Pharmacotherapy of Restless Legs Syndrome with Pramipexole

Restless Legs Syndrome (RLS) is one of the most common neurological diseases characterized by an urge to move the legs, often associated with unpleasant sensations relieved by movement. It is engendered by rest, and is worse in the evening or at night. Patients affected by severe RLS should be treated pharmacologically. Dopamine-agonists represent the first-line treatment for RLS symptoms. Pramipexole is a non-ergot derived dopamine agonist with a high selectivity for D2 and D3 receptors. At doses comprised between 0.125 and 0.75 mg, pramipexole improves subjective symptoms and objective signs of primary RLS even after the first administration. In addition, pramipexole seems to be safe and well tolerated. However, physicians should be aware that augmentation and compulsive behaviours might occur in their RLS patients treated with pramipexole. Further studies are needed to confirm the efficacy of pramipexole in uremic RLS and in children affected by the sleep disorder.

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Gabapentin treatment in clozapine-induced restless legs syndrome: two cases and a review of the literature

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125316672133 ◽

2016 ◽

Vol 7 (1) ◽

pp. 42-47 ◽

Cited By ~ 4

Author(s):

Vijaya Kumar ◽

Ganesan Venkatasubramanian

Keyword(s):

Restless Legs Syndrome ◽

Dopamine Agonists ◽

Clinical Presentation ◽

Dopamine Antagonists ◽

Review Of The Literature ◽

First Line ◽

Restless Legs ◽

Sensory Disturbances ◽

Antiepileptic Medications ◽

First Line Treatment

Restless legs syndrome (RLS) is a neuro-sensorimotor disorder affecting 2–4% of adults. It is characterized by intense urges to move the legs, associated with unpleasant sensory disturbances in the legs occurring at rest and manifests mostly in the evening and night, relieved by movement. Diagnosis is primarily based on clinical presentation and the consensus criteria for the diagnosis have been established. Antipsychotics, the dopamine antagonists, have been reported to induce RLS. Dopamine agonists, the effective first-line treatment of RLS, carry the risk of inducing or worsening psychosis. Many nondopaminergic agents including antiepileptic medications have also been used in the treatment of primary RLS. In this report we describe clozapine-induced RLS in two patients with schizophrenia and its successful treatment with gabapentin, a nondopaminergic agent. In addition, we have reviewed the available literature on clozapine-induced RLS and its management.

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Guidelines for the first-line treatment of restless legs syndrome/Willis–Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation

Sleep Medicine ◽

10.1016/j.sleep.2016.01.017 ◽

2016 ◽

Vol 21 ◽

pp. 1-11 ◽

Cited By ~ 124

Author(s):

Diego Garcia-Borreguero ◽

Michael H. Silber ◽

John W. Winkelman ◽

Birgit Högl ◽

Jacquelyn Bainbridge ◽

...

Keyword(s):

Disease Prevention ◽

Restless Legs Syndrome ◽

Task Force ◽

Line Treatment ◽

First Line ◽

Restless Legs ◽

Prevention And Treatment ◽

First Line Treatment

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Treatment Options for Idiopathic Restless Legs Syndrome

European Neurological Review ◽

10.17925/enr.2015.10.01.45 ◽

2015 ◽

Vol 10 (01) ◽

pp. 45 ◽

Cited By ~ 1

Author(s):

Félix Javier Jiménez-Jiménez ◽

Hortensia Alonso-Navarro ◽

Elena García-Martín ◽

José AG Agúndez ◽

◽

...

Keyword(s):

Restless Legs Syndrome ◽

Dopamine Agonists ◽

Treatment Options ◽

Drug Group ◽

First Line ◽

Preliminary Results ◽

Restless Legs ◽

Exponential Increase ◽

Alternative Drug ◽

Drug Treatments

The emergence of new effective therapies for idiopathic restless legs syndrome (iRLS) or WillisEkbom disease (WED) during the last 15 years resulted in an exponential increase of reports regarding this syndrome and, especially, treatment options. In this review, we summarise the main findings related to neuropharmacological aspects and non-pharmacological therapies of idiopathic RLS (iRLS). As was previously reported in several guidelines, dopamine agonists (fundamentally nonergotic derivatives), gabapentin and pregabalin should be considered as first-line therapies, as well as opiates as an alternative drug group. Preliminary results suggest that several non-pharmacological therapies should be promising as alternatives or adjuvants to drug treatments.

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Review of the Treatment of Restless Legs Syndrome: Focus on Gabapentin Enacarbil

Journal of Central Nervous System Disease ◽

10.4137/jcnsd.s9107 ◽

2012 ◽

Vol 4 ◽

pp. JCNSD.S9107 ◽

Cited By ~ 4

Author(s):

Rachel A. Burke ◽

Michele A. Faulkner

Keyword(s):

Clinical Trials ◽

Restless Legs Syndrome ◽

Dopamine Agonists ◽

First Line ◽

Gabapentin Enacarbil ◽

Restless Legs ◽

First Line Therapy ◽

Line Therapy ◽

Dopaminergic Agent

The FDA approved gabapentin enacarbil in 2011 as the first non-dopaminergic agent for the treatment of restless legs syndrome (RLS) symptoms. Although gabapentin enacarbil is a pro-drug of gabapentin, its pharmacokinetics differ. Absorption of gabapentin enacarbil is more predictable, and inter-patient variability in bioavailability is lower than that of gabapentin. Studies have demonstrated superiority of gabapentin enacarbil compared to placebo. Comparisons to currently available RLS treatments are lacking, but clinical trials demonstrate comparable improvement in RLS symptoms to the dopamine agonists ropinirole and pramipexole, which are usually considered first-line therapy for daily RLS symptoms. Gabapentin enacarbil was well tolerated in clinical trials. The role of the drug in RLS treatment remains undefined, although it will likely be used as an alternative for refractory RLS when other treatments have failed. Additionally, gabapentin enacarbil may be recommended for patients with daily RLS symptoms that are less intense or are associated with pain as an alternative to dopamine agonists.

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Dopamine Agonists and Impulse Control Disorders in Parkinson’s Disease

US Neurology ◽

10.17925/usn.2013.09.01.13 ◽

2013 ◽

Vol 09 (01) ◽

pp. 13 ◽

Cited By ~ 4

Author(s):

Daniel O Claassen ◽

Kristen Kanoff ◽

Scott A Wylie ◽

◽

...

Keyword(s):

Dopamine Agonist ◽

Clinical Features ◽

Impulse Control ◽

Dopamine Agonists ◽

Behavioral Syndrome ◽

Clinical Use ◽

Line Treatment ◽

Imaging Studies ◽

First Line ◽

First Line Treatment

The emergence of the behavioral syndrome known as impulse control disorder (ICD) in Parkinsons disease (PD) has increasingly been associated with dopamine agonist (DAA) use. Clinical reports emphasize the presence of excessive, disruptive, and atypical behaviors in PD patients that resolve after discontinuation or reductions of DAA therapy. The severity of these behaviors has resulted in a heightened clinical vigilance, especially in patients prescribed DAA. This review will discuss the historical rationale for the clinical use of DAA in PD, highlighting the increased association of ICD in patients prescribed DAA therapy. The association between DAA and the emergence of ICD supports the hypothesis that altered mesocorticolimbic function, further emphasized in behavioral and imaging studies, may account for the distinct compulsive hedonic behaviors that characterize the clinical features of this disorder. While the first-line treatment option is reduction and discontinuation of DAA therapy, other therapeutic options are discussed.

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MRI follow-up is unnecessary in patients with macroprolactinomas and long-term normal prolactin levels on dopamine agonist treatment

Acta Endocrinologica ◽

10.1530/eje-16-0897 ◽

2017 ◽

Vol 176 (3) ◽

pp. 323-328 ◽

Cited By ~ 8

Author(s):

J Eroukhmanoff ◽

I Tejedor ◽

I Potorac ◽

T Cuny ◽

J F Bonneville ◽

...

Keyword(s):

Multicenter Study ◽

Prolactin Level ◽

Dopamine Agonists ◽

Tumor Volume ◽

Line Treatment ◽

First Line ◽

Retrospective Multicenter Study ◽

First Line Treatment

Objective Both antitumor and antisecretory efficacies of dopamine agonists (DA) make them the first-line treatment of macroprolactinomas. However, there is no guideline for MRI follow-up once prolactin is controlled. The aim of our study was to determine whether a regular MRI follow-up was necessary in patients with long-term normal prolactin levels under DA. Patients and methods We conducted a retrospective multicenter study (Marseille, Paris La Pitie Salpetriere and Nancy, France; Liege, Belgium) including patients with macroprolactinomas (largest diameter: >10 mm and baseline prolactin level: >100 ng/mL) treated by dopamine agonists, and regularly followed (pituitary MRI and prolactin levels) during at least 48 months once normal prolactin level was obtained. Results In total, 115 patients were included (63 men and 52 women; mean age at diagnosis: 36.3 years). Mean baseline prolactin level was 2224 ± 6839 ng/mL. No significant increase of tumor volume was observed during the follow-up. Of the 21 patients (18%) who presented asymptomatic hemorrhagic changes of the macroprolactinoma on MRI, 2 had a tumor increase (2 and 7 mm in the largest size). Both were treated by cabergoline (1 mg/week) with normal prolactin levels obtained for 6 and 24 months. For both patients, no further growth was observed on MRI during follow-up at the same dose of cabergoline. Conclusion No significant increase of tumor size was observed in our patients with controlled prolactin levels on DA. MRI follow-up thus appears unnecessary in patients with biologically controlled macroprolactinomas.

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