A randomized controlled study of pergolide in patients with restless legs syndrome
ABSTRACT Open clinical trials indicate that low doses of pergolide, a long-acting D1 and D2 dopamine agonist, lead to a reduction in the symptoms of restless legs syndrome (RLS) with subjective improvement in sleep quality.
To assess the therapeutic efficacy of pergolide in improving sleep and subjective measures of well-being in patients with idiopathic RLS using polysomnography and clinical ratings.
In a randomized, double-blind, placebo-controlled crossover design we enrolled 30 patients with idiopathic RLS according to the criteria of the International RLS Study Group. All patients were free of psychoactive drugs for at least 2 weeks before the study. Patients were monitored using polysomnography, clinical ratings, and sleep diaries at baseline and at the end of a 4-week pergolide or placebo treatment period. The initial dosage of 0.05 mg pergolide was increased to the best subjective improvement paralleled by 20 mg domperidone tid.
At a mean dosage of 0.51 mg pergolide as a single daily dose 2 hours before bedtime, there were fewer periodic leg movements per hour of time in bed (5.7 versus 54.9, p < 0.0001), and total sleep time was significantly longer (373 versus 261 minutes, p < 0.0001). Ratings of subjective sleep quality, quality of life, and severity of RLS were improved significantly without relevant adverse events.
Pergolide given as a single low-to-medium bedtime dose in combination with domperidone provides a well-tolerated and effective treatment of sensorimotor symptoms and sleep disturbances in patients with primary RLS.
- SourceAvailable from: Yong-Ku Kim
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- "The cause of RLS has yet to be identified, but a large body of evidence suggests that it is caused by impairment of the central dopaminergic system. Some of the evidence to support this idea includes that the fact that RLS symptoms improve after treatment with dopamine-mimetic agents and the results of recent neuroimaging studies (Montplaisir et al., 1999; Ruottinen et al., 2000; Turjanski et al., 1999; Wetter et al., 1999). RLS is also thought to occur more frequently in patients who take antipsychotics that block dopamine receptors. "
ABSTRACT: This study aimed to investigate whether the monoamine oxidase (MAO) A and B genes are associated with antipsychotic-induced restless legs syndrome (RLS) in schizophrenia. We assessed antipsychotic-induced RLS symptoms in 190 Korean schizophrenic patients and divided the subjects into two groups: those with RLS symptoms (n = 96) and those without RLS symptoms (n = 94). Genotyping was performed for the variable number of tandem repeat (VNTR) polymorphism of the MAOA gene and A644G polymorphism of the MAOB gene. There was no significant difference in the genotype and allele frequencies of all polymorphisms investigated between these two groups. However, the result of global haplotype analysis showed a significant difference in haplotype frequencies between male subjects with and without RLS symptoms (p = 0.013). The interaction between two polymorphisms had a significant effect on the RLS scores of both male (p = 0.047) and female (p = 0.028) patients. These data do not suggest that the MAOA gene VNTR and MAOB gene A644G polymorphisms are associated with antipsychotic-induced RLS symptoms in schizophrenia. However, we found that the haplotype frequencies differed between the male schizophrenic patients with and without RLS symptom and the interaction between the two polymorphisms had a significant influence on the RLS scores of patients with schizophrenia.Human Psychopharmacology Clinical and Experimental 07/2010; 25(5):397-403. DOI:10.1002/hup.1130 · 1.85 Impact Factor
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- "While iron appears to play a key role in secondary RLS, it is more likely that RLS relates directly to dysfunction in production of dopamine, which is dependent on availability of iron  . Furthermore , centrally acting dopaminergic antagonists tend to exacerbate RLS, whereas peripherally active dopaminergic antagonists do not . There have been three prior case reports of phantom restless legs   , all of whom responded well to dopaminergic agonist treatment. "
ABSTRACT: Chronic pain conditions often "mimic" the symptoms of restless legs syndrome (RLS) with worse pain in the evening and upon rest, associated with an urge to move and relief upon movement. We propose that too little has been made of these parallels, with pain conditions resembling RLS being dismissed as mimics. We found, in a large questionnaire study (n=283) on phantom limb perception, a pattern of phantom pain that resembled RLS: amputees with nocturnal phantom pain were more likely to report worse pain upon rest and/or lying down, with an urge to move the phantom and/or walk to relieve their pain, and to experience spontaneous limb movements akin to periodic leg movements of RLS. We present the hypothesis that a model of restless legs syndrome may provide new insights into the mechanisms underlying phantom pain, and lead to new mechanism-based phantom pain treatment. In particular, central changes associated with sensory and motor symptoms of RLS, neuropathy, and dopamine may also be involved in those predisposed to experience phantom pain that mimics the symptoms of RLS. Ultimately, restless legs syndrome may indeed be a pain syndrome, and warrants further investigation in chronic pain populations.Medical Hypotheses 06/2010; 74(6):968-72. DOI:10.1016/j.mehy.2009.12.009 · 1.07 Impact Factor
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- "Metoclopramide, a dopamine antagonist that crosses the blood–brain barrier, can markedly worsen symptoms of RLS and neutralize the therapeutic effect of dopamine agonists.32 However, dopamine antagonists that do not cross the blood–brain barrier, such as domperidone, are void of RLS-exacerbating effects.33 Functional magnetic resonance imaging (fMRI) has been used to study what sites of the brain are involved in involuntary leg movements in RLS. "
ABSTRACT: Restless legs syndrome and periodic limb movement disorder of sleep are now recognized as prevalent, distinct, yet overlapping disorders affecting all age groups. Although delineation of the mechanisms underlying these disorders continues to be the focus of very intense research efforts, it has become apparent that there is a prominent role for dopaminergic agents in the clinical management of these patients. Among the various dopaminergic drugs, ropinirole has undergone relatively intense and critical scrutiny, and appears to provide a safe and efficacious treatment option for patients with these two conditions. The more recent development of a controlled formulation for this drug is likely to yield additional benefits such as improved adherence and reduced fluctuations in daytime and nighttime symptoms. However, there is not enough evidence at this time to support such assumption.Therapeutics and Clinical Risk Management 04/2010; 6:173-82. · 1.47 Impact Factor