Increased risk of somnolence with the new dopamine agonists in patients with Parkinson's disease: a meta-analysis of randomised controlled trials.

BACKGROUND: Recent case reports and letters have alerted practitioners to the risk of sleep attacks, usually preceded by somnolence, in patients with Parkinson's disease treated with pramipexole and ropinirole. OBJECTIVE: To quantify the risk of somnolence with the new dopamine agonists pramipexole and ropinirole in patients with Parkinson's disease. METHODS: We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts and Cochrane Library, contacted experts and pharmaceutical manufacturers, and manually reviewed all references retrieved to identify possible articles to include. Information on randomisation, blinding, type of treatment and reporting of somnolence were abstracted by 2 independent reviewers. Disagreements were resolved by a third author. ANALYSIS: We made 2 separate analyses. The first analysis compared the risk of somnolence in patients taking either pramipexole or ropinirole to that in patients taking placebo. The second analysis compared the risk of somnolence with these drugs (plus levodopa) versus that with levodopa alone. We calculated pooled relative risk estimates using the random effects model and when no heterogeneity was detected we used the fixed effects model. RESULTS: Four trials were included in the analysis of patients taking pramipexole or ropinirole compared with those taking placebo. The pooled relative risk of somnolence in this analysis was 4.98 [95% confidence interval (CI) 1.79 to 13.89]. Seven trials were included in the analysis of patients taking levodopa and pramipexole or ropinirole compared with those taking levodopa alone. The pooled relative risk was 2.06 (95% CI 1.47 to 2.88). CONCLUSION: Patients with Parkinson's disease using pramipexole or ropinirole are at higher risk of experiencing somnolence relative to patients taking placebo. Patients taking levodopa plus either one of these dopamine agonists are at higher risk than those taking levodopa alone. Clinicians should carefully weigh this risk against the benefit of these agents when prescribing these drugs.     

Drug safety evaluation of rotigotine

INTRODUCTION: Rotigotine, a non-ergolinic dopamine-receptor agonist, is currently approved as monotherapy in early idiopathic Parkinson's disease (IPD), in moderate to severe idiopathic restless legs syndrome (RLS) and as adjunct therapy to levodopa in advanced IPD. Randomized, double-blind, placebo-controlled, as well as open-label studies were conducted in IPD and RLS patients to evaluate the efficacy, tolerability and safety of rotigotine in dosages up to 16 mg/24 h. Overall, these trials have shown that rotigotine has a similar adverse event (AE) profile as other non-ergolinic dopamine agonists such as pramipexole or ropinirole, inducing typical dopaminergic effects like nausea, daytime somnolence, peripheral edema or impulse control disorders. In addition, the most common AE seen with transdermal delivery of rotigotine are local skin reactions, which may lead to a treatment discontinuation in approximately 8% of patients. AREAS COVERED: This review outlines Phase II and III trials that were published between 2003 and 2011. The focus of this review is on the safety profile of rotigotine but it also goes into detail about clinical trial data, pharmacokinetics and pharmacodynamics. EXPERT OPINION: The emergent safety profile is similar to other non-ergolinic dopamine agonists. In addition, transdermal delivery is associated with local skin reactions, which are usually mild but may lead to a treatment discontinuation in a minority of patients.     

Treatment options for restless legs syndrome

Background: Restless legs syndrome (RLS) is a common condition characterized by dysesthesia and an urge to move. Predominantly, symptoms occur at rest in the evening or at night, and they are alleviated by moving the affected extremity or by walking. Although the etiopathogenesis of RLS is still unknown, the rapid and dramatic improvement of RLS with dopaminergic agents suggests that dopaminergic system dysfunction may be a basic mechanism. Dopaminergic agents are the best-studied agents, and are considered first-line treatment of RLS. Objective: To review all options for the treatment of RLS, including the non-pharmacological ones. Methods: The treatment suggestions are based on evidence from studies published in peer-reviewed journals, or upon a comprehensive review of the medical literature. Results/conclusion: Extensive data are available for levodopa and dopamine agonists, especially for pramipexole and ropinirole. Pharmacological treatment should be limited to those patients who suffer from clinically relevant RLS with impaired sleep quality or quality of life. A treatment on demand is a clinical need in RLS cases that present intermittent symptoms.     

