Restless Legs Syndrome

From: 5 minutes clincal consultation

Restless Legs Syndrome
Description


Restless legs syndrome (RLS) is a sensorimotor disorder defined by 4 criteria in adults (123)[A]:
A strong urge to move the legs, usually accompanied by discomfort.
The urge to move and discomfort occur during inactivity (seated or recumbent).
Movement such as stretching or walking immediately relieves the symptoms, but they recur with subsequent inactivity.
Symptoms occur primarily in the evening/night.
Symptoms may instead or also involve the arms, or be more generalized.
Patients may also complain of repeated involuntary jerking of legs while sitting or lying awake.
System(s) affected: Musculoskeletal; Nervous
Synonym(s): Ekbom syndrome; Leg akathisia


Medication (Drugs)

First Line

FDA-approved dopamine agonists (3,4,5)[A]:
Pramipexole (Mirapex): 0.125–1.5 mg 1 hour before bed; increase by 0.125 mg every 3 days to optimal efficacy
Ropinirole (Requip): 0.25–4.0 mg 1 hour before bed; increase by 0.25 mg every 3 days
Divide dose to treat afternoon/evening and bedtime symptoms
Off-label dopamine agonists:
Cabergoline: 0.25–3.0 mg
Carbidopa-levodopa (Sinemet or Sinemet CR): 25/100–100/400; use only PRN for intermittent symptoms.
Augmentation (increased symptom severity, occurrence earlier in day, and/or spreading to arms or torso) can occur with prolonged use of dopamine agonists:
Daily levodopa or Sinemet carry highest risk.
Requires reduction of dopaminergic agent and addition of adjunct medication.
Watch for rebound while reducing dopaminergics.
Avoid dopamine agonists in psychotic patients, including those taking dopamine antagonists.

Second Line
Anticonvulsants: Useful for painful or neuropathic RLS:
Gabapentin (Neurontin): 300–1,800 mg/d
Carbamazepine: 200–800 mg/d
Pregabalin (Lyrica): 50–300 mg/d
Benzodiazepines and agonists: Useful for associated insomnia and/or anxiety:
Clonazepam (Klonopin): 0.5–3.0 mg/d
Temazepam, triazolam, alprazolam, zaleplon, zolpidem, and diazepam.
Opioids: Low risk of tolerance/addiction with single daily bedtime dose:
Hydrocodone: 5–20 mg/d
Tramadol: 50 mg/d
Oxycodone: 2.5–20 mg/d
Severe or refractory RLS and augmentation require combination therapy.
Daytime sleepiness side effect is unusual with the doses and timing used for RLS.
OTC sleeping aids may treat mild intermittent RLS.
Studies of RLS medications show a high placebo response rate (~40%) (3,4,5)[B].

ALERT
Pregnancy Considerations

Initial approach: Iron supplementation and nonpharmacologic therapies.
Ist-line RLS medications are class C or D and should not be used.
In the 3rd trimester, opioids at the lowest effective dose may be considered.

Pediatric Considerations

Medications are less studied; Ist-line treatment is nonpharmacologic.
Low-dose clonidine, clonazepam, or gabapentin may be considered.

Geriatric Considerations

In weak or frail patients, avoid medications that may cause dizziness or unsteadiness.
Many medications given to the elderly may cause or exacerbate RLS.