Restless legs syndrome (RLS) is a common disorder, characterized by a pressing need to move the extremities. It is associated with paraesthesias, motor restlessness, and worsening of symptoms at rest and during the evening or at night. It is classified as idiopathic or symptomatic (secondary). In secondary RLS, the primary illness should be identified and treated if possible. Levodopa is the agent of first choice; alternatives include other dopamine agonists, opioids and benzodiazepines. Patients also benefit from general measures, including initiation of good sleep hygiene practices.

The most important symptomatic form of RLS is that caused by uremia. Prevalence ranges from 20 to 40% in patients with end-stage renal disease. In these patients, RLS is known to be associated with the uremia itself and not to be an adverse effect of hemodialysis. RLS may also be an early manifestation of iron deficiency, although the mechanism involved is not known. RLS is seen in 12 to 20% of pregnant women.

Other causes are as follows:

·          peripheral neuropathy [e.g. associated with diabetes mellitus or alcohol (ethanol) toxicity] 

·          lumbosacral radiculopathy 

·          Hypothyroidism, Hyperthyroidism, Rheumatoid arthritis, Folic acid deficiency, Porphyria.

·         All dopamine D2 receptor blocking drugs (e.g. classical antipsychotic agents, sulpiride and metoclopramide) can evoke RLS, and there are case reports of the condition in patients receiving lithium.

·          Caffeine-containing beverages and medications can exacerbate RLS (as well as causing new symptoms in some individuals) and should be avoided. Stopping smoking may also be helpful, as may reductions in alcohol intake.

·          Patients should be made aware of the importance of a regular bedtime routine. Excessive sleep during the day may contribute to sleep disturbance; alternatively, excessive physical activity during the day may exacerbate RLS in some individuals. A hot bath before bedtime may help in some.

Treatment:

Dopaminergic drugs, in particular levodopa, are currently the treatment of first choice for idiopathic or uremic RLS. Levodopa itself is always given with a dopa decarboxylase inhibitor (DDCI) such as carbidopa or benserazide, and its efficacy has been verified in a number of nonblind and controlled trials. Bromocriptine (primarily a dopamine D2 receptor agonist) and pergolide (a combined D1 and D2 agonist) improve both subjective sleep quality and PLMS in patients with RLS. To avoid adverse effects, treatment should be started with low dosages that are increased with caution over 1 to 2 weeks. The new non-ergot dopamine agonist pramipexole has also been associated with improvements in symptoms of RLS, and preliminary data suggest that cabergoline and ropinirole may also be useful. Unlike levodopa; however, these agents are not suitable for use on an as-needed basis, although levodopa can be added to therapy with another dopamine agonist if necessary.

Opioids. Benzodiazepines a Useful Alternative. Anticonvulsants When Others Fail.

Place of Other Agents less Clear

There is some evidence that clonidine, a centrally acting inhibitory presynaptic alpha2-adrenergic agent, has a favourable effect on uremic and idiopathic RLS, although reports have been contradictory.[1] The GABA-ergic agonist baclofen has also been reported to improved RLS symptoms and sleep quality, but not to reduce frequency of PLMS. Other agents that have been tried include propranolol, tricyclic antidepressants, and 5-hydroxytryptophan and L-tryptophan. Anecdotal reports suggest benefit of tocopherol (vitamin E), ascorbic acid (vitamin C) and magnesium supplements.

Comparison of selected features of various drugs used to treat restless legs syndrome (RLS)

Prepared by Mostafa Tabassomi, M.D.