Dopaminergic agents are the first-line treatment of restless legs syndrome (RLS), and have been used for the treatment of this disorder since the 1980s. The major issue with this class of drugs is augmentation of RLS symptoms during treatment. The first report of augmentation found an occurrence among 73% of patients treated with levodopa. Subsequent studies have reported somewhat lower incidences, but augmentation remains a clinically significant issue with all dopaminergic agents. It was not until 2007 that an operational, empirical definition of augmentation (Max Planck Institute Criteria) was made. This late development and the fact that studies have not been specifically designed to assess augmentation, have made it particularly difficult to compare the incidence rates for the different RLS treatments. As the primary neural and molecular substrates underlying idiopathic RLS are not known, the pathophysiology of augmentation remains unclear, however there are several hypotheses that concern the role of dopaminergic hyperstimulation, of iron deficiency, the genetic component, the effect of a reduction in responsiveness of tubero-infundibular dopamine receptors, and the role of chronobiotic mechanisms. RLS is treated by maintaining low doses of dopaminergic agents and ensuring iron sufficiency. Non-dopaminergics and opiates can be used when patients experience augmentation with more than one dopaminergic agent.
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