Non-ergot Dopamine Agonists Research Articles

National Trends of Antiparkinsonism Treatment in Taiwan: 2004-2011.

Background. Several guidelines for Parkinson's disease (PD) management were recently updated. We examined temporal trends for antiparkinsonism drugs in Taiwan. Methods. Antiparkinsonism prescriptions, including levodopa, ergot/nonergot dopamine agonists (DAs), amantadine, selegiline, entacapone, and anticholinergics, were identified in the Taiwan National Health Insurance Database from 2004 to 2011. Time trend analyses were estimated assuming Poisson distribution. Results. A total of 19,302 PD patients in 2004 and 41,606 PD patients in 2011 were analyzed. Antiparkinsonism prescriptions increased significantly from 187,137 in 2004 to 414,587 in 2011. Levodopa monotherapy or combination therapy was the mainstay. Levodopa monotherapy comprised 37.4% of prescriptions in 2004 and 44.2% in 2011, with an annual increase rate of 18.14%. There was a substantially increasing trend of DA prescriptions, which were higher in younger-aged patients (<60 years) than in older-aged group (p = 0.0006). Among combination therapy, DA combined with levodopa or other antiparkinsonism medications became the main combinations for younger-aged patients after 2009. After 2005, the proportion of ergot DA usage markedly decreased and PD patients using nonergot DA increased. Conclusions. Levodopa was the major treatment from 2004 to 2011. There was a steeply increased trend of DA use, especially in younger-aged patients. Nonergot agents comprised the major DA group after 2005.

Associations Between Cardiovascular Events and Nonergot Dopamine Agonists in Parkinson's Disease.

Knowledge of possible cardiovascular risks from Parkinson's disease (PD) medications is critical to informing safe and effective treatment decisions. The objective of our study was to determine whether PD patients treated with nonergot dopamine agonists (DAs) are at increased risk of adverse cardiovascular or cerebrovascular outcomes, relative to PD patients receiving other treatments. Matched case-control studies were conducted within a cohort of 14,122 inpatients receiving treatment for PD who were identified in the Cerner Health Facts database. Primary outcomes were associations between nonergot DA use and diagnosis of adverse cardiovascular events (acute myocardial infarction, heart failure [HF], hypotension, and valvulopathy). Secondary outcomes included associations between nonergot DA use and diagnosis of adverse cerebrovascular events (cerebrovascular accident and ischemic stroke) and odds of significant exposure-outcome relationships by patient factors. HF was the only adverse event that demonstrated a significant association with nonergot DA use. Individuals treated with pramipexole were more likely to be diagnosed with HF, relative to no use (adjusted odds ratio [AOR]: 1.28; 95% confidence interval [CI]: 1.07-1.53). The association between pramipexole and HF was greater among individuals treated with pramipexole monotherapy (relative to levodopa monotherapy) (AOR, 1.50; 95% CI: 1.09-2.06). Compared to nonusers, men and older individuals treated with pramipexole were more likely to be diagnosed with HF. Results from our study suggest an association between pramipexole use and HF. Findings warrant replication; however, individuals with PD and independent risk factors for, or a history of, HF may benefit from limited use of this drug.

Risks of Cardiac Valve Regurgitation and Heart Failure Associated with Ergot- and Non-Ergot-Derived Dopamine Agonist Use in Patients with Parkinson's Disease: A Systematic Review of Observational Studies.

