Sleep Strategies

Restless legs syndrome: Update on evaluation and treatment


Restless legs syndrome (RLS) is a very common disease affecting about 10% of Caucasian adults with about one third of them having RLS symptoms severe enough to require treatment.

Dr. Mark J. Buchfuhrer, Stanford (Calif.) University, department of psychiatry and behavioral sciences in the school of medicine, division of sleep medicine.

Dr. Mark J. Buchfuhrer

Although many patients still go undiagnosed or misdiagnosed, the diagnosis is easily established with the five diagnostic criteria that are simplified by the acronym URGES:

1. Urge to move the legs associated with unpleasant leg sensations.

2. Rest induces symptoms.

3. Gets better with activity.

4. Evening and nighttime worsening.

5. Solely not accounted by another medical or behavioral condition.

The diagnosis is based completely upon the history. However, supplemental tests can be helpful to rule out underlying conditions that increase the risk of RLS. Routine lab tests, such as serum creatinine (to rule out renal disease), TSH (to rule out thyroid disease), and a CBC/ferritin/iron with transferrin saturation (to rule out low iron stores) should be ordered if not done recently.

A polysomnographic sleep study should not be ordered unless there is a strong suspicion that sleep apnea is present. Even very frequent PLM (periodic limb movements) are not that helpful in confirming the diagnosis of RLS since they are nonspecific and often occurring with drug treatment (SSRIs, SNRIs) and many medical conditions such as sleep apnea, narcolepsy, and REM behavior disorder.

The paradigm for treating RLS has been presented in the consensus article published in 2013 (Silber MH, et al. Mayo Clin Proc. 2013 Sep;88[9]:977). Since 2013, there has been a gradual shift of that paradigm that recommended starting an approved dopamine agonist (pramipexole, ropinirole, or rotigotine) or an alpha-2-delta ligand (gabapentin enacarbil, gabapentin, or pregabalin) as first-line treatment. Although dopamine agonists provide excellent relief of RLS symptoms initially, with time, they tend to markedly worsen RLS. This process is called RLS augmentation and has become one of the most common causes of refractory RLS and difficult-to-treat patients.

RLS augmentation typically onsets a few months to several years after starting a short-acting dopamine agonist (DA) like pramipexole or ropinirole. It presents with symptoms occurring a few hours earlier than prior to starting the medication, symptoms becoming more intense with less rest time needed to trigger RLS symptoms, drugs becoming less effective both in effectiveness and duration of action, and spread of symptoms to other body parts (arms, trunk, and even head). The majority of physicians mistake this worsening of RLS for the natural progression of the disease and, thus, increase the dose of the DA, which provides temporary improvement. Further increases become progressively necessary until the patient is receiving very large doses, often exceeding 10 times the FDA maximum recommended doses. Eventually, further dose increments provide minimal additional benefit, leaving patients with severe, around the clock RLS symptoms causing extreme misery. To be more aware of augmentation, physicians should consider augmentation may be occurring whenever a patient who has been on a regimen of stable dopamine agonist treatment for at least 6 months requests more medication.


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