Cost-effectiveness of licensed treatment options for restless legs syndrome in the UK and Sweden

ABSTRACT

Objective: To estimate the cost-effectiveness of pramipexole versus no treatment and ropinirole in moderate to very severe idiopathic restless legs syndrome (RLS) in the UK and Sweden.

Methods: A Markov model was developed using clinical trial data for pramipexole and ropinirole. Model health states were based on the International RLS Study Group Rating Scale (IRLS) scores. Health states were: no (IRLS 0), mild (IRLS 1–14), moderate (IRLS 15–24), severe (IRLS 25–34), very severe RLS (IRLS 35–40) and death. Patients entered the model with an IRLS score?>?15 matching the trial inclusion criteria of the pramipexole trials. Resource use and utilities were based on trial data, literature, a patient survey and a panel of physicians from the UK and Sweden in the absence of published information. A healthcare sector perspective was taken for the UK and a societal perspective for Sweden using 2004–2005 unit costs. The base case analysis took a 1-year timeframe.

Results: In the UK the incremental cost per quality-adjusted life year (QALY) for pramipexole was £3349 versus no treatment and a cost-saving of £92 against ropinirole. In Sweden, pramipexole produced cost-savings of Swedish Krona (SEK) 2381 (£176) versus no treatment and SEK?3564 (£264) against ropinirole. QALY gains in both countries were 0.095 versus no treatment and 0.007 versus ropinirole. Results compare well with UK cost–effectiveness thresholds of £20?000/£30?000 per QALY and are cost-saving for Sweden. One-way and probabilistic sensitivity analyses showed results to be robust.

Conclusions: Pramipexole is cost-effective compared to no treatment and ropinirole for patients with moderate to very severe RLS.     

Role of dopamine receptor agonists in the treatment of restless legs syndrome

The restless legs syndrome (RLS) is defined by four essential criteria obligatory for clinical diagnosis which were established, and recently revised, by the International RLS Study Group. These are (i) the urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs, which are (ii) worse during rest/inactivity, (iii) partially or totally relieved by movement and (iv) worse at night/in the evening. Treatment with levodopa leads to symptom relief, but augmentation (occurrence of symptoms before levodopa administration in the evening) may occur, limiting the long-term use of this drug. This article gives an overview of the treatment in general and the role of dopamine receptor agonists in the therapy of RLS and periodic limb movements (PLMs). Dopamine receptor agonists are widely used as an effective treatment for RLS and PLMs, presumably because of their longer half-lives, lower likelihood of augmentation and good tolerability compared with levodopa. It was shown that, for example, pergolide, ropinirole, pramipexole and cabergoline alleviated RLS symptoms in 70-90% of patients. A new non-oral (transdermal) formulation of one dopamine receptor agonist, rotigotine, has recently been developed and shown to be efficacious in RLS. Further research should focus on long-term observations and comparisons of different dopamine receptor agonists in RLS.     

Current treatment options for restless legs syndrome

Restless legs syndrome (RLS) is a common but often underdiagnosed neurological disorder characterised by an imperative desire to move the extremities associated with paraesthesias, motor restlessness, worsening of symptoms at rest in the evening or at night and, as a consequence, sleep disturbances particulary. Additionally, most patients with RLS have periodic limb movements during sleep and relaxed wakefulness. The aetiology of RLS remains unknown. Treatment of RLS is generally symptomatic, a causal therapy is possible only in the secondary forms. Dopaminergic agents including levodopa and dopamine agonists such as pergolide, pramipexole, cabergoline and ropinirole are regarded as the treatment of choice for idiopathic RLS, however, the development of augmentation of symptoms, especially under levodopa therapy, may be a major problem. Except in special circumstances, opioids and anticonvulsants such as gabapentin or benzodiazepines, are regarded as second-line treatment. In secondary RLS, the underlying illness should first be treated, although dopaminergic drugs may also be helpful.     

