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Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study

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Abstract

Comorbid depressive symptoms in restless legs syndrome (RLS) remain a treatment challenge, as some antidepressants aggravate RLS symptoms. Preliminary data in depressive patients suggest antidepressant properties of ropinirole. The present study investigates the effects of ropinirole immediate release (IR) on depressive symptoms and RLS severity. A multicenter, placebo-controlled, double-blind randomized (3:1) study was performed including patients with moderate to severe idiopathic RLS and at least mild depressive symptoms. Ropinirole IR (in flexible doses up to 4 mg/day) or placebo was given for 12 weeks including an uptitration phase of 7 weeks. Visits were scheduled at screening, baseline, and weeks 1, 4, and 12 with additional telephone contacts for dosing decisions. The modified intent to treat population comprised 231 patients (171 ropinirole, 60 placebo). The MADRS (Montgomery–Asberg Depression Rating Scale) scores decreased from baseline to week 12 from 18.8 to 8.7 in the ropinirole group and from 18.4 to 12.1 in the placebo group (primary endpoint, adjusted mean treatment difference −3.6 (95% CI: −5.6 to −1.6, significance in favor of ropinirole: P < 0.001). The superiority of ropinirole compared to placebo was confirmed by the Hamilton Scale for Depression and Beck Depression Inventory-II scores. RLS severity scores (IRLS) decreased by 14.7 (ropinirole) and by 9.9 (placebo, P < 0.001) points. Three out of four subdomains of the Medical Outcomes Study Sleep Scale improved significantly. The findings indicate that mild to moderate depressive symptoms should not be treated before sufficient therapy for RLS. Antidepressant medication can be necessary if depression symptoms still persist even if RLS symptoms are ameliorated.

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Acknowledgments

The study was sponsored by GlaxoSmithKline Research and Development and GlaxoSmithKline Germany.

Conflict of interest

HB received honoraria and/or lecture fees from Boehringer Ingelheim, Germany; GlaxoSmithKline, Germany; Pfizer, Germany; Axxonis, Germany; Roche, Germany; UCB, Germany; Jazzpharma, USA. MH received honoraria and/or lecture fees from Boehringer Ingelheim, Germany; GlaxoSmithKline, Germany; Roche, Germany; Pfizer Inc., Germany. RK received honoraria for advisory board membership from Pfizer, Germany; Axxonis, Germany; Roche, Germany; UCB, Germany; Jazzpharma, USA. WM received honoraria and/or lecture fees from GlaxoSmithKline, Germany; Pfizer, Germany; Novartis, Germany; Schwabe, Germany; MSD, Germany; Sanofi, Germany; UCB, Germany; Bayer, Germany; Astra Zeneca, Germany; Lilly, Germany; Janssen-Cilag, Germany; Lundbeck, Germany; Neurochem, Canada; Bristol-Myers-Squibb, Germany; Boehringer Ingelheim, Germany. IP received honoraria and/or lecture fees from AstraZeneca, Germany; Aventis, Germany; Axxonis, Germany; Biogen, Germany; Boehringer Ingelheim, Germany; GlaxoSmithKline, Germany; Janssen-Cilag, Lundbeck, Germany; Novartis, Germany; Pfizer, Germany; Roche, Germany; Takeda, Germany; Teva, Germany; UCB, Germany. TD has no conflict of interest to declare. CH, NB, SWS, and LB are employees of GlaxoSmithKline GmbH & Co. KG.

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Authors and Affiliations

  1. Somni-Bene Institute for Medical Research and Sleep Medicine, Schwerin, Germany

    Heike Benes

  2. Bochum, Germany

    Wolfgang Mattern

  3. Berlin, Germany

    Ines Peglau

  4. Klinische Forschung Berlin, Berlin, Germany

    Tillmann Dreykluft

  5. GlaxoSmithKline GmbH & CO. KG, Munich, Germany

    Lars Bergmann, Corinna Hansen, Norbert Banik & S. W. Schoen

  6. RPS Research Germany GmbH, Nuremberg, Germany

    Ralf Kohnen

  7. Department of Psychology, University Erlangen-Nuremberg, Nuremberg, Germany

    Ralf Kohnen

  8. Interdisciplinary Pain Center, University Medical Center, Breisacherstrasse 64, 79106, Freiburg, Germany

    Magdolna Hornyak

Authors
  1. Heike Benes
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  2. Wolfgang Mattern
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  3. Ines Peglau
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  4. Tillmann Dreykluft
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  5. Lars Bergmann
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  6. Corinna Hansen
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  7. Ralf Kohnen
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  8. Norbert Banik
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  9. S. W. Schoen
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  10. Magdolna Hornyak
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Corresponding author

Correspondence to Magdolna Hornyak.

Additional information

On behalf of the ROAD-RLS study group. The members of study group are listed in the Appendix.

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Appendix

Appendix

Members of the ROAD-RLS study group

W Albrecht, D Backhaus, S Behrens, H Benes, B Bergtholdt, J Boehringer, HJ Boldt, T Dreykluft, I Eisensehr, I Fietze, P Franz, P Geisler, B Gestewitz, S Happe, A Hause, M Hirschberg, M Hornyak, A Hufnagel, J Kassubek, J Koppai-Reiner, T Krohn, B Kukowski, M Lang, W Lueer, W Mattern, T Mueller, D Noack, KU Oehler, C Oehlwein, V Otto, I Peglau, J Peltz, GD Roth, K Sallach, W Scheunemann, K Schlinsog, I Schoell, N Schulte, A Schulze, E Schumacher, G Schumann, M Siepmann, A Siever, KO Sigel, A Simonow, H Sommer, M Sommer, T Spieker, K Tinschert, and C Trenkwalder.

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Benes, H., Mattern, W., Peglau, I. et al. Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study. J Neurol 258, 1046–1054 (2011). https://doi.org/10.1007/s00415-010-5879-7

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  • DOI: https://doi.org/10.1007/s00415-010-5879-7

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