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Abstract: Cabergoline is a dopamine 2 receptor agonist used as first-line treatment of pituitary prolactinomas. Here, we describe the case of a 32-year-old woman with a pituitary prolactinoma who was treated with cabergoline for 1 year, during which time she developed delusions. We also discuss the use of aripiprazole to mitigate the psychotic symptoms, while maintaining the efficacy of cabergoline treatment., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Patients with early Parkinson disease (PD) frequently defer initiation of levodopa treatment to minimize long-term complications. Nonergoline dopamine agonists, such as pramipexole and piribedil, are frequent first-line therapies for early PD patients, yet limited head-to-head randomized controlled trial (RCT) evidence exists for dopamine agonists in this population. We therefore conducted a systematic literature review and network meta-analysis., Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched (until January 7, 2020), identifying RCTs assessing the efficacy of piribedil or pramipexole in early PD. Eligible trial data were incorporated into fixed- and random-effects Bayesian network meta-analyses., Results: No RCTs were identified directly comparing piribedil with pramipexole, but 6 trials provided data for pramipexole versus placebo and 2 compared piribedil versus placebo, facilitating indirect comparisons. Across all time points assessed, no significant differences were found between pramipexole and piribedil for change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline. Piribedil and pramipexole demonstrated superiority relative to placebo for UPDRS II/III change at weeks 22 to 30. No significant differences were noted between the treatments at weeks 20 to 35 for anxiety, constipation, hypotension, nausea, and somnolence. Sensitivity analyses on adjustment for dose titration periods and baseline risk yielded the same pattern of results., Conclusions: No significant differences were found for pramipexole versus piribedil in the UPDRS II/III scores from baseline in early PD, with similar safety profiles.

Camptocormia, a condition that involves the abnormal flexion of the trunk and results in a forward-bending posture, is relatively common during the course of Parkinson disease (PD). Despite this, there is ongoing controversy concerning its mechanisms and no consensus regarding the underlying etiology. This report demonstrates a case in which a dopaminergic agonist (DA) was implicated in the onset of camptocormia episodes in a non-PD patient who developed camptocormia after the start of DA treatment. Over a course of 8 years, the patient experienced intermittent camptocormia, which resulted in multiple falls. After cessation of the DA, the patient showed decreased camptocormia symptoms. This case report suggests that clinicians should consider the possibility of DA-induced camptocormia in patients with PD and non-PD patients receiving DA treatments, and serves to caution clinicians regarding the administration of DAs.

Dropped head (DH) syndrome is a phenomenon of disproportionate neck anteflexion that has been reported in patients with Parkinson disease (PD). Antiparkinsonian medications such as dopaminergic agonists (DAs) have been implicated in the onset of DH episodes. Deep brain stimulation (DBS) is an important therapeutic option after the failure of conventional treatments such as DA therapy in patients with PD. Here, we report the case of a patient with rigid-akinetic parkinsonism who developed DH syndrome after the initiation of DA treatment. Dopaminergic agonist treatment was required to stabilize motor dysfunction during a period of 5 years; yet, the patient experienced no improvements in DH during this time. Thus, we initiated DBS as an alternative therapy and gradually withdrew DA therapy. The patient recovered from long-term DH after the discontinuation of rotigotine treatment. Accordingly, this case highlights DA treatment as a possible cause of DH and the use of DBS to allow the discontinuation of DA treatment while preserving motor function in patients with PD.

Objectives: Impulse control disorder (ICD) is a common adverse effect in patients with Parkinson disease who receive dopamine agonists; however, other factors are involved in its manifestations. To study the frequency and factors involved in the development of this adverse effect in a Latin American population, we conducted a cross-sectional multicenter study., Methods: Two hundred fifty-five patients in 3 Latin American centers were evaluated by examination and application of scales (Unified Parkinson's Disease Rating Scale, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Hoehn and Yahr, Clinical Impression of Severity Index for Parkinson's Disease)., Results: Of the patients, 27.4% had ICD, most of whom were on dopamine agonists. Other associated risk factors included a younger age at onset of Parkinson disease, moderate symptoms, a shorter evolution of the clinical manifestations, rapid eye movement (REM) sleep disorder behavior, and the consumption of tea, mate, and alcohol., Conclusions: The frequency of ICD is higher in Latin America than in Anglo-Saxon populations. Consuming tea and mate, in addition to the use of dopamine agonists, is a factor that may demonstrate a genetic link that predisposes patients to the establishment of an ICD.

Objectives: The aims of the study were to report the case of a male patient who developed a first episode of Pisa syndrome (PS) to the right side and a second episode to the left side and to discuss the hypothesis that states that denervation is one of the main mechanisms implicated in the development of PS., Methods: We report on the case of a 71-year-old patient with Parkinson disease who developed PS to the right side while on dopaminergic treatment with pramipexol and levodopa. The dopamine agonist was discontinued and the postural abnormality was corrected increasing the levodopa dose. Six years later, while on ropinirole and levodopa, he developed PS again but this time the lean was to the left. Even though the dopamine agonist was discontinued, this condition failed to improve., Conclusions: Mechanisms other than denervation and its relationship with the more or less affected side contribute to the development of the syndrome.This is the first report of a case of recurrent alternating PS and highlights the need for research on this topic to better understand this disorder.

This article reports the case of a 29-year-old schizophrenic woman without somatic illness in whom switching from olanzapine to aripiprazole induced hiccups. Antipsychotics are thought to be effective in the treatment of hiccups; however, they have rarely been reported to induce hiccups. Within 24 hours of taking aripiprazole, the patient began having hiccups continuously. One week after the hiccups ceased, the patient resumed taking aripiprazole, and the hiccups began again. Although rare, this case study suggests that aripiprazole induces hiccups.

