Abstract / Summary
Background: Sleep disturbances are amongst the most prevalent and disabling non-motor symptoms in Parkinson's disease (PD), encompassing excessive daytime sleepiness (EDS), poor sleep quality, insomnia, and REM sleep behaviour disorder (RBD). The pharmacological evidence base remains fragmented across phenotypes, drug classes, and outcome instruments.
Objectives: To evaluate the efficacy and safety of pharmacological interventions for sleep disorders in PD, stratified by sleep phenotype, through a systematic review and meta-analysis of randomised controlled trials (RCTs).
Methods: Six databases were searched without restrictions. Eligible studies were RCTs in adults with PD and any sleep disturbance. Pooling was performed using random-effects models. Risk of bias was assessed with the Cochrane RoB 2 tool. The protocol was registered in PROSPERO (CRD420261412614).
Results: Twenty-nine RCTs (1913 participants; 2002 to 2025) were included. Only 17.2% of trials were at low overall risk of bias. For EDS (k = 6), the pooled ESS estimate was directionally favourable but non-significant (MD 1.75; 95% CI -0.26 to 3.75; I2 = 91%), driven predominantly by a single influential crossover trial. For overall sleep quality (k = 6), pharmacological treatment produced a statistically significant improvement in PSQI scores (MD 2.66; 95% CI 1.63 to 3.69; I2 = 71%). For insomnia symptoms (k = 3) and RBD (k = 2), pooled estimates were non-significant with high heterogeneity (I2 = 96% and 99%, respectively), precluding reliable conclusions. Given this level of heterogeneity (I2 > 90%), pooled estimates for these two domains, as well as for EDS, are presented as exploratory only and narrative synthesis is emphasised over meta-analytic pooling. No unexpected safety signals were identified, although safety reporting was heterogeneous and quantitative pooling was not performed.
Conclusions: Pharmacological treatment, particularly with chronobiotic agents and dopaminergic receptor agonists, may produce improvement in overall sleep quality (low-certainty evidence). Evidence for EDS, insomnia symptoms, and RBD remains insufficient for definitive recommendations, and pooled estimates in these domains should not be over-interpreted given their very high statistical heterogeneity. Phenotype-specific RCTs with harmonised outcome measures are needed.