Is gabapentin (Neurontin) effective for treating Restless Legs Syndrome (RLS)?

From the Guidelines

Gabapentin is recommended for the treatment of restless leg syndrome (RLS) in adults, particularly those with end-stage renal disease (ESRD), as it has shown to be effective in reducing symptoms with a moderate certainty of evidence 1.

Key Points to Consider

• The American Academy of Sleep Medicine (AASM) suggests the use of gabapentin over no gabapentin in adults with RLS, especially in those with ESRD, with a conditional recommendation and very low certainty of evidence 1.
• The AASM also recommends the use of gabapentin enacarbil and pregabalin for the treatment of RLS in adults, with strong recommendations and moderate certainty of evidence 1.
• Gabapentin should be started at a dose of 300mg, taken 1-2 hours before bedtime, and gradually increased as needed up to 1800mg daily, divided into multiple doses.
• Common side effects of gabapentin include dizziness, drowsiness, and unsteadiness, which often improve with time.
• It is essential to taper off gabapentin gradually under medical supervision to avoid withdrawal symptoms.

Comprehensive Approach

• Gabapentin should be used as part of a comprehensive approach to manage RLS, including avoiding caffeine, maintaining good sleep habits, and treating underlying conditions like iron deficiency.
• The treatment plan should be individualized, taking into account the patient's medical history, lifestyle, and preferences.

Evidence-Based Recommendation

• The recommendation to use gabapentin for RLS is based on the most recent and highest-quality evidence available, including studies published in 2025 1.
• The AASM clinical practice guidelines provide a comprehensive review of the evidence and recommend gabapentin as a treatment option for RLS in adults.

From the Research

Gabapentin for Restless Leg Syndrome

• Gabapentin is considered a viable treatment option for restless leg syndrome (RLS), particularly for refractory cases 2.
• The medication is an alpha2-delta calcium channel ligand, which has been shown to be effective in treating RLS symptoms 3, 4.
• Studies have demonstrated that gabapentin enacarbil, a pro-drug of gabapentin, is superior to placebo in treating RLS symptoms and has a more predictable absorption rate compared to gabapentin 4.
• Meta-analyses have found that anticonvulsants, including gabapentin, have comparable efficacy to dopamine agonists in treating RLS, with a mean reduction in the international RLS study group severity scale (IRLS) of -5.12 points 5.
• Gabapentin is now considered a first-line treatment for patients with troublesome RLS, particularly due to the potential problems associated with long-term dopamine agonist treatment, such as augmentation and impulse control disorder 6.

Comparison to Other Treatments

• Dopamine agonists are still considered a common treatment for RLS, but they can produce augmentation, a progressive worsening of RLS symptoms, in some patients 3.
• Opioids may be considered as an alternative therapy, particularly in patients with dopamine agonist-related augmentation 2, 6.
• Iron treatments, such as oral or intravenous iron supplementation, may be efficacious in patients with low normal serum indexes, but further studies are needed to fully evaluate their efficacy 3, 5.

Treatment Considerations

• The treatment of RLS should address underlying causes, such as iron deficiency or medication-induced worsening of symptoms 3, 2.
• A combination therapy may be required in more severe cases of RLS 6.
• Gabapentin and other alpha2-delta drugs may be a good alternative for patients who experience adverse effects or lack efficacy with dopamine agonists 3, 4.