Background: It has been hypothesized that glutamatergic dysfunction may play a role in the development of obsessive compulsive disorder (OCD) and that glutamatergic modulation may ameliorate some of the OC symptoms. We evaluated the effectiveness of amantadine (AMN)- a weak, noncompetitive, antagonist of the N-methyl-D-aspartic acid (NMDA) receptor-as an adjunctive therapy to selective serotonin reuptake inhibitors (SSRIs), and its role in improving OC symptoms in cases refractory to SSRI pharmacotherapy alone., Methods: Eight patients (5 males and 3 females, aged 42.6 ± 13.1 years) that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD, scored above 20 points on Yale Brown Obsessive Compulsive Scale (Y-BOCS) and were unresponsive to at least one SSRI, completed an open label study of 6 weeks duration. AMN was added to the current stable SSRI regimen and baseline and endpoint changes in Y-BOCS, depression and anxiety levels were analyzed., Results: Significant reductions in total Y-BOCS (28 ± 4.5 vs. 18.8 ± 8.8; P < 0.01; df = 7; t = 2.36), Y-BOCS compulsion sub-scale (15.3 ± 3.2 vs. 10.6 ± 4.7; P < 0.02; df = 7; t = 2.36), and Y-BOCS obsession sub-scale (12.7 ± 3.3 vs. 8.1 ± 5; P < 0.05; df = 7; t = 2.36) scores were obtained at endpoint. The anxiety and depression levels remained unaltered., Conclusions: AMN adjunction to SSRI treatment may lead to a significant reduction in OC symptoms, supporting the hypothesis that transduction of the glutamate signal via NMDA receptor may play a role in OCD. A large scale, double-blind, placebo-controlled study is warranted to confirm our results.

Pisa syndrome (PS), also known as pleurothotonus, is an abnormal posture characterized by lateral flexion of the trunk that typically disappears in supine position. In Parkinson disease (PD), an abnormal forward flexion of the trunk (defined as camptocormia) is a common observation and has been interpreted as a sign of dystonia. Few reports have described PS mainly related to dopaminergic therapy in this kind of patients.Levodopa/carbidopa, levodopa/benserazide, levodopa/carbidopa/entacapone, pergolide, and pramipexole may cause PS, whereas no reports for ropinirole have been described.Here, we describe a case of a patient with PD who developed severe and reversible PS due to ropinirole intake.

Impulse control disorders (ICDs) constitute socially disruptive behaviors such as pathological gambling, impulsive eating, compulsive shopping, and hypersexuality. These conditions are well recognized in patients on dopamine agonist (DA) therapy for Parkinson disease. Dopamine agonists are widely used as first-line agents in the treatment of prolactinomas, but ICDs in this group of patients are relatively rare, perhaps because of lower therapeutic doses used. A review of the literature yielded only a few cases of ICDs in patients on DA treatment for prolactinomas. These symptoms are perhaps underreported because of lack of awareness among patients and health care professionals. Impulse control disorders are recognized psychiatric disorders that have significant psychological and social implications, and patients need to be counselled about this rare possibility when embarking on prolonged DA therapy. We describe a young patient with severe, socially disruptive impulsivity manifesting with pathological gambling who had been on long-term bromocriptine therapy for a macroprolactinoma.

Background: Impulse-control disorders (ICDs) occur in patients with Parkinson disease (PD), especially in younger patients on dopamine therapies., Objective: To assess the prevalence of ICD symptoms and its pharmacological correlations in a sample of French patients with PD and without PD (poststroke)., Methods: Outpatients with PD and without PD (poststroke) were screened for compulsive behaviors related to hypersexuality, compulsive shopping, pathological gambling, or compulsive eating by means of the Questionnaire for Impulse-Control Disorders--short version. Full medical history and Unified Parkinson's Disease Rating Scale scores were also recorded. Dose of dopamine agonists were converted to defined daily doses (DDDs), according to the World Health Organization Anatomical Therapeutic Chemical classification system classification system., Results: Two hundred three patients with PD and 52 patients without PD were recruited (mean ± SD age, 67 ± 1 vs 69 ± 2, P= 0.4; males: 62% vs 55% P= 0.2). Symptoms of ICDs were reported by 0% of poststroke patients and 25% of the patients with PD (P < 0.001). Hypersexuality was reported by 10% of the patients with PD, compulsive shopping by 6%, pathological gambling by 3%, and compulsive eating by 14%. A logistic regression analysis found that age younger than 68 years (odds ratio [OR], 3.3; 95% confidence interval, 1.6-6.6) and exposure to dopamine agonists (OR, 20.3; 95% confidence interval, 2.7-65.0) or monoaminooxidase-B inhibitor (OR, 3.7; 95% confidence interval, 1.1-12.6) were significant factors associated with increased ICD frequency. Patients with ICD symptoms were exposed to higher dopamine doses than those without them (1.6 ± 0.1 vs 1.0 ± 0.1 daily-defined doses; P < 0.001). A dose-response pharmacodynamic model disclosed a significant nonlinear dose-response relationship between dopamine agonists and frequency of ICD symptoms (P < 0.01)., Conclusions: Impulse-control disorder symptoms were more frequent in the patients with PD than in the poststroke patients with PD. Impulse-control disorder symptoms were related to younger age and exposure to monoaminooxidase-B inhibitors, and showed a nonlinear dose-response relationship with dopamine agonists.

Unlabelled: Pathological gambling (PG) is a potential complication related to the treatment of Parkinson disease (PD) with dopamine agonists (DA). The cause of this disorder is unknown, but altered dopamine neurotransmission may be involved., Objective: We evaluated the efficacy and tolerability of the opioid antagonist naltrexone in the treatment of PG in PD., Methods: Our cases included 3 patients with PD who developed PG after DA treatment., Results: Pathological gambling did not improve after reduction or discontinuation of DA. These patients responded poorly to serotonin reuptake inhibitors, whereas treatment with opioid antagonist naltrexone resulted in the remission of PG. Naltrexone treatment was well tolerated. In one patient, higher dose of naltrexone resulted in hepatic abnormalities, which resolved after dosage reduction., Conclusions: The opioid antagonist naltrexone could be an effective option for the treatment of PG in PD.

Objective: Impulse control disorders (ICDs) such as pathological gambling, compulsive shopping, compulsive eating, and hypersexuality are a matter of growing interest, especially in patients with Parkinson disease who are on dopamine replacement therapy. It was recently reported that ICDs are associated with other disorders also treated with dopaminergic drugs (dopamine agonists) such as restless legs syndrome, multiple system atrophy, progressive supranuclear palsy, and fibromyalgia. The aim of this study was to determine the prevalence of ICDs in patients with pituitary adenomas who take dopamine agonists (DAs)., Methods: Twenty consecutive patients with pituitary adenomas (mostly prolactinomas) taking DAs were assessed. All participated in a structured interview focused on ICDs, which was conducted by a physician., Results: Two (10%) of 20 subjects had a condition diagnosed as ICD. The first patient is a 35-year-old man with giant macroprolactinoma who was alternately treated with different types of DAs (cabergoline, bromocriptine, and quinagolide). He developed compulsive eating and pathological gambling. The second patient is a 53-year-old man with macroprolactinoma who suffered from severe hypersexuality after cabergoline was begun., Conclusions: This study demonstrates the importance of systematic screening for ICDs in patients taking dopaminergic medication regardless of their primary condition.

