Rotigotine and specific non-motor symptoms of Parkinson's disease: Post hoc analysis of RECOVER
Introduction
Non-motor symptoms occur across all stages of Parkinson's disease (PD), can precede the onset of motor symptoms, and have been identified as having a more significant impact on health-related quality of life than motor symptoms [1], [2], [3], [4], [5], [6]. However, they are often under-recognized, and their treatment remains an unmet need of patients with PD [2]. Dysfunction of dopaminergic and non-dopaminergic systems contribute to the development of non-motor symptoms in PD [7]; symptoms such as depression, anxiety, fatigue, sleep disorders, and pain may have a dopaminergic basis [4], [8]. However, there are insufficient good-quality trial data on dopaminergic treatment of non-motor symptoms, and the effect of dopaminergic drugs on non-motor symptoms of PD remains poorly understood [2], [4], [9].
Rotigotine transdermal system, a non-ergoline dopamine receptor agonist, is administered transdermally via a patch, resulting in stable plasma levels over 24 h [10], [11]. RECOVER (Randomized Evaluation of the 24-Hour Coverage: Efficacy of Rotigotine), a double-blind, placebo-controlled trial in patients with PD and unsatisfactory control of early morning motor function, demonstrated significant improvements in early morning motor impairment and nocturnal sleep disturbances with rotigotine [12]. RECOVER was also the first large-scale trial to extensively investigate non-motor symptoms of PD using the Non-Motor Symptoms Scale (NMSS) [12]. Significantly greater improvements with rotigotine were seen in NMSS total score, and “Sleep/fatigue” and “Mood/apathy” (formerly termed “Mood/cognition” [13], [14]) domains [12]. This post hoc analysis investigated the effects of rotigotine on the individual non-motor symptoms pertaining to the “Sleep/fatigue” and “Mood/apathy” domains of the NMSS to further characterize the nature of these apparent symptomatic improvements.
Section snippets
Patient eligibility
Patients enrolled in the RECOVER study were at least 18 years of age with idiopathic PD (Hoehn and Yahr [H&Y] Stage I–IV) and unsatisfactory control of early morning motor symptoms, as determined by the investigator. Immediate-release levodopa (in combination with benserazide or carbidopa) was permitted, provided the dose was stable for at least 28 days prior to baseline. The full study design including complete inclusion/exclusion criteria has been previously published [12].
Standard protocol approvals, registrations, and patient consents
RECOVER
Patient disposition and baseline characteristics
Of 287 patients randomized (190 rotigotine and 97 placebo), 246 (86%) completed the study. The full analysis set comprised 267 patients. Baseline demographic data of the full analysis set were similar between treatment groups (Table 1).
Assessment of non-motor symptoms
As previously reported, the mean NMSS total score showed significantly greater improvement with rotigotine than placebo from baseline to end of treatment, and significant differences in the individual scores of 2 of the 9 domains: “Sleep/fatigue” and
Discussion
The RECOVER study was the first prospective randomized controlled trial to use the NMSS as an exploratory outcome for the assessment of treatment effects on non-motor symptoms in PD [12]. This post hoc analysis of individual items of the NMSS suggests that rotigotine transdermal system may have a positive effect on fatigue and mood disturbances (symptoms of depression, anhedonia), and apathy in patients with PD.
Sleep disturbances and fatigue are common problems in PD, and range from motor
Acknowledgments
This study was supported by UCB Pharma, Brussels, Belgium. K. Ray Chaudhuri serves as the European Editor of Basal Ganglia, as an editorial board member of Parkinsonism and Related Disorders, and the Journal of Parkinson's disease, and as the Liaison and PR Committee Chairman of the Movement Disorder Society; has received honoraria for academic lectures at sponsored symposiums from UCB Pharma, Britannia, GSK, Abbott, Teva, Medtronic, and Boehringer Ingelheim; and has received educational grants
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