Dopamine agonists (DAs) are commonly used in the therapy of Parkinson's disease (PD). However, several observational studies have suggested a putative association between DAs and specific cardiac adverse events. The aim of this study was to systematically review and summarize the available epidemiologic evidence on the association between use of ergot- and non-ergot-derived DAs and the risk of valvular heart disease, specifically cardiac valve regurgitation (CVR) and heart failure (HF) in patients with PD. The databases MEDLINE/PubMed and EMBASE were searched for all relevant articles published before February 2015. Studies were eligible if they met the following inclusion criteria: exposure to any approved non-ergot- or ergot-derived DA, presentation of original data, inclusion of an unexposed reference group, and valvular heart disease or heart failure as the primary outcome of interest. Thirteen publications for CVR were identified (two nested case-control, one cohort and ten cross-sectional studies). Compared with non-ergot DAs or other anti-parkinsonian drugs, exposure to ergot-derived DAs pergolide and cabergoline was associated with an increased risk of CVR among PD patients. Incidence rate ratios (IRR) in the nested case-control and cohort studies ranged from 2.00 to 7.10 and 4.58 to 4.90, respectively. Longer treatment duration and higher dose of those DAs was also associated with a higher risk of CVR. Risk of HF was estimated in three nested case-control studies and one cohort study. Use of cabergoline (IRR range 1.30-2.39) and the non-ergot-derived DA pramipexole (IRR range 1.40-1.81) was associated with a higher HF risk among patients with PD. Pergolide may also be associated with a higher risk of HF. Despite the heterogeneous methodological approaches of the included studies, there is strong evidence that treatment with pergolide and cabergoline is associated with a higher risk of CVR, and moderate evidence that treatment with pramipexole and cabergoline is associated with a higher risk of HF in patients with Parkinson's disease.

Rotigotine Transdermal Patch Does Not Make Parkinson Disease Patients Sleepy During Daytime.

To assess quantitatively the influence of rotigotine transdermal patch on daytime sleepiness, the most common adverse event by non-ergot dopamine agonists (DAs), in Parkinson disease (PD) patients. An open-label study enrolled PD patients with unsatisfactory control of motor symptoms. Treatment with rotigotine transdermal patch was titrated to optimal dose (4-8 mg/24 hours) over 2 to 4 weeks. Primary outcome was Epworth Sleepiness Scale (ESS) for daytime sleepiness. Secondary outcomes included Hoehn&Yahr stage, time spent with dyskinesia, Clinical Global Impression of Improvement (CGI-I) of motor symptoms, adverse events, and compliance. The subjects were 31 PD patients (age 72 ± 8, Hoehn &Yahr stage 2.7 ± 0.9, mean ± SD). The ESS did not increase after rotigotine treatment (7.2 ± 4.9 before treatment, 6.2 ± 4.0 with 4 mg/24 hour, and 8.1 ± 6.4 with 8 mg/24 hour). The CGI-I score improved after treatment; responder rate reached 88.9% with 8 mg/24 hours. No patients showed worsening in other secondary outcomes. In 13 patients treated with equivalent doses of rotigotine switched from other DAs (pramipexole, ropinirole, and cabergoline), ESS did not increase after treatment (10.0 ± 4.6 before and 8.6 ± 4.5 after treatment) and decreased without worsening of CGI-I in 54% patients. Other secondary outcomes did not worsen after treatment. Twenty four-hour transdermal delivery of rotigotine at doses up to 8 mg/24 hours does not worsen the daytime sleepiness in PD patients and often improves it when switched from other non-ergot DAs. This is achieved together with satisfactory improvement in motor symptoms, demonstrating that this new modality of non-ergot DA is well tolerated and beneficial in PD patients.

Non-ergot dopamine agonists and the risk of heart failure and other adverse cardiovascular reactions in Parkinson's disease

Non-ergot dopamine agonists and the risk of heart failure and other adverse cardiovascular reactions in Parkinson's disease

Dopamine Agonists: Time Pattern of Adverse Effects Reporting in Australia

BackgroundIn Australia, there is voluntary reporting of suspected adverse events (AEs) of therapeutic medicines. Some dopamine agonists (DAs) have serious AEs.ObjectiveWe aimed to explore the pattern of DA AE reporting over two decades.MethodsWe analysed AE case line listings obtained from the Australian Committee on the Safety of Medicines (ACSOM) for bromocriptine, cabergoline, pergolide, pramipexole and ropinirole, and related these to drug utilisation data (1992–2012). We noted the AE nature, frequency, onset, novelty, severity and outcome.ResultsThe 220 suspected AEs fell into five categories: (i) syncopal/pre-syncopal, (ii) fibrotic, (iii) psychotic, (iv) obsessive-compulsive behaviours (OCB) and (v) increased sleep. There were differential lag times between initial individual drug registration and reporting of suspected AEs, with a lag of at least one year for fibrotic reactions and OCB compared to more contemporaneous reporting of other AEs. Consistent with the published literature, ACSOM data showed that ergot DAs share fibrotic reactions as a class AE, whereas symptomatic hypotensive reactions, psychosis and OCB occurred in both ergot and non-ergot DAs, cabergoline and pramipexole, respectively. Reports of syncopal and pre-syncopal reactions seemed to diminish as ergot-based DA use declined. Levodopa was taken simultaneously with DAs in 87 instances. Of those treated, 92 % were 50 years or older. Parkinson’s disease accounted for 89 % of use (119 reports).ConclusionsExploring the temporal relationship between post-marketing AE reporting and utilisation data, as exemplified by DAs, can be a valuable pharmacovigilance tool to encourage targeted adverse event monitoring and reporting.

