Original ArticleA 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome
Introduction
The initial excitement associated with the discovery of levodopa’s remarkable effectiveness in treating restless legs syndrome (RLS) symptoms was followed by the recognition that most patients developed severe, drug-related exacerbation (augmentation) of their RLS symptoms with longer-term treatment [1]. The dopamine (DA) agonists initially appeared to offer the same degree of treatment benefit with less augmentation. But these controlled studies of DA agonists were too short to give a clear picture of either continued efficacy or rates of RLS augmentation [2], [3], [4], [5], [6], [7], [8], [9], [10]. The follow-up periods in these studies averaged about 34 weeks and never exceeded one year. There are several longer-term treatment studies but even those provide data on only a few patients who had more than two years of medication use [11], [12], [13]. These studies, however, do suggest that augmentation associated with DA agonist treatment has a risk of occurring even after the first year of treatment, which is at least as large as the risk of developing augmentation in the first year of treatment.
Although there are limited data on the long-term effects and side effects of DA agonists, there are even less available on the non-DAergic treatments that are commonly used in RLS like gabapentin or the various opiates [14]. Augmentation has not yet been reported for these other types of medications with the exception of tramadol [15], [16]. The short observation period in these studies of non-DAergic medications precludes excluding augmentation as a potential long-term consequence.
The aim of this retrospective consecutive case series study was to examine the longer-term efficacy and, specifically, the rates of augmentation of several RLS medications over a 10-year time period.
Section snippets
Methods
The Johns Hopkins Center for restless legs syndrome has maintained a database on all patients seen in the Johns Hopkins Bayview Sleep Disorders Center with a final diagnosis of RLS since 1993. The diagnosis of RLS is based on the four clinical criteria, a thorough sleep history, medical examination and exclusion of potential mimic or confounder by other investigation (e.g., polysomnogram to verify periodic limb movements [PLMs] in complicated cases). All patients within this database were
Results
Adequate data were available from 164 patients on pramipexole, 77 patients on pergolide, and 76 patients on methadone. The percentage of patients discontinuing a medication during the first year of treatment was 17% for pramipexole, 23% for pergolide, and 15% for methadone. The annual percentage of patients discontinuing a medication for each subsequent year after the first was fairly consistent over each of the ensuing years: 9% for pramipexole, 8% for pergolide, and 0% for methadone (Fig. 1
Discussion
There are several notable findings in this study. First, the rate of augmentation severe enough to lead to discontinuing dopaminergic medication is not high in any given year, but continues to occur at about the same annual rate for up to 10 years (see Fig. 2). The lower augmentation rate observed in the first year and the persistence at a higher rate thereafter would be consistent with the concept that augmentation occurs because of some physiological response dependent on length of exposure to
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: doi:10.1016/j.sleep.2010.11.002.
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