Appropriate Use of Dopamine Agonists and Levodopa in Restless Legs Syndrome in an Ambulatory Care Setting

Ogochukwu Chidozie Molokwu, PharmD


The Annals of Pharmacotherapy. 2008;42(5):627-632. 

In This Article

Abstract and Introduction

Background: Dopaminergic agents are the mainstay therapy for the management of restless legs syndrome (RLS). There are no clear guidelines on RLS management, and no study has evaluated the appropriate use of dopaminergic agents in RLS.
Objective: To evaluate the appropriateness of use of dopaminergic agents in RLS management in an ambulatory care setting based on the most current scientific evidence.
Methods: A retrospective drug utilization evaluation was conducted in patients who received levodopa or dopamine agonist for RLS from July 1, 2006, to July 31, 2007. Patients' medical records were reviewed and data were collected on demographics; comorbidities; laboratory values; doses of levodopa or dopamine agonists; prescribing physician's specialty; and use of alcohol, tobacco, and caffeine.
Results: A total of 27 patients were included in the study for data collection and analysis. Twenty-two (81%) patients were on levodopa and 5 (19%) were on ropinirole. RLS severity was documented in only 2 (7%) patients. Serum ferritin levels and transferrin-iron saturation (Tsat) percentages were not obtained in 18 (67%) and 20 (74%) of the patients, respectively. Two (7%) patients had ferritin levels less than 50 ng/mL, and 7 (26%) patients had ferritin levels greater than 50 ng/mL. Fourteen (52%) patients were taking concurrent antidepressants and 6 (22%) were taking sedating antihistamines. Alcohol and tobacco use was documented in 2 (7%) and 8 (30%) patients, respectively. Twenty-six (96%) of the prescribing physicians were primary care providers.
Conclusions: The findings of this study confirm the need for provider education about the appropriate use of levodopa and dopamine agonists in patients with RLS. Appropriate use of these drugs may help decrease unnecessary adverse effects, complications, and costs.

Restless legs syndrome (RLS) is characterized mainly by the urge to move the legs. The urge occurs especially at rest and in the evening and is relieved partially or completely by movement. Prevalence studies show that RLS affects approximately 10% of the US population.[1,2] It is more prevalent in women than in men, and the incidence increases with age.[2,3] RLS was first described by a Swedish neurologist, Karl Ekbom, in 1945.[4] Over recent years, there has been more focus on RLS, with increased clinical trials and education to bolster awareness, recognition, and diagnosis. In 1995, the International Restless Legs Syndrome Study Group released formal diagnostic criteria for RLS[5] and, more recently, developed updated diagnostic criteria in collaboration with the National Institutes of Health.[6]

Currently, there are no clear guidelines on the management of RLS, but in 2004, an expert panel of the Medical Advisory Board of Restless Legs Syndrome Foundation developed an algorithm for the management of RLS based on scientific evidence and expert opinion (Figures 1 and 2). [7] The algorithm divides RLS into intermittent, daily, and refractory, and includes both pharmacologic and nonpharmacologic recommendations. Although the pathophysiology of primary RLS is not well understood, current scientific evidence suggests that it can result from a disorder in the dopaminergic system, and several studies have shown that patients with RLS responded well to dopaminergic agents.[8,9,10] Conditions such as end-stage renal disease, iron deficiency, pregnancy, and neuropathies, as well as certain medications and lifestyle factors (eg, alcohol, caffeine, nicotine), have been associated with induction or exacerbation of RLS.[11,12,13,14,15,16,17,18,19]

Algorithm for the management of intermittent RLS.a RLS = restless legs syndrome.
aAdapted with permission.[7]

Algorithm for the management of daily and refractory RLS.a RLS = restless legs syndrome.
aAdapted with permission.[7]

Dopamine agonists are considered first-line treatment of RLS. Dopamine precursors like levodopa are also widely used for this disorder. In May 2005, ropinirole became the first Food and Drug Administration (FDA)-approved agent for the treatment of moderate-to-severe primary RLS, and in November 2006, pramipexole was approved for the same indication. With the approval of these drugs, it is no surprise that there has been an increase in media reporting to bolster awareness and diagnosis of RLS, as well as a barrage of direct-to-consumer drug advertising.[20]

Although several clinical trials have shown significant benefits of these drugs, no study has looked at their appropriate use. Appropriate use of dopaminergic agents in RLS management can be defined as selecting drug therapy based on an individual's RLS symptom severity. Appropriate use also involves incorporating nonpharmacologic therapy before or with drug therapy depending on an individual's RLS symptom severity. Inappropriate use of these agents could lead to increased cost, unnecessary adverse effects, and complications. Ropinirole and pramipexole produce a number of adverse effects, most commonly, nausea, dizziness, fatigue, insomnia, hallucinations, and peripheral edema. Augmentation and rebound are also well-known complications of dopaminergic agents, especially levodopa.

The goal of this study was to retrospectively evaluate the utilization and appropriate use of ropinirole and pramipexole in the treatment of RLS, based on the most current scientific evidence.


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