Realization of symptom relief from RLS demands a thorough clinical evaluation to rule out co-existing conditions that enhance RLS expressivity.  There is an absence of evidence-based medicine as to the positive or negative effects of lifestyle and diet upon RLS/PLMs.  That being said, sleep restriction, tobacco, alcohol, and caffeine have all been implicated in worsening of RLS and should be avoided as recommended by expert opinion. Medications known or suspected to worsen RLS should be discontinued when feasible. These include the non-specific anti-histamines (e.g., diphenhydramine and meclizine), dopamine antagonists (e.g., metaclopramide), antidepressants, neuroleptics, and lithium.

 Another common exogenous factor influencing RLS expressivity is iron deficiency, and this should be routinely assessed for at the initial evaluation and at yearly follow-up.  Because a substantial number (~ 2/3rds of our clinic population) of iron deficient RLS patients do not exhibit coexisting anemia (i.e., they have pre-anemic iron deficiency), and ferritin being an acute-phase reactant prone to false elevations, a complete serum iron panel (iron, total iron binding capacity, percent transferrin saturation, and ferritin) is preferred.  The RLS Foundation treatment algorithm recommends iron repletion when ferritin is below 20 ng/mL and consideration of iron repletion on a case-by-case basis when the ferritin is between 20 and 50 ng/mL . Although this is an expert guideline, data to support iron supplementation are still mixed.

 When pharmacologic treatment for RLS is needed, the first line of treatment are dopamine-like drugs. It is important to bear in mind that many clinical trials establishing efficacy of these medications excluded individuals with iron deficiency because this was a suspected ‘cause’ of secondary RLS/PLMs (e.g., ferritin < 15-20ng/ml) and were largely derived from patient populations that were 2/3rds women, and therefore might not be generalizable.    The medication class in which there is the largest published experience includes the dopamine agonists which were the first agents approved by the United States Food & Drug Administration (FDA) for RLS treatment. Dopamine agonists alleviate RLS symptoms in 70-90% of patients.  There are many different formulatons of dopamine agents and these need to be tailored to individual patient needs.  It still remains unknown why dopamine-like drugs work so well for most RLS patients, and where in the brain, spinal cord, or nerves they exert their beneficial affects.