What is the recommended dosing for Lyrica (pregabalin) in the treatment of restless leg syndrome?

Lyrica (Pregabalin) Dosing for Restless Leg Syndrome

The American Academy of Sleep Medicine strongly recommends pregabalin as first-line therapy for restless legs syndrome, with typical dosing of 300 mg daily, though this can be adjusted based on symptom severity and tolerability. 1

Initial Assessment Before Starting Pregabalin

Before initiating pregabalin, you must check morning fasting iron studies (ferritin and transferrin saturation) after avoiding iron supplements for at least 24 hours. 1, 2

• If ferritin ≤75 ng/mL or transferrin saturation <20%, start iron supplementation first, as this alone may significantly improve RLS symptoms independent of pregabalin. 1, 2
• Address exacerbating factors including alcohol, caffeine, antihistamines, serotonergic medications, and untreated obstructive sleep apnea. 1

Pregabalin Dosing Protocol

Start pregabalin at 300 mg daily, which is the evidence-based dose used in the landmark trial that demonstrated superiority over dopamine agonists. 3

• The 300 mg daily dose can be given as a single dose or divided into twice-daily dosing (pregabalin has superior bioavailability compared to gabapentin, allowing for less frequent dosing). 1, 2
• This dose was shown to reduce IRLS scores by 4.5 points more than placebo (P<0.001) and achieved symptom improvement in 71.4% of patients. 3

Why Pregabalin Over Dopamine Agonists

The evidence strongly favors pregabalin as first-line therapy rather than dopamine agonists like pramipexole or ropinirole. 1, 4

• Augmentation risk is dramatically lower with pregabalin (2.1%) compared to pramipexole 0.5 mg (7.7%, P=0.001). 3
• The American Academy of Sleep Medicine now suggests against standard use of dopamine agonists due to augmentation concerns. 1, 4
• Augmentation manifests as earlier onset of symptoms during the day, increased intensity, and spread to other body parts—a paradoxical worsening that occurs with long-term dopaminergic therapy. 1, 4

Monitoring and Side Effects

Common side effects include somnolence and dizziness, which are typically transient and mild. 1

• Critical safety warning: There were six cases of suicidal ideation with pregabalin in the pivotal trial, requiring monitoring for mood changes. 3
• Monitor for misuse potential, as alpha-2-delta ligands have increasing evidence of abuse in certain populations. 1
• Avoid in patients with untreated obstructive sleep apnea or COPD due to respiratory depression risk. 1

Special Populations

For patients with end-stage renal disease, pregabalin carries higher risks of altered mental status and falls (50-68% higher hazard), making gabapentin the preferred alpha-2-delta ligand in this population at reduced doses (100-300 mg daily). 1

Clinical Algorithm Summary

1. Check morning fasting ferritin and transferrin saturation 2
2. Supplement iron if ferritin ≤75 ng/mL or transferrin saturation <20% 2
3. Start pregabalin 300 mg daily 3
4. Monitor for efficacy at 1-2 weeks and side effects 3
5. Continue long-term if effective, as augmentation risk remains low 3