% v 13%; p < 0.001) and hallucinations (14% v 3%; p < 0.01) on pergolide. No difference was found in the numbers remaining on treatment at the end of the study (pergolide 84% v placebo 82%) but withdrawals due to adverse events were greater in those taking pergolide (10% v 4%). Based on this single large multicentre study, pergolide reduces 'off' time and improves impairment and disability due to Parkinson's disease whilst allowing a reduction in levodopa dose. This is at the expense of dopaminergic adverse events. Further trials are required to compare pergolide with the newer dopamine agonists.

A review of the efficacy of the dopamine agonists pergolide and bromocriptine in the treatment of Parkinson's disease

This review summarizes those studies, completed over the last 15 years, which compare the clinical benefit of the two most commonly used dopamine agonists, pergolide and bromocriptine. In these studies, both drugs were evaluated as adjunctive therapy to levodopa for the treatment of Parkinson's disease (PD). Ten studies are analyzed and the affect of pergolide and bromocriptine on PD compared. Although variation in study design and disease rating scales prevents the opportunity for a true meta‐analysis, this review analyses the outcome of each individual study to assess the benefit of pergolide over bromocriptine. Pergolide improves patients' activities‐of‐daily‐living and their clinical PD symptoms over bromocriptine. Additionally, a large percentage of patients who do not respond to bromocriptine, or whose PD symptoms worsened, improved on pergolide. Furthermore, patients who are adequately treated with bromocriptine experienced additional improvement with pergolide therapy. In summary, pergolide provided benefits to PD patients over bromocriptine in nine studies and was equivalent in the tenth. The benefits associated with pergolide may be partly due to the action of pergolide on dopamine D1 and D2 receptors (bromocriptine is associated with the D2 agonism). In conclusion, in the majority of completed studies to date, pergolide provided greater improvement to the clinical signs and symptoms of PD than bromocriptine.

Pergolide : A Review of its Pharmacology and Therapeutic Use in Parkinson's Disease.

Pergolide : A Review of its Pharmacology and Therapeutic Use in Parkinson's Disease.

Dopamine agonist treatment of fluctuating parkinsonism. D-2 (controlled-release MK-458) vs combined D-1 and D-2 (pergolide)

Adjunctive treatment with the very potent and selective dopamine D-2 agonist MK-458 (controlled-release formulation) improved the control of parkinsonism in patients with fluctuating responses to levodopa therapy (with carbidopa). We subsequently switched patients to adjunctive treatment with pergolide, a less potent D-2 agonist. Pergolide therapy controlled parkinsonism more effectively than controlled-release MK-458. Unlike MK-458, pergolide mesylate also has D-1 agonist properties, apparently accounting for its greater antiparkinsonism efficacy. Adjunctive treatment with controlled-release MK-458 elicited less choreiform dyskinesias than either pergolide adjunctive therapy or therapy with carbidopa-levodopa alone; this finding suggests that D-1 receptor stimulation contributes to the elicitation of medication-induced chorea. The highest doses of controlled-release MK-458 resulted in paradoxical freezing of gait in almost one third of patients. This finding suggests that gait freezing, common in untreated parkinsonism, can also be elicited by excessive D-2 stimulation.

Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged-Fischer-344 rats

Pergolide, a potent D 2 presynaptic agonist with postsynaptic D 2 agonist activity and some D 1 agonist activity was administered in the diet (0.5 mg/kg/day) of male Fischer 344 rats from age 3 to age 26 months. We hypothesized that the potent D 2 presynaptic activity would reduce the baseline release of dopamine (DA) and thereby slow the formation of toxic oxidative metabolites that lead to age-related deterioration of nigrostriatal DA neurons. Pair-fed rats served as controls. We observed age-related losses of fluorescent DA cell bodies in the substantia nigra pars compacta and of fluorescent DA terminals in the striatum; chronic pergolide administration prevented these losses. Pergolide administration also prevented the age-related diminution of DA fluorescence intensity in substantia nigra cell bodies. A large decline in 3H-DA uptake with age was partially prevented by pergolide administration. We found no age-related alteration in the concentration of DA in the striatum and pergolide did not alter this concentration. Pergolide treatment resulted in only minor alterations in striatal 3H-spiperone binding and no change in dendritic arborizations of either DA substantia nigra neurons or medium spiny striatal neurons. Pergolide administration also prevented an age-related decline in circulating FSH levels. The uptake data and quantitative morphological findings suggest that pergolide administration in the diet for 2 years exerts a protective effect on age-related deterioration of DA nigrostriatal neurons. This finding was consistent with clinical reports of a subset of patients with Parkinson's disease in whom long-term efficacy of pergolide therapy is observed.

