Effects of levodopa/carbidopa intestinal gel infusion on autonomic symptoms in advanced Parkinson’s disease: a systematic review

Purpose Autonomic failure has a major impact on the quality of life of individuals with Parkinson’s disease (PD), especially in advanced stages of the disease. Levodopa/carbidopa intestinal gel (LCIG) infusion is a well-established treatment for advanced PD with severe motor fluctuations and provides substantial benefit in managing some non-motor symptoms (NMS), such as sleep, fatigue, and neuropsychiatric issues. The effect of LCIG on autonomic symptoms is by contrast not well known. Here we performed a systematic review on the influence of LCIG therapy on autonomic dysfunction in PD individuals. Methods Following the PRISMA guidelines, we systematically searched for studies that included autonomic outcome measures in LCIG-treated PD individuals, limiting the search to articles written in English and published between January 2005 and June 2023. We evaluated improvement, stability, or worsening of gastrointestinal, urinary, and cardiovascular symptoms at six different timepoints according to clinimetric scale changes compared to baseline. Data on autonomic adverse events (AEs) possibly related to LCIG treatment were also collected. Results Of the 1476 studies identified in the initial search, 16 ultimately met the inclusion criteria and underwent quality assessment and data extraction, with data from 1361 PD patients (18.3 months mean follow-up). Thirteen studies reported improvement or stability of gastrointestinal, urinary, and cardiovascular symptoms over the interventional period. One study found a worsening of cardiovascular symptoms and two of urological symptoms. Regarding safety, seven studies reported gastrointestinal (8.4%), urinary (0.5%), and cardiovascular (1.1%) autonomic LCIG-related AEs. Conclusions LCIG infusion may help to reduce the burden of autonomic symptoms in advanced PD. Prospective studies specifically addressing the effect of LCIG on autonomic function in advanced PD are warranted.