Mark J. Buchfuhrer

An Algorithm for the Management of Restless Legs Syndrome

Restless legs syndrome (RLS) is a common disorder with a prevalence of 5% to 15%. Primary care physicians must become familiar with management of this disorder. This algorithm for the management of RLS was written by members of the Medical Advisory Board of the Restless Legs Syndrome Foundation and is based on scientific evidence and expert opinion. Restless legs syndrome is divided into intermittent, daily, and refractory types. Nonpharmacological approaches, including mental alerting activities, avoiding substances or medications that may exacerbate RLS, and addressing the possibility of iron deficiency, are discussed. The role of carbidopa/levodopa, dopamine agonists, opioids, benzodiazepines, and anticonvulsants for the different types of the disorder is delineated.

Guidelines for the first-line treatment of restless legs syndrome/Willis–Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation

A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) in conjunction with the European Restless Legs Syndrome Study Group (EURLSSG) and the RLS Foundation (RLS-F) to develop evidence-based and consensus-based recommendations for the prevention and treatment of long-term pharmacologic treatment of dopaminergic-induced augmentation in restless legs syndrome/Willis-Ekbom disease (RLS/WED). The Task Force made the following prevention and treatment recommendations: As a means to prevent augmentation, medications such as α2δ ligands may be considered for initial RLS/WED treatment; these drugs are effective and have little risk of augmentation. Alternatively, if dopaminergic drugs are elected as initial treatment, then the daily dose should be as low as possible and not exceed that recommended for RLS/WED treatment. However, the physician should be aware that even low dose dopaminergics can cause augmentation. Patients with low iron stores should be given appropriate iron supplementation. Daily treatment by either medication should start only when symptoms have a significant impact on quality of life in terms of frequency and severity; intermittent treatment might be considered in intermediate cases. Treatment of existing augmentation should be initiated, where possible, with the elimination/correction of extrinsic exacerbating factors (iron levels, antidepressants, antihistamines, etc.). In cases of mild augmentation, dopamine agonist therapy can be continued by dividing or advancing the dose, or increasing the dose if there are breakthrough night-time symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. For severe augmentation the patient can be switched either to an α2δ ligand or rotigotine, noting that rotigotine may also produce augmentation at higher doses with long-term use. In more severe cases of augmentation an opioid may be considered, bypassing α2δ ligands and rotigotine.

Strategies for the Treatment of Restless Legs Syndrome

Restless legs syndrome (RLS) is a common neurological disorder of unknown etiology that is managed by therapy directed at relieving its symptoms. Treatment of patients with milder symptoms that occur intermittently may be treated with nonpharmacological therapy but when not successful, drug therapy should be chosen based on the timing of the symptoms and the needs of the patient. Patients with moderate to severe RLS typically require daily medication to control their symptoms. Although the dopamine agonists, ropinirole and pramipexole have been the drugs of choice for patients with moderate to severe RLS, drug emergent problems like augmentation may limit their use for long term therapy. Keeping the dopamine agonist dose as low as possible, using longer acting dopamine agonists such as the rotigotine patch and maintaining a high serum ferritin level may help prevent the development of augmentation. The α2δ anticonvulsants may now also be considered as drugs of choice for moderate to severe RLS patients. Opioids should be considered for RLS patients, especially for those who have failed other therapies since they are very effective for severe cases. When monitored appropriately, they can be very safe and durable for long term therapy. They should also be strongly considered for treating patients with augmentation as they are very effective for relieving the worsening symptoms that occur when decreasing or eliminating dopamine agonists.

The Appropriate Use of Opioids in the Treatment of Refractory Restless Legs Syndrome

&NA; Restless legs syndrome (RLS) is a distinct disorder, differing from chronic pain in many ways. Refractory RLS is characterized by unresponsiveness to dopamine agonists or alpha‐2‐delta ligands due to inadequate efficacy, augmentation, or adverse effects. This may result in severely impaired quality of life, profound insomnia, and suicidal depression. Opioid therapy is a mainstay in the management of these patients. This article summarizes the basic science and clinical evidence in support of their use, including the positive result of a large controlled multicenter study of 306 subjects, and outlines an approach to their use in clinical practice. Treatable explanations for RLS refractoriness, such as low iron stores, and other therapeutic options, such as combination therapy, should be considered before prescribing opioids. The agents most commonly used are oxycodone and methadone, but tramadol, codeine, morphine, and hydrocodone can also be considered. Controlled‐release medication should be used for evening dosage and short‐acting drugs, if needed, during the day. Effective doses are considerably lower than used for chronic pain (oxycodone 10‐30 mg daily; methadone 5‐20 mg daily) and the risk of opioid use disorder is relatively low. However, sensible precautions should be undertaken, including assessing opioid risk with standard questionnaires, using an opioid contract, using urine drug screens, consulting state prescription drug monitoring programs, and frequent reevaluation of effectiveness and side effects. Opioid use in selected patients with refractory RLS may be life‐transforming with favorable risk‐benefit ratio.

Treatment Options When Short-Acting Dopamine Agonists Fail or Cause Augmentation: Switching or Adding Medications

Short-acting dopamine agonists are currently the most commonly prescribed drugs for treating RLS. Although many patients may do well with low doses of these drugs, the majority of patients may eventually fail this treatment or develop augmentation. These patients may need to change their treatment or add other therapy to control their RLS symptoms. This chapter discusses the different reasons for treatment failure and the various options for managing them. Guidelines include a revised algorithm for dealing with augmentation from short-acting dopamine agonists.