Maladaptive reward-learning and impulse control disorders in patients with Parkinson's disease: a clinical overview and pathophysiology update.

Impulse control disorders (ICD) in Parkinson’s disease (PD) are a disabling non-motor symptom with frequencies of 13–35% among patients receiving dopamine replacement therapy. ICD in PD is strongly associated with dopaminergic drug use, especially non-ergot dopamine agonists (DA). However, individual susceptibility and disease-related neural changes are also important contributors to the development of ICD. Discrepancies between nigrostriatal and mesolimbic dopaminergic degeneration and non-physiological administration of dopaminergic drugs may induce abnormal ’hyperstimulation’ of the mesolimbic system, which alters reward-learning behaviors in PD patients. In addition, DA can make patients more impulsive during decision-making and seek risk-taking behaviors. DA intake is also related to the biased representation of rewards. Ultimately, loss of negative feedback control due to dysfunctional frontostriatal connections is necessary for the establishment of ICD in PD. The subsequent behavioral and neural changes are affected by PD treatment and disease progression; thus, proper treatment guidelines for physicians are needed to prevent the development of ICD. Future studies aimed at producing novel therapeutics to control the risk factors for ICD or treat ICD behaviors in PD are warranted. This review summarizes recent advances from epidemiological and pathophysiological studies on ICD in PD. Management principles and limitations of current therapeutics are briefly discussed.

The benefits of pramipexole selection in the treatment of Parkinson's disease.

Levodopa administration as a gold standard in Parkinson's disease (PD) treatment is very valuable, however, long-term administration may cause some motor complications such as abnormal unintended movements and shortening response to each dose (wearing off phenomenon). Dopamine agonists were developed to reduce duration of immobile off periods and dependence to levodopa for improving motor impairments (Clarke et al., Cochrane Libr 1:1-23, 2000). Pramipexole is one of these nonergot dopamine agonists with high relative in vitro specificity and full intrinsic activity at D2 subfamily of dopamine receptors, with a higher binding affinity to D3 than to D4 or D2 receptor subtypes (Piercey, Clin Neuropharmacol 21:141-151, 1998). It can be advantageously administered as monotherapy or adjunctive therapy to levodopa to decrease side effects and increase effectiveness in both early and advanced PD treatment.

Prescribing pattern of anti-Parkinson drugs in Japan: a trend analysis from 2005 to 2010.

ObjectiveTherapeutic options for Parkinson's disease mainly consist of L-dopa and dopamine agonists. However, in Japan, the product labeling of the ergot dopamine agonists, cabergoline and pergolide, was revised in April 2007 due to the risk of developing cardiac valvulopathy. Here, we describe the prescribing trends of anti-Parkinson drugs from 2005 through 2010 in Japan, and examined whether these trends changed after the drug safety measures in 2007.Methods and PatientsWe used medical claim data from January 2005 to December 2010 for Parkinson's disease patients older than 30 years who were prescribed anti-Parkinson drugs. We calculated the proportion of patients prescribed each drug for each year, and compared the proportions of first-line drugs prescribed before and after April 2007. We also examined the prescription variations of cabergoline/pergolide users one year before or after April 2007.ResultsL-dopa was the most frequently prescribed drug for Parkinson's disease (2005, 58%; 2010, 51%). The proportion of patients prescribed ergot dopamine agonists markedly decreased and non-ergot dopamine agonists increased after 2007. Among first-line drugs, the proportion of non-ergot agents increased after April 2007. Among 54 cabergoline/pergolide users, 24 (44%) discontinued these drugs, nine of whom switched to non-ergot agents.ConclusionL-dopa was the mainstay of Parkinson's disease treatment between 2005 and 2010 in Japan. There was a decrease in ergot agents and an increase in non-ergot agents prescribed after the regulatory actions in 2007.

