Top

Sleep and Breathing

Published in:

01-03-2022 | Restless Legs Syndrome | Neurology • Original Article

Augmentation in patients with restless legs syndrome receiving pramipexole therapy: a retrospective study in a single center from China

Authors: Tiantian Wang, Miaofa Ying, Rui Zhao, Danyan Zhu, Lisan Zhang

Published in: Sleep and Breathing | Issue 1/2022

Abstract

Purpose

Augmentation is a major complication of long-term pramipexole treatment of restless legs syndrome (RLS). However, there have been no studies on augmentation in Chinese patients with RLS. We therefore investigated the clinical characteristics of augmentation in RLS patients treated with pramipexole in a real-world Chinese setting.

Methods

This study was an observational, retrospective assessment of 103 patients with RLS, who had been continuously treated with pramipexole for at least one month between January 2016 and December 2018 in a tertiary hospital in East China. Demographic data and disease and drug treatment information were collected from electronic medical records and telephone interviews to analyze the rate and clinical features of augmentation. Augmentation was confirmed by Max Planck Institute criteria. Comparisons were made between patients with and without augmentation.

Results

Fifteen patients (15%) were classified as having augmentation. Compared to RLS patients without augmentation, more patients with augmentation switched from other dopaminergic drugs (P<0.05) and had a longer duration of RLS symptoms before pramipexole treatment (P<0.05). In addition, patients with augmentation had a longer duration (P<0.05) and higher dosage (P<0.05) of pramipexole than those without augmentation. Augmentation was possibly associated with pramipexole tolerance (P<0.01).

Conclusion

The augmentation rate of the Chinese RLS patients in our study was 15%. Augmentation may be associated with switching from other dopaminergic drugs, long disease duration before pramipexole use, the dose and duration of pramipexole, and tolerance to pramipexole.

Garcia-Borreguero D, Cano-Pumarega I (2017) New concepts in the management of restless legs syndrome. BMJ 356:j104CrossRef

Mackie S, Winkelman JW (2015) Long-term treatment of restless legs syndrome (RLS): an approach to management of worsening symptoms, loss of efficacy, and augmentation.CNS. DRUGS 29(5):351–357

Winkelman JW, Armstrong MJ, Allen RP, Chaudhuri KR, Ondo W, Trenkwalder C, Zee PC, Gronseth GS, Gloss D, Zesiewicz T (2016) Practice guideline summary: treatment of restless legs syndrome in adults: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 87(24):2585–2593CrossRef

Trenkwalder C, Allen R, Högl B, Clemens S, Patton S, Schormair B, Winkelmann J (2018) Comorbidities, treatment, and pathophysiology in restless legs syndrome. Lancet Neurol

Winkelmann J, Allen RP, Hogl B, Inoue Y, Oertel W, Salminen AV, Winkelman JW, Trenkwalder C, Sampaio C (2018) Treatment of restless legs syndrome: evidence-based review and implications for clinical practice (Revised 2017)(section sign). Mov Disord 33(7):1077–1091CrossRef

Garcia-Borreguero D, Silber MH, Winkelman JW, Hoegl B, Bainbridge J, Buchfuhrer M, Hadjigeorgiou G, Inoue Y, Manconi M, Oertel W, Ondo W, Winkelmann J, Allen RP (2016) Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation. Sleep Med 21:1–11CrossRef

Garcia-Borreguero D, Cano-Pumarega I, Marulanda R(2018)Management of treatment failure in restless legs syndrome (Willis-Ekbom disease). Sleep Med Rev

Tanioka K, Okura M, Inoue M, Taniguchi K, Taniguchi M, Hamano T, Naoko T (2018) Rate of augmentation and risk factors with long-term follow-up in Japanese patients with restless legs syndrome. Neurol Sci 39:1559–1564CrossRef

Jeon J, Moon H, Song ML, Lee HB, Cho YW (2015) Augmentation in restless legs syndrome patients in Korea.SLEEP. Breath 19(2):523–529CrossRef

10.

Takahashi M, Nishida S, Nakamura M, Kobayashi M, Matsui K, Ito E, Usui A, Inoue Y (2017) Restless legs syndrome augmentation among Japanese patients receiving pramipexole therapy: rate and risk factors in a retrospective study. PLOS ONE 12(e01735353):e0173535CrossRef

11.

Inoue Y, Kuroda K, Hirata K, Uchimura N, Kagimura T, Shimizu T (2010) Long-term open-label study of pramipexole in patients with primary restless legs syndrome.J. Neurol Sci 294(1-2):62–66CrossRef

12.

Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB (2014) Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med 15(8):860–873CrossRef

13.

Garcia-Borreguero D, Allen RP, Kohnen R, Hogl B, Trenkwalder C, Oertel W, Hening WA, Paulus W, Rye D, Walters A, Winkelmann J, Earley CJ (2007) Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine-International Restless Legs Syndrome Study Group consensus conference at the Max Planck Institute. Sleep Med 8(5):520–530CrossRef

14.

Garcia-Borreguero D, Benitez A, Kohnen R, Allen R (2015) Augmentation of restless leg syndrome (Willis-Ekbom disease) during long-term dopaminergic treatment. Postgrad Med 127(7):716–725CrossRef

15.

Silber MH, Girish M, Izurieta R (2003) Pramipexole in the management of restless legs syndrome: an extended study. Sleep 26(7):819–821CrossRef

16.

Winkelman JW, Johnston L (2004) Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med 5(1):9–14CrossRef

17.

Lipford MC, Silber MH (2012) Long-term use of pramipexole in the management of restless legs syndrome. Sleep Med 13(10):1280–1285CrossRef

18.

