Restless Leg Syndrome Relief Found In Rotigotine Skin Patch

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 Bene??, Werner Poewe, Wolfgang H Oertel,
Diego Garcia-Borreguero, Al W de Weerd, Luigi Ferini-Strambi, Pasquale
Montagna, Per Odin, Karin Stiasny-Kolster, Birgit H?¶gl, K Ray
Chaudhuri, Markku Partinen, Erwin Schollmayer, Ralf Kohnen, for the
SP790 Study Group

The Lancet Neurology (2008)

DOI:10.1016/S1474-4422(08)70112-1

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Here to View Abstract



Written by: Peter M Crosta