Long‐Acting Versus Standard Non‐Ergot Dopamine Agonists in Parkinson's Disease: A Meta‐Analysis of Randomized Controlled Trials

To evaluate the efficacy, tolerability, and safety of long-acting versus standard non-ergot dopamine agonists (NEDAs) in Parkinson's disease (PD), we performed a meta-analysis of randomized controlled trials (RCTs). The PubMed, EMBASE, Cochrane Library databases, and Web of Knowledge were searched up to November 20th 2013. The pooled weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Eight large-scale RCTs, involving 2402 patients, were included in this meta-analysis. Compared with the standard NEDAs, long-acting NEDAs exhibited similar improvements in Unified Parkinson's Disease Rating Scale activities of daily living (ADL) score (WMD 0.09, 95% CI -0.33 to 0.50), motor score (WMD -0.35, 95% CI -1.60 to 0.90), and "off" time (WMD 0.18, 95% CI -0.14 to 0.50). No differences were found in overall withdrawals (RR 1.11, 95% CI 0.94 to 1.32), withdrawals due to adverse events (RR 1.19, 95% CI 0.91 to 1.56), or the ten commonly reported adverse events between the two formulations. Our meta-analysis showed long-acting NEDAs were noninferior to standard NEDAs in efficacy, tolerability, and safety in the treatment of PD.

Rotigotine transdermal patch for the treatment of Parkinson’s Disease

Rotigotine, a non-ergot dopamine agonist, has been developed as a novel transdermal formulation. The rotigotine transdermal patch has received EMEA marketing authorization for the treatment of adult patients with early or advanced Parkinson's disease (PD) or with moderate to severe restless legs syndrome (RLS). FDA originally granted a marketing authorization for early PD, which was later suspended, and is now studying the authorization for RLS. The aim of this review is to review the pharmacokinetics, pharmacodynamics as well as the clinical efficacy and tolerability of the rotigotine transdermal patch in PD. Source material was identified using a PubMed search for the term 'rotigotine' and PD. Articles published up to January 2011 or abstract submitted to most relevant international neurology congresses were reviewed. The rotigotine transdermal patch is efficacious for the treatment of PD. Tolerability profile appears to be well within the range of that observed with other non-ergot dopamine agonists in PD. Application-site reactions were the most frequent adverse event, and they were considered mild to moderate in the majority of cases. The rotigotine transdermal patch offers a safe and efficacious alternative for the treatment of PD. Further studies should focus on the possibility that continuous dopamine stimulation by means of the transdermal patch has any influence on levodopa-related motor complications.

Risk of Cardiac Valve Regurgitation with Dopamine Agonist use in Parkinsonʼs Disease and Hyperprolactinaemia

There is growing evidence that ergot dopamine agonists may induce cardiac valve regurgitation (CVR) in persons with Parkinson's disease. It is unclear whether the CVR risk is increased with ergot-dopamine agonist use in persons with hyperprolactinaemia, in whom the dose is much lower. The aim of the study was to explore the association between different dopamine agonists and CVR in patients with Parkinson's disease or hyperprolactinaemia. Nested case-control studies conducted separately in cohorts of Parkinson's disease and hyperprolactinaemia patients. Cases were patients who developed newly diagnosed CVR. Controls were CVR-free patients from the same cohorts and were matched to cases by age, sex, database and calendar year. Study patients were identified from over 4.5 million persons in The Health Improvement Network (THIN; UK), Health Search (Italy), and Integrated Primary Care Information (IPCI; the Netherlands) general practice databases in the years 1996-2007. The Parkinson's disease cohort included new users of dopamine agonists or levodopa, while the hyperprolactinaemia cohort included new users or non-users of dopamine agonists. Risk of newly diagnosed CVR with dopamine agonist use compared with levodopa use in the Parkinson's disease cohort, and dopamine agonist-naïve patients in the hyperprolactinaemia cohort. In the Parkinson's disease cohort (7893 dopamine agonist users, 11 766 levodopa users), 85 incident CVR cases were identified. Increased CVR risk was observed for ergot dopamine agonists (adjusted OR [OR(adj)] 3.82; 95% CI 2.14, 6.81), but not for non-ergot dopamine agonists (OR(adj) 1.20; 95% CI 0.63, 2.29). In the hyperprolactinaemia cohort (6740 dopamine agonist users and 14 299 dopamine agonist-naïve patients), 37 CVR cases were identified during a mean follow-up of 4.5 years and 3.5 years for new users and non-users of dopamine agonists, respectively. However, no association with ever use of ergot dopamine agonists was observed (OR(adj) 0.47; 95% CI 0.20, 1.19). Ergot-derived dopamine agonists are associated with an increased risk of CVR in Parkinson's disease but not in hyperprolactinaemia patients.

