Use of skin patches containing the drug rotigotine can relieve restless legs syndrome (RLS) during both the day and night. These are the conclusions of authors of an Article published early Online and in the July edition of The Lancet Neurology.
Recent studies on the genetic basis of RLS have suggested that it needs to be treated as a general neurological disorder. Dopaminergic* drugs are currently used as the first-line treatment for this condition. Rotigotine is a dopaminergic drug that is already used for treating Parkinson's disease. Dr Claudia Trenkwalder, Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany and colleagues did a randomised controlled trial to investigate the efficacy of transdermal rotigotine patches in treatment of RLS.
The trial looked at 458 patients with moderate-to-severe RLS, with an average baseline score on the International Restless Leg Syndrome study group severity rating scale (IRLS) of 28.1 and a score of 4 or more on the clinical global impressions (CGI) item 1 score, which measures severity of symptoms. The patients were randomly assigned to receive transdermal rotigotine 1mg (115 patients), 2mg (112), or 3mg (114) over 24 h, or to receive placebo (117). The medication was delivered via patches, applied once a day for 6 months. Efficacy was measured by absolute change from baseline to end of maintenance in IRLS score, and the change in CGI item 1 score.
The researchers found that mean change in IRLS score was -13.7 in the 1mg group, -16.2 in the 2mg group, -16.8 in the 3mg group, and -8.6 in the placebo group. The change in CGI item 1 score was -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. 75% of patients rated their rotigotine patches as good or very good. Skin reactions, mostly mild or moderate, were seen in 145 of 341 patients (43%) who received rotigotine, and in 2 of 117 (2%) of patients who received placebo. Ten patients had serious adverse events that were deemed to be related to rotigotine: elevation of liver enzymes (1), worsening of tinnitus (1), non-response to anticoagulation (1), electrocardiogram changes (1), and application site reactions (6). No admissions to hospital were needed for the application site reactions, and they all resolved within a short time of patch removal without any other therapeutic intervention. The rate of typical dopaminergic side-effects in patients who received rotigotine was low, with no signs of augmentation** noted.
The authors conclude: "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."
In an accompanying Comment, Dr Kapil Sethi, Medical College of Georgia, Augusta, GA, USA, says: "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."
Notes to editors:
*Dopaminergic drugs: Drugs which stimulate the body's dopamine system. The dopamine system has many roles in the brain, including its involvement in motor functions.
**Augmentation is an overall increase in severity of symptoms in RLS during treatment, mainly under dopaminergic treatments
***Dopamine agonists are drugs which, when they bind to the cell surface active sites for dopamine, produce the same effect that dopamine would.
Dr Claudia Trenkwalder, Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany T) +49 561 6009 200 E) ctrenkwalder@gmx.de
Dr Kapil Sethi, Medical College of Georgia, Augusta, GA, USA T) +1 706 721 2798 E) ksethi@mcg.edu
http://www.eurekalert.org/jrnls/lance/pdfs/TLNrestlegcommentfinal.pdf
http://www.eurekalert.org/jrnls/lance/pdfs/TLNrestlesslegfinal.pdf
Journal
The Lancet Neurology