Antipsychotics are thought to be effective in the treatment of hiccups; however, they are rarely reported to induce hiccups. We report a case of persistent hiccups after administration of aripiprazole in a patient with concurrence of schizophrenia and cerebral palsy. Prior brain injury and switching antipsychotics may precipitate the development of hiccups in the present case. Aripiprazole with a partial agonist of dopamine D2 receptors and serotonin 1A receptors may play a crucial role in the pathophysiology of hiccups.

Introduction: The Restless Legs Syndrome is a common sensorimotor disorder, typically amenable to treatment with dopamine agonist therapy. Dopamine agonists have been associated with emergent impulse control disorders (ICDs) when used in patients with Parkinson disease, and ICDs have now been reported in individuals with RLS on dopamine agonist therapy. Our aim was to characterize cases of emergent ICDs in Australian patients with focus on the dopamine agonists implicated and the social significance of ICDs., Method: A series of RLS patients on dopamine agonist therapy were identified with ICDs over a 2-year period. Additional cases of ICDs were found using a mailout questionnaire designed to capture those with high impulsivity. These patients were assessed using the Barratt Impulsiveness Scale, Version 11, and a modified Minnesota Impulse Disorders Interview. Case records and medication schedules were evaluated., Results: Twelve cases of patients with de novo ICDs were found with a range of impulsive behaviors including pathological gambling, kleptomania, compulsive shopping, and hypersexuality. Criminality, suicidality, and marital discord also were featured. These occurred over a wide range of latencies and l-dopa exposures., Discussion: This group of Australian RLS patients with ICDs display high levels of impulsivity and is the first to use the BIS-11 questionnaire in this setting. Impulse control disorders can occur over a wide range of dopamine agonist therapy types and dose exposures. Impulse control disorder tendencies may persist, despite withdrawal of dopamine agonists. The emergence of ICDs needs careful consideration in light of their potentially devastating financial, social, and marital consequences.

Objectives: To assess frequency and characteristics of excessive daytime sleepiness (EDS) in restless legs syndrome (RLS) and the evolution of EDS under different RLS therapies., Methods: We analyzed data from the "Swiss RLS" study, which was conducted to compare treatment efficacy and safety of the dopamine agonist pramipexole (PPX) versus L-dopa/benserazide (L/B) in de novo patients with idiopathic RLS and performed as a randomized, double-dummy, comparative crossover trial. Primary outcome measure of the present study was the change in subjective sleepiness (as measured by Epworth sleepiness scale [ESS] score). There were 37 patients (21 women) included. Mean age was 56.6 years (range, 25-85 years), and mean body mass index was 24.6 (SD, ±3.5)., Results: At baseline, EDS (as determined by an ESS score of >10) was found in 32% of the patients. Sleepy RLS patients were younger (P < 0.001) than non-sleepy patients. Pramipexole and L/B both were effective in the treatment of RLS symptoms (IRLS score, P < 0.001 and P = 0.002). Overall, ESS was reduced (main effect for "time", P = 0.02) independent from the dopaminergic substance. In 5 of 37 patients, ESS score deteriorated to greater than 10 under treatment (PPX = 3 patients, L/B = 2 patients). No sleep attack occurred., Conclusions: Excessive daytime sleepiness is frequent in RLS patients. Dopaminergic treatment usually promotes wakefulness, but infrequently leads to daytime sleepiness.

Parkinson disease is a progressive movement disorder caused by loss of dopaminergic neurons in the substantia nigra. Of unknown etiology, Parkinson disease is characterized by 4 cardinal symptoms: tremor at rest, bradykinesia, postural instability, and rigidity. The current criterion-standard drug used in the management of parkinsonian symptoms is levodopa (l-dopa). However, long-term l-dopa therapy is associated with the development of motor complications; approximately 50% to 80% of patients will develop motor complications within 5 to 10 years of l-dopa treatment initiation. Motor complications can be divided into motor fluctuations, caused largely through pulsatile dopamine stimulation and low l-dopa concentrations, and dyskinesia, associated more often with peak l-dopa concentrations. Ultimately, the main goal was to provide steady l-dopa concentrations, without peaks and troughs. Empirical investigations using parenteral infusions of l-dopa and highly soluble l-dopa prodrugs have shown that there is benefit in ameliorating the peaks and troughs associated with traditional oral l-dopa formulations. Recently, the development of highly soluble oral l-dopa prodrugs has facilitated rapid, regular, and reliable l-dopa availability. This review evaluates some of the pharmacologic strategies in the management of motor complications in Parkinson disease and therapy optimization, with a focus on the use of CHF 1512 (Sirio), a combination of melevodopa (l-dopa methylester, a highly soluble prodrug of l-dopa) plus carbidopa in an effervescent tablet formulation.

This study evaluated the effects of ropinirole prolonged-release (RPR) in comparison with ropinirole immediate-release (RIR) on sleep-related disorders in Parkinson disease (PD).Thirty-three PD patients (aged 62.5 [SD, 8] years; PD duration, 9 [SD, 4] years) were evaluated on a stable dose of RIR and 5 to 13 weeks after switch to the closest possible dose of RPR. The following questionnaires were administered: Epworth Sleepiness Scale, PD Sleep Scale, Pittsburgh Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, and PD Questionnaire 39. We further monitored the occurrence of restless legs syndrome and sleep attacks (SAs). Motor disability was evaluated by PD diary and by Unified Parkinson Disease Rating Scale part 3 on medication (ON) and after medication withdrawal (OFF). In 8 patients with marked subjective sleep disturbance, polysomnography, and multiple sleep latency test were performed.After switching to RPR, there was an improvement in PD Sleep Scale (94.9 [SD, 23] vs 102.2 [SD, 27]; P < 0.05 corrected), Pittsburgh Sleep Quality Index (7.2 [SD, 3] vs 5.8 [SD, 3]; P < 0.05 corrected), Epworth Sleepiness Scale (14.1 [SD, 5] vs 12.0 [SD, 6]; P < 0.05 corrected) and Unified Parkinson Disease Rating Scale part 3 in the ON state (20.9 [SD, 10] 10 vs 17.6 [SD, 10]; P < 0.05 corrected). Thirteen patients reported disappearance of SAs on RPR. Polysomnography and multiple sleep latency test showed no changes in a subgroup of 8 patients after the switch to RPR.Ropinirole prolonged-release compared with RIR improved subjective quality of sleep, reduced daytime sleepiness, and led to disappearance of SAs in some patients possibly due to a more stable plasma level of ropinirole.

