Patients with restless leg syndrome (RLS) – the irresistible urge to move one’s body to limit uncomfortable or odd sensations – may get some relief during day and night by using skin patches that contain the drug rotigotine. The findings come from a randomized, placebo-controlled, double-blind study published in the July edition of The Lancet Neurology.

Researchers studying RLS have analyzed the genetic basis of the disease and determined that it should be treated as a general neurological disorder. Currently, many patients with this condition are prescribed dopaminergic drugs that stimulate the body’s dopamine system – a first line of treatment. Rotigotine is a type of dopaminergic drug, and it has been used to treat Parkinson’s disease. To investigate the effects of transdermal rotigotine patches as treatment of RLS, Dr Claudia Trenkwalder (Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany) and colleagues conducted a randomized controlled trial.

The researchers analyzed a sample of 458 patients with moderate-to-sever RLS. Their average baseline score on the International Restless Leg Syndrome study group severity rating scale (IRLS) was 28.1, and they had a score of 4 or more on a test to measure severity of symptoms called the clinical global impressions (CGI) item 1 assessment. Random assignment resulted in 115 patients receiving transdermal rotigotine 1 mg, 112 patients receiving a 2 mg dose, 114 receiving a 3 mg dose, and 117 receiving placebo. Rotigotine was delivered via skin patches that were applied one time a day over a 6 month period. The main outcome measures were the changes from baseline to the end of the treatment period in the IRLS score and in the CGI item 1 score.

The mean changes in the IRLS group were as follows:

  • -13.7 in the 1 mg group,
  • -16.2 in the 2 mg group,
  • -16.8 in the 3 mg group, and
  • -8.6 in the placebo group.

The mean changes in the CGI item 1 score were:

  • -2.09 in the 1 mg group,
  • -2.41 in the 2 mg group,
  • -2.55 in the 3 mg group, and
  • -1.34 in the placebo group.

Three quarters of patients indicated that their rotigotine patches were “good” or “very good” in a follow-up survey, though 43% of patients (145 of 341) had (mostly mild or moderate) skin reactions to rotigotine. Only 2% of participants who received placebo reported skin reactions. Rotigotine was associated with serious adverse events in 10 patients: one patient had an elevation of liver enzymes, one had a worsening of tinnitus, one had a non-response to anticoagulation, one had electrocardiogram changes, and six had reactions at the application site. Skin reactions at the patch site were not severe enough to warrant hospital treatment, and shortly after removing the patch, the issues were resolved. There were no signs of an increase in the severity of symptoms in RLS during dopaminergic treatment, and the patients demonstrated a low the rate of typical dopaminergic side-effects.

“The results of this 6-month trial indicate that transdermal delivery of low doses of rotigotine for 24 h per day are more effective than placebo in relieving the symptoms of RLS in patients who are moderately to severely affected. This trial, together with a pilot study and dose-finding trial, suggest that, despite differences in treatment duration and other design features, there exists a clear therapeutic window in terms of dose of rotigotine to treat restless legs syndrome between 1 mg over 24 h to 3 mg over 24 h,” conclude the authors.

A comment accompanying the research article is written by Dr Kapil Sethi (Medical College of Georgia, Augusta, GA, USA). Dr. Sethi notes that, “The introduction of a patch with a constant delivery of a dopamine agonist is a welcome addition to the armamentarium. Unfortunately, the rotigotine patch has been temporarily withdrawn from the US market because of problems with manufacturing and the unreliable delivery of the drug.

“RLS causes significant discomfort and adversely affects the quality of life of patients. Whether it has more ominous consequences is unclear. A recent study showed that RLS is associated with a greater risk of cardiovascular disease, particularly in patients with greater frequency or severity of RLS symptoms. Whether treatment of RLS will reduce this risk is unknown, and further studies should help answer this question.”

Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial
Claudia Trenkwalder, Heike Beneš, Werner Poewe, Wolfgang H Oertel, Diego Garcia-Borreguero, Al W de Weerd, Luigi Ferini-Strambi, Pasquale Montagna, Per Odin, Karin Stiasny-Kolster, Birgit Högl, K Ray Chaudhuri, Markku Partinen, Erwin Schollmayer, Ralf Kohnen, for the SP790 Study Group
The Lancet Neurology (2008)
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Written by: Peter M Crosta