The risk of new onset heart failure associated with dopamine agonist use in Parkinson's disease

The aim of present study was to investigate the risk of heart failure associated with dopamine agonist use in patients with Parkinson's disease.The data sources of this study were four different population-based, healthcare databases in United Kingdom, Italy and Netherlands. A case control study nested within a cohort of Parkinson's disease patients who were new users of either dopamine agonist or levodopa was conducted. Incident cases of heart failure were identified and validated, using Framingham criteria. Controls were matched to cases on age, gender and database. To estimate the risk of newly diagnosed heart failure with ergot and non-ergot derived dopamine agonists, as compared to levodopa, odds ratios and 95% confidence intervals were calculated through conditional logistic regression.In the cohort of 25,459 Parkinson's disease patients (11,151 new users of dopamine agonists, 14,308 new users of levodopa), 518 incident heart failure cases were identified during follow-up. Compared to levodopa, no increased risk of heart failure was found for ergot dopamine agonists (odds ratio: 1.03; 95% confidence interval: 0.69–1.55). Among non-ergot dopamine agonists, only pramipexole was associated with an increased risk of heart failure (odds ratio: 1.61; 95%confidence interval: 1.09–2.38), especially in the first three months of therapy (odds ratio: 3.06; 95% confidence interval: 1.74–5.39) and in patients aged 80 years and older (odds ratio: 3.30; 95% confidence interval: 1.62–7.13).The results of this study indicate that ergot dopamine agonist use in Parkinson's disease patients was not associated with an increased risk of newly diagnosed heart failure. Among non-ergot dopamine agonists, we observed a statistically significant association between pramipexole use and heart failure, especially during the first months of therapy and in very old patients.

Agonistas dopaminérgicos en la enfermedad de Parkinson

Background Non-ergot dopamine agonists (DA) are effective treatments for Parkinson's disease (PD). A review is presented of the pharmacology, evidence of efficacy and safety profile of pramipexole, ropinirole and rotigotine, and practical recommendations are given regarding their use in clinical practice. Results Extended release formulations of pramipexole and ropinirole and transdermal continuous delivery rotigotine patches are currently available; these may contribute to the stability of plasma levels and continuous dopaminergic stimulation. In early PD, the three of them significantly improved disability scales, delay time to dyskinesia and allow a later introduction of levodopa. In late PD they reduced total off-time, improved Unified Parkinson's Disease Rating Scale (UPDRS) in both on and off state and allowed a reduction in total levodopa dosage. Also, a significant improvement in quality of life scales has been demonstrated. Extended release formulations have proved to be non-inferior to the immediate release formulations, and even better tolerated (ropinirole). Despite a generally good safety profile, serious adverse events, such as impulse control disorder and sleep attacks need to be routinely monitored. Although combination therapy has not been addressed in scientific literature, certain combinations, such as apomorphine and another DA, may be helpful. Switching from a DA to another is feasible and safe, although in the first days an overlap of dopaminergic side effects may occur. When treatment with DA is stopped, dopamine withdrawal syndrome needs to be prevented. On suspension of a DA, especially pramipexole, the risk of producing apathy has to be considered. Conclusions New non-ergot DA are a valuable option for the treatment of both early and late PD. Despite a good safety profile, serious adverse effects may appear and need to be monitored. A pathoplastic effect on the course of the disease cannot be ruled out.

Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study

Safety and efficacy of non-ergot dopamine agonists for the treatment of idiopathic restless legs syndrome have been shown in short-term trials. We did a prospective open-label extension of a 6-week, double-blind randomised trial to assess the safety, tolerability, and efficacy of rotigotine transdermal patch for up to 5 years in patients with restless legs syndrome. Patients (aged 18-75 years) with moderate-to-severe idiopathic restless legs syndrome were treated with once-daily rotigotine transdermal patch in 33 centres in Austria, Germany, and Spain between July 31, 2003, and April 15, 2009. The dose was titrated in weekly increments (up to 4 weeks) from 0·5 mg/24 h to a maximum of 4 mg/24 h, and was followed by up to 5 years of maintenance at the optimum dose. Primary safety outcomes included occurrence of adverse events and dropouts. Efficacy assessments were secondary and included the International Restless Legs Syndrome study group severity rating scale (IRLS). Augmentation of symptoms was assessed by means of standard diagnostic criteria and was confirmed by an international expert panel. All patients who received at least one dose of study drug were included in assessments. This study is registered with ClinicalTrials.gov, number NCT00498186. 295 patients entered the open-label study, of whom 126 (43%) completed 5 years of follow-up. 169 (57%) patients discontinued treatment, 89 (30%) because of adverse events and 31 (11%) because of lack of efficacy. 70 patients (24%) discontinued during year 1 of maintenance. The most common adverse events were application site reactions, which occurred in 37% (106/290) of patients in year 1, 17% (38/220) of patients in year 2, 14% (27/191) of patients in year 3, and in less than 6% of patients during year 4 (8/159) and year 5 (8/147). 56 patients (19%) discontinued because of application site reactions. Mean rotigotine dose was 2·43 mg/24 h (SD 1·21) after initial titration and 3·09 mg/24 h (1·07) at the end of maintenance. Of 89 patients who discontinued because of adverse events, 28 (31%) were on 4 mg/24 h rotigotine. Mean IRLS score of patients entering the open-label study was 27·8 (SD 5·9) at baseline of the double-blind trial. In patients who completed the maintenance period, mean IRLS score was reduced from a baseline score of 27·7 (SD 6·0) by a mean of 18·7 points (SD 9·5) to a score of 9·0 (SD 9·2) at the end of maintenance. 39% (48/123) of patients who completed the trial were classified as symptom free according to the IRLS. Clinically significant augmentation was recorded in 39 patients (13%), of whom 15 (5%) were receiving a dose of rotigotine within the range approved by the European Medicines Agency (EMA; 1-3 mg/24 h) and 24 (8%) were receiving 4 mg/24 h rotigotine. Rotigotine transdermal patch is generally well tolerated after 1 year and provides sustained efficacy for patients with moderate-to-severe restless legs syndrome at a stable dose for up to 5 years. Thus, rotigotine transdermal patch is an appropriate long-term treatment option for moderate-to-severe restless legs syndrome, a disorder that often requires lifelong treatment. UCB BioSciences, on behalf of Schwarz Pharma, Ireland.

Effect of chronic kidney disease on excessive daytime sleepiness in Parkinson disease

Excessive daytime sleepiness (EDS) is a common sleep disorder in patients with Parkinson disease (PD). Non-ergot dopamine agonists increase the risk of unanticipated sleep episodes. We aimed to assess the influence of renal function on EDS in patients with PD. Sixty-two patients treated with ropinirole or pramipexole were recruited for this study. We evaluated the historical and clinical characteristics including the motor symptom rating scales, Epworth Sleepiness Scale (ESS), and estimated glomerular filtration rate (eGFR). An ESS score of 10 or greater was defined as EDS. Participants with eGFR < 60 ml/min/1.73 m(2) were determined to have chronic kidney disease (CKD). Multiple logistic regression analysis was performed to determine the predictive factors of EDS. Chronic kidney disease was found to be a significant predictive factor for EDS in all patients (P = 0.014). We observed a negative correlation between the severity of daytime sleepiness and renal function in patients treated with pramipexole alone (r(s) = -0.637, P < 0.001). Chronic kidney disease may be a risk factor for EDS, especially in patients treated with pramipexole, which is directly excreted in the urine.