Objective: This study investigated the feasibility, safety, and potential benefit in motor symptom control when switching from a dopamine agonist to tolcapone as an adjunctive therapy in patients with Parkinson's disease with a fluctuating response to levodopa (l-dopa). We determined the efficacy of 2 replacement strategies., Methods: In this 10-week, randomized, open-label, stratified, parallel-group trial, 150 patients on a stable regimen of l-dopa/decarboxylase inhibitor in combination with bromocriptine, lisuride, or pergolide were switched to tolcapone. Primary end point was the change in daily "off" time from baseline to the end of week 10 as assessed by patient "on-off" diaries. Patients had their respective dopamine agonist reduced and finally withdrawn either by day 6 (short-term replacement, n = 72) or by day 23 (long-term replacement, n = 78)., Results: At week 10, a significant reduction from baseline in daily "off" time (-15.9 +/- 19.3%; P < 0.001) and a significant increase of "on" time (14.6 +/- 19.8%; P < 0.001) were observed. Other efficacy variables (Unified Parkinson's Disease Rating Scale II, III, and IVb and Investigator's Global Assessment scores) improved significantly after switching to tolcapone. In general, there was no significant difference between the 2 replacement strategies. Treatment was better tolerated after the switch to tolcapone according to the IGA of tolerability., Conclusions: Tolcapone, in principle, seems to be an alternative adjunct for patients, who fail to receive sufficient benefit from a dopamine agonist, for example, in case they do not tolerate an increase in dose or have unacceptable side effects. The switch from a dopamine agonist to tolcapone can be done safely within a few days.

Objective: To determine whether adding orally disintegrating selegiline (ODS) while decreasing dopamine agonist (DA) dosages would reduce DA-related adverse effects (AEs) of excessive daytime sleepiness (EDS), pedal edema, hallucinations, and impulse control disorders (ICDs) without compromising efficacy in Parkinson disease (PD) patients., Methods: This was a 12-week open-label study of 60 PD patients with motor fluctuations and DA-related AEs of EDS, pedal edema, hallucinations, and ICDs. Orally disintegrating selegiline was initiated at 1.25 mg once daily, and down titration of the DA was started with a goal of a 50% reduction by 1 week. At week 6, ODS was increased to 2.5 mg, and further reductions of the DA were allowed if the AEs were not resolved., Results: The addition of ODS allowed a reduction in the mean daily dose of pramipexole from 2.3 to 0.5 mg and immediate-release ropinirole from 11.2 to 2.9 mg. Most subjects reported a reduction or resolution of DA-related AEs; 94% with EDS (n = 50), 73% with pedal edema (n = 26), 86% with hallucinations (n = 15), and 84% with ICDs (n = 25). Mean activities of daily living and motor scores from the Unified Parkinson's Disease Rating Scale as well as quality-of-life scores were significantly improved without an increase in daily "off" time. The most common AEs, most of which resolved after titration, were worsening of PD, nausea/vomiting, dyskinesia, increased off time, body aches, insomnia, orthostatic hypotension, and increased anxiety and depression., Conclusions: In most subjects, the addition of ODS with decreasing dosages of DAs substantially reduced EDS, pedal edema, hallucinations, and ICDs without compromising efficacy.

Somnolence is one of the most common adverse effects of a dopaminergic agonist, rotigotine. We report putative adverse effects experienced by a spouse of a man treated with this compound because of advanced Parkinson disease. We propose the exposure to rotigotine through the seminal fluid because protected sexual intercourse eliminated her postcoital symptoms. This previously unrecognized mechanism may be more common and associated with other psychoactive compounds penetrating the blood-testis barrier, and it may account for otherwise unexplained postcoital somnolence or fatigue.

The treatment of Parkinson disease (PD) involves pharmacological treatment, often with levodopa or dopamine agonists, to restore the dopaminergic deficit associated with parkinsonian symptoms. Either agent provides symptom relief that becomes less effective in the course of PD, and switching or combining these agents or adding other therapies becomes necessary for symptom control. In an effort to delay the development of motor complications, dopamine agonists are often used in the initial treatment of PD. However, control of PD symptoms is superior with levodopa. Moreover, dopamine agonists are less well tolerated overall and are associated with a number of rare but serious adverse effects. In the long-term management of PD, treatment-associated dyskinesia often becomes sufficiently troublesome as to compromise the effective dosing of antiparkinsonian medication. More effective strategies for managing dyskinesia are needed.

Background: Cabergoline is an ergotic dopamine agonist with D2 receptor activity and a very long half-life. This pharmacological profile may result in clinically different effects. Small clinical trials indicate that overnight switching from 1 agonist to another can be performed safely., Objective: To determine safety and efficacy of overnight switching from dopamine agonists to cabergoline in patients with advanced Parkinson disease (PD)., Methods: Patients with advanced PD and motor complications not optimally controlled by levodopa and a stable dose of bromocriptine, pergolide, pramipexole, and ropinirole were converted to cabergoline overnight. Patients were assessed by using an on-off diary, Unified Parkinson Disease Rating Scale (subscales I-IV), Parkinson's Disease Quality of Life 8 (PDQ-8), an ad hoc sleep questionnaire and an ad hoc off-period severity questionnaire. All rating scales were administered just before conversion and after 2, 6, and 12 weeks of treatment, when patients were on an optimal dose of cabergoline. Adverse effects were assessed at every visit following a check list., Results: One hundred twenty-eight patients were included in the trial. Forty were on pergolide (mean dose, 2.8 mg/d), 38 on pramipexole (mean dose, 2.1 mg/d), and 32 on ropinirole (mean dose, 8.1 mg/d). Patients on bromocriptine (n = 18) were excluded from the analysis because of the small sample size. Three patients reported serious side effects (respiratory arrest, dyskinesias, and face edema and abdominal pain). Twenty-eight patients reported 41 adverse events. Twelve patients were withdrawn due to adverse effects (hallucinations [n = 5], dyspnea [n = 1], dizziness [n = 4], and vascular problems [n = 2]). A significant improvement in assessed parameters was obtained (P < 0.0001). Mean levodopa dose remained unchanged. After 12 weeks, the mean dose of cabergoline was 3.2 mg, and 25% of patients were taking the drug twice a day., Conclusions: Switching from pergolide, ropinirole, and pramipexole to cabergoline in an overnight schedule is safe. The observed clinical improvement may be related to a placebo effect, to the use of low doses of dopamine agonists, or to a direct effect of cabergoline.

