Treatment of restless legs syndrome (RLS) in nonpregnant adults

IV: intravenous; PRN: as needed.
* Unless symptoms are severe, we replete iron stores when appropriate before initiating a first-line medication.
¶ Aggravating factors for RLS include sleep deprivation, untreated comorbid sleep disorders, and certain medications (eg, antidepressants, dopamine receptor blocking agents, sedating antihistamines).
Δ Behavioral strategies include mental alerting activities, moderate regular exercise, reducing caffeine intake, soaking affected limbs, and leg massage. In patients with mild and/or intermittent symptoms, these therapies may be sufficient for symptom relief.
◊ In patients with acute or chronic inflammatory disorders, transferrin saturation <20% may be a more accurate measure of low iron stores than serum ferritin. Importantly, any adult with iron deficiency (eg, serum ferritin level <30 ng/mL) should be evaluated for the underlying cause, which may include gastrointestinal blood loss, especially for adults over 40 to 50 years, or a condition that interferes with iron absorption.
§ Augmentation refers to an overall worsening of symptom severity while taking a dopaminergic medication for RLS, with earlier onset of symptoms, shorter symptom latency with rest, shorter duration of action of drugs, or spread of symptoms to trunk or arms. It is the most common complication of long-term dopaminergic therapy.
¥ Among the 3 gabapentinoid drugs, choose based on factors that include pharmacokinetics, symptom pattern, and cost. When RLS symptoms occur predominantly in the evening or night, we start with pregabalin or gabapentin; pregabalin is preferred because of straightforward pharmacokinetics and better data on efficacy, but gabapentin is often cheaper and can be substituted if cost is a factor. For patients with RLS symptoms throughout most of the day and night, we prefer gabapentin enacarbil because it provides 24-hour coverage with the convenience of once-daily dosing.