Restless Legs Syndrome

Melody Ryan; John T. Slevin

Am J Health Syst Pharm. 2006;63(17):1599-1612.

Treatment Options and Guidelines

See Table 1 for common starting and final doses for the more common medications used to treat RLS. Few guidelines have been developed for RLS treatment. The American Academy of Sleep Medicine has issued two practice parameters for the dopaminergic treatment of RLS and PLMD.^[124,125] The most recent was released in early 2004, before publication of the studies of ropinirole and FDA approval of its labeling for treatment of RLS.^[125] This document recommended levodopa with a decarboxylase inhibitor or pergolide as having the most evidence for efficacy. Pramipexole was suggested as a second-line agent, and ropinirole and other agonists were suggested as treatment options. The guideline acknowledges issues with augmentation caused by levodopa, but does not mention heart valve issues with pergolide.

An algorithm published by the Medical Advisory Board of the Restless Legs Syndrome Foundation advises clinicians to take different treatment approaches for intermittent and daily RLS.^[51] Some of the recommended treatments have no clinical data to support their use but are related to other agents that have been shown to improve RLS symptoms.

Because the risk of augmentation from treatment of intermittent RLS is less, the authors recommended carbidopa-levodopa and nonpharmacologic therapy.^[51] Other agents recommended for intermittent RLS include codeine, propoxyphene, temazepam, tramadol, triazolam, zaleplon, and zolpidem. Dopamine agonists are also recommended; however, because of their slow onset of action, they are not considered as effective for intermittent use.

For daily RLS, nonpharmacologic therapy is recommended.^[51] When it is insufficient, dopamine agonists, particularly pramipexole and ropinirole, are the drugs of choice. These agents are considered first line because of their favorable outcomes and less risk of augmentation, and they usually require once-daily administration compared with carbidopa-levodopa. Alternatives include codeine, gabapentin, propoxyphene, and tramadol, especially if RLS is associated with a painful neuropathy or other painful condition.

In addition to frequency of symptoms, treatment of RLS should be individualized with considerations for age, concomitant medications, co-morbid disease states, and history of augmentation or rebound. An algorithm for approaching a patient with RLS is proposed in Figure 1. Medications are usually initiated between one and three hours before bedtime. If the patient experiences rebound, either a controlled-release preparation of carbidopa-levodopa or additional doses of the other medications should be administered. Should augmentation develop, either the agent should be changed or additional doses should be given earlier during the day.

(Enlarge Image)

Figure 1.

Proposed algorithm for the treatment of restless legs syndrome (RLS).

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Cite this: Restless Legs Syndrome - Medscape - Sep 01, 2006.

Editor's Note
Signs and Symptoms
Epidemiology
Etiology
Pathophysiology
Diagnosis
Treatment
Dopaminergic Agents
Treatment Options and Guidelines
Conclusion
References
Appendix A: Diagnostic criteria for restless legs syndrome
Appendix B: Evaluation methods used in restless legs syndrome studies

Table 1. Common Dosages of Medications Used To Treat Restless Legs Syndrome ^{[68,69,70,71,72,73,74,75,76,77,78,79,80,85,86,87,88,89,103,104,105,109,110,112,113,114,115,116,120,121,122,123]}
Medication	Starting Dosage (mg/day)	Final Dosage (mg/day)
Oral iron replacement^a
Ferrous sulfate	975	Not applicable
Ferrous gluconate	1950	Not applicable
Ferrous fumarate	600	Not applicable
Dopaminergic agents
Carbidopa or benserazide with	25	50
levodopa	100	200
Ropinirole^b	0.25	1.5-2
Pergolide^c	0.05	0.35-0.5
Pramipexole dihydrochloride	0.375	0.5-1.50
Anticonvulsants
Gabapentin	100-300	200-900
Carbamazepine	200	200-400
Benzodiazepines
Clonazepam	1	1

^aListed salts supply approximately 200 mg of elemental iron daily.
^bAs the hydrochloride salt.
^cAs the mesylate salt.

Appendix B: Evaluation methods used in restless legs syndrome studies

Rating scales

The Clinician Global Impression-Improvement scale is a rating system in which the clinician assigns a score from 1 (very much improved) to 7 (very much worse). It is not specific to restless legs syndrome (RLS).
The International Restless Legs Syndrome scale is a 10-item scale with scores ranging from 0 (best) to 40 (worst). Items assess the intensity and frequency of the primary features of RLS, associated sleep problems, and the impact of RLS on mood and daily functioning. Patients' RLS can be classified as mild (1-10), moderate (11-20), severe (21-30), or very severe (31-40).^[8]
The Medical Outcomes Study Sleep Scale has been validated in the general population but is not specific to RLS. Patients self-rate sleep disturbance, sleep adequacy, daytime somnolence, sleep quantity, respiratory impairments, and snoring. The score on each item ranges from 0 to 100.^[9]
The Pittsburgh Sleep Quality Index is a 19-item questionnaire to assess sleep quality and sleep disturbances. Patients score between 0 (best) and 21 (worst).
The Restless Legs Syndrome Quality of Life questionnaire is a validated 18-item questionnaire. Ten items are used to calculate an overall life impact score ranging from 0 (lowest quality of life) to 100 (best quality of life). The remaining items assess employment, work, and sexual interest.^[10]
The Short Form-36 is a well-validated, 36-item questionnaire. Quality of life is assessed in the domains of physical function, social function, role disturbances resulting from physical and emotional problems, mental health, energy and vitality, pain, and general health perception. It is not specific to RLS.
Sleep diaries are used daily to document the time the patient sleeps and subjective sleep quality.
The Standardized Sleep Inventory Schlaf-Fragebogen, part A, is a 22-item questionnaire that assesses sleep patterns and mood.

Clinical tests

Actigraphy is a method of counting movements during sleep. An activity meter is placed around the ankle. While not as detailed as polysomnography, actigraphy can be performed in the patient's home and is more economical.
Polysomnography is almost always performed in a sleep laboratory. Electroencephalography, surface electromyography (EMG), and video recordings of sleep are performed over one or more nights. From these data, a number of criteria can be derived: the total number of periodic limb movements of sleep (PLMS), PLMS index (number of PLMS per hour), PLMS arousal index (number of PLMS associated with arousal per hour), total number of arousals, sleep efficiency, and sleep latency (time for an individual to go to sleep).^[8]
The suggested immobilization test assesses RLS symptoms while the patient is awake. EMG surface electrodes are placed on the legs, and the patient is instructed to sit on the bed with eyes open and legs outstretched without moving. The patient indicates RLS sensations during the test.^[8]

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Restless Legs Syndrome

Treatment Options and Guidelines

Tables

References

Authors and Disclosures

Authors and Disclosures

Appendix

Appendix A: Diagnostic criteria for restless legs syndrome

Appendix

Appendix B: Evaluation methods used in restless legs syndrome studies

Figure 1.

Figure 1.

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