From the Guidelines
The most effective medication for restless leg syndrome is ferrous sulfate, which should be used over no ferrous sulfate in patients with appropriate iron status, as suggested by the American Academy of Sleep Medicine (AASM) in their 2025 clinical practice guideline 1.
Treatment Options
When considering treatment for restless leg syndrome (RLS), it's essential to evaluate the patient's iron status, as iron deficiency can exacerbate symptoms.
- Ferrous sulfate is recommended for patients with appropriate iron status, with a conditional recommendation and moderate certainty of evidence 1.
- Other treatment options, such as dipyridamole, extended-release oxycodone, and bilateral high-frequency peroneal nerve stimulation, may be considered, but with varying levels of certainty and recommendation strength 1.
Medications to Avoid
Certain medications are suggested against for the standard treatment of RLS, including:
- Levodopa, pramipexole, transdermal rotigotine, ropinirole, bupropion, carbamazepine, clonazepam, valproic acid, and cabergoline, due to concerns about adverse effects, augmentation, or low certainty of evidence 1.
Special Considerations
In adults with RLS and end-stage renal disease (ESRD), gabapentin, IV iron sucrose, and vitamin C may be considered, with conditional recommendations and varying levels of certainty 1.
Lifestyle Changes
In addition to medication, lifestyle changes such as regular exercise, good sleep habits, avoiding caffeine and alcohol, and practicing relaxation techniques can help manage RLS symptoms.
From the FDA Drug Label
The effectiveness of ropinirole in the treatment of RLS was demonstrated in randomized, double-blind, placebo-controlled trials in adults diagnosed with RLS using the International Restless Legs Syndrome Study Group diagnostic criteria Patients were required to have a history of a minimum of 15 RLS episodes/month during the previous month and a total score of ≥15 on the International RLS Rating Scale (IRLS scale) at baseline. All trials employed flexible dosing, with patients initiating therapy at 0. 25 mg ropinirole once daily. Patients were titrated based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily. In all 3 trials, a statistically significant difference between the treatment group receiving ropinirole and the treatment group receiving placebo was observed at Week 12 for both the mean change from baseline in the IRLS scale total score and the percentage of patients rated as responders (much improved or very much improved) on the CGI-I
Ropinirole is a medication used to treat Restless Legs Syndrome (RLS). The medication is taken once daily, with a starting dose of 0.25 mg and titrated up to a maximum of 4 mg based on clinical response and tolerability.
- The medication has been shown to be effective in reducing symptoms of RLS, with a statistically significant difference in the mean change from baseline in the IRLS scale total score and the percentage of patients rated as responders on the CGI-I.
- The mean dose at Week 12 was approximately 2 mg/day for the 3 trials 2 2.
- Ropinirole has been demonstrated to have long-term maintenance of efficacy in the treatment of RLS, with a significantly lower relapse rate compared with patients randomized to placebo.
From the Research
Medications for Restless Leg Syndrome
- Dopaminergic agents, such as levodopa, ropinirole, pramipexole, and rotigotine, are effective in treating RLS, but may be associated with augmentation, a paradoxical treatment-related increase in RLS symptoms 3, 4, 5
- Alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur 4, 6, 7
- Opioids may be considered for severe augmentation or refractory RLS, but their use is limited due to potential side effects and risk of dependence 6, 7
- Iron supplementation may be beneficial for patients with low iron stores, as iron deficiency can exacerbate RLS symptoms 6, 7
Treatment Approaches
- Nonpharmacologic approaches, such as mental alerting activities, avoidance of substances or medications that may exacerbate RLS, and oral and intravenous iron supplementation, may be effective in managing RLS symptoms 7
- Intermittent treatment may be considered for patients with mild or intermittent RLS symptoms, while daily treatment may be necessary for patients with more severe symptoms 5, 7
- Combination therapy, including the use of multiple medications or nonpharmacologic approaches, may be necessary for patients with refractory RLS 7