Sleep is crucial to wellness, but it is disrupted in almost all patients with Parkinson's disease. Many factors can cause disturbed sleep in people with Parkinson's disease, such as motor dysfunction at night, altered sleep architecture, and medication effects, and problems with sleep might also result in daytime somnolence. Patients rate sleep dysfunction as one of their top ten “most bothersome” symptoms, 1 Politis M Wu K Molloy S Bain PG Chaudhuri KR Piccini P Parkinson's disease symptoms: the patient's perspective. Mov Disord. 2010; 25: 1646-1651 Crossref PubMed Scopus (340) Google Scholar and bedside assessment of sleep—with validated tools such as the Parkinson's disease sleep scale (PDSS)—has shone a light on the high prevalence and broad effects of poor sleep on quality of life for patients and their carers. 2 Chaudhuri KR Pal S DiMarco A et al. The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2002; 73: 629-635 Crossref PubMed Scopus (497) Google Scholar In case series and open-label studies, improvements in PDSS scores have been noted after subthalamic deep brain stimulation 3 Kharkar S Ellenbogen JR Samuel M et al. Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. npj Parkinson's Disease. 2018; 4: 16 Crossref PubMed Scopus (9) Google Scholar and continuous drug delivery of dopaminergic therapies such as levodopa-carbidopa intestinal gel infusion, 4 Honig H Antonini A Martinez-Martin P et al. Intrajejunal levodopa infusion in Parkinson's disease: a pilot multicenter study of effects on nonmotor symptoms and quality of life. Mov Disord. 2009; 24: 1468-1474 Crossref PubMed Scopus (232) Google Scholar rotigotine patch, 5 Trenkwalder C Kies B Rudzinska M et al. Rotigotine effects on early morning motor function and sleep in Parkinson's disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord. 2011; 26: 90-99 Crossref PubMed Scopus (324) Google Scholar and ropinirole prolonged release 6 Chaudhuri KR Martinez-Martin P Rolfe KA et al. Improvements in nocturnal symptoms with ropinirole prolonged release in patients with advanced Parkinson's disease. Eur J Neurol. 2012; 19: 105-113 Crossref PubMed Scopus (64) Google Scholar (table). Although the effects of dopamine agonists on sleep in Parkinson's disease are complex (eg, low doses can cause daytime somnolence, whereas high doses can cause insomnia), the potential beneficial effects of these treatments on sleep dysfunction in Parkinson's disease have not been investigated. Apomorphine infusion is a device-aided therapy for Parkinson's disease that, in the 1990s, showed substantial effects on sleep disruption in a small pilot study, 7 Reuter I Ellis CM Chaudhuri KR Nocturnal subcutaneous apomorphine infusion in Parkinson's disease and restless legs syndrome. Acta Neurol Scand. 1999; 100: 163-167 Crossref PubMed Scopus (142) Google Scholar but nocturnal apomorphine infusion has not been studied since then in larger trials. TableStudies of dopaminergic treatment on sleep dysfunction in Parkinson's disease Study design and population Main sleep-related outcome measures Main results* For PDSS, high scores indicate better sleep quality, whereas for PDSS-2, high scores indicate worse sleep quality. Apomorphine Cochen de Cock et al, 2022 Multicentre, randomised, double-blind, placebo-controlled, crossover (night-time apomorphine vs placebo); 46 patients with fluctuating Parkinson's disease and moderate to severe insomnia PDSS, ISI, and polysomnography-related outcomes Night-time apomorphine increased PDSS and decreased ISI total scores compared with placebo at maintenance week 1; no changes in sleep duration and latency Bhidayasiri et al, 2016 Single-centre, open-label, prospective (20-h apomorphine); ten patients with Parkinson's disease on daytime apomorphine with nocturnal hypokinesia Wearable sensor-related parameters and PDSS-2 20-h apomorphine increased number of turns in bed, turning velocity, degree of turning, and decreased PDSS-2 total scores at day 1 Fernández-Pajarín et al, 2016 Single-centre, open-label, prospective (24-h apomorphine); 17 patients with Parkinson's disease on daytime apomorphine with sleep dysfunction SCOPA-sleep and PDSS 24-h apomorphine increased PDSS and decreased SCOPA-sleep total scores at week 6 Martinez-Martin et al, 2011 Multicentre, open-label, controlled (daytime apomorphine vs best conventional care), retrospective; 34 patients with Parkinson's disease and motor complications NMSS (sleep domain) Daytime apomorphine decreased NMSS sleep domain scores compared to best conventional care at year 1 Garcia Ruiz et al, 2006 Case report (nocturnal apomorphine); one patient with Parkinson's disease with severe refractory sleep disturbances Ambulatory activity monitor Nocturnal apomorphine normalised sleep–wake cycle at days 1 and 3 Reuter et al, 1999 Case series, open-label, prospective, controlled (nocturnal apomorphine vs saline); six patients with Parkinson's disease, motor fluctuations, and refractory sleep disturbances Sleep diary Nocturnal apomorphine decreased frequency of nocturnal awakenings, nocturnal off periods, pain, dystonia