Infusion therapies for advanced Parkinson’s disease: current evidence and practical challenges — a narrative review

Abstract

Advanced Parkinson’s disease (PD) is marked by motor fluctuations and dyskinesias that progressively lose responsiveness to optimized oral therapy, making continuous dopaminergic delivery an essential therapeutic strategy. This narrative review examines infusion-based treatments for advanced PD, focusing on their clinical rationale, efficacy, safety, and practical implementation. Currently available infusion therapies include continuous subcutaneous apomorphine infusion (CSAI), intrajejunal levodopa–carbidopa gel (LCIG), intrajejunal levodopa–carbidopa–entacapone gel (LECIG), and subcutaneous foslevodopa––foscarbidopa (LDp/CDp) infusion. These modalities provide more continuous dopaminergic stimulation than oral therapy, substantially reducing daily OFF time and increasing ON time without disabling dyskinesias, thereby improving quality of life (QoL). Their use may, however, be limited by adverse effects (AEs), including infusion-site reactions (ISR) (CSAI, LDp/CDp), the risk of hallucinations with LDp/CDp, and their invasive nature, as well as potential device-related complications or polyneuropathy associated with LCIG. Levodopa–carbidopa–entacapone gel offers improved levodopa bioavailability and a more user-friendly device design compared with LCIG. A fully subcutaneous levodopa–carbidopa (LD/CD) infusion (ND0612) is also under investigation, with preliminary results suggesting acceptable safety-to-adverse-events risk ratio and clinical benefit. Despite increasing availability of infusion therapies in recent years, their utilization in clinical practice remains markedly lower than the estimated proportion of eligible patients, underscoring persistent systemic barriers. Further efforts aimed at optimizing qualification pathways, decentralizing access, and enhancing the integration of device-aided therapies (DAT) into routine advanced PD management are warranted.