Ferini_EU Neurology 09/03/2010 11:51 Page 85
Treatment of Restless Legs Syndrome
Table 1: Studies of Rotigotine in Idiopathic Restless Legs Syndrome
Authors Patients Outcome Measures Dose Range (mg/24 hours) Duration Side Effects*
Stiasny-Kolster et al., 2004
54
63 IRLS 0.5–2 1 week ASR
RLS-6 Headache
CGI Pruritus
ESS Nausea
Insomnia
Increased sweating
Increased fatigue
Abnormal vision
Oertel et al., 2008
55
341 IRLS 0.5–4 6 weeks ASR
RLS-6 Pruritus
CGI Nausea
RLS-QoL Vomiting
ESS Constipation
Headache
Fatigue
Dizziness
Nasopharyngitis
Back pain
Trenkwalder et al., 2008
57
458 IRLS 1–3 6 months ASR
RLS-6 Nausea
CGI Headache
RLS-QoL Fatigue
MOS Dry mouth
ASRS Insomnia
Hyperhidrosis
Dizziness
Vertigo
Oertel et al., 2008
56
295 IRLS 0.5–4 1 year** ASR
RLS-6 Nausea
CGI Erythema
RLS-QoL Back pain
ESS Fatigue
ASRS
*Most frequently reported side effects (reported by at least 5% of patients in at least one rotigotine treatment group). Treatment-related side effects are reported for Stiasny-Kolster et al.,
54
2004. **While so far only one-year results of this trial (SP710) are fully published, this study was prospectively designed for five years of follow-up; two and three year results are available in
abstract form. ASR = application-site reactions; ASRS = Augmentation Severity Rating Scale; CGI = Clinical Global Impressions; ECG = electrocardiogram; ESS = Epworth Sleepiness Scale;
IRLS = International Restless Legs Syndrome Severity Scale; MOS = Medical Outcomes Study; RLS-QoL = Restless Legs Syndrome Quality of Life questionnaire.
agonists.
43
Recently, behavioural complications, such as pathological extensive gastrointestinal metabolism.
47
High lipid solubility makes
gambling and punding, have also been reported in some RLS cases rotigotine an ideal candidate for transdermal application. Recent
under dopaminergic treatment.
44
experimental data on pharmacokinetics with the patch show that
rotigotine has the potential to induce continuous dopamine receptor
Opioids may be prescribed for severe cases of RLS, especially in patients stimulation.
48
Rotigotine, as a transdermal patch, is absorbed through
unresponsive to other treatments.
20
Although there is little evidence of the skin by transcellular, intercellular (lipophilic) and follicular
tolerance of or addiction to opioids in the RLS literature,
20
the (hydrophilic) routes.
49
After transdermal application, the drug reaches
prescription of these compounds should be restricted to patients the systemic circulation with a lag-time of two to three hours, and
without a previous history of substance abuse. maximum plasma concentration is reached after 16 hours.
50
In healthy
subjects treated with a dose of 4mg/24 hours for a period of 14 days,
A subjective improvement of RLS with gabapentin at doses of plasma level analysis showed a stable level after two to three days,
200–2,000mg/day has been reported in some open-label trials and one consistent throughout the subsequent treatment period without
placebo-controlled study.
27
As shown in a six-week placebo-controlled accumulation or change in clearance.
51
Dose adjustment due to age,
study, gabapentin has a good side-effect profile.
45
Other anticonvulsants, gender, weight or renal or hepatic impairment is not necessary.
52
such as carbamazepin and valproic acid, have been evaluated in RLS but Moreover, rotigotine showed no effects on CYP450 enzyme activity in in
seem to be less effective than gabapentin.
20
vitro and in vivo studies, indicating a low risk of drug–drug interactions.
53
Rotigotine – A New Non-ergot Dopamine Agonist Rotigotine for the Treatment of
Rotigotine is the levorotary enantiomer of a racemic aminotetraline Restless Legs Syndrome
compound with structural similarity to dopamine. It is a non-ergot In the last few years, from January 2004 to December 2009 (PubMed
agonist of all dopamine receptors (D
1
–D
5
), with the strongest affinity for database), four studies on rotigotine in RLS have been published.
54–57
D
3
receptors.
46
Its bioavailability after oral ingestion is very low due to These four European studies included one proof-of-principle study (one
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