Treatment for restless legs syndrome and periodic limb movements of sleep/wakefulness
Most cases of restless legs syndrome and periodic limb movements are mild and don't need treatment. Mild, infrequent symptoms may respond to lifestyle changes alone, mainly physical exercise and good sleep practices. Exclude iron deficiency, as it can cause and aggravate restless legs syndrome. Replace iron so the serum ferritin concentration is at least 50 micrograms/L.
If lifestyle changes are not sufficient, drug therapy may be needed. Start treatment at a low dose and titrate gradually to minimise adverse effects. When using a dopaminergic drug to treat restless legs syndrome and periodic leg movements, the maximum dose is lower than in Parkinson disease. Behavioural adverse effects (eg pathological gambling, hypersexuality) due to dopamine agonists can occur, even at these lower doses. Common adverse effects of all dopaminergic drugs are nausea and orthostatic hypotension.
If limb movements at sleep onset are mild and infrequent, use:
1 levodopa+benserazide 100+25 to 200+50 mg orally, before bedtime when needed restless legs syndrome or periodic limb movements of sleep/wakefulness levodopa + benserazide
OR
1 levodopa+carbidopa 100+25 to 200+50 mg orally, before bedtime when needed. restless legs syndrome or periodic limb movements of sleep/wakefulness levodopa + carbidopa
More severe symptoms are treated with a calcium channel alpha 2 delta ligand or a dopamine agonist. For therapy with an alpha 2 delta ligand, use:
1 gabapentin 100 to 300 mg orally, once daily at night. Gradually increase dose every 3 to 7 days as tolerated and according to response, up to 2400 mg daily. If the daily dose is more than 1200 mg, give one-third in the evening and two-thirds at bedtime restless legs syndrome or periodic limb movements of sleep/wakefulness gabapentin
OR
1 pregabalin 75 mg orally, once daily at night. If needed, gradually increase dose every 3 to 7 days as tolerated and according to response, up to 450 mg daily. restless legs syndrome or periodic limb movements of sleep/wakefulness pregabalin
For therapy with a dopamine agonist, use:
1 pramipexole 0.125 mg orally, once daily 2 to 3 hours before bedtime. If needed, after 4 to 7 days increase dose to 0.25 mg at night, then increase daily dose by 0.25 mg every 4 to 7 days as tolerated and according to response, up to 0.75 mg daily restless legs syndrome or periodic limb movements of sleep/wakefulness pramipexole
OR
1 ropinirole 0.25 mg orally, once daily 1 to 3 hours before bedtime. If initial dose is tolerated, after 2 days increase dose to 0.5 mg once daily for 5 days, then increase daily dose by 0.5 mg every 7 days according to response, up to 4 mg daily (usual daily dose is 2 mg) restless legs syndrome or periodic limb movements of sleep/wakefulness
OR
1 rotigotine 1 mg transdermally, once daily applied for 24 hours. If needed, increase dose as tolerated and according to response, up to 3 mg daily1. restless legs syndrome or periodic limb movements of sleep/wakefulness rotigotine
If therapy is not effective, refer for expert advice.
Augmentation is when the symptoms of restless legs and periodic limb movements of sleep/wakefulness get worse after treatment—the symptoms may shift to an earlier time in the day, have greater intensity and involve new limb areas. Augmentation is mainly a problem with dopaminergic drugs, particularly levodopa, and may occur as early as 3 to 4 weeks after starting treatment.
Risk factors for augmentation are taking more than 200 mg levodopa daily, and taking levodopa early in the day.
Strategies to reduce or stop augmentation include having a drug holiday, stopping the drug or using an alternative drug.
Rebound restless leg symptoms occur when drug treatment has worn off, similar to ‘wearing off’ in Parkinson disease. These symptoms often occur late at night or early in the morning, and are treated by using long-acting preparations (eg transdermal rotigotine) or divided levodopa doses.
Refer patients with augmentation or rebound to an expert.