Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study
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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.
KeywordsRestless legs syndrome Depressive symptoms Ropinirole Treatment RCT
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.
- 18.Trenkwalder C, Garcia -Borreguero D, Montagna P, On behalf of the TREAT RLS 1 (Therapy with Ropinirole; Efficacy And Tolerability in RLS 1) study group et al (2004) Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry 75:92–97PubMedGoogle Scholar
- 19.Walters A, Ondo W, Dreykluft T, On behalf of the TREAT RLS 2 (Therapy with Ropinirole: Efficacy And Tolerability in RLS 2) study group et al (2004) Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study. Mov Disord 19(12):1414–1423PubMedCrossRefGoogle Scholar
- 21.Bogan RK, Fry JM, Schmidt MH, For the TREAT RLS US (Therapy with ropinirole And Efficacy, Tolerability in RLS US) study group et al (2006) Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc 81:17–27PubMedCrossRefGoogle Scholar
- 30.Beck AT, Steer RA, Brown GK (1996) Manual for the Beck depression inventory-II. Psychological corporation, San AntonioGoogle Scholar