What is the normal dosage of Lyrica (Pregabalin) for Restless Legs Syndrome (RLS)?

Pregabalin Dosing for Restless Legs Syndrome

The American Academy of Sleep Medicine strongly recommends pregabalin as first-line therapy for RLS, with typical dosing starting at 75 mg once daily 1-2 hours before bedtime, titrating up to an effective dose range of 150-450 mg/day based on symptom response and tolerability. 1

Starting Dose and Titration Schedule

• Begin with pregabalin 75 mg once daily, taken 1-2 hours before bedtime when symptoms typically worsen 1
• If inadequate response after 3-7 days, increase to 150 mg daily 1
• Continue titrating by 75-150 mg increments every 3-7 days as needed 1
• The therapeutic range is 150-450 mg/day, with most patients responding between 300-450 mg/day 2, 3

Evidence-Based Dosing Data

• A dose-response study demonstrated that 123.9 mg/day provides 90% of maximal efficacy (ED90), though clinical trials typically use 300 mg/day as the standard effective dose 3
• The landmark comparative trial used pregabalin 300 mg/day and showed superior outcomes compared to placebo, with a 4.5-point greater improvement on the International RLS Rating Scale and 71.4% of patients achieving "much improved" or "very much improved" status 2
• Higher doses (450 mg/day) showed increased efficacy but also higher rates of dizziness and somnolence 3

Critical Advantages Over Dopamine Agonists

• Pregabalin has a significantly lower augmentation rate (2.1%) compared to pramipexole 0.5 mg (7.7%) over 40-52 weeks of treatment, which is the primary reason the American Academy of Sleep Medicine now recommends alpha-2-delta ligands as first-line therapy 2, 1
• Augmentation—the paradoxical worsening of RLS symptoms with earlier onset during the day and spread to other body parts—is a major limitation of dopaminergic agents that pregabalin avoids 1

Special Populations and Dose Adjustments

• In chronic kidney disease or dialysis patients, pregabalin carries a 50-68% higher risk of altered mental status and falls, even at low doses, and should be avoided or used with extreme caution with significant dose reduction 4
• For patients with end-stage renal disease, gabapentin (not pregabalin) is the preferred alpha-2-delta ligand, starting at 100 mg post-dialysis with a maximum of 200-300 mg daily 4

Common Pitfalls to Avoid

• Do not use single low doses (50-100 mg) and declare treatment failure—most patients require 300 mg/day or higher for adequate symptom control 2, 3
• Always assess and correct iron deficiency first (ferritin ≤75 ng/mL or transferrin saturation <20%) before initiating or escalating pregabalin, as iron supplementation alone may significantly improve symptoms 1
• Monitor for suicidal ideation, as six cases occurred in the pregabalin group in the major comparative trial 2
• Warn patients about dizziness and somnolence, which are dose-dependent and the most common side effects, particularly during titration 3

Monitoring and Maintenance

• Assess response using validated scales (International RLS Rating Scale) at 1 week and 12 weeks 2
• Once effective dose is established, continue indefinitely as RLS is typically a chronic condition requiring long-term management 1
• Pregabalin is particularly valuable for patients with comorbid neuropathic pain, as it treats both conditions simultaneously 5