Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study.
The European Restless Legs Syndrome (RLS) Study Group performed the first multi-center, long-term study systematically evaluating RLS augmentation under levodopa treatment. This prospective, open-label 6-month study was conducted in six European countries and included 65 patients (85% treatment naive) with idiopathic RLS. Levodopa was flexibly up-titrated to a maximum dose of 600 mg/day. Presence of augmentation was diagnosed independently by two international experts using established criteria. In addition to the augmentation severity rating scale (ASRS), changes in RLS severity (International RLS severity rating scale (IRLS), clinical global impression (CGI)) were analyzed. Sixty patients provided evaluable data, 35 completed the trial and 25 dropped out. Augmentation occurred in 60% (36/60) of patients, causing 11.7% (7/60) to drop out. Median time to occurrence of augmentation was 71 days. The mean maximum dose of levodopa was 311 mg/day (SD: 105). Patients with augmentation compared to those without were significantly more likely to be on higher doses of levodopa (> or =300 mg, 83 vs. 54%, P = 0.03) and to show less improvement of symptom severity (IRLS, P = 0.039). Augmentation was common with levodopa, but could be tolerated by most patients during this 6-month trial. Patients should be followed over longer periods to determine if dropout rates increase with time.
Högl
Birgit
B
Department of Neurology, Innsbruck Medical University, Anichstr. 35, 6020, Innsbruck, Austria. birgit.ho@i-med.ac.at
García-Borreguero
Diego
D
Kohnen
Ralf
R
Ferini-Strambi
Luigi
L
Hadjigeorgiou
Georgios
G
Hornyak
Magdolna
M
de Weerd
Al
A
Happe
Svenja
S
Stiasny-Kolster
Karin
K
Gschliesser
Viola
V
Egatz
Renata
R
Frauscher
Birgit
B
Benes
Heike
H
Trenkwalder
Claudia
C
Hening
Wayne A
WA
Allen
Richard P
RP
D015259:Dopamine Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D015259:Dopamine Agents; D007980:Levodopa