What are the recommended medications for treating restless leg syndrome?

From the Guidelines

The most effective medications for treating restless leg syndrome (RLS) include gabapentin, pregabalin, and gabapentin enacarbil, as recommended by the American Academy of Sleep Medicine (1).

Medication Options

• Gabapentin is recommended over no gabapentin for adults with RLS, with a strong recommendation and moderate certainty of evidence (1).
• Pregabalin is also recommended over no pregabalin for adults with RLS, with a strong recommendation and moderate certainty of evidence (1).
• Gabapentin enacarbil is recommended over no gabapentin enacarbil for adults with RLS, with a strong recommendation and moderate certainty of evidence (1).

Additional Considerations

• Iron supplementation, such as ferrous sulfate, is suggested for patients with low ferritin levels, as it may help alleviate RLS symptoms (1).
• Opioids, such as oxycodone or methadone, may be prescribed at low doses for severe or refractory cases, but their use should be carefully considered due to the risk of abuse and overdose (1).
• Non-pharmacological approaches, such as regular exercise, good sleep hygiene, and avoiding caffeine, alcohol, and nicotine, can complement medication therapy and help manage RLS symptoms.

Special Populations

• For adults with end-stage renal disease (ESRD), gabapentin, IV iron sucrose, and vitamin C are conditionally recommended, while levodopa and rotigotine are conditionally recommended against (1).
• For children with RLS, oral iron supplementation is suggested, but more research is needed to fully understand the pathobiology of RLS and develop effective treatments (1).

From the FDA Drug Label

2.3 Dosing for Restless Legs Syndrome The recommended adult starting dose for RLS is 0.25 mg once daily 1 to 3 hours before bedtime. After 2 days, if necessary, the dose can be increased to 0.5 mg once daily, and to 1 mg once daily at the end of the first week of dosing, then as shown in Table 2 as needed to achieve efficacy. Titration should be based on individual patient therapeutic response and tolerability, up to a maximum recommended dose of 4 mg daily. For RLS, the safety and effectiveness of doses greater than 4 mg once daily have not been established.

Recommended Medications for Restless Leg Syndrome:

• Ropinirole (PO) is a recommended medication for treating restless leg syndrome.
• The initial dose is 0.25 mg once daily, which can be increased as needed and tolerated, up to a maximum dose of 4 mg daily.
• Dose titration should be based on individual patient response and tolerability.
• The safety and effectiveness of doses greater than 4 mg once daily have not been established 2.

Key Points:

• Ropinirole is effective in treating RLS, as demonstrated in randomized, double-blind, placebo-controlled trials 2 2.
• Flexible dosing is employed, with patients initiating therapy at 0.25 mg once daily and titrating up to a maximum of 4 mg once daily as needed and tolerated.

From the Research

Medications for Restless Leg Syndrome

The following medications are commonly used to treat restless leg syndrome (RLS):

• Dopaminergic agents, such as levodopa, pramipexole, ropinirole, and rotigotine patch, which are considered first-line therapy for RLS 3, 4, 5, 6
• Alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, which are effective for RLS without known occurrence of augmentation or impulse control disorders 4
• Opioids and clonazepam, which may provide benefit in individual patients, but do not have sufficient evidence to recommend them as treatment for RLS 4
• Iron supplementation, which may be used in patients with iron deficiency or insufficiency 3

Dopaminergic Agents

Dopaminergic agents are the most well-studied and effective medications for RLS:

• Pramipexole and ropinirole have been shown to be effective in improving RLS symptoms and suppressing periodic leg movements during sleep 7
• Levodopa is also effective, but chronic use can lead to augmentation, which is defined as an earlier occurrence of symptoms, frequently associated with worsening severity and sometimes spread to other body areas 4, 6
• Rotigotine patch is a dopamine agonist that has been shown to be effective in treating RLS 4

Treatment Considerations

Treatment of RLS should be individualized and based on the severity of symptoms and the presence of any underlying medical conditions:

• Pharmacological treatment should be limited to patients who suffer from clinically relevant RLS with impaired sleep quality or quality of life 5
• A treatment on demand may be necessary in patients with intermittent symptoms 5
• Patients should be monitored for potential side effects, such as daytime sleepiness, impulse control disorders, and augmentation 4, 7