How should I manage a 43‑year‑old woman with hypertension, hyperlipidemia and restless‑leg syndrome (RLS) whose symptoms have progressed to daytime discomfort and pruritus despite ropinirole 5 mg daily and a normal glycated hemoglobin?

Management of Augmentation in Restless Legs Syndrome

This patient is experiencing augmentation—a paradoxical worsening of RLS symptoms on ropinirole—and should be transitioned to an alpha-2-delta ligand (gabapentin or pregabalin) as first-line therapy, not dose-escalated on ropinirole. 1

Recognizing Augmentation

This clinical presentation is classic for dopaminergic augmentation:

• Daytime symptom onset is the cardinal sign of augmentation—symptoms that previously occurred only at night now appear during the day 1, 2
• Spread of symptoms to new body areas (the itching sensation) suggests anatomic extension typical of augmentation 3, 1
• Worsening intensity despite ongoing treatment at 5 mg daily (exceeding the FDA-approved maximum of 4 mg for RLS) 4
• The patient is already on a dose above the recommended maximum of 4 mg daily for RLS, which itself increases augmentation risk 4, 2

Augmentation occurs in approximately 7-10% of patients annually on dopamine agonists like ropinirole, and the 2025 American Academy of Sleep Medicine guidelines now conditionally recommend against standard use of ropinirole specifically because of this high augmentation risk 1.

Critical Management Error to Avoid

Do not increase the ropinirole dose—this is the most common prescribing error in augmentation management 3, 1. Dose escalation provides only brief, temporary relief before symptoms deteriorate further, creating a vicious cycle 2.

Evidence-Based Transition Strategy

Step 1: Initiate Alpha-2-Delta Ligand Before Tapering Ropinirole

Start gabapentin or pregabalin immediately while the patient is still on ropinirole to ensure symptom control during the transition 1:

• Gabapentin: Start 300 mg three times daily, increase by 300 mg/day every 3-7 days to a maintenance dose of 1800-2400 mg/day divided TID (maximum studied dose 3600 mg/day) 1
• Pregabalin: 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

Pregabalin offers the advantage of twice-daily dosing and superior bioavailability compared to regular gabapentin 1.

Step 2: Taper Ropinirole Very Slowly

Once adequate symptom control is achieved on the alpha-2-delta ligand (typically 2-4 weeks), begin very slow tapering of ropinirole 1:

• Reduce by 0.25-0.5 mg every 1-2 weeks 1
• Anticipate rebound RLS symptoms and insomnia during the taper 1
• The FDA label recommends a 7-day taper for Parkinson's disease, but augmentation cases require a much slower taper 4

Step 3: Assess Iron Status

Before finalizing the treatment plan, check morning fasting ferritin and transferrin saturation after withholding iron supplements for at least 24 hours 1:

• Supplement if ferritin ≤75 ng/mL or transferrin saturation <20% (RLS-specific thresholds, higher than general population) 1
• Consider IV ferric carboxymaltose 750-1000 mg for rapid correction if oral iron fails or ferritin remains 75-100 ng/mL despite oral therapy 1

Iron deficiency impairs dopamine transport in the substantia nigra and directly contributes to RLS pathophysiology 5.

Step 4: Address Exacerbating Factors

Review all medications for RLS-exacerbating agents 1:

• Antihistamines (including over-the-counter sleep aids)
• Serotonergic antidepressants (SSRIs, SNRIs)
• Antidopaminergic agents (metoclopramide, prochlorperazine)
• Screen for untreated obstructive sleep apnea 1

Eliminate alcohol, caffeine, and nicotine, especially within 3 hours of bedtime 1, 6.

Why Alpha-2-Delta Ligands Are Now First-Line

The 2025 American Academy of Sleep Medicine guidelines represent a major shift from older 2009 recommendations 1:

• Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) are now strongly recommended as first-line therapy (strong recommendation, moderate certainty of evidence) 1
• Dopamine agonists are conditionally recommended against for standard use due to augmentation risk (conditional recommendation, moderate certainty of evidence) 1
• Ropinirole may be considered only for short-term use in patients who prioritize immediate symptom relief over long-term adverse effects—this is explicitly not the standard approach 1

Special Considerations for This Patient

Hypertension Management

Monitor blood pressure closely during the transition, as ropinirole can cause orthostatic hypotension 7. One case report documented a prescribing cascade in a 71-year-old man where ropinirole-induced orthostatic hypotension led to falls, hospital admissions, and unnecessary prescriptions for midodrine and compression stockings 7. Symptoms resolved completely after ropinirole discontinuation 7.

HbA1c 5.0%

The normal HbA1c rules out diabetes as a contributor to neuropathic symptoms, but does not exclude iron deficiency as a secondary cause of RLS 5.

If Symptoms Remain Refractory

If augmentation symptoms persist despite adequate trials of alpha-2-delta ligands and iron optimization, consider 1:

• Extended-release oxycodone 5-10 mg at bedtime (conditional recommendation, moderate certainty of evidence) 1
• Bilateral high-frequency peroneal nerve stimulation (conditional recommendation, moderate certainty of evidence) 1

Long-term studies of low-dose opioids in RLS show relatively low risks of abuse/overdose in appropriately screened patients, with only small dose increases over 2-10 years 1.

Common Pitfalls

• Do not label this as "worsening RLS" requiring higher ropinirole doses—this is augmentation, a treatment-induced phenomenon 1, 2
• Do not switch to another dopamine agonist (pramipexole, rotigotine)—all carry similar augmentation risk 1, 2
• Do not use clonazepam as monotherapy—it provides only sedation without addressing the underlying RLS pathology 1
• Do not assume ferritin >50 ng/mL is adequate—RLS requires ferritin >75 ng/mL for optimal brain iron stores 1

Monitoring and Follow-Up

• Reassess RLS severity at 4-6 weeks after initiating alpha-2-delta ligand therapy 1
• Monitor for side effects of gabapentin/pregabalin: dizziness and somnolence (typically transient and mild) 1
• Repeat iron studies every 6-12 months, as brain iron deficiency may persist despite clinical improvement 1
• Evaluate both nighttime symptom relief and daytime functional outcomes (alertness, mood, quality of life) 1