Cabergoline,pramipexole and ropinirole used as monotherapy in early Parkinson's disease: an evidence-based comparison

Dopamine agonists have been widely used as add-on to levodopa in the treatment of Parkinson's disease with motor fluctuations. However, the use of dopamine agonists in early Parkinson's disease and levodopa-naive patients is controversial. Although dopamine agonists have been compared with levodopa, no studies exist which directly compare one dopamine agonist with another. This evidence-based review compares the results of large published studies of early treatment of Parkinson's disease with dopamine agonists (cabergoline, ropinirole or pramipexole) with similar studies using levodopa. Because of their design, the common variables analysed in all studies were the proportion of patients who developed dyskinesia, those withdrawn from the trial and the mean change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III scores. Cabergoline, pramipexole and ropinirole were similarly effective in reducing the risk for dyskinesia relative to levodopa (p < 0.01 for all three). The reduction in risk for dyskinesia was slightly more evident for pramipexole and ropinirole (p < 0.0001) than cabergoline (p = 0.0074). Odds ratios (95% confidence intervals [CI]) relative to levodopa were 0.38 (0.19-0.78) for cabergoline, 0.25 (0.13-0.47) for pramipexole and 0.31 (0.18-0.53) for ropinirole. The absolute risk reductions (95% CI) were, respectively, 8% (2.2-13.7), 20% (11.7-29.8) and 25% (13.6-36.7), ropinirole reducing the risk significantly more than cabergoline. The mean change from baseline UPDRS was similar for pramipexole and ropinirole (not evaluated for cabergoline). The proportion of withdrawn patients and the adverse effect profiles of the three agonists were similar to each other, with the exception of oedema, which was less prominent for ropinirole than for the other two agonists. Cabergoline, pramipexole and ropinirole are comparable choices for the delay of dyskinesia. Their adverse effect profiles are also similar, but they are less well tolerated than levodopa. The motor antiparkinsonian benefit of dopamine agonists is somewhat smaller than that of levodopa.     

Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis.

BACKGROUND: Pramipexole and ropinirole are relatively new dopamine agonists, both of which have proven efficacy in the treatment of Parkinson's disease. There is, however, uncertainty regarding differences in the adverse event profiles associated with each drug.Objective: To compare the adverse events of pramipexole and ropinirole as reported in the peer-reviewed medical literature. METHODS: We systematically reviewed the medical literature to identify randomised controlled trials of pramipexole and ropinirole used in the management of Parkinson's disease. Computerised databases (including Medline, Embase, the Cochrane Library, and the International Pharmaceutical Abstracts) were used to identify pertinent articles for inclusion in this study. Trials that compared the dopamine agonists to either levodopa or placebo were included. ANALYSIS: Adverse events with these drugs included dizziness, nausea, hypotension, hallucinations, and somnolence. We made two separate analyses. In the first analysis, we estimated the pooled relative risk (RR) of adverse events with either pramipexole or ropinirole as compared with levodopa. In the second analysis, the pooled RRs of adverse events with pramipexole and ropinirole were compared with placebo. We used the random-effects model of DerSimonian and Laird to estimate the RRs and their corresponding 95% CIs. We tested for study heterogeneity using Q statistics. RESULTS: There was no significant difference in the risk of dizziness, nausea, or hypotension with either drug individually or in combination when compared with levodopa. The risk of hypotension was approximately four times higher with ropinirole than pramipexole when each drug was individually compared with placebo (6.46 [95% CI 1.47-28.28] for ropinirole, and 1.65 [0.88-3.08] for pramipexole). The pooled RR (for pramipexole and ropinirole combined) of hallucinations was 1.92 (95% CI 1.08-3.43) when compared with levodopa. Relative to placebo, pramipexole had a significantly higher risk of hallucinations than ropinirole (pramipexole 5.2 [95% CI 1.97-13.72] vs ropinirole 2.75 [95% CI 0.55-13.73]). There was no significant difference in the risk of somnolence between the two drugs when each was individually compared with levodopa. When compared with placebo, the pooled RR (pramipexole and ropinirole combined) of somnolence was 3.16 (95% CI 1.62-6.13). Relative to placebo, the risk of somnolence was 2.01 (95% CI 2.17-3.16) with pramipexole and 5.73 (95% CI 2.34-14.01) with ropinirole. CONCLUSIONS: Use of ropinirole seems to be associated with a higher risk of hypotension and somnolence than use of pramipexole when compared with placebo. Use of pramipexole seems to be associated with a higher risk of hallucinations than use of ropinirole when compared with placebo.     