Pergolide

When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options.

Pergolide: Long-Term Use in Parkinson's Disease

Previous short-term studies have shown that the dopamine agonist pergolide improves control of Parkinson's disease when used in conjunction with carbidopa-levodopa (Sinemet). We assessed the long-term outcome (2 1/2- to 3-year follow-up) in patients with Parkinson's disease who participated in our previous pergolide double-blind trial and were subsequently switched to open-label pergolide therapy. Of 41 evaluable patients who began pergolide therapy, 10 (24%) experienced sustained substantial benefit that persisted to the end of this investigation. A total of 23 patients (56%) remained on pergolide therapy and, as a group, had considerable improvement over baseline at 2 1/2 to 3 years on the basis of several measurements of efficacy. A tendency toward deterioration could be reversed in many patients by larger or more frequent doses of carbidopa-levodopa; nevertheless, all but four patients were still taking the same dose or less of carbidopa-levodopa at the end of this study as at the onset. Patients with the best initial response to pergolide seemed most likely to experience long-term benefit. Confusion and hallucinations were the side effects most likely to necessitate discontinuation of pergolide. Symptoms suggestive of dose-related angina pectoris occurred in four patients in the open-label phase and two patients in the earlier double-blind phase (13% of patients who started pergolide therapy); these symptoms were easily controlled by dose reduction or discontinuation of pergolide, without sequelae. Dose-related leukopenia developed in one patient.

Long-term study of pergolide in Parkinson's disease.

In 18 patients with Parkinson's disease, the effects of pergolide after 28 months of treatment were compared with the response after the initial 10-week therapy. At a mean 3.2-mg daily dose of pergolide, the daily dose of levodopa was still 33% lower than at the onset of pergolide therapy. The mean motor disability score, which decreased by 65% during the first 10 weeks of pergolide, was still decreased by 42% after 28 months. In the 12 patients with on-off effect, the percent time on increased 117% during the first phase of the study and was still increased 63% after more than 2 years of pergolide therapy. Sudden freezing episodes became the most disabling problem in the majority of patients. "Down-regulation" of dopamine receptors may contribute, but it is not the only cause of loss of responsiveness to pergolide.

Pergolide therapy in Parkinson's disease.

A total of 26 patients were treated with pergolide mesylate, a semi-synthetic ergot derivative with the property of direct dopamine activity. Of these patients, 18 suffered from late failure of L-dopa, while the remaining 8 had never before been treated with L-dopa. The aim of the trial was to study the activity of pergolide, either by giving it to untreated patients or by reducing as much as possible the L-dopa given in patients with parkinsonism. Adverse effects and failure rate were reduced by slowly increasing the daily dosage, by giving considerable dose flexibility whenever side-effects were manifest, and by the use of relatively low doses (mean of 3.8 mg in the L-dopa-group and 2.9 in the other group). At present, from 26 patients, 13 (50%) still remain in the study for an average treatment period of 16 months (3 weeks to 25 months for the group as a whole). All patients experienced a beneficial effect from pergolide, especially during the first months of treatment, in selfcare, rigidity, gait and automatic movements. Slight or no improvement was seen in tremor, speech and posture. The most frequent side-effects were nausea and vomiting (in the initial phase of the treatment), insomnia and psychotoxic reactions (mostly periods of confusion accompanied by visual hallucinations and paranoid illusions). The study indicated that pergolide mesylate is a useful additive for treatment of parkinsonism, but special attention should be paid to the important psychotoxic adverse effects that may appear, even at a low dose.