Night-time apomorphine improves sleep disturbances in people with Parkinson’s disease
By Shreeya Nanda, medwireNews Reporter
A night-time only infusion of the dopamine agonist apomorphine could help to reduce sleep disturbances in patients with advanced Parkinson’s disease and moderate-to-severe insomnia, suggest the results of the APOMORPHEE trial.
“Apomorphine improved insomnia as well as self-reported motor condition on morning awakening”, and overall the drug was well tolerated, report Valérie Cochen De Cock, from the University of Montpellier in France, and co-researchers in The Lancet Neurology.
They therefore believe that night-time apomorphine “could be an effective option” for such patients, adding that “[n]ight-time administration could render apomorphine infusion more acceptable (compared with a 24-h infusion) because patients will not have to deal with the device-related constraints during the daytime.”
For the double-blind, crossover trial, the investigators recruited 46 individuals aged 35–90 years (mean, 63.6 years) with Parkinson’s disease and a score of at least 15 points on the Insomnia Severity Index (ISI) from 11 centres in France. Participants were randomly assigned to receive apomorphine or placebo first for a 10-night titration phase followed by a 7-night fixed dose phase, a 3-night tapering phase and a 14-night washout period before switching. The patients took the assigned treatment at home with technical support from a healthcare professional and daily follow-up by telephone.
The primary endpoint of change in Parkinson’s disease sleep scale (PDSS) score from baseline to the end of the study was significantly greater with night-time apomorphine than placebo, at an average of 15.18 versus 5.23 points, equating to a treatment effect of 9.95 points.
Furthermore, the apomorphine treatment period was associated with significant improvements in insomnia as indicated by the ISI score (treatment effect, –2.23 points), self-estimated clinical global impression of sleep quality (1.40 points) as well as in the morning motor state (–0.57 points) compared with the placebo period.
But there were no significant improvements with the use of night-time apomorphine in other efficacy measures including pain, fatigue, symptoms of sleep apnoea, presence and severity of restless legs syndrome and impulse control disorders.
Study participants also underwent a night of audio and video polysomnography at the end of each treatment period, but the assessments did not show any clinically significant changes with apomorphine.
The authors of a related commentary believe that this highlights “the possible limitations of polysomnography to assess sleep dysfunction in Parkinson’s disease.”
They congratulate the study authors “for choosing a non-motor outcome measure (PDSS) as the primary endpoint, and for selecting pragmatic and broad eligibility criteria, thus ensuring robust external validity of their data.”
K Ray Chaudhuri and Valentina Leta, both from King’s College London in the UK, believe that the APOMORPHEE results “could help clinicians to personalise their treatment strategy for patients with Parkinson’s disease, sleep dysfunction, and symptoms related to early-morning off periods.”
But they stress the need for “[l]ong-term safety and efficacy data for night-time apomorphine infusion” in this setting.
The current safety data encompassing the 54-day study period show that “[t]he apomorphine infusion was well tolerated overall with no unexpected safety signals”, say Cochen De Cock and colleagues.
Adverse events occurred in 54% of participants receiving apomorphine and 37% of those receiving placebo, a nonsignificant difference. However, the incidence of dizziness was significantly more common with apomorphine than placebo (15 vs 0%), and two participants discontinued the study during the apomorphine treatment phase due to dizziness and headache considered related to apomorphine.
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Lancet Neurol 2022; 21: 428–437
Lancet Neurol 2022; 21: 395–398