Management of restless legs syndrome in patients on dialysis

Restless legs syndrome (RLS) is characterised by an urge to move the legs, uncomfortable sensations in the legs and worsening of these symptoms during rest with at least temporary relief brought on by activity. RLS occurs in 3-15% of the general population and in 10-30% of patients on maintenance dialysis. RLS may lead to severe sleep onset or maintenance insomnia, and greatly impaired quality of life. Current recommendations suggest dopaminergic therapy (levodopa or dopamine receptor agonists: pramipexol, ropinirole, pergolide or cabergoline) as the first-line treatment for RLS. This group of medications is effective in reducing RLS symptoms in the general population; limited information is available on the effect of these drugs in patients with renal failure. However, it must be noted that most published studies in uraemic patients had short treatment periods and insufficient statistical power because of small sample size. Frequent adverse effects of levodopa, seen mainly with continuous use, may limit its use significantly. Rebound and augmentation, problems relatively frequently seen with levodopa, seem to be less prevalent with the use of dopamine receptor agonists, although properly designed comparative trials are still needed to address this question. Alternative treatment options for RLS are gabapentin, benzodiazepines and opioids. For all of these medications, there are only very limited data available on their effectiveness and safety profile in patients on maintenance dialysis. Referral to a specialist for RLS management should be considered for patients with refractory RLS.     

Ropinirole: for the treatment of restless legs syndrome

Ropinirole is a non-ergoline dopamine agonist that exhibits a high affinity for D(2) and D(3) receptors but little or no affinity for D(1)-like and non-dopaminergic receptors. Symptoms of restless legs syndrome (RLS) [measured using the International Restless Legs scale and Clinical Global Impression-Global Improvement Scale scores] significantly improved with ropinirole compared with placebo in large, randomised, double-blind trials. Ropinirole reduced periodic leg movements and improved sleep efficiency relative to baseline and placebo in several trials (two of which were randomised, double-blind and relatively large) in patients with RLS. Ropinirole was generally well tolerated in patients with RLS; adverse events were generally mild to moderate in nature and consistent with those expected of dopamine agonists. Few patients receiving ropinirole withdrew from therapy because of adverse events, the most predominant of which were nausea and headache.     

Restless legs syndrome in the older adult: diagnosis and management

Restless legs syndrome (RLS) is common in the elderly, with an estimated prevalence of 10 to 35% in individuals over 65 years of age. RLS is characterised by paraesthesias and dysaesthesias of the legs, typically occurring in the evening. The symptoms occur at rest and result in motor restlessness; movement often temporarily relieves the symptoms. Patients with poorly controlled RLS may develop related problems including insomnia (due to sleep-onset restlessness or periodic limb movements or related sleep fragmentation) and depression. RLS can be a primary disorder that develops in the young and includes familial cases. Secondary RLS occurs in association with iron-deficiency anaemia, uraemia and polyneuropathies. Typically, RLS is misdiagnosed or undiagnosed for years. In the elderly, both primary and secondary types of the disorder are common. It is thought that RLS represents lower CNS levels of, or reduced responsiveness to, dopamine. The symptoms improve with dopaminergic therapy. Ergotamine dopamine-receptor agonists such as pergolide, and the non-ergotamine dopamine-receptor agonists pramipexole and ropinirole, are becoming more commonly used to treat RLS. The dopamine precursor levodopa, in combination with carbidopa, is another effective therapeutic agent. An advantage of levodopa is lower cost than non-ergotamine and ergotamine dopamine-receptor agonists. However, the adverse effect of symptom augmentation appears to develop more frequently with levodopa than dopamine-receptor agonists; therefore, levodopa may currently be used somewhat less often as first-line therapy. Patients with painful symptoms may respond favourably to the anticonvulsants gabapentin and carbamazepine. Opioids and hypnosedatives are helpful in selected patients; however, these agents may have troubling adverse effects in the elderly. Correction of iron deficiency improves symptoms in patients with low ferritin levels. Lifestyle modification may also be helpful. Therapy is directed at symptoms, and most symptomatic patients benefit from treatment. It is important to consider RLS in the differential diagnosis of any patient with paraesthesias of the limbs.     

