To assess the long-term efficacy and safety of glycopyrrolate for moderate-to-severe sialorrhea in Parkinson’s disease (PD).

A systematic review reported that sialorrhea affects approximately 50% of patients with PD and concluded that drooling is a significant problem in about a quarter of PD patients. Chronic moderate-to-severe sialorrhea leads to substantial social issues with a detrimental effect on quality of life. An evidence-based review of commercially available therapies by the MDS in 2019 rated glycopyrrolate and botulinum toxin as the only efficacious therapies for the short-term treatment of sialorrhea in PD. There is no evidence for more prolonged treatments for sialorrhea in PD. 

We conducted an exploratory, two-centred, double-blinded placebo-controlled two-arm parallel-group superiority phase II study, with block randomization and 1:1 allocation. Oral glycopyrrolate 1.5 mg TID (maximum dose) was compared to an equivalent dose of placebo for the reduction of sialorrhea related-disability (ROMP-saliva, primary outcome measure) at three months, in patients older than 30, with PD and moderate-to-severe sialorrhea (MDS-UPDRS, item 2.2>2). We used an intention-to-treat analysis. A P<0.05 was deemed significant.

We recruited 28 patients with PD (age: 71.1±6.9 years ;disease duration: 11.4±7.2;ROMP-saliva: 22.7±5.4). At 90 days, there was a treatment difference for ROMP saliva of -5.8 (95% CI: 10.16, -1.52) in favour of glycopyrrolate, present at day 45 (-4.4, 95% CI:-8.0, -0.8). There were six early terminations due to adverse events (glycopyrrolate, n=5). Dry mouth was the most common side effect (glycopyrrolate, n=6 vs. placebo, n=2) followed by constipation (glycopyrrolate, n=4 vs. placebