Restless Legs Syndrome: Lyrica Found Superior to Mirapex Interview with:
Dr. Richard P. Allen
Department of Neurology
Johns Hopkins University
Baltimore, MD 21224, What are the main findings of the study?

Dr. Allen:  This study should serve to change medical practice by reducing use of pramipexole and ropinirole to avoid the insidious worsening of restless legs syndrome that occurs for many on these drugs.

Pramipexole (Mirapex) a medication that mimics dopamine in the brain  in usual therapeutic doses for treatment of restless legs syndrome (RLS) works at first but over time one year makes the disease worse for up to 9% of the patients on 0.5 mg a day.

Pregabalin (Lyrica) an anti-convulsant and pain drug  that works on a calcium channel in the brain in therapeutic dose for RLS (300 mg a day) does not make the disease worse  (There is some natural progression of the disease shown to occur fro 1 – 2% or patients over a year.. seen in this study).

Pregabalin is in the short run as effective as pramipexole (over 12 weeks) and in the long run over 52 weeks more effective.

These results confirm what had been expected that the dopamine drug pramipexole makes worse Restless Legs Syndrome while a drug not directly acting on the dopamine system does NOT make restless legs syndrome worse. Were any of the findings unexpected?

Dr. Allen:

1. The amount of restless legs syndrome worsening with pramipexole at 0.5 mg over was more than expected for only one year of treatment- indicating a possible bigger than anticipated problem.

2.  The non-dopamine drug pregabalin was as effective and in the long run slightly more effective than the dopamine drug pramipexole. What should clinicians and patients take away from your report?


1. The commonly used drug pramipexole (Mirapex)  and the similar drug ropinirole (Requip) are deceptive in that they work great for restless legs syndrome a while but then with continued use for many make the RLS disease worse than before treatment.

2. Pramipexole and ropinirole make a bad disease worse.

3. Alternative treatments should be considered where appropriate.

4. The alternative non-dopamine drug pregabalin (Lyrica) and its similar drug gabapentin enacarbil (Horizant) do not make the disease worse and are as effective.

5. Also the very long acting dopamine drug rotigotine (Nupro patch) appears not to make the disease worse at least over 1 – 5 years of treatment and is also effective. What recommendations do you have for future research as a result of this study?

Dr. Allen:

1. Evaluation of mechanisms producing the worsening of restless legs syndrome on the short and intermediate acting dopamine drugs that does not appear to occur as much if at all on very long acting dopamine drugs.

This is suggested in clinical data but not proven, it needs to be established in long-term trials  along with study of effects that produce the worsening of RLS.  This wold help design better drugs.

2. Evaluation of how pregabalin makes RLS better.

3. The interaction of these drugs and the worsening of restless legs syndrome with iron status of RLS  (Low iron status increases the risk of drug induced worsening of RLS in clinical studies).


Comparison of Pregabalin with Pramipexole for Restless Legs Syndrome

Richard P. Allen, Ph.D., Crystal Chen, M.D., Diego Garcia-Borreguero, M.D., Ph.D., Olli Polo, M.D., Sarah DuBrava, M.S., Jeffrey Miceli, Ph.D., Lloyd Knapp, Pharm.D., and John W. Winkelman, M.D., Ph.D.

N Engl J Med 2014; 370:621-631February 13, 2014DOI: 10.1056/NEJMoa1303646



Last Updated on April 19, 2014 by Marie Benz MD FAAD