Long-term open-label study of pramipexole in patients with primary restless legs syndrome

A phase III, open-label, long-term clinical study was performed to evaluate the safety and efficacy of pramipexole in a cohort of 141 Japanese patients with primary restless legs syndrome (RLS). The patients were started on pramipexole 0.25 mg/day and were subsequently maintained on that dose or switched to 0.125, 0.5, or 0.75 mg/day to achieve optimal efficacy and tolerability. The International Restless Legs Syndrome Study Group Rating Scale for restless legs syndrome (IRLS) score improved from 22.3 ± 4.7 at baseline to 11.1 ± 7.7 at week 8 and 4.9 ± 5.9 at week 52. IRLS responders, defined as patients whose IRLS total score decreased by ≥ 50% from baseline, accounted for 67.4% at week 12 and 86.6% at week 52. Over 90% of patients were Clinical Global Impression-global improvement (CGI-I) and Patient Global Impression (PGI) responders. The Pittsburgh Sleep Quality Index (PSQI) score decreased from 7.9 ± 3.1 at baseline to 4.6 ± 2.9 at week 52. Similarly, the Japanese version of the Epworth Sleepiness Scale score decreased from 9.3 ± 5.2 to 4.9 ± 3.8. Baseline IRLS score ≤ 20 was significantly associated with a complete IRLS response in this long-term study. Adverse events were typical of nonergot dopamine agonists, mild in intensity, and decreased in frequency as the study progressed. RLS augmentation was not observed. Pramipexole 0.25–0.75 mg/day is efficacious, safe, and well tolerated in patients with RLS. Pramipexole showed good efficacy, particularly in patients with an IRLS total score < 20.

Rotigotine transdermal delivery for the treatment of restless legs syndrome

Importance of the field: Rotigotine is a non-ergot dopamine agonist devised to be applied transdermally as a patch. It is currently licensed for treatment of early (USA and Europe) and advanced (Europe) Parkinson's disease, as well as for the treatment of moderate to severe restless legs syndrome (RLS) (Europe). Constant drug delivery and ease of use due to the application of an adhesive patch once daily are the potential advantages of the rotigotine patch for the treatment of RLS.Areas covered in this review: The evidence on the efficacy, tolerability and safety of rotigotine in the treatment of RLS is reviewed. Source material was identified using a PubMed search using the key words ‘rotigotine’ (up to September 2009) and using data from rotigotine trials being submitted or published in abstract form. This review focuses only on publications related to rotigotine for the treatment of RLS.What the reader will gain: In the drug trials summarized here, rotigotine transdermal patch is efficacious for the treatment of RLS, using dosages between 1 and 3 mg/24 h, up to 30% of severely affected patients reached freedom of symptoms with an IRLS (International Restless Legs Syndrome Severity Scale) of zero. Safety and tolerability are similar to other non-ergot dopamine agonists, except for application site reactions, which may limit practicability. Retrospective analysis of augmentation were 1.5% in placebo-controlled 6-month trials and 2.9% in a 1-year open trial.Take home message: The rotigotine transdermal patch can provide ‘around the clock’ treatment for moderate to severe RLS. Further comparative studies need to clarify whether continuous low-dose dopamine-agonist therapy will have any influence on augmentation rates.

P1.017 Treatment of chorea in Huntington disease with oral non-ergot dopamine agonists

P1.017 Treatment of chorea in Huntington disease with oral non-ergot dopamine agonists

AGONIST OR LEVODOPA FOR PARKINSON DISEASE? ULTIMATELY, IT DOESN'T MATTER; NEITHER IS GOOD ENOUGH

I disagree with conclusions outlined in the editorial by Drs. Weiner and Reich.1 The authors attempt the wholesale importation of experiences with bromocriptine into consideration of non-ergot dopamine agonists, yet a 10-year follow-up with ropinirole demonstrated very different results.2 The authors also group disabilities long recognized as refractory to dopaminergic therapies into the overall assessments of levodopa and dopamine agonist efficacies. Furthermore, the editorial implicitly suggests an either/or scenario; one either uses dopamine agonists with higher incidence of side effects, or uses levodopa where evidence supports a higher incidence of long-term motor complications.2 Unlike randomized clinical trials that necessitate dichotomous treatment arms and resistance to protocol variations, clinicians can exercise their judgment and supplement or replace dopamine agonists with levodopa as needed. Provided adequate follow-up, there is no reason why the prevalence, rather than the incidence, of side effects or subtherapeutic control should be any greater in those initially treated with dopamine agonist compared to initial treatment with levodopa. Unfortunately, the converse cannot be assured with respect to long-term motor complications. The authors also mention “levodopa phobia,” which is pejoratively characterized and associated with …