One goal of RLS therapy is to reduce its symptoms, including decreasing the number of nights with RLS symptoms, the severity of RLS symptoms, and nighttime awakenings. Another goal pertains to quality of life, including improving the overall quality of life, decreasing daytime somnolence, and improving the quality of sleep. These goals are addressed through nonpharmacologic and pharmacologic therapies.
There have been no systematic trials of nonpharmacologic therapies for RLS patients. Thus, the only support for the use of the following nonpharmacologic therapies is from case series or anecdotal reports. Many experts recommend good sleep hygiene, including rising and going to bed at the same times each day.[63,64] Avoidance of alcohol, caffeine, and nicotine may improve symptoms. Other recommendations include hot baths, massage, stretching, and moderate exercise. For symptoms that occur in the evening, patients may find that activities that alert the mind, such as crossword puzzles and video games, reduce symptoms. Many patients also benefit from RLS support groups; a list of local support groups can be located at www.RLS.org.
There are limited data on the treatment of RLS. Most of the trials have been quite small, with less than 15-20 patients, and they have been likely underpowered to detect statistical significance. The reasons for the small number of patients may be multifactorial. The lack of awareness of RLS by patients and the medical community probably contributes to trials with few subjects because many patients may not seek medical care, or they may not be referred to a research center. This same lack of awareness tends to bias studies because only patients with the most severe RLS seek treatment and participate in trials. A polysomnographic evaluation requires staying in a sleep laboratory for one or two nights, and it is very expensive in cost and technician time. Therefore, investigators may not have the resources to enroll many patients in trials, and patients may be reluctant to undergo monitoring. In addition, some studies enroll all patients with RLS, regardless of etiology, and some studies include patients with only PLMS. This diverse population makes interpretation of study outcomes difficult.
Until very recently, almost all studies used a crossover design to maximize data obtainable from each patient. Some of the trials used washout periods between treatments, but many did not. The other predominant type of study is an open-label case series. These patient data are usually compared to baseline data and do not have the advantages of blinding or randomization. In most studies, doses are increased until symptoms are relieved, the subject experiences intolerable adverse effects, or a maximum dosage is reached.
Methods of evaluation vary considerably between studies; thus, study outcomes are difficult to compare. Some trials use measures of limb activity during sleep or number of awakenings through the sleep period. Others rely on various rating scales. Of note, a validated instrument for self-assessment of RLS symptoms was not developed until 2003. These evaluation methods are described in Appendix B.
Accurate assessments of the adverse-effect profile of potential therapeutic agents are also elusive. Many studies are so small that it is difficult to amass much information on adverse effects. While it is reasonable to assume many adverse effects of medicines would be the same regardless of the illness treated, adverse effects more prominent in or unique to RLS treatment have emerged. Contributing to the dearth of information, many therapeutic studies fail to mention adverse effects at all.
As part of the patient evaluation for RLS, it is important to measure the serum ferritin concentration as well as the usual anemia markers of red blood cell count, hemoglobin, and hematocrit. The normal ferritin range for adults is 20-300 µg/L for men and 20-150 µg/L for women. Because individuals may experience symptoms when ferritin is in the low normal range, most experts recommend iron supplementation if ferritin concentrations are below 50 µg/L.[51,65] It should be noted that Davis et al. reported that iron supplementation is not effective in RLS patients who do not have frank iron deficiency.
There are no double-blind, placebo-controlled studies of oral iron replacement therapy in RLS patients with iron deficiency. However, a study comparing placebo with a one-time dose of i.v. iron dextran equivalent to iron 1000 mg demonstrated improvement in RLS symptoms and increased serum ferritin concentrations in patients with end-stage renal disease. In this study, subjects were administered an equivalent of iron 30 mg over three minutes and then were observed for an hour. If no test dose reactions were detected, the remainder of the dose was infused over three hours. Improvement in RLS symptoms was detected at the one-week assessment, peaked at two weeks (p = 0.03), and began to decline thereafter.
There is no consensus regarding oral iron replacement specifically for secondary RLS treatment. Many clinicians follow standard recommendations for iron-deficiency anemia and supply 200 mg of elemental iron, divided into two or three daily doses as tolerated by the patient. Dark feces, nausea, vomiting, and diarrhea can complicate oral iron therapy and may cause adherence problems among patients.
Am J Health Syst Pharm. 2006;63(17):1599-1612. © 2006 American Society of Health-System Pharmacists
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