Non-ergot dopamine agonist-induced sleep attacks

Two patients with Parkinson's disease received treatment with ropinirole and/or pramipexole, during which both experienced sleep attacks. These attacks may be a class effect of non-ergot dopamine agonists. Health care professionals should be aware of the potential of these agents to cause sleep attacks and caution patients about this potentially life-threatening adverse effect.     

Cost effectiveness of pharmacotherapies in early Parkinson's disease

Parkinson's disease is one of the most common chronic neurodegenerative diseases. The progression of disease and the psychosocial consequences exert a major impact on patients' health-related quality of life. Although levodopa provides the best symptomatic benefit with the fewest short-term adverse effects, long-term treatment results in motor complications that are associated with both higher costs and considerable increase in patients' discomfort. The introduction of dopamine agonists early in the treatment of Parkinson's disease leads to a delay of these motor complications, but the treatment is associated with higher costs.In this review we evaluate available cost-effectiveness analyses of the dopamine agonists pramipexole, pergolide, bromocriptine, ropinirole, cabergoline and levodopa in the treatment of early Parkinson's disease. Considerable methodological differences in the identified studies complicate a comparison and impede clear evidence as to which dopamine agonist treatment is the most cost effective in early Parkinson's disease. Novel head-to-head comparisons considering the actual treatment guidelines are necessary to identify the most cost-effective alternative in treating de novo Parkinson's disease patients.     

Pharmacotherapy for restless legs syndrome

Introduction: Restless legs syndrome (RLS) is a common condition characterized by paresthesia and an urge to move. Predominantly, symptoms occur at rest in the evening or at night, and they are alleviated by moving the affected extremity. RLS prevalence in the general population has been estimated to be approximately 5%.

Areas covered: This review presents all options for the treatment of RLS.

Expert opinion: Pharmacological treatment should be limited to those patients who suffer from clinically relevant RLS, that is, when symptoms impair the patient's quality of life, daytime functioning, social functioning or sleep. Treatment on demand is a clinical need in some RLS patients, and medications include carbidopa/levodopa, pramipexole, ropinirole, oxycodone, methadone, codeine and tramadol. Chronic RLS should be treated with either a nonergot dopamine agonist or an α-2-δ calcium channel ligand. A dopamine agonist is a more appropriate choice in the presence of depression and overweight. As α-2-δ ligands can alleviate chronic pain and may be helpful in treating anxiety and insomnia, the presence of any of these comorbidities may favor their use. For RLS present through much of the day and night, the use of long-acting agents, such as the rotigotine patch or gabapentin enacarbil should be considered. In refractory RLS, oral prolonged release oxycodone–naloxone should be considered.     

Restless legs syndrome.

