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Medicines such as gabapentin, gabapentin enacarbil and pregabalin are the first line of treatment for most people with RLS. These medicines can cause side effects such as dizziness, unsteadiness, mental fog and weight gain. Treatment of Restless Legs Syndrome in Adults This information sheet is provided to help you understand the evidence for treating restless legs syndrome (RLS). It is a service of the American Academy of Neurology (AAN). Description Gabapentin enacarbil is used to treat moderate-to-severe primary Restless Legs Syndrome (RLS). RLS is a neurologic disorder that makes the legs feel uncomfortable. This results in an irresistible feeling of wanting to move your legs to make them comfortable. Gabapentin enacarbil is also used to manage a condition called postherpetic neuralgia, which is pain that occurs after Gabapentin enacarbil (marketed as Horizant) carries an FDA indication for the treatment of restless legs syndrome at a dose of 600 mg in the early evening, although FDA-approved doses of 1200 mg are permitted for other indications and used in some of the RLS clinical trials. Gabapentin’s effectiveness for RLS may take weeks, with dosage ranging from 300 mg to 3,600 mg daily. It’s initiated at a low dose and increased gradually. Continuity in usage is crucial, as full effects may take up to four weeks. Gabapentin has common side effects and rare serious reactions. Gabapentin typically takes about 1 to 2 hours to start working for restless legs, providing relief from discomfort and restlessness. Restless Legs Syndrome (RLS) is a condition that can significantly impact one’s quality of life. 3. NONDopaminergic drugs 3.1. α2δ Ligands α2δ Ligands drugs have been used for the treatment of RLS since the 2000s. Representative drugs are gabapentin enacarbil, gabapentin, and pregabalin. Gabapentin enacarbil is effective at dose of 1200 mg and well tolerated, and is a pro-drug of gabapentin, which has received regulatory approval in the U.S. and Japan [44]. On the other hand, only one Restless legs syndrome: Gabapentin Last revised in June 2025 The use of gabapentin for restless legs syndrome (RLS) is off-label. Initial dose of 300 mg if the person is under 65 years old and 100 mg if the person is over 65 years old. Practice Guideline: Treatment of Restless Legs Syndrome in Adults This is a summary of the American Academy of Neurology (AAN) guideline, “Treatment of restless legs syndrome in adults,” which was published in Neurology® online on November 16, 2016, and appears in the December 13, 2016, print issue. Gabapentin enacarbil is a type of anticonvulsant approved by the FDA for moderate to severe primary RLS. Learn how it works, what side effects and interactions to watch out for, and other RLS treatments. Gabapentin has been shown to improve RLS in a small number of clinical studies, but is limited by its short half-life and variable bioavailability. Gabapentin enacarbil is a novel prodrug of gabapentin designed to overcome these pharmacokinetic limitations. Most RLS patients require 1200 to 1800 mg of gabapentin daily, but doses up to 3600 mg daily can be used. Because of nonlinear kinetics and substantial interindividual variability, the gabapentin dose often does not always reflect serum level, especially at single doses above 600 mg. Management strategies for restless legs syndrome and periodic limb movement disorder in adults to improve sleep quality and reduce symptoms. Gabapentin and pregabalin may be preferred in restricted patient groups, including patients with severe sleep disturbance (disproportionate to other RLS symptoms), co-morbid insomnia or anxiety, RLS related or co-morbid pain, or with a history of ICD. 3 However, in the first instance it is recommended that these co-morbidities are investigated Introduction:This guideline establishes clinical practice recommendations for treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in adults and pediatric patients.M This article explains what gabapentin is, its approved and off-label uses, and how the drug works to treat restless legs syndrome and other medical conditions. It also describes the possible side effects and risks and lists other drugs and treatments that may help ease RLS symptoms. The American Academy of Sleep Medicine recommends gabapentin, gabapentin enacarbil, and pregabalin as strong options for restless legs syndrome (RLS) treatment. These medications are not associated with the augmentation of RLS symptoms observed with dopamine agonists. In patients with RLS, gabapentin may help modulate the abnormal nerve signaling that causes the uncomfortable sensations and urge to move the legs. Gabapentin is often preferred for the treatment of RLS due to its ability to relieve both the sensory and motor symptoms associated with the condition. The FDA approved gabapentin enacarbil in 2011 as the first non-dopaminergic agent for the treatment of restless legs syndrome (RLS) symptoms. Although gabapentin enacarbil is a pro-drug of gabapentin, its pharmacokinetics differ. Absorption of Studies have shown that gabapentin can reduce the frequency and intensity of RLS symptoms, improve sleep quality, and help patients fall asleep faster. It is particularly effective in individuals who have painful RLS or experience significant sleep disturbances due to the condition.
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