Medication Summary
Medications used in the treatment of restless legs syndrome (RLS) include the following:
-
Dopaminergic agents
-
Benzodiazepines
-
Opioids
-
Anticonvulsants
-
Alpha2 -adrenergic agonists
-
Iron salt
A network meta-analysis of 10,674 participants found that, compared with placebo, only levodopa is inefficient to relieve symptoms of RLS. The researchers recommend gabapentin, gabapentin enacarbil, and pregabalin as first-line treatement. Oxycodone-naloxone could be considered in patients with severe or very severe RLS who failed in treatment with other drugs. [38]
Antiparkinson Agents, Dopamine Agonists
Class Summary
Dopamine agonists may improve sensory symptoms associated with RLS. Agents such as pramipexole, ropinirole, and bromocriptine are less likely to produce augmentation or rebound than the combination of levodopa and carbidopa is. These agents can be used alone or along with levodopa.
Pramipexole (Mirapex, Mirapex ER)
Pramipexole is a dopamine D2- and D3-receptor agonist that has been approved by the US Food and Drug Administration (FDA) for the treatment of Parkinson disease. It is also used effectively in patients with RLS.
Ropinirole (Requip, Requip XL)
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 dosage of 50/200 mg/day.
Dosages higher than 50/200 mg/day are accompanied by marked augmentation of symptoms in 85% of patients. Adjunctive therapy with reduction of levodopa dose or discontinuance 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)
Rotigotine is a dopamine agonist stimulating D3, D2, and D1 receptors. It is indicated for treatment of moderate-to-severe primary RLS. It is available as a transdermal patch that provides continuous delivery for 24 hours.
Anxiolytics, Benzodiazepines
Class Summary
A benzodiazepine may be used as monotherapy in patients with mild or intermittent symptoms of RLS or as a component of 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.
Opioid Analgesics
Class Summary
Low-potency opioids (eg, codeine) can benefit patients with mild and intermittent symptoms; higher-potency agents (eg, oxycodone hydrochloride, methadone hydrochloride, and levorphanol tartrate), 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
Codeine 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 have caused augmentation problems.
Anticonvulsants, Other
Class Summary
Anticonvulsants 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, has been approved by the FDA. In a randomized, placebo-controlled study, 600 mg orally, taken once daily at 5 PM, provided sustained gabapentin exposure and maintained improvements in RLS symptoms in comparison with placebo. [29]
Gabapentin (Neurontin)
Gabapentin is indicated for patients whose symptoms include pain, neuropathy, or both. 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. It is not FDA-approved for the treatment of RLS.
Alpha2-Adrenergic Agonists
Class Summary
Presynaptic alpha2 -adrenergic 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.