Ferini-Strambi L (2002) Restless legs syndrome augmentation and pramipexole treatment. Sleep Med 3 Suppl:S23–S25CrossRef

19.

Högl B, Garcia-Borreguero D, Trenkwalder C, Ferini-Strambi L, Hening W, Poewe W, Brenner SS, Fraessdorf M, Busse M, Albrecht S, Allen RP (2011) Efficacy and augmentation during 6 months of double-blind pramipexole for restless legs syndrome. Sleep Med 12(4):351–360CrossRef

20.

Allen RP, Chen C, Garcia-Borreguero D, Polo O, DuBrava S, Miceli J, Knapp L, Winkelman JW (2014) Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med 370(7):621–631CrossRef

21.

Högl B, García-Borreguero D, Kohnen R, Ferini-Strambi L, Hadjigeorgiou G, Hornyak M, de Weerd A, Happe S, Stiasny-Kolster K, Gschliesser V, Egatz R, Frauscher B, Benes H, Trenkwalder C, Hening WA, Allen RP (2010) Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study. J Neurol 257(2):230–237CrossRef

22.

Allen RP, Ondo WG, Ball E, Calloway MO, Manjunath R, Higbie RL, Lee MR, Nisbet PA (2011) Restless legs syndrome (RLS) augmentation associated with dopamine agonist and levodopa usage in a community sample. Sleep Med 12:431–439CrossRef

23.

Garcia-Borreguero D, Hoegl B, Ferini-Strambi L, Winkelman J, Hill-Zabala C, Asgharian A, Allen R (2012) Systematic evaluation of augmentation during treatment with ropinirole in restless legs syndrome (Willis-Ekbom Disease): results from a prospective, multicenter study over 66 weeks. Mov Disord 27(2):277–283CrossRef

24.

Dinkins ML, Lallemand P, Clemens S (2017) Long-term treatment with dopamine D3 receptor agonists induces a behavioral switch that can be rescued by blocking the dopamine D1 receptor. Sleep Med 40:47–52CrossRef

25.

Earley CJ, Uhl GR, Clemens S, Ferre S (2017) Connectome and molecular pharmacological differences in the dopaminergic system in restless legs syndrome (RLS): plastic changes and neuroadaptations that may contribute to augmentation. Sleep Med 31:71–77CrossRef

26.

Casoni F, Galbiati A, Ferini-Strambi L (2019) D3 receptor agonist efficacy in restless legs syndrome. Adv Pharmacol 84:21–35CrossRef

27.

Ondo WG, Hermanowicz N, Borreguero DG, Jaros MJ, Kim R, Shang G (2015) Effect of prior exposure to dopamine agonists on treatment with gabapentin enacarbil in adults with moderate-to-severe primary restless legs syndrome: pooled analyses from 3 randomized trials. J Clin Mov Disord 2:9CrossRef

28.

Stefani A, Mitterling T, Heidbreder A, Steiger R, Kremser C, Frauscher B, Gizewski ER, Poewe W, Högl B, Scherfler C (2019) Multimodal magnetic resonance imaging reveals alterations of sensorimotor circuits in restless legs syndrome. Sleep 42(12)

29.

Li T, Liu C, Lyu H, Xu Z, Hu Q, Xu B, Wang Y, Xu J (2018) Alterations of sub-cortical gray matter volume and their associations with disease duration in patients with restless legs syndrome. Front Neurol 9:1098CrossRef

30.

Mitelman SA, Buchsbaum MS, Christian BT, Merrill BM, Buchsbaum BR, Mukherjee J, Lehrer DS (2020) Dopamine receptor density and white mater integrity: (18)F-fallypride positron emission tomography and diffusion tensor imaging study in healthy and schizophrenia subjects. Brain Imaging Behav 14(3):736–752CrossRef

31.

Koblinger K, Füzesi T, Ejdrygiewicz J, Krajacic A, Bains JS, Whelan PJ (2014) Characterization of A11 neurons projecting to the spinal cord of mice. PLoS One 9(10):e109636CrossRef

32.

Zhang L, Sun Y, Wang T, Pan Y, Yao Y, Pan L, Xu Q, Zhang W, Xu J, Hu X (2019) Restless legs syndrome in ischemic stroke patients: clinical features and significance. Zhejiang Da Xue Xue Bao Yi Xue Ban 48(3):275–281PubMed

Title: Augmentation in patients with restless legs syndrome receiving pramipexole therapy: a retrospective study in a single center from China
Authors: Tiantian Wang
Miaofa Ying
Rui Zhao
Danyan Zhu
Lisan Zhang
Publication date: 01-03-2022
Publisher: Springer International Publishing
Keywords: Restless Legs Syndrome
Pramipexole
Published in: Sleep and Breathing / Issue 1/2022
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI: https://doi.org/10.1007/s11325-021-02353-9

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Augmentation in patients with restless legs syndrome receiving pramipexole therapy: a retrospective study in a single center from China

Abstract

Purpose

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2022

Tracheostomy decannulation to noninvasive positive pressure ventilation in congenital central hypoventilation syndrome

Economic evaluation of CPAP therapy for obstructive sleep apnea: a scoping review and evidence map

The effect of continuous positive airway pressure treatment on hypertensive disorder in pregnant women with obstructive sleep apnea

Use of average volume-assured pressure support as a therapeutic option in patients with central sleep apnea syndrome

Metabolic outcomes in adults with type 2 diabetes and sleep disorders

Initiation of therapy for obstructive sleep apnea syndrome: a randomized comparison of outcomes of telemetry-supported home-based vs. sleep lab-based therapy initiation

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page