Subcutaneous Levodopa in Parkinson's Disease: A Systematic Review and Meta‐Analysis

Journal article : Review

Background: Many Parkinson's disease patients receiving oral levodopa/carbidopa experience a troublesome wearing off effect. Higher doses to mitigate OFF‐time are limited by adverse effects occurring at peak dopamine levels, particularly dyskinesia. A novel strategy to reduce OFF‐time without increasing peak dopamine levels is the continuous subcutaneous infusion of levodopa/carbidopa, or their prodrug equivalents foslevodopa/foscarbidopa. Objectives: Assess whether subcutaneous infusion therapies safely reduce OFF‐time and improve quality of life scores compared to oral levodopa/carbidopa. Methods: We searched MEDLINE, Embase, CENTRAL and ICTRP up to 28th October 2024 for clinical trials comparing subcutaneous infusions of levodopa or foslevodopa to oral levodopa in Parkinson's disease. Results: Screening of 1114 records identified seven studies in which 725 patients received subcutaneous infusion regimens of levodopa/carbidopa (ND0612) (407 patients) or foslevodopa/foscarbidopa (318 patients). Moderate quality evidence indicated subcutaneous infusion reduced the daily duration of OFF‐time by 1.98 h (p = 0.0004). Moderate quality evidence indicated improvements in health‐related quality of life score PDQ‐39 (p = 0.0003) and sleep score PDSS‐2 (p = 0.02), but an increase in the rate of treatment‐emergent adverse events, mostly related to the infusion site (p = 0.04). Conclusions: Subcutaneous infusion therapies produce a clinically and statistically significant reduction in the duration of OFF‐time experienced by patients with Parkinson's disease, compared to oral levodopa/carbidopa. Patient experience is improved by a statistically, but not clinically, significant degree. There are increased adverse events, mostly related to the infusion site. Overall, subcutaneous infusion regimens could provide a meaningful alternative for Parkinson's disease patients who experience severe motor fluctuations with existing levodopa formulations.

Authors: Burton, M; Marsden, D; Harish, D; Morris, P; Heneghan, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: European Journal of Neurology
• Volume: 33
• Issue: 2
• Article number: e70506
• Publication date: 2026-01-29
• Acceptance date: 2026-01-07
• DOI: 10.1111/ene.70506
• EISSN: 1468-1331
• ISSN: 1351-5101
• Language: English
• Keywords: Parkinson disease; subcutaneous infusions; systematic review; clinical trials; levodopa
• Subtype: Review