Objectives: Do patients with restless legs syndrome (RLS) report gambling or other abnormal behaviors as previously reported in Parkinson disease., Methods: This survey study was sent to 261 idiopathic RLS patients, and it included the Gambling Symptoms Assessment Scale, Altman Self-Rating Mania Scale, and questions pertaining to sexual activity and novelty-seeking behaviors., Results: Ninety-nine patients responded to the survey, and 77 were actively taking 1 or more dopaminergic medications. Of the 70 respondents who answered the gambling questions, 5 (7%) noted a change in gambling, with 4 (6%; 95% confidence interval, 2%-14%) stating that increased urges and time spent gambling occurred specifically after the use of dopaminergic medications (2 on pramipexole, 1 on ropinirole, and 1 on levodopa and pramipexole). Increased sexual desire was reported by 4 (5%) of the 77 respondents, 3 (4%; 95% confidence interval, 1%-11%) reported that this occurred specifically after the use of dopaminergic medications (1 on pramipexole, 1 on ropinirole, and 1 on levodopa). One patient reported both an increase in gambling and sexual habits., Conclusions: This exploratory survey study revealed the development of gambling and/or increased sexuality in patients with RLS. These data raise the possibility that, as in Parkinson disease, RLS patients should be cautioned about potential behaviors that may occur with the use of dopaminergic medications. Further prospective studies are needed to assess the relationship between these medications and compulsive behaviors associated with the treatment of RLS.

Objective: Rotigotine (Neupro) is formulated as a transdermal delivery system designed to provide a selective, non-ergot D3/D2/D1 agonist to the systemic blood flow over a 24-hour period. In clinical trials, patches were applied once daily and uptitrated to the individual effective dose in increments of 2 mg/24 h every week. The aim of this analysis was to determine the safety of a more rapid titration of rotigotine by assessing the tolerability of escalating transdermal doses of rotigotine given in 2 different titration schemes., Methods: We analyzed the safety of rotigotine in 2 groups of patients with advanced stage Parkinson Disease. The starting dose of 4 mg/24 h was increased every week by 2 mg/24 h in the slow-titration group and 4 mg/24 h in the fast-titration group. The primary focus of this subanalysis was the separate tolerability of rotigotine in each randomized treatment arm, during the dose-escalation period. However, the 2 titration schemes were also compared with each other., Results: The dose of first reported nausea and/or vomiting was 8 mg/24 h for the fast-titration group and 4 mg/ 24 h for the slow-titration group. There were no remarkable differences concerning the side-effect profile between the 2 different titration schemes., Conclusions: The fast-titration regimen had a similar adverse event profile to slower titration, and allowed rotigotine to be introduced quickly. This subanalysis suggests that rotigotine may be uptitrated more rapidly.

Objectives: The high incidence of fibrotic cardiac valvulopathies reported in association with the 8beta-ergoline dopamine (DA) agonist, pergolide, and also case reports for cabergoline and bromocriptine have made it necessary to review the theoretical basis and actual findings in the case of another DA agonist, the 8alpha-ergoline lisuride (used since the 1970s for migraine prophylaxis as well as since the 1980s for its prolactin-lowering and anti-Parkinson activity)., Methods: We have reviewed the pharmacology of lisuride in relation to other DA agonists, and we have performed a throughout literature search as well as a search of our own and other adverse drug reaction databases for a possible relationship of lisuride with cardiac valvulopathy or for any reports of fibrosis in other locations., Results: Our review of the pharmacology and the literature strongly suggests that drug-induced cardiac valvulopathies are always related to a stimulatory drug effect on trophic 5-HT(2B) receptors. As lisuride is devoid of such an effect, but on the contrary is an extremely potent 5-HT(2B) antagonist, an association of lisuride therapy with cardiac valvulopathies seems to be highly unlikely. In agreement with this hypothesis, not a single report of a cardiac valvulopathy associated with lisuride therapy has been identified in any database so far.Furthermore, against a background of an estimated 360,000 patient years, we have found only a very small number of cases of any other form of fibrosis (1x retroperitoneal, 2x pleural, 2x pulmonary, 1x interstitial pulmonary changes), in part combined with other risk factors and confounding variables. This closely matches 4 reports available from WHO (1x retroperitoneal, 3x pleural fibrosis). In addition, only 5 other possibly related conditions (3x pleural effusion, 1x pleuritis, 1x pericarditis) were identified in the lisuride adverse drug reaction database of Schering, Berlin., Conclusions: No link has been found between lisuride use and fibrotic cardiac valvulopathy, in agreement with the 5-HT(2B) receptor antagonist effect of this drug. The very low incidence of spontaneous reports of any other fibrosis could be even compatible with an association by chance in the population exposed to lisuride. Although close monitoring for this kind of side effects is still to be recommended in the therapy with lisuride, our data do not support the concept of a class effect suggesting that all ergot-derived drugs and especially DA receptor agonists with some chemical similarity to the ergot structure will cause or facilitate cardiac valvulopathies as observed with pergolide.

