Restless Legs Syndrome Medication
- Author: Ali M Bozorg, MD; Chief Editor: Selim R Benbadis, MD more...
Medication Summary
Medications used in the treatment of restless legs syndrome (RLS) include the following:
- Dopaminergic agents
- Benzodiazepines
- Opioids
- Anticonvulsants
- Presynaptic alpha2-adrenergic agonists
- Iron salt
All patients with low iron levels (ferritin < 50 ng/mL) should receive supplemental iron therapy.[24] In iron deficiency, ferrous sulfate 325 mg may be given with 250 mg of vitamin C. Absorption is increased by taking this on an empty stomach and waiting 60 minutes before eating.
Parenteral iron may also have a role in the treatment of RLS secondary to iron deficiency anemia.[26]
Anecdotal evidence from Japan shows effectiveness of yokukansan (an herbal remedy) in the treatment of RLS.[27] Oral corticosteroids have also been used for the treatment of RLS in exceptional circumstances.[28] Steroids and yokukansan are not approved by the US Food and Drug Administration (FDA) for the treatment of RLS.
Pharmacotherapy in children
No specific recommendations or FDA-approved medications exist for the treatment of RLS in children. Children with low serum ferritin (< 50 ng/mL) should be treated with supplemental iron therapy. Dopaminergic therapy was found to be effective in small series in children with RLS.
Antiparkinson Agents, Dopamine Agonists
Class Summary
These agents may improve sensory symptoms associated with RLS. Agents like pramipexole, ropinirole,[18] and bromocriptine are less likely than the combination drug levodopa/carbidopa to produce augmentation or rebound. They can be used alone or along with levodopa in patients in whom 1 of these conditions develops.
Adverse effects of dopamine agonists include nausea, light-headedness, drowsiness, and postural hypotension. Levodopa/carbidopa is generally reserved for patients with infrequent symptoms, because of problems with augmentation and rebound.[29, 30] A positive response to dopaminergic therapy supports the diagnosis of RLS.
Pramipexole (Mirapex)
Pramipexole is a D2- and D3-receptor agonist that has been approved by the FDA for the treatment of Parkinson disease. It is also used effectively in patients with RLS.
Ropinirole (Requip)
Ropinirole is a dopamine D2-receptor agonist that has been approved by the FDA for the treatment of Parkinson disease. It has also has been used in patients with RLS. Ropinirole is a nonergoline, nonphenolic indolone derivative.
Levodopa with carbidopa (Sinemet, Parcopa)
Levodopa with carbidopa can improve sensory symptoms and periodic leg movements of sleep (PLMS) in primary RLS and in secondary RLS due to uremia. Most patients experience benefits with doses of 25/100 mg (in mild cases), with a maximum dose of 50/200 mg/day.
Doses of greater than 50/200 mg are accompanied by marked augmentation of symptoms in 85% of patients. Adjunctive therapy with reduction of levodopa dose or discontinuation of levodopa and substitution with a dopamine agonist drug may help. Sinemet is preferred for patients with occasional and mild symptoms.
Bromocriptine mesylate (Parlodel, Cycloset)
Bromocriptine mesylate is a dopamine D2-receptor agonist that has been found to be effective in RLS. However, it is usually poorly tolerated because of nausea and orthostatic hypotension.
Other dopamine agonists, such pramipexole, are preferred.
Rotigotine (Neupro)
Dopamine agonist stimulating D3, D2, and D1 receptors. Indicated for treatment of moderate-to-severe primary restless legs syndrome. Available as transdermal patch that provides continuous delivery for 24 h.
Anxiolytics, Benzodiazepines
Class Summary
These agents may be used as monotherapy in patients with mild or intermittent symptoms of RLS or as combination therapy in severe cases. Clonazepam has been shown to ease sensory symptoms and PLMS in RLS. Other benzodiazepines, such as temazepam and alprazolam, also can be effective.
Clonazepam (Klonopin)
No controlled trials have demonstrated that clonazepam or any other gamma-aminobutyric acid (GABA)–ergic sedative hypnotic actually reduces the symptoms of RLS. Clonazepam's therapeutic benefit appears to arise from sleep-promoting properties that allow the patient to continue to sleep despite disturbances from RLS symptoms
Opioids Analgesics
Class Summary
Low-potency opioids, such as codeine, can benefit patients with mild and intermittent symptoms; higher-potency agents, such as oxycodone hydrochloride (Roxicodone), methadone hydrochloride (Dolophine), and levorphanol tartrate (Levo-Dromoran), may have a role in refractory cases. Because of the risk of addiction, these drugs should be used with caution; their use usually is recommended only in refractory cases, especially in ones with a prominent pain component.
Codeine
This and other opioids can be helpful in decreasing the symptoms of RLS, serving as a treatment of second choice when other treatments have failed or caused augmentation problems.
Anticonvulsants, Other
Class Summary
These agents are being used more frequently for the treatment of moderate to severe RLS. They are particularly helpful in patients with a strong neuropathic symptom component or with comorbid neuropathy.
Gabapentin Enacarbil (Horizant)
A prodrug of gabapentin, gabapentin enacarbil (Horizant), has been approved by the FDA. In a randomized, placebo-controlled study, 600 mg oral, taken once daily at 5 pm, provided sustained gabapentin exposure and maintained improvements in RLS symptoms compared with placebo.[31]
Gabapentin (Neurontin)
Gabapentin is indicated for patients whose symptoms include pain and/or neuropathy. It may be used as a single treatment or with other treatments.
Pregabalin (Lyrica)
Pregabalin binds with high affinity to the alpha2-delta site (a calcium channel subunit). Its mechanism of action is unknown. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. This agent is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures. Pregabalin is not FDA-approved for the treatment of RLS.
Presynaptic Alpha2-Adrenergic Agonists
Class Summary
These agents stimulate alpha2 adrenoreceptors in the brainstem, activating an inhibitory neuron, which in turn results in reduced sympathetic outflow.
Clonidine hydrochloride (Catapres, Kapvay, Nexiclon XR)
Clonidine hydrochloride may be effective in primary RLS, as well as in RLS associated with uremia. However, it has no effect on PLMS.
Iron Salt
Class Summary
Iron salt is used to correct iron deficiency resulting from chronic hemodialysis.
Iron sucrose (Venofer)
Iron sucrose is used to treat iron deficiency (in conjunction with erythropoietin) due to chronic hemodialysis. Iron sucrose has shown a lower incidence of anaphylaxis than other parenteral iron products. Parenteral iron sucrose has also been shown to improve symptoms of RLS in patients with RLS and low ferritin levels. Parenteral iron sucrose is not FDA approved for the treatment of RLS.
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