title: Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study.
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.
authors.affiliation: Somni-Bene Institute for Medical Research and Sleep Medicine, Schwerin, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Benes
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mattern
authors.forename: Ines
authors.initials: I
authors.lastname: Peglau
authors.forename: Tillmann
authors.initials: T
authors.lastname: Dreykluft
authors.forename: Lars
authors.initials: L
authors.lastname: Bergmann
authors.forename: Corinna
authors.initials: C
authors.lastname: Hansen
authors.forename: Ralf
authors.initials: R
authors.lastname: Kohnen
authors.forename: Norbert
authors.initials: N
authors.lastname: Banik
authors.forename: S W
authors.initials: SW
authors.lastname: Schoen
authors.forename: Magdolna
authors.initials: M
authors.lastname: Hornyak
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012148:Restless Legs Syndrome / Q000150:complications / Q000188:drug therapy*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018491:Dopamine Agonists; D007211:Indoles; C046649:ropinirole