Rotigotine is a new dopamine agonist with transdermal patch formulation for the treatment of Parkinson disease. The aim of this study was to investigate safety and efficacy of rotigotine in patients with early-stage Parkinson disease. In this open-label, dose-escalation, safety and efficacy study, 31 patients in the early stages of idiopathic Parkinson disease received rotigotine to a maximum of 18.0 mg/day. Of the 29 patients who completed the 28-day treatment phase, 24 were maintained at the maximum dose level. The drug was well tolerated, and skin reactions were mild. A statistically significant improvement in UPDRS I, II, and III scores was observed from baseline to end of treatment for the 29 subjects who completed the trial. Mean improvement (+/- standard deviation) was -0.41 +/- 0.78 on UPDRS I (P = 0.0078), -2.76 +/- 3.31 on UPDRS II (P = 0.0001), and -4.62 +/- 5.32 on UPDRS III (P < 0.0001). When results were stratified by maximum dose achieved, significant improvements were seen on all 3 subscores for patients achieving the maximum dose. These data suggest that rotigotine is a safe, well-tolerated, and effective treatment for early-stage Parkinson disease.

Objective: This study aimed to compare the efficacy and safety of quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis in a randomized, open-label, blinded-rater, parallel group trial., Methods: Forty-five patients with Parkinson disease (PD) and psychosis induced by antiparkinsonian drugs were randomly assigned to receive either quetiapine or clozapine. The duration of the trial was 12 weeks. Forty patients, 20 in each treatment group, completed the study. The final dose of quetiapine (mean +/- SD) was 91 +/- 47 mg/d and that of clozapine 26 +/- 12 mg/d. The severity of psychosis was assessed using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale-Severity Subscale (CGI-S). The Unified Parkinson's Disease Rating Scale (UPDRS) III was used to assess motor conditions during the study period. The Abnormal Involuntary Movement Scale (AIMS) was performed to evaluate dyskinesias., Results: Forty patients, 20 on clozapine and 20 on quetiapine, completed the study. The psychopathologic state improved significantly (P < 0.001) from baseline in both treatment groups. No differences were found between clozapine and quetiapine at any assessment time. Motor conditions remained unchanged after clozapine and quetiapine. Dyskinesias decreased significantly (P < 0.05) in both groups. Side effects were mild, generally transient, and well tolerated., Conclusions: Quetiapine and clozapine appear equally efficacious for treatment of dopaminergic psychosis in patients with PD.

Because migraine has been associated with dopaminergic receptor hypersensitivity, the authors hypothesized that patients with Parkinson disease with current or prior migraine have better dopaminergic response and less motor disability than Parkinson disease patients without migraine. Twenty-eight patients with Parkinson disease were included and matched (10 patients with migraine and 18 patients without migraine). Patients with Parkinson disease and migraine showed greater motor improvement during the ON state than patients without migraine with the same medication exposure. These data support the hypothesis that migraine may be associated with dopaminergic hypersensitivity.

Pleuropulmonary fibrosis is a rare, but well-recognized adverse effect of ergot alkaloids. We report on four patients who developed pleural and/or pulmonary fibrosis during treatment with pergolide and give characteristics of 87 cases with one or more symptoms of serosal fibrosis. Retroperitoneal and pleuropulmonary fibrosis are serious conditions, which are often irreversible after drug withdrawal. Increased awareness may help to diagnose these complications at an earlier stage and to minimize any permanent damage to the patient.

Introduced on the market in 1989, pergolide, a D1/D2 dopamine receptor agonist, is still widely prescribed for the treatment of patients with early and advanced Parkinson's disease (PD). Initially, pergolide was introduced as an adjunct therapy to levodopa treatment in patients exhibiting fluctuating motor responses and dyskinesias. Results of recent randomized controlled clinical trials in de novo patients with PD show that pergolide is able to improve parkinsonian symptoms when used as monotherapy. Moreover, preliminary results of a long-term monotherapy study in early PD suggest that pergolide is as effective as levodopa, and that a significant delay in the time of the onset of levodopa-induced motor complications can be obtained. A number of randomized studies have shown that pergolide is more effective than bromocriptine as adjunct therapy to levodopa in patients with advanced PD; the greater benefit found with pergolide could be ascribed to its action on both D1 and D2 dopamine receptors. However, controlled comparative studies with new dopamine agonists, such as ropinirole, cabergoline, and pramipexole, have not been performed yet. Interestingly, few open studies in patients with complicated PD have shown that high doses of pergolide (> 6 mg/d) are able to improve motor fluctuations and dyskinesias through a dramatic reduction of levodopa dosage. The side-effect profile of pergolide is similar to that of other dopamine agonists, and complications such as sleep attack and serosal fibrosis have been rarely reported.

The objective of the study was to determine the safety and efficacy of increasing doses of Rotigotine CDS in patients with advanced Parkinson's disease. The development of motor complications in Parkinson's disease has been linked to intermittent stimulation of dopamine receptors. Continuous, noninvasive, dopaminergic stimulation has not been available to date. Rotigotine CDS is a lipid-soluble D2 dopamine agonist in a transdermal delivery system that could fill this void. This inpatient study consisted of a 2-week dose escalation phase followed by a 2-week dose maintenance phase at the highest dose (80 cm2). Each individual's L-Dopa dose was back-titrated as feasible. The primary outcome measure was L-Dopa dose, and secondary outcome measures included early morning "off"-L-Dopa Unified Parkinson's Disease Rating Scale motor scores by a blinded evaluator and motor fluctuation data obtained from patient diaries ("on" without dyskinesia, "on" with dyskinesia, and "off"). Seven of 10 subjects provided data that could be evaluated. There were two administrative dropouts, and one individual was eliminated from the study because of recrudescence of hallucinations. The median daily L-Dopa dose decreased from 1,400 to 400 mg (p = 0.018, Wilcoxon test). Unified Parkinson's Disease Rating Scale motor scores were unchanged. Although diary variables improved in most individuals, only the reduction in "off" time attained statistical significance. Adverse effects were mild and consisted mainly of dopaminergic side effects and local skin reactions. The data suggest that Rotigotine CDS is an effective treatment for advanced Parkinson's disease and permits patients to substantially lower L-Dopa doses without loss of antiparkinsonian efficacy. Full-scale controlled clinical trials are warranted. In addition to potential therapeutic benefits, this drug can be used to test the hypothesis that continuous dopaminergic stimulation from the initiation of Parkinson's disease therapy will limit the development of motor complications.

