Effects of Continuous Infusion Therapies on Non-Motor Symptoms in Advanced Parkinson’s Disease: A Systematic Review

Background/Objectives: Non-motor symptoms (NMS) are highly prevalent in advanced Parkinson’s disease (PD) and substantially affect quality of life. Continuous infusion therapies are established treatment options for motor fluctuations not controlled by oral medication, but their effects on NMS remain incompletely characterized. We aimed to evaluate the effects of continuous infusion therapies on NMS in advanced PD. Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, Embase, and Cochrane were searched for English-language original studies published between January 2005 and 1 March 2026. Eligible studies included patients with PD treated with levodopa–carbidopa intestinal gel (LCIG), continuous subcutaneous apomorphine infusion (CSAI), subcutaneous levodopa formulations, or levodopa–entacapone–carbidopa intestinal gel (LECIG) and reported quantitative NMS outcomes. Due to methodological heterogeneity, results were synthesized qualitatively. Results: Fifty-four studies were included. Most evaluated LCIG (n = 38), followed by CSAI (n = 14), subcutaneous levodopa formulations (n = 6), and LECIG (n = 2). Overall, 4157 patients were assessed at baseline and 2919 at follow-up. Global non-motor burden improved in 33/45 (73.3%) baseline-to-follow-up comparisons. NMSS total score decreased from 84.4 ± 35.2 to 54.9 ± 17.6. The most consistent benefits were observed for sleep/fatigue and gastrointestinal symptoms. Sleep/fatigue outcomes improved in 26/31 (83.9%) baseline-to-follow-up comparisons. Cognitive outcomes were mostly stable, while cardiovascular, urinary, sexual, and mood-specific outcomes showed less consistent benefit. Conclusions: Continuous infusion therapies may be associated with reduced global non-motor burden in advanced PD, particularly sleep/fatigue and gastrointestinal symptoms. Evidence is strongest for LCIG, while data for CSAI, LECIG, and subcutaneous levodopa formulations remain limited.