What is the optimal management of restless‑legs syndrome in an elderly woman, including evaluation for low ferritin and the safest first‑line pharmacologic therapy?

Optimal Management of Restless Legs Syndrome in an Elderly Woman

Start with alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) as first-line pharmacological therapy after checking iron status, and avoid dopamine agonists due to high augmentation risk and increased fall hazard in elderly patients. 1

Initial Iron Assessment

Before initiating any medication, check morning fasting serum ferritin and transferrin saturation after avoiding iron supplements for at least 24 hours. 1, 2, 3

• Supplement with iron if ferritin ≤75 ng/mL or transferrin saturation <20%—this threshold is higher than general population guidelines because brain iron deficiency plays a central role in RLS pathophysiology. 1, 3
• IV ferric carboxymaltose (750-1000 mg in one or two infusions) is strongly recommended for rapid correction if oral iron is not tolerated or ineffective after 3 months. 1, 3
• Oral ferrous sulfate is an alternative but works more slowly. 1, 3

First-Line Pharmacological Treatment: Alpha-2-Delta Ligands

The American Academy of Sleep Medicine strongly recommends gabapentin, gabapentin enacarbil, or pregabalin as first-line therapy with moderate certainty of evidence. 1, 3

Gabapentin Dosing

• Start 300 mg three times daily (not single nighttime dosing, which fails to address daytime symptoms). 1
• Titrate by 300 mg/day every 3-7 days until reaching maintenance dose of 1800-2400 mg/day divided three times daily. 1, 2
• Maximum studied dose is 3600 mg/day. 1
• Common side effects include somnolence and dizziness, typically transient and mild. 1

Pregabalin Alternative

• Allows twice-daily dosing with potentially superior bioavailability compared to regular gabapentin. 1, 3
• Strongly recommended as first-line therapy with moderate certainty of evidence. 1, 3

Why Alpha-2-Delta Ligands Are Preferred in the Elderly

• Lower fall risk compared to dopamine agonists—gabapentin has lower rates of dizziness and somnolence with long-term use than rotigotine. 1
• No augmentation risk—unlike dopamine agonists, which cause paradoxical worsening of symptoms in 7-10% annually. 1

Medications to Avoid in Elderly Women

Dopamine agonists (pramipexole, ropinirole, rotigotine) are NOT recommended for standard use due to high augmentation risk and increased fall hazard. 1, 3

• Augmentation presents as earlier symptom onset during the day, increased intensity, and spread to arms/trunk. 1
• Dopamine agonists cause higher rates of dizziness and somnolence, directly increasing fall risk in elderly patients. 1
• The American Academy of Sleep Medicine suggests against standard use with conditional to moderate certainty of evidence. 1, 3

Strong recommendation against: cabergoline, bupropion, carbamazepine, clonazepam, valproic acid, and valerian. 1

Addressing Exacerbating Factors

Eliminate or reduce the following before or alongside pharmacological treatment: 1, 2

• Alcohol, caffeine, and nicotine—especially within 3 hours of bedtime. 1
• Antihistaminergic medications (common in over-the-counter sleep aids). 1
• Serotonergic medications (SSRIs, SNRIs). 1
• Antidopaminergic medications (antipsychotics like lurasidone). 1
• Screen for and treat untreated obstructive sleep apnea. 1

Non-Pharmacological Interventions

• Moderate exercise (aerobic, resistance, flexibility) in morning/afternoon, but avoid vigorous exercise close to bedtime. 2
• Sleep hygiene: dark, quiet room at comfortable temperature; avoid heavy meals within 3 hours of bedtime. 2
• Smoking cessation. 2

Second-Line Options for Refractory Cases

If alpha-2-delta ligands and iron supplementation fail: 1, 3

• Extended-release oxycodone and other low-dose opioids are conditionally recommended for moderate to severe refractory RLS, with evidence showing relatively low risks of abuse and overdose in appropriately screened patients. 1, 3
• Bilateral high-frequency peroneal nerve stimulation is conditionally recommended as a non-pharmacological option with moderate certainty. 1, 3

Critical Pitfalls to Avoid

• Do NOT use dopamine agonists as first-line therapy in elderly patients—the augmentation risk and fall hazard outweigh short-term symptom relief. 1
• Do NOT use single nighttime dosing of gabapentin—it fails to address daytime symptoms and provides suboptimal 24-hour coverage. 1
• Do NOT assume "normal" ferritin levels are adequate—supplement if ferritin ≤75 ng/mL, not the general population threshold of 30 ng/mL. 1
• Do NOT overlook medication review—antidepressants, antihistamines, and antipsychotics commonly worsen RLS. 1

Monitoring and Follow-Up

• Reassess iron studies every 6-12 months, as RLS symptoms may recur if iron stores decline. 1
• Monitor for side effects of alpha-2-delta ligands, particularly dizziness and somnolence. 1
• Evaluate improvement in both nighttime RLS symptoms and daytime functioning (alertness, concentration, mood). 1