This study was designed to assess the effects of bromocriptine, a dopamine D2 receptor agonist, on sleep bruxism. Seven otherwise healthy patients with severe and frequent sleep bruxism participated in this randomized, double-blind, placebo-controlled study. The study used a crossover design that included 2 weeks of active treatment or placebo with a washout period of 1 week. To further evaluate whether bromocriptine influences striatal D2 receptor binding, we used iodine-123-iodobenzamide single photon emission computed tomography (SPECT) under both placebo and bromocriptine regimens. Bromocriptine did not reduce the frequency of episodes of bruxism during sleep (mean +/- SEM, 9.0 +/- 1.0 and 9.6 +/- 1.5 bruxism episodes per hour for placebo and bromocriptine, respectively) or the amplitude of masseter muscle contractions (root mean square values, 48.2 +/- 15.5 microV and 46.9 +/- 12.7 microV for placebo and bromocriptine, respectively). SPECT also failed to reveal that either treatment had any influence on striatal D2 binding (values for total binding in counts/pixel, 1.80 [1.72-1.93] and 1.79 [1.56-1.87] for placebo and bromocriptine, respectively). This study shows that a nightly dose of bromocriptine does not exacerbate or reduce sleep bruxism motor activity.

Patients with Parkinson's disease frequently have depression, anxiety, and obsessive-compulsive disorder. We observed two patients who had episodes of pathologic gambling. At the same time, their Parkinson's disease deteriorated and they initiated self-medication with dopaminergic drugs. In both patients, signs were present of an addiction to dopaminergic medication. Pathologic gambling ceased in these patients after a few months. The significance of an insufficient dopaminergic reward system in patients with stereotypical addictive-like behavior (e.g., pathologic gambling) is discussed in this report. The most likely explanation for this newly recognized behavioral disorder in patients with Parkinson's disease is enhanced novelty seeking as a consequence of overstimulation of mesolimbic dopamine receptors resulting from addiction to dopaminergic drugs.

The contribution of dopamine D1 receptor stimulation to the motor effects of dopaminergic drugs in patients with Parkinson's disease remains undetermined. The authors of this article studied the clinical efficacy, pharmacokinetics, and tolerability of the full D1 receptor agonist dihydrexidine, (+/-)-trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine hydrochloride in a double-blind, placebo-controlled trial in four patients with Parkinson's disease. Single intravenous doses were carefully titrated according to a fixed schedule ranging from 2 mg to the highest tolerated dose (or a maximum of 70 mg) infused over either 15 or 120 minutes. The only patient to achieve a plasma drug concentration greater than 100 ng/ml had a brief but definite motor improvement accompanied by choreic dyskinesias similar to the response to levodopa. Dose-limiting adverse effects, including flushing, hypotension, and tachycardia, were observed in all cases, especially with rapid infusions. No nausea or emesis occurred. Pharmacokinetic studies yielded a plasma half-life < 5 minutes. These preliminary data suggest that dihydrexidine has a marginal therapeutic window for providing an antiparkinsonian effect, although it remains uncertain how much of this effect is attributable to pure D1 receptor stimulation.

A new experimental strategy was applied to determine the concentration-effect relation and the therapeutic window of apomorphine in individual patients with Parkinson's disease. Apomorphine was administered by a stepwise intravenous infusion. The infusion rate was increased by 10 micrograms/kg/h every 20 minutes, up to 100 micrograms/kg/h or less when adverse effects occurred. Thereafter, the infusion rate was decreased in a stepwise fashion until zero. Plasma apomorphine concentrations were measured every 20 minutes. Clinical efficacy (tapping score and tremor), dyskinesia, and adverse effects were monitored at the same time. The mean clearance of apomorphine was 4.5 L/min (2.2 to 6.6 L/min). Of the 10 patients, 8 responded to apomorphine. The effects were quantal rather than continuous. Within each patient, the concentrations at onset and offset of effect generally were similar. Significant interpatient variability was observed with respect to minimal concentration for each of the effects. Clinical efficacy occurred at a mean minimal effective concentration (MEC) of 4.7 ng/mL (range 1.4 to 10.7 ng/mL). Dyskinesia was observed at a mean concentration of 8.5 ng/mL (range 2.7 to 20 ng/mL). This value was not significantly different from the MEC. The mean minimal toxic concentration was 16.7 ng/mL (8.5 to 24.5 ng/mL) and was significantly different from the mean MEC. In conclusion, the stepwise increase and decrease of the intravenous infusion rate is a suitable tool for the establishment of the concentration-effect relation of apomorphine in individual patients. The finding of a narrow therapeutic window, in which the onset concentrations vary from patient to patient, underlines the need for accurate and individualized dosing.

Ropinirole is a novel, nonergoline, selective D2-type dopamine agonist developed to treat Parkinson's disease. Safety data from therapeutic studies involving 1364 patients receiving ropinirole are reported (mean daily dose 8.7 mg, early therapy; 8.2 mg adjunct therapy). In early therapy, the emergent adverse experiences more common with the ropinirole group compared with placebo were nausea, somnolence, leg edema, abdominal pain, vomiting, dyspepsia, and hallucinations. In adjunct therapy, they were dyskinesia, nausea, hallucinations, and confusion. Most adverse experiences were mild and associated with a similar withdrawal rate compared with the placebo group. Except for hallucinations, the incidence of emergent adverse experiences decreased with time, despite increasing doses. Long-term adverse experiences particularly associated with ergoline-type dopamine agonists have so far not been observed with ropinirole. Only 1.2% of patients receiving ropinirole developed dyskinesia compared with 11.2% receiving L-dopa in early therapy over a mean period of 17 months. There were no clinically significant changes in cardiovascular parameters or laboratory data. The incidence of adverse experiences in the bromocriptine group was low, possibly because of a slow titration scheme and low average dose. Overall, the safety profile of ropinirole appears similar to that of other dopamine agonists. Clinical studies are continuing to assess the long-term safety and efficacy of ropinirole.

We evaluated the responsiveness of tap rate (TR), movement time (MT), and reaction time (RT) to intravenous (i.v.) (n = 10) and subcutaneous (s.c.) (n = 16) administration of apomorphine in patients with Parkinson's disease (PD). In the second part of this study, we evaluated the feasibility of the commonly used 15% TR threshold, above which a patient is considered to be a responder. Compared to MT, TR emerged as the most responsive measure of bradykinesia during both i.v. and s.c. administration of apomorphine. RT showed no response to dopaminergic stimulation. To evaluate the influence of threshold on the number of responsive sessions, we determined the baseline variability of TR by means of the coefficient of variation (CV) in 39 patients with PD. Our results show approximately similar numbers of responsive sessions using the 15% and 2CV threshold. Our findings suggest that a simple repetitive motor task--TR--is more responsive than is the MT task. Finally, the 15% threshold may be considered an adequate threshold for TR in assessment of dopaminergic responsiveness of bradykinesia.

A similar pattern of psychosexual disorders has been observed after long-term treatment with levodopa therapy in four male parkinsonian patients treated with apomorphine for severe on-off motor fluctuations. An acute episode in each case had led them to the hospital in the context of a psychiatric emergency (after punishable sexual acts in two cases). In each case, this episode had been preceded by an increase of self-administered apomorphine, whereas other antiparkinsonian drugs remained unchanged. Questioning had revealed psychosexual disturbances as early as the onset of apomorphine treatment, which tended to progressively worsen with the number of apomorphine daily doses. A decrease in the dosage of apomorphine had been followed by the improvement of the psychiatric condition without worsening of the motor status. Recurrence of psychiatric disorders with similar features had been observed when two patients again increased the number of apomorphine daily injections. The absence of somatic manifestations when apomorphine treatment was withdrawn or reduced, with persistence of psychosexual disturbances, could suggest a psychological dependence from the drug.

Eleven patients with levodopa-related motor fluctuations were scored before and after intranasal apomorphine monotherapy, and the motor responses were compared with those with levodopa/carbidopa in this openlabel study. Oral trimethobenzamide was used to prevent apomorphine-induced nausea. Three measures of motor performance were employed: (a) the Unified Parkinson's Disease Rating Scale (UPDRS) motor battery; (b) a timed hand-tapping test; and (c) the Webster's step-seconds test. The magnitude of the motor-score improvement after apomorphine administration was very similar to that after the usual doses of levodopa/carbidopa in the 10 patients completing the study; this was true for all three outcome measures. A major advantage of apomorphine was the rapid onset of clinical response, which typically occurred in < 10 min, as well as the ease of administration. Major side effects, beyond those experienced with levodopa/carbidopa, were limited to nausea and vomiting (three patients) and orthostatic hypotension (one patient); however, only a single patient dropped out of the study as a consequence. These results indicate that intranasal apomorphine is effective in rapidly relieving parkinsonian "off" states and that, for most patients, trimethobenzamide is an effective and well-tolerated antiemetic for use with apomorphine.

Adjunctive cabergoline or placebo, in doses up to 5 mg daily, were administered to Parkinson's disease patients with short-duration levodopa responses in a 6-month double-blind trial. The 13 patients randomized to cabergoline and completing the study had significantly improved Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and timed hand-tapping test scores. Serial measurements on test days documented improved scores: (a) before the first levodopa (and cabergoline) dose of the day, (b) at the time of the peak levodopa effect, and (c) at the end of the levodopa response cycle, 5 h after test doses. Continued testing verified that these therapeutic responses were sustained for at least 48 h after the last cabergoline dose. Patients randomized to placebo failed to improve on any of these measures. In a subsequent open-label dose-escalation phase, further improvement was documented as the dosage was gradually raised to 10 mg daily. As in the double-blind phase, levodopa reduction allowed the improvement to occur in the absence of significantly increased dyskinesias. Other side effects were more substantial with higher doses, however, including two of 11 patients with hallucinations and confusion. In summary, adjunctive single-daily-dose cabergoline therapy resulted in long-lasting, dose-related improvement in parkinsonism not seen in patients receiving placebo.

Forty-six patients with Parkinson's disease experiencing motor fluctuations and not optimally controlled on levodopa received as adjunct therapy a new nonergoline dopamine agonist, ropinirole, in a 3-month randomized placebo-controlled trial. Ropinirole significantly reduced the duration of off periods as assessed by self-scoring diary cards. There were more nonserious dopaminergic adverse events in the ropinirole group. More patients withdrew because of adverse events or insufficient therapeutic effect in the placebo group. Ropinirole has beneficial adjuvant effects in parkinsonian patients with moderate motor disability and motor fluctuations.

In a randomized double-blind study, 20 parkinsonian patients (suffering from the disease for 2-18 years), chronically treated with levodopa (500-750 mg/day for 0.5-12 years), received terguride (1 mg b.i.d.) or placebo for 4 weeks. Growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and insulin-like growth factor (IGF-I) secretions were studied before and after the morning dose of levodopa (250 mg p.o.), both before and at the end of study period. At the beginning of the study, basal hormonal levels were within normal limits, and levodopa administration induced a significant suppression in PRL and TSH levels (both p < 0.01)) and a significant increase in GH (p < 0.01). The same results were observed at the end of the study period in the placebo group. Addition of terguride induced a significant suppression in basal PRL levels (p < 0.01), whereas levodopa-induced hormonal changes were unaffected. These data suggest that the hypothalamic dopaminergic function that controls anterior pituitary hormones is preserved in parkinsonian patients, regardless of both the duration of the disease and the long-term treatment with levodopa. The strong additional prolactin-lowering effect of terguride indicates long-lasting dopaminergic effects, as is already known from hyperprolactinemic conditions. The dopaminergic effects of levodopa on TSH, GH, and IGF-I secretion were unchanged by terguride treatment. The anti-dopaminergic effects of terguride observed in the motor system in animal studies, as well as in levodopa-induced dyskinesias in parkinsonian patients, could not be observed in the case of the dopaminergic control of anterior pituitary hormones under the conditions of this study.

Dopamine agonists have been used with some success in treating cocaine addiction. However, both cocaine and psychostimulants have been reported to produce neurotoxic effects. We evaluated the effect of the stimulant diethylpropion on cognitive performance in a double-blind, placebo-controlled trial. Forty-six abstinent crack-cocaine users received either placebo, 25-mg, 50-mg, or 75-mg doses of diethylpropion. Patients were tested at baseline and again after 9-14 days of medication. There were no differences between placebo and medication groups on any test, indicating that, within the time frame studied, diethylpropion does not produce neurotoxic effects that can be detected with standardized neuropsychological tests.

We describe a 68-year-old patient with Parkinson's disease who developed retroperitoneal fibrosis during pergolide treatment. Because pergolide is an ergot derivative, it could be related to the development of this complication.