and nocturia at day 6 Intrajejunal levodopa infusion Standaert et al, 2021 Multicentre, open-label, prospective (daytime intrajejunal levodopa infusion); 195 patients with Parkinson's disease PDSS-2 Daytime intrajejunal levodopa infusion decreased PDSS-2 total scores at month 12 Ricciardi et al, 2016 Case series, open-label (24-h intrajejunal levodopa infusion); eight patients with Parkinson's disease and refractory nocturnal akinesia NMSS (sleep domain) 24-h intrajejunal levodopa infusion decreased NMSS sleep domain scores at year 3 (on 24-h intrajejunal levodopa infusion for 26 months) Antonini et al, 2017 Multicentre, open-label (daytime intrajejunal levodopa infusion); 375 patients with advanced Parkinson's disease NMSS (sleep domain) Daytime intrajejunal levodopa infusion decreased NMSS sleep domain scores at month 24 Honig et al, 2009 Multicentre, open-label, prospective (daytime intrajejunal levodopa infusion vs placebo); 22 patients with advanced Parkinson's disease NMSS (sleep domain) and PDSS Daytime intrajejunal levodopa infusion increased PDSS and NMSS sleep domain scores compared to placebo at month 6 Ropinirole Pahwa et al, 2007 and Chaudhuri et al, 2012 Multicentre, double-blind, placebo controlled (24-h prolonged-release ropinirole vs placebo); 393 patients with Parkinson's disease suboptimally controlled with levodopa PDSS 24-h prolonged-release ropinirole increased PDSS total scores at week 24 compared with placebo Rotigotine Pierantozzi et al, 2016 Single-centre, randomised, double-blind, placebo-controlled, parallel-group (nocturnal rotigotine vs placebo); 42 patients with moderately advanced Parkinson's disease and sleep dysfunction PDSS, PSQI, and polysomnography-related outcomes Nocturnal rotigotine increased PDSS total scores, decreased PSQI total scores, increased sleep efficiency, and decreased both wakefulness after sleep onset and sleep latency compared with placebo at maintenance week 2 Pagonabarraga et al, 2015 Multicentre, open-label, prospective (24-h rotigotine); 62 patients with Parkinson's disease PDSS-2 and PD-SFQ 24-h rotigotine decreased PDSS-2 and PD-SFQ total scores at month 3 Trenkwalder et al, 2011 and Chaudhuri et al, 2013 Multicentre, randomised, double-blind, placebo-controlled (24-h rotigotine vs placebo); 287 patients with Parkinson's disease and early-morning off periods PDSS-2 and NMSS (sleep domain) 24-h rotigotine decreased PDSS-2 and NMSS sleep domain scores compared with placebo at week 4 Tolcapone Ebersbach et al, 2010 Multicentre, open-label, prospective (tolcapone three times a day); 61 patients with advanced Parkinson's disease PDSS-2 Tolcapone three times a day decreased PDSS-2 total scores at week 4 Multiple interventions Poewe et al, 2007 Multicentre, randomised, double-blind, double-dummy placebo-controlled and pramipexole-controlled, three-arm parallel group (24-h rotigotine vs daytime pramipexole vs placebo); 204 patients with Parkinson's disease and motor fluctuations PDSS 24-h rotigotine and daytime pramipexole were similarly efficacious and both treatments increased PDSS total scores compared to placebo at month 6 Dafsari et al, 2019 Multicentre, open-label, prospective, controlled (daytime apomorphine vs daytime intrajejunal levodopa infusion vs STN-DBS); 173 patients with Parkinson's disease and motor complications NMSS (sleep domain) STN-DBS decreased NMSS sleep domain scores compared to daytime intrajejunal levodopa infusion and daytime apomorphine at month 6 Martinez-Martin et al, 2015 Multicentre, open-label, prospective, controlled (daytime apomorphine vs daytime intrajejunal levodopa infusion); 87 patients with Parkinson's disease and motor complications NMSS (sleep domain) Daytime intrajejunal levodopa infusion and daytime apomorphine infusion decreased NMSS sleep domain scores at month 6 (apomorphine < intrajejunal levodopa infusion) Park et al, 2020 Open-label (bedtime levodopa-carbidopa-entacapone initiated at bedtime); 54 patients with Parkinson's disease and sleep disturbances PDSS Bedtime levodopa-carbidopa-entacapone increased PDSS total scores at month 1 and 3 References and search strategy are available in the appendix. ISI=Insomnia Severity Index. NMSS=non-motor symptoms scale. PDSS=Parkinson's disease sleep scale. PD-SFQ=Parkinson's Disease Sleep Fragmentation Questionnaire. PSQI=Pittsburgh Sleep Quality Index. SCOPA=Scales for Outcomes in Parkinson's disease. STN-DBS=subthalamic nucleus deep brain stimulation. * For PDSS, high scores indicate better sleep quality, whereas for PDSS-2, high scores indicate worse sleep quality. Open table in a new tab References and search strategy are available in the appendix. ISI=Insomnia Severity Index. NMSS=non-motor symptoms scale. PDSS=Parkinson's disease sleep scale. PD-SFQ=Parkinson's Disease Sleep Fragmentation Questionnaire. PSQI=Pittsburgh Sleep Quality Index. SCOPA=Scales for Outcomes in Parkinson's disease. STN-DBS=subthalamic nucleus deep brain stimulation. Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover studySubcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia. Full-Text PDF