Original ArticleLong-term use of pramipexole in the management of restless legs syndrome
Introduction
Restless legs syndrome (RLS) (Willis–Ekbom disease) is characterized by an urge to move the legs, usually associated with uncomfortable sensations. RLS symptoms manifest during rest, are relieved with movement and are typically most severe in the evening or night [1], [2]. RLS is associated with insomnia in 50–85% of cases, affecting both sleep onset and sleep maintenance [3]. At least 80% of patients with RLS have periodic limb movements of sleep, which may lead to sleep disruption [4]. RLS is a common disorder affecting between 5% and 15% of the general population, and prevalence has been observed to rise with age [4], [5], [6], [7], [8], [9], [10]. The prevalence of symptomatic primary RLS in the United States and Europe is estimated to be 2.4–4.4%, and 1.5–2.7% experience symptoms at least twice a week, resulting in moderate to severe distress [5], [6], [7], [8], [9], [10], [11], [12]. Pharmacologic treatment options for RLS include dopamine agonists, opioids, benzodiazepines and anticonvulsants.
Dopamine agonists, including pramipexole, are the mainstay of treatment for daily RLS (defined as symptoms frequent and troublesome enough to require daily therapy) [13]. Multiple controlled studies have demonstrated their efficacy; however, long-term use in clinical practice is constrained by the development of side effects and augmentation in many patients [3]. Although the mechanism of dopamine agonists in treating RLS is uncertain, it likely involves stimulation of dopamine receptors in the striatum. Pramipexole, a non-ergot agonist, is primarily metabolized through the kidneys and has a half-life of 8–12 h [14].
We have previously reported a study of 60 RLS patients initiated on pramipexole and followed for a mean of 27 months [2]. We now report an extended study on a cohort of 50 of these patients followed for a mean of 8 years. The goals of our study were to determine over an extended period the duration of therapy in this patient cohort, dosing parameters, long-term efficacy, side-effect profile and development of augmentation.
Section snippets
Methods
Fifty of the original 60 adult patients were recruited from the previous study [2]. The other 10 patients had discontinued pramipexole within 4 months of initiation of therapy due to either side effects or lack of efficacy. Each patient was diagnosed with RLS in the Mayo Clinic Center for Sleep Medicine. Patients were initiated on pramipexole therapy between 1 January 1998, and 31 December 1999.
Our study used data obtained from a retrospective chart review (n = 50), a written survey (n = 22) (
Demographic information
Fifty patients were identified and studied. Forty-six patients (92%) resided in Minnesota, Iowa or Wisconsin. Thirty-one were females (62%); 19 were males (38%). The mean age at onset of RLS symptoms was 42 years. The mean age at time pramipexole therapy was initiated was 60 years. Co-existing medical, sleep and psychiatric conditions included peripheral neuropathy (two patients), parkinsonism (one patient), obstructive sleep apnea (eight patients), central sleep apnea (one patient) and
Discussion
The results of our study suggest that pramipexole decreases in efficacy over time, dose increases are required and patients frequently need adjunct therapies. Data previously gathered on this cohort over a mean follow-up time of 27 months demonstrated that pramipexole was completely effective in 67% of patients [2]. In our study, after a mean follow-up period of 8 years, pramipexole was found to be completely effective in only 40% of patients. Despite this decrease in efficacy, 82% of our
Conflict of interest
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2012.08.004.
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