title: Pharmacological interventions for daytime sleepiness and sleep disorders in Parkinson's disease: Systematic review and meta-analysis.
abstract: Daytime sleepiness and sleep disorders are frequently reported in Parkinson's disease (PD). However, their impact on quality of life has been underestimated and few clinical trials have been performed.
  
  
  
  We aimed to assess the efficacy and safety of pharmacological interventions for daytime sleepiness and sleep disorders in PD.
  
  
  
  Systematic review of randomized controlled trials comparing any pharmacological intervention with no intervention or placebo for the treatment of daytime sleepiness and sleep problems in PD patients.
  
  
  
  Ten studies (n = 338 patients) were included. Four trials addressed interventions for excessive daytime sleepiness. Meta-analysis of the three trials evaluating modafinil showed a significant reduction in sleepiness, as assessed by the Epworth Sleepiness Scale (ESS) (- 2.24 points, 95% CI - 3.90 to - 0.57, p < 0.05). In one study, treatment with caffeine was associated with a non-significant improvement of 1.71 points in ESS (95% CI, - 3.57 to 0.13). The six remaining trials assessed interventions for insomnia and REM sleep Behaviour Disorder (RBD). Single study results suggest that doxepin and YXQN granules might be efficacious, while pergolide may be deleterious for insomnia and that rivastigmine may be used to treat RBD in PD patients. However, there is insufficient evidence to support or refute the efficacy of any of these interventions. No relevant side effects were reported.
  
  
  
  Whilst providing recommendations, this systematic review depicts the lack of a body of evidence regarding the treatment of sleep disorders in PD patients; hence, further studies are warranted.
authors.affiliation: Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal; Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Portugal; Unit of Neurosciences, Instituto de Medicina Molecular, Lisbon, Portugal.
authors.forename: Tiago Martins
authors.initials: TM
authors.lastname: Rodrigues
authors.affiliation: Department of Neurosciences, Hospital de Santa Maria, Lisbon, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Castro Caldas
authors.affiliation: Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal; Department of Neurosciences, Hospital de Santa Maria, Lisbon, Portugal; Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal. Electronic address: joaquimjferreira@gmail.com.
authors.forename: Joaquim J
authors.initials: JJ
authors.lastname: Ferreira
mesh_terms: D006970:Disorders of Excessive Somnolence / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D018491:Dopamine Agonists / Q000627:therapeutic use; D006801:Humans; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012893:Sleep Wake Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use*
chemical_list: D018491:Dopamine Agonists; D064690:Wakefulness-Promoting Agents
keywords: Daytime somnolence; Nocturnal sleep problems; Parkinson's disease; Pharmacological interventions; Systematic review