Drug Therapies for Restless Legs Syndrome

Drug Therapies for Restless Legs Syndrome
Drug Therapies for Restless Legs Syndrome

Willis-Ekbom disease (WED), otherwise known as restless legs syndrome (RLS), is a neurologic disorder that affects up to 10% of Americans.1 Individuals with RLS develop irresistible urges to move their legs accompanied by unusual or unpleasant sensations in the legs. These sensations may be described as creeping, tugging, or pulling. Many people have a mild form of the disorder. Usually RLS occurs in the evening which may disrupt sleep and reduce quality of life.

A recent study conducted by Yanping Li and colleagues demonstrated that men with RLS have a significantly higher overall mortality despite adjustments in BMI, lifestyle factors, chronic conditions, sleep duration, and sleep-related disorders. The correlation persisted even after men with major chronic conditions (cancer, high blood pressure, cardiovascular disease, and other comorbidities) were excluded. These findings stress the need for RLS awareness and education.2

Currently only four FDA-approved RLS treatment options are available: Horizant3, Mirapex4, Neupro5, and Requip6. Positron Emission Tomographic (PET) studies suggest that a mild striatal presynaptic dopaminergic dysfunction may be involved in the pathogenesis of RLS.4

Horizant


(gabapentin enacarbil extended-release tablets; XenoPort)

Approved 4/6/2011

How It Works:

Gabapentin enacarbil, a prodrug of gabapentin, is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA) but has no effect on GABA binding, uptake, or degradation. The mechanism by which gabapentin enacarbil exerts its therapeutic effect is unknown.

Things to Look Out for:

  • Driving impairment
  • Somnolence/Sedation
  • Dizziness
  • Suicidal behavior and ideation
  • Multiorgan hypersensitivity
  • If discontinuing, taper dose if >600mg daily

Use in Special Populations:

  • Pregnancy: Category C. No adequate and well-controlled studies in pregnant women.
  • Nursing mothers: It is not known whether this drug is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug.
  • Children: Safety and effectiveness in pediatric patients have not been established.
  • Elderly: Clinical trials did not include a sufficient number of patients 65yrs and older to determine whether they respond differently.
  • Renal impairment: Adjust dose based on creatinine clearance. CrCl<15mL/min on hemodialysis: not recommended.

What to Tell Your Patients:

  • Avoid alcohol.
  • Do no interchange with other gabapentin products.
  • Take at the same time each day at about 5PM.
  • May have sedating effects.
  • Be alert for the emergence or worsening of depression symptoms, unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or self-harm thoughts. Report immediately.
  • Patients should report signs or symptoms of multiorgan hypersensitivity (eg, fever, rash, lymphadenopathy).

Mirapex


(pramipexole dihydrochloride tablets; Boehringer Ingelheim)

Approved 6/1/1997

How It Works:

Pramipexole is a nonergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. The mechanism by which pramipexole exerts its therapeutic effects in RLS is unknown, but may involve the primary dopaminergic system.

Thinks to Look Out for:

  • Somnolence - falling asleep during daily activities
  • Symptomatic orthostatic hypotension
  • Reduced impulse control
  • Compulsive behaviors
  • Hallucinations
  • Dyskinesia
  • Rebound or augmentation of RLS symptoms
  • Melanoma

Use in Special Populations:

  • Pregnancy: Category C. No adequate and well-controlled studies conducted in pregnant women.
  • Nursing mothers: It is not known whether this drug is excreted in human milk. A decision should be made whether to discontinue nursing or discontinue the drug.
  • Children: Safety and effectiveness in pediatric patients has not been established.
  • Elderly: Clinical studies demonstrate no apparent differences in efficacy or safety between older and younger patients.
  • Renal impairment: Caution in moderate to severe (CrCl 20-60mL/min) renal impairment.

What to Tell Your Patients:

  • Take with food if nausea occurs.
  • May have sedating effects. Caution with other sedating medications or alcohol.
  • May experience intense urges and the inability to control these urges.
  • May develop hypotension; caution against rising rapidly after sitting or lying down.
  • Women should notify their physician if they become pregnant, intend to become pregnant, intend to breastfeed or are breastfeeding during therapy.