PURPOSE: The signs and symptoms, epidemiology, etiology, pathophysiology, diagnosis, pharmacologic and nonpharmacologic treatments, and options and guidelines for the treatment of restless legs syndrome (RLS) are reviewed. SUMMARY: RLS was first described in the 17th century and further characterized in 1945. RLS is a common disorder, occurring in about 10% of the population. Patients with RLS often describe the urge to move, uncomfortable sensations, and pain, which begin or worsen during rest or inactivity such as lying or sitting. Symptoms of RLS make sleeping difficult for many patients, and significant daytime difficulties result from the condition. RLS can either be primary or arise from secondary causes that lead to iron deficiency. There is a familial component in primary RLS, but its underlying mechanisms remain unknown. Of individuals with conditions associated with iron-deficiency states, including pregnancy, renal failure, and anemia, 25-30% may develop RLS. The goals of RLS treatment include improving its symptoms and the patient's quality of life. There are limited data on the treatment of RLS. Pharmacologic therapies include iron replacement, dopaminergic agents (e.g., levodopa), dopamine agonists, anticonvulsants, opioids, and benzodiazepines. There have been no systematic trials of nonpharmacologic therapies for RLS, but good sleep hygiene and avoidance of alcohol, caffeine, and nicotine may improve symptoms. CONCLUSION: RLS is a common disorder thought to involve abnormal iron metabolism and dopaminergic systems. Nonpharmacologic therapy should be suggested for all patients with RLS, but pharmacologic therapy may be required, and evidence is strongest for levodopa and dopamine agonists.     

Are dopamine receptor agonists neuroprotective in Parkinson's disease?

Dopamine receptor agonists are playing an increasingly important role in the treatment of not only patients with advanced Parkinson's disease and those with levodopa-induced motor fluctuations, but also in the early treatment of the disease. This shift has been largely due to the demonstrated levodopa-sparing effect of dopamine agonists and their putative neuroprotective effect, with evidence for the latter being based largely on experimental in vitro and in vivo studies. In this article we review the evidence for neuroprotection by the dopamine agonists pramipexole, ropinirole, pergolide, bromocriptine and apomorphine in cell cultures and animal models of injury to the substantia nigra. Most of the studies suggest that dopamine agonists may have neuroprotective effects via direct scavenging of free radicals or increasing the activities of radical-scavenging enzymes, and enhancing neurotrophic activity. However, the finding that pramipexole can normalise mitochondrial membrane potential and inhibit activity of caspase-3 in cytoplasmic hybrid cells derived from mitochondrial DNA of patients with nonfamilial Alzheimer's disease suggests an even broader implication for the neuroprotective role of dopamine agonists. Although the clinical evidence for neuroprotection by dopamine agonists is still limited, the preliminary results from several ongoing clinical trials are promising. Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progression of Parkinson's disease using various surrogate markers of neuronal degeneration such as 18F-levodopa positron emission tomography and 123I beta-CIT (carbomethoxy-beta-4-iodophenyl-nortropane) single positron emission computed tomography. The results of these experimental and clinical studies will improve our understanding of the action of dopamine agonists and provide critical information needed for planning future therapeutic strategies for Parkinson's disease and related neurodegenerative disorders.     

Discontinuation of ropinirole and pramipexole in patients with Parkinson’s disease: clinical practice versus clinical trials

Objective  To compare characteristics and incidence of discontinuation of Parkinson’s disease (PD) patients starting ropinirole or pramipexole in clinical practice with data from randomised controlled clinical trials (RCTs). Methods  Included in the retrospective clinical-practice cohort were first-time users of ropinirole or pramipexole diagnosed with PD before 2005. Baseline characteristics and incidence of discontinuation were compared between the clinical-practice cohort and RCTs. Treatment discontinuation was defined as more than 180 days between two refills of ropinirole or pramipexole. The incidence of discontinuation in RCTs was based on the reported rate of discontinuation for any cause. Results  Included were 45 patients who started with ropinirole and 59 patients who started with pramipexole. Treatment was discontinued within 3 years in 51% (ropinirole) and 60% (pramipexole) of the patients. Ten RCTs with ropinirole and 12 with pramipexole were identified. Baseline characteristics did not differ between the clinical-practice cohort and RCTs. RCTs reported discontinuation rates comparable with those at the same timepoint in the clinical practice until 1 year of follow-up. Conclusion  This study shows that the overall incidence of discontinuation of ropinirole and pramipexole between the patients in our clinical-practice cohort and patients in the RCTs was comparable for the short term. However for the long term, discontinuation in practice is possibly higher.     

