TY - JOUR
T1 - Efficacy and augmentation during 6months of double-blind pramipexole for restless legs syndrome
AU - Högl, Birgit
AU - Garcia-Borreguero, Diego
AU - Trenkwalder, Claudia
AU - Ferini-Strambi, Luigi
AU - Hening, Wayne
AU - Poewe, Werner
AU - Brenner, Stefanie S.
AU - Fraessdorf, Mandy
AU - Busse, Michael
AU - Albrecht, Stefan
AU - Allen, Richard P.
PY - 2011/4
Y1 - 2011/4
N2 - Background: Pramipexole is an effective treatment for restless legs syndrome (RLS), but no controlled studies have lasted >12 weeks. Methods: RLS patients (N=331) with pretreatment serum ferritin >30. ng/mL were randomly assigned to take double-blind optimized pramipexole (0.125-0.75. mg/d) or placebo for 26. weeks. The primary efficacy endpoint was change in International RLS Study Group Rating Scale (IRLS) score. Other endpoints assessed global change, symptoms, and QoL. Patients maintained symptom diaries. Cases meeting predefined criteria for suspected augmentation were reviewed by a blinded expert panel, which used a predefined algorithm. Results: Among 321 patients providing post-baseline data, of whom 234 completed 26. weeks, pramipexole was more effective than placebo by multiple endpoints, including an adjusted mean IRLS score change of -13.7 vs. -11.1 (p=0.0077) and an IRLS responder rate (≥50% score reduction) of 58.6% vs. 42.8% (p=0.0044). Efficacy showed considerable country-to-country variability. Six-month incidence of confirmed augmentation was 9.2% for pramipexole and 6.0% for placebo. The rate increased with treatment duration for pramipexole but not placebo. Treatment-related adverse events (AEs) were more likely for pramipexole than for placebo, but discontinuation due to AEs was less likely. Conclusions: During a 6-month period, pramipexole was effective, safe, and generally well tolerated. Because risk of augmentation may have increased over 6. months, it should be studied in longer trials. Beginning or mild augmentation is difficult to distinguish from natural RLS fluctuation, at least in a non-iron-deficient population.
AB - Background: Pramipexole is an effective treatment for restless legs syndrome (RLS), but no controlled studies have lasted >12 weeks. Methods: RLS patients (N=331) with pretreatment serum ferritin >30. ng/mL were randomly assigned to take double-blind optimized pramipexole (0.125-0.75. mg/d) or placebo for 26. weeks. The primary efficacy endpoint was change in International RLS Study Group Rating Scale (IRLS) score. Other endpoints assessed global change, symptoms, and QoL. Patients maintained symptom diaries. Cases meeting predefined criteria for suspected augmentation were reviewed by a blinded expert panel, which used a predefined algorithm. Results: Among 321 patients providing post-baseline data, of whom 234 completed 26. weeks, pramipexole was more effective than placebo by multiple endpoints, including an adjusted mean IRLS score change of -13.7 vs. -11.1 (p=0.0077) and an IRLS responder rate (≥50% score reduction) of 58.6% vs. 42.8% (p=0.0044). Efficacy showed considerable country-to-country variability. Six-month incidence of confirmed augmentation was 9.2% for pramipexole and 6.0% for placebo. The rate increased with treatment duration for pramipexole but not placebo. Treatment-related adverse events (AEs) were more likely for pramipexole than for placebo, but discontinuation due to AEs was less likely. Conclusions: During a 6-month period, pramipexole was effective, safe, and generally well tolerated. Because risk of augmentation may have increased over 6. months, it should be studied in longer trials. Beginning or mild augmentation is difficult to distinguish from natural RLS fluctuation, at least in a non-iron-deficient population.
KW - Augmentation
KW - Dopamine agonists
KW - Long-term treatment
KW - Pramipexole
KW - Restless legs syndrome
KW - Therapy
KW - Withdrawal
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U2 - 10.1016/j.sleep.2010.12.007
DO - 10.1016/j.sleep.2010.12.007
M3 - Article
C2 - 21354368
AN - SCOPUS:79953057218
VL - 12
SP - 351
EP - 360
JO - Sleep Medicine
JF - Sleep Medicine
SN - 1389-9457
IS - 4
ER -