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.     

The effect of dopamine agonist therapy on dopamine transporter imaging in Parkinson's disease.

Single-photon emission computed tomography (SPECT) imaging with the dopamine transporter ligand, [123I] beta-CIT (2beta-carboxymethoxy-3beta-[4-iodophenyl] tropane), has been proposed as a means of measuring Parkinson's disease (PD) progression. To be useful in this role, however, [123I] beta-CIT imaging should not be influenced by the medications used to treat PD, including the dopamine agonist drugs such as pergolide. We assessed the effect of adjunctive pergolide administration on [123I] beta-CIT uptake in 12 patients with PD, who were being treated with levodopa, initiating pergolide therapy for motor fluctuations. Patients underwent [123I] beta-CIT imaging at baseline, subsequently while on pergolide therapy (6 weeks), and again 4 weeks after pergolide wash-out. Uptake in the striatum was averaged for the two sides and expressed as (striatum - occipital)/occipital, with similar calculations for putamen and caudate. Consistent with PD, the patients' mean striatal and putamen uptake ratios at baseline were significantly less (p <0.001) than the mean values from 26 normal control subjects of similar age. During pergolide treatment, the striatal and putamen [123I] beta-CIT uptake ratios were each statistically similar to baseline, although there was a slight trend toward an increased striatal value (8% higher on pergolide; p = 0.105). Caudate [123I] beta-CIT uptake was 11% higher on pergolide therapy (nominal p = 0.042, but not significant when adjusted for multiple comparisons: p = 0.126). After pergolide wash-out, the striatal, putamen, and caudate uptake ratios did not differ from baseline. Therefore, we found that pergolide therapy did not significantly affect [123I] beta-CIT SPECT imaging but we cannot exclude a small influence.     

Resolution of dopamine dysregulation syndrome following cessation of dopamine agonist therapy in Parkinson's disease.

Repetitive and compulsive behaviours can occur in association with the use of dopaminergic medications for the treatment of Parkinson's disease (PD). This syndrome has been referred to as the 'dopamine dysregulation syndrome'. The prognosis for patients with this syndrome is unclear. We report five PD patients in whom the abnormal behaviours resolved completely after withdrawal of dopamine agonist therapy. We alert clinicians to the apparent role of dopamine agonists in this syndrome. In addition, we highlight the potential reversibility of the syndrome, its varied phenomenology and its potential pathophysiology.     

Partial dopamine agonist therapy of levodopa-induced dyskinesias.

We administered the partial dopamine agonist terguride under controlled conditions to patients with Parkinson's disease (PD), both as monotherapy and in conjunction with intravenous levodopa. Terguride produced a dose-dependent decrease in levodopa-induced dyskinesias (up to 53%) in seven patients without concomitant worsening of parkinsonism, and had no significant antiparkinsonian effect when administered alone. Partial dopamine agonists may hold some promise in the adjuvant therapy of patients with advanced PD.     

Treatment of Parkinson's disease should begin with a dopamine agonist.

The occurrence of side effects with long-term levodopa therapy, such as fluctuations in motor performance or abnormal movements, led to a search for new antiparkinsonian drugs. Dopamine agonists include ergot derivatives such as bromocriptine, lisuride, pergolide, and cabergoline and other agents which do not possess the ergot structure such as pramipexole and ropinirole. They all are powerful stimulators of the D2 dopamine receptor which probably underlies their therapeutic effects. The clinical consequences of their binding to other dopamine receptor subtypes (D1 or D3) remains unknown. They are usually prescribed in combination with levodopa when late side effects begin to occur. This review summarizes the available pharmacologic and clinical data to support the early use of dopamine agonists in Parkinson's disease. Several strategies can be used, such as monotherapy or "early" or "late" combination with levodopa. Results of recent well-performed, modern clinical trials show that early use of the new dopamine agonists is able to effectively control the clinical symptoms for more than 3 years thereby offering the possibility of delaying the occurrence of levodopa-induced late motor side effects.     

Pathological gambling associated with dopamine agonist use in restless legs syndrome

Dopamine agonists (DA) have been associated with pathological gambling (PG) and other compulsive behaviors in Parkinson's disease (PD). Although these medications are used in other conditions, we are not aware of other reports of PG exclusive to treatment for idiopathic PD. We present a case of PG arising in the context of DA use for restless legs syndrome.     

Benign intracranial hypertension associated with the withdrawal of a non-ergot dopamine agonist

The cases are reported of two patients who developed benign intracranial hypertension after the withdrawal of the novel non-ergot derived dopamine agonist CV 205 502 (quinagolide).     

Slowing Parkinson's disease progression: recent dopamine agonist trials

In recent clinical trials, chronic treatment of patients with PD with pramipexole or ropinirole was associated with a slower decline of imaged striatal dopaminergic signal, compared to levodopa monotherapy. Although this could reflect slowed progression of PD, equally plausible is a pharmacologic effect on proteins that interact with the imaging radioligands. To date, there is no compelling evidence favoring dopamine agonists over levodopa; either is an appropriate choice for initial treatment of PD.     

Association of dopamine agonist use with impulse control disorders in Parkinson disease

OBJECTIVE: To determine the frequency and correlates of impulse control disorders (ICDs) in Parkinson disease (PD). DESIGN: An unstructured screening interview for ICDs (compulsive gambling, buying, and sexual behavior) followed by a telephone-administered structured interview for screen-positive patients. SETTING: Two university-affiliated movement disorders centers. PARTICIPANTS: A convenience sample of 272 patients with idiopathic PD who were screened for psychiatric complications. MAIN OUTCOME MEASURES: Presence of compulsive gambling, buying, or sexual behavior as assessed by the Minnesota Impulsive Disorders Interview. RESULTS: Eighteen patients (6.6%) with PD met criteria for an ICD at some point during the course of PD, including 11 (4.0%) with an active ICD. Compulsive gambling and compulsive sexual behavior were equally common. In a multivariate model, treatment with a dopamine agonist (P = .01) and a history of ICD symptoms prior to PD onset (P = .02) predicted current ICD. There were no differences between the dopamine agonists in their association with ICDs (P = .21), and daily doses of dopamine agonists were higher in patients with an ICD than in dopamine agonist-treated patients without an ICD (P < .001). CONCLUSIONS: Patients with PD treated with a dopamine agonist should be made aware of the risk of developing an ICD and monitored clinically. Because dopamine agonists are increasingly being used for other indications, future research should assess the dopamine agonist-associated risk for ICDs in other populations.