Rotigotine transdermal patch: a review of its use in the management of Parkinson's disease

A transdermal patch formulation of the non-ergolinic dopamine agonist rotigotine (Neupro) is indicated for use as monotherapy in the treatment of early-stage Parkinson's disease or, in the EU, as an adjunct to levodopa across all disease stages. Transdermal rotigotine is an effective and generally well tolerated addition to the armamentarium for the control of Parkinson's disease, with the once-daily transdermal patch system offering several practical advantages and the possible benefits of avoiding pulsatile dopaminergic stimulation. Transdermal rotigotine was superior to placebo in patients with early-stage and advanced Parkinson's disease, although noninferiority to the oral dopamine agonists ropinirole or pramipexole was not consistently demonstrated. Additional active comparator trials would be of interest. In the meantime, transdermal rotigotine offers a convenient new treatment option for patients with Parkinson's disease.     

'Sleep attacks' or 'unintended sleep episodes' occur with dopamine agonists: is this a class effect?

Controversial reports of sudden onset 'sleep attacks' resulting in road traffic accidents have recently been reported in patients with Parkinson's disease (PD) taking the non-ergot dopamine D(2 )/D(3) receptor agonists pramipexole and ropinirole. These reports have generated considerable debate as the concept of 'sleep attacks' is disputed amongst sleep specialists and most believe that isolated 'sleep attacks' not preceded by warning on the background of chronic sleepiness or 'unintended sleepiness' do not exist. A series of case reports suggested that this phenomenon may not be exclusive to the non-ergot dopamine agonists such as pramipexole or ropinirole and indeed may occur with most dopaminergic agents. Recent evidence suggest that a 'sleepiness' or 'hypoactivity' reaction to dopaminergic therapy may be related to underlying dopamine deficiency of PD rather than a drug effect. In this report we provide the evidence for the phenomenon being a class effect attributable to all dopamine agonists currently employed in the management of PD. Controversy surrounding excessive daytime sleepiness (EDS) in PD and the use of the Epworth Sleepiness Scale (ESS) in relation to PD is also discussed. In spite of variable reports, EDS is recognised to be common in PD and is likely to be related to both the disease process and drug therapy. Studies using multiple sleep latency tests have also reported differing results in PD although a recent study indicated that a subset of 'sleepy' patients with PD may experience pathological somnolence with resultant detrimental consequence on daytime and cognitive functions. We recommend that the issue of 'sleepiness' or 'sleep attacks' in PD should be routinely checked in all patients with PD and indirectly assessed by using either the ESS or the recently introduced Parkinson's Disease Sleep Scale. Those with reported 'sleep attacks' or 'unintended sleep episodes' and excessive daytime sleepiness while taking dopamine agonists or dopaminergic agents such as levodopa should have a review of their medication, should not be driving a car on their own and some may merit formal sleep architecture studies. The latter may identify sleep disorders such as secondary narcolepsy which may benefit from the use of a wakefulness promoting agent.     

Spotlight on rotigotine in Parkinson's disease

A transdermal patch formulation of the non-ergolinic dopamine receptor agonist rotigotine (Neupro) is indicated for use as monotherapy in the treatment of early-stage Parkinson's disease or, in the EU, as an adjunct to levodopa across all disease stages. Transdermal rotigotine is an effective and generally well tolerated addition to the armamentarium for the control of Parkinson's disease, with the once-daily transdermal patch system offering several practical advantages and the possible benefits of avoiding pulsatile dopaminergic stimulation. Transdermal rotigotine was superior to placebo in patients with early-stage and advanced Parkinson's disease, although noninferiority to the oral dopamine receptor agonists ropinirole or pramipexole was not consistently demonstrated. Additional active comparator trials would be of interest. In the meantime, transdermal rotigotine offers a convenient new treatment option for patients with Parkinson's disease.