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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.

While microfluidics enables chemical stimuli application with high spatio-temporal precision, light-sheet microscopy allows rapid imaging of entire zebrafish brains with cellular resolution. Both techniques, however, have not been combined to monitor whole-brain neural activity yet. Unlike conventional microfluidics, we report here an all-glass device (NeuroExaminer) that is compatible with whole-brain in vivo imaging using light-sheet microscopy and can thus provide insights into brain function in health and disease. Kai Mattern, Jakob W. von Trotha, et al. develop NeuroExaminer, an all glass device for whole-brain in vivo imaging in zebrafish. The method is based on light-sheet microscopy and microfluidics and provides insights on brain function in live zebrafish.