In the Clinic
Restless Legs
Syndrome
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
What is RLS?
 Diagnostic criteria (all criteria must be met)
 Urge to move legs, usually accompanied by uncomfortable,
unpleasant sensations in legs
 Begins or worsens during rest or inactivity
 Partially or totally relieved by movement
 Only occurs or worsens in the evening or night
 Not attributable to another condition
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
What symptoms should prompt clinicians
to consider RLS?
 Insomnia
 Urge to move the legs or leg dysesthesia
 Other common symptoms
 Leg pain
 Fatigue
 Leg jerks
 Daytime sleepiness
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
What physical examination findings
indicate possible RLS?
 No physical findings are associated with idiopathic RLS
 RLS may accompany
 Low iron stores
 Pregnancy
 Renal disease
 Diabetes
 Neuropathy
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
What other evaluation should be performed
in patients suspected of having RLS?
 Assess
 Timing and severity of RLS symptoms
 Impact on daytime mood and function
 Medical history
 Symptoms of other sleep disorders
 Family history
 Medication use
 Some experts recommend iron studies, even in absence
of anemia
continued…
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
 Common mimics
 Leg cramps
 Neuropathy
 Arthritis
 Peripheral vascular disease
 Akathisia
 Refer to sleep specialist or neurologist
 Uncertain diagnosis or coexisting sleep disorder
 Neurologic disorder or other complex medical condition
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
CLINICAL BOTTOM LINE: Diagnosis...
 Diagnosis is based on clinical criteria
 Symptom timing, frequency, and severity are important
 History and physical exam distinguishes RLS from mimics
 Other diagnostic studies only for possible associated
conditions (iron deficiency)
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
What nondrug therapies should clinicians
recommend for RLS?
 Distracting activities
 Mental-alerting strategies (knitting, video games)
 Activities requiring standing, locomotion, movement
 Activities that may improve symptoms
 Pneumatic compression devices
 Near-infrared light-treatment
 Aerobic or resistance training, intradialytic exercise
 Avoid drugs that might provoke RLS
 Avoid sleep deprivation
 The role of supplemental iron is uncertain
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
How should clinicians choose and dose
drugs?
 Mild or intermittent symptoms
 Only use pharmacologic therapy for situations that limit
mobility (e.g., air travel)
 Moderate or severe symptoms that interfere with sleep
or impair daytime functioning
 Reserve drugs for those with near daily or daily symptoms
 Dopamine agonists (pramipexole, ropinorole, rotigotine)
 Alpha-2 delta ligands (gabapentin encarbil)
 Off label: other alpha-2 delta ligands and opioids
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
Dopamine agonists
 Recommended for patients with very severe RLS, comorbid
depression/dysthymia, and obesity/metabolic syndrome
 Initiate with lowest recommended dose
 Don’t exceed in 24-hour period: 1 mg pramipexole; 4 mg
ropinirole; 3 mg rotigotine
 For pramipexole and ropinirole: take 1-2 hours before
expected symptom onset
 Side effects: nausea, somnolence, and site application
reactions with rotigotine, impulse control disorders
 Augmentation is possible
 Worsening of symptoms earlier in the day
 Increased intensity or spread of symptoms to the arms
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
Alpha-2 delta ligands
 Recommended for patients with comorbid pain, anxiety,
insomnia, or previous impulse control disorder or
addiction
 Gabapentin is poorly absorbed
 Gabapentin encarbil is a pro-drug that provides better
bioavailability and is FDA-approved for RLS
 Pregabalin is another option
 Adverse effects include dizziness, somnolence, weight
gain, and depression/suicidal ideation
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
Other Medications
 Benzodiazepines generally ineffective for RLS
 Opioids not well-studied for RLS
 Potential to improve symptoms but high rate of AEs
 Only consider after other strategies are exhausted
and potential for misuse is carefully assessed
 Consult with a sleep specialist before prescribing
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
How should clinicians monitor patients?
 Titrate to lowest effective dose
 Monitor for side effects and augmentation
 Reassess patients who don’t improve for changes in
aggravating factors
 Beware of rebound with shorter-acting medications
 Consider natural disease progression and variation
 If augmentation occurs, split dose or switch to longeracting agent in same class
 Consider substituting alpha-2 delta ligand or high-potency
opioid for dopaminergic agent
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
When should clinicians consider
consulting a sleep specialist or
neurologist?
 Atypical presentation of symptoms
 Loss of treatment efficacy despite increased dosage
 Intolerable side effects
 Augmentation
 Coexisting sleep disorder, neurologic disorder, or other
complex medical conditions
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.
CLINICAL BOTTOM LINE: Treatment...
 Nonpharmacologic therapies
 Distracting activities
 Planned ambulation
 Avoiding putative triggers may not alleviate symptoms
 Consider iron supplementation on a case-by-case basis
 Pharmacologic treatment
 Only for moderate-severe and bothersome symptoms
 Start with alpha-2 delta ligands
 Dose prior to expected symptom onset and titrate to lowest
effective dose
 Monitor for side effects
 Refer patients with loss of efficacy, adverse effects, or
augmentation to a sleep specialist or neurologist
© Copyright Annals of Internal Medicine, 2009
Ann Int Med. 163 (6): ITC6-1.