The impact of restless legs syndrome (RLS) can range from nuisance symptomatology requiring modest interruption of sleep to major decrements in quality of life for the patient and/or bed partner. Although dopaminergic medications have become the mainstay of therapy, they are sometimes associated with “augmentation;” a worsening of symptom intensity, symptom frequency, or increase in areas of the body involved with symptoms, over long-term treatment. Since there is no known cure for RLS, many patients require lifelong treatment, necessitating alternatives in the event that RLS augmentation occurs. To complicate the picture further, not everyone agrees that augmentation is a pharmacologically related issue; instead, the worsening of symptoms over time may simply reflect disease progression in susceptible individuals.
Allen et al performed a randomized, double-blind trial to compare the initial success rate for RLS symptoms (over 12 weeks) as well as frequency of augmentation over an additional 40 weeks of treatment with either pregabalin (300 mg/d), pramipexole (0.25 or 0.5 mg/d), or placebo (n = 719).
Both active treatments were effective in reducing RLS symptoms, although only higher dose pramipexole (0.5 mg) and pregabalin were statistically significantly superior to placebo. For the endpoint of augmentation, pregabalin was superior to both placebo and pramipexole 0.5 mg.
The underlying assumptions prompting treatment choices for RLS presume dopaminergic deficits. Since pregabalin has no known dopaminergic activity, and was found to be as effective as the dopaminergic treatment (pramipexole), the current understanding of the pathophysiologic basis for RLS has been challenged.
Source: Allen RP, et al. N Engl J Med 2014;370:621-631.