What is a good prescription for restless legs syndrome in a 32-year-old premenopausal female?

Treatment Recommendation for Restless Legs Syndrome in a 32-Year-Old Female

Start with gabapentin 300 mg at bedtime, titrating up to 1800-2400 mg/day divided into 2-3 doses, while simultaneously checking iron studies and supplementing if ferritin ≤75 ng/mL or transferrin saturation <20%. 1

First-Line Pharmacological Treatment

Alpha-2-delta ligands are the definitive first-line therapy for RLS in your patient, not dopamine agonists. 1 The American Academy of Sleep Medicine strongly recommends gabapentin, gabapentin enacarbil, or pregabalin as initial treatment with moderate certainty of evidence. 1

Specific Dosing Options:

• Gabapentin: Start 300 mg at bedtime, increase by 300 mg every 3-7 days as needed, target maintenance dose 1800-2400 mg/day divided 2-3 times daily (maximum 3600 mg/day). 1

• Pregabalin: Allows twice-daily dosing with potentially superior bioavailability compared to regular gabapentin, strongly recommended with moderate certainty. 1

• Gabapentin enacarbil: Extended-release formulation with improved bioavailability, strongly recommended with moderate certainty. 1

The advantage of alpha-2-delta ligands over dopamine agonists is the dramatically lower risk of augmentation—a paradoxical worsening of symptoms characterized by earlier onset, increased intensity, and spread to other body parts that occurs with long-term dopamine agonist use. 1, 2

Mandatory Iron Assessment

Before or concurrent with starting medication, check morning fasting serum ferritin and transferrin saturation (avoid iron supplements for 24 hours before testing). 1

• If ferritin ≤75 ng/mL or transferrin saturation <20%: Start oral ferrous sulfate supplementation (conditional recommendation, moderate certainty). 1

• If oral iron fails after 3 months or symptoms are severe: Consider IV ferric carboxymaltose 750-1000 mg in one or two infusions (strong recommendation, moderate certainty). 1

Iron deficiency plays a key role in RLS pathophysiology even when serum iron appears normal, and correction can significantly improve symptoms independent of other medications. 1

Why NOT Dopamine Agonists First

The American Academy of Sleep Medicine explicitly suggests against standard use of dopamine agonists (pramipexole, ropinirole, rotigotine) due to high augmentation risk. 1 While ropinirole is FDA-approved for RLS at doses of 0.25-4 mg once daily 3, and clinical trials show efficacy 3, the 2026 guidelines prioritize alpha-2-delta ligands because:

• Augmentation occurs in a significant proportion of patients on long-term dopamine agonist therapy. 4, 2
• Augmentation causes earlier symptom onset, increased severity, and anatomic spread requiring higher doses that worsen the problem. 4, 2
• Dopamine agonists should only be considered for short-term use in patients who prioritize immediate symptom relief over long-term safety. 1

Non-Pharmacological Interventions (Concurrent with Medication)

• Eliminate caffeine, alcohol, and nicotine, especially within 3 hours of bedtime—even moderate evening consumption significantly worsens RLS symptoms. 5

• Discontinue exacerbating medications: Check for antihistamines, SSRIs, tricyclic antidepressants, and antipsychotics (all can worsen RLS through dopamine antagonism or other mechanisms). 5, 1

• Regular moderate exercise in morning/afternoon, but avoid vigorous exercise close to bedtime. 5

Second-Line Options (If First-Line Fails)

• Extended-release oxycodone or other low-dose opioids: Conditional recommendation for refractory cases, with appropriate monitoring for respiratory depression and abuse potential. 1, 4

• IV ferric carboxymaltose: If iron parameters are borderline and oral supplementation ineffective. 1

Critical Pitfalls to Avoid

• Do not start with dopamine agonists despite FDA approval—the 2026 guidelines supersede older practices due to augmentation concerns. 1

• Do not use clonazepam as monotherapy—insufficient efficacy evidence, does not reduce objective RLS markers, and causes sedation. 1

• Do not assume "normal" ferritin (>50 ng/mL) means iron is adequate—RLS requires higher brain iron stores, hence the ≤75 ng/mL threshold. 1

• Do not increase dopamine agonist doses if symptoms worsen—this likely represents augmentation and will make the problem worse. 4, 2

Monitoring and Follow-Up

• Reassess symptoms in 2-4 weeks after starting gabapentin/pregabalin and titrating to therapeutic doses. 1

• Recheck iron studies every 6-12 months even after symptom resolution, as brain iron deficiency may persist despite normal serum parameters. 1

• Monitor for alpha-2-delta ligand side effects: dizziness and somnolence (typically transient and mild). 1

• Evaluate improvement in both nighttime RLS symptoms and daytime functioning (alertness, concentration, mood). 1

Special Consideration for Your 32-Year-Old Female Patient

At 32 years old and premenopausal, your patient may have higher iron requirements due to menstruation. 1 Iron supplementation is particularly important in this demographic, and the safety profile favors oral formulations initially. 1 If she is planning pregnancy, note that medication safety profiles require special consideration, though iron supplementation remains safe and important throughout gestation. 1