Can the ropinirole (Requip) dose be increased from 0.25 mg to 0.5 mg at bedtime for an adult with restless‑legs syndrome that is not adequately controlled?

Ropinirole Dose Increase for Inadequately Controlled Restless Legs Syndrome

Do not increase the ropinirole dose from 0.25 mg to 0.5 mg—instead, transition to an alpha-2-delta ligand (gabapentin, gabapentin enacarbil, or pregabalin) as first-line therapy, because the 2025 American Academy of Sleep Medicine guidelines now recommend against the standard use of ropinirole due to high risk of augmentation (paradoxical worsening of symptoms with long-term use). 1, 2

Why Ropinirole Is No Longer Recommended

• The American Academy of Sleep Medicine suggests against the standard use of ropinirole with a conditional recommendation and moderate certainty of evidence, representing a paradigm shift away from dopamine agonists. 1
• Augmentation occurs in a substantial proportion of patients taking ropinirole, causing symptoms to worsen, appear earlier in the day (afternoon instead of evening), increase in intensity, and spread to arms or trunk. 1, 3, 4
• The annual augmentation incidence with dopamine agonists ranges from 7–10%, and increasing the dose when symptoms worsen actually perpetuates a vicious cycle of progressive augmentation requiring ever-higher doses. 2, 3
• Ropinirole may only be considered for short-term use in patients who place higher value on immediate symptom reduction and lower value on long-term adverse effects, but this is explicitly not the standard approach. 1

Recommended Management Algorithm

Step 1: Assess Iron Status First

• Check morning fasting serum ferritin and transferrin saturation after avoiding iron supplements for ≥24 hours. 2
• Supplement with oral ferrous sulfate if ferritin ≤75 ng/mL or transferrin saturation <20% (different threshold than general population). 2
• Consider IV ferric carboxymaltose for rapid correction if oral iron is not tolerated or symptoms are severe. 2

Step 2: Transition to Alpha-2-Delta Ligand

• Gabapentin: Start 300 mg three times daily; increase by 300 mg/day every 3–7 days; target maintenance 1800–2400 mg/day divided TID; maximum 3600 mg/day. 2, 4
• Pregabalin: Allows twice-daily dosing with superior bioavailability compared to regular gabapentin. 2, 4
• Gabapentin enacarbil: Prodrug formulation with improved pharmacokinetics. 2
• These agents are strongly recommended as first-line therapy with moderate certainty of evidence and do not carry augmentation risk. 1, 2

Step 3: Taper Ropinirole Gradually

• Once the alpha-2-delta ligand reaches therapeutic dose and symptoms are controlled, taper ropinirole gradually over 7 days to avoid withdrawal symptoms. 4, 5
• Expect temporary worsening of RLS symptoms during the transition period, but this resolves as the new medication takes effect. 3
• Do not increase ropinirole dose during this transition, as this worsens augmentation. 3, 4

Critical Pitfalls to Avoid

• Never simply increase the ropinirole dose when symptoms worsen—this is likely augmentation, not inadequate dosing, and increasing the dose creates a cycle of progressive worsening. 3, 4
• Do not switch to another dopamine agonist (pramipexole, rotigotine, levodopa)—these carry the same augmentation risk, with one study showing 50% of patients who switched to rotigotine discontinued within one year. 3, 4
• Do not use levodopa as a bridge medication—it has an even higher augmentation rate than ropinirole. 3
• Correct iron deficiency before assuming medication failure—iron deficiency exacerbates RLS and may be contributing to apparent inadequate control. 2, 3

Alternative Options for Refractory Cases

• Extended-release oxycodone or low-dose methadone/buprenorphine are conditionally recommended for severe refractory RLS, particularly when treating augmentation from dopamine agonists. 2, 3
• Screen for untreated obstructive sleep apnea before initiating any opioid due to respiratory depression risk. 2, 3
• Bilateral high-frequency peroneal nerve stimulation is conditionally recommended as a non-pharmacological option. 2

What the FDA Label Says (For Context Only)

• The FDA-approved titration schedule for ropinirole in RLS starts at 0.25 mg once daily 1–3 hours before bedtime, increasing to 0.5 mg after 2 days, then 1 mg at the end of week 1, with maximum dose 4 mg daily. 5
• However, this FDA dosing schedule predates the 2025 guideline evidence demonstrating high augmentation risk, which is why current guidelines now recommend against standard use. 1, 2

Summary of Evidence Quality

The 2025 American Academy of Sleep Medicine guideline 1, 2 represents the highest-quality, most recent evidence and should guide clinical decision-making over older research studies 6, 7, 8, 9 that supported ropinirole before augmentation risks were fully characterized. The guideline reviewed 13 RCTs and 2 observational studies demonstrating clinically significant improvements in disease severity with ropinirole, but also identified 3 observational studies showing clinically significant augmentation risk, leading to the conditional recommendation against standard use. 1