Is baclofen an appropriate treatment for restless legs syndrome (RLS) and what is the recommended dosing regimen?

Baclofen for Restless Legs Syndrome

Baclofen is not recommended for the treatment of restless legs syndrome (RLS) and does not appear in any current evidence-based treatment guidelines. 1

Why Baclofen Is Not Appropriate

• The American Academy of Sleep Medicine 2025 guidelines—the most recent and authoritative source—do not include baclofen among recommended treatments for RLS, and it has no established role in the management of this condition. 1

• Baclofen is a GABA-B agonist muscle relaxant that lacks evidence for efficacy in RLS, unlike medications that target the specific pathophysiology of the disorder (dopaminergic dysfunction and iron deficiency). 1

Evidence-Based Treatment Algorithm for RLS

Step 1: Assess and Correct Iron Status

• Check morning fasting serum ferritin and transferrin saturation after avoiding iron supplements for ≥24 hours before starting any medication. 1

• Initiate iron supplementation if ferritin ≤75 ng/mL or transferrin saturation <20% in adults (ferritin <50 ng/mL in children). 1

• IV ferric carboxymaltose is strongly recommended for rapid correction if oral iron is not tolerated or ineffective after 3 months. 1

Step 2: First-Line Pharmacological Treatment

• Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) are strongly recommended as first-line therapy with moderate certainty of evidence. 1

• Gabapentin dosing: Start 300 mg three times daily; increase by 300 mg/day every 3–7 days; target maintenance 1800–2400 mg/day divided TID; maximum 3600 mg/day. 1

• Pregabalin allows twice-daily dosing with superior bioavailability: start 50 mg TID or 75 mg BID, increase to 300 mg/day after 3–7 days, then by 150 mg every 3–7 days as tolerated; maximum 600 mg/day. 1

Step 3: Medications to Avoid

• Dopamine agonists (pramipexole, ropinirole, rotigotine) are NOT recommended for standard use due to high risk of augmentation—a paradoxical worsening of symptoms with earlier onset, increased intensity, and spread to arms/trunk. 1

• The American Academy of Sleep Medicine strongly recommends against cabergoline, bupropion, carbamazepine, clonazepam, valproic acid, and valerian. 1

• Baclofen, tizanidine, and other muscle relaxants have no evidence base and should not be used. 1

Step 4: Refractory Cases

• Extended-release oxycodone and other low-dose opioids are conditionally recommended for moderate to severe refractory RLS, particularly when treating augmentation from dopamine agonists. 1

• Bilateral high-frequency peroneal nerve stimulation is conditionally recommended as a non-pharmacological option. 1

Critical Pitfalls to Avoid

• Do not use baclofen, benzodiazepines (including clonazepam), or muscle relaxants as they lack efficacy data and may worsen sleep architecture without addressing RLS pathophysiology. 1

• Do not start dopamine agonists as first-line therapy—older literature from 2003–2014 recommended these agents, but the 2025 American Academy of Sleep Medicine guidelines now recommend against their standard use due to augmentation risk (annual incidence 7–10%). 1, 2, 3, 4, 5, 6

• Address exacerbating factors including alcohol, caffeine, antihistamines, serotonergic medications, antidopaminergic medications, and untreated obstructive sleep apnea. 1

Special Populations

• End-stage renal disease: Gabapentin 100 mg post-dialysis or at bedtime, maximum 200–300 mg daily; IV iron sucrose if ferritin <200 ng/mL and transferrin saturation <20%. 1

• Pregnancy: Iron supplementation is particularly important; medication safety profiles must be carefully considered. 1