ObjectiveTo evaluate the long-term, real-life effects on non-motor symptoms (NMS) of opicapone compared to entacapone in levodopa-treated people with Parkinson’s disease (PwP).MethodsA retrospective data analysis, with pre- and post-opicapone initiation data of 17 PwP with motor fluctuations compared to a comparable group of 18 PwP introduced on entacapone. The primary outcome was changes in the NMS Scale (NMSS) total score after 1-year follow-up. Secondary outcomes included changes in the NMSS domains, and Parkinson’s Disease Sleep Scale (PDSS) total and item scores after the same time span.ResultsGroups were comparable for baseline demographics and Parkinson’s-related features (p ≥0.314) as well as duration of follow-up (1.33 ± 0.66 years for PwP on opicapone and 1.23 ± 0.49 years for those on entacapone;p =0.858). PwP who were introduced on opicapone showed no changes in NMSS and PDSS total scores after 1 year (p =0.605 andp =0.507, respectively), whereas PwP who were introduced on entacapone showed significant worsening of NMSS and PDSS total scores at follow-up (p =0.005 andp =0.001, respectively). In neither group changes in individual NMSS domains from baseline to follow-up were observed (p ≥0.288 for entacapone andp ≥0.816 for opicapone, respectively). In PwP on entacapone significant worsening was seen in the distressing dreams, hallucinations, and limb numbness items of the PDSS (p ≤0.05).ConclusionsIntroduction of opicapone in real-life PwP with motor fluctuations seems to stabilise NMS burden and aspects of sleep dysfunction, in contrast to entacapone where there was a worsening of NMS burden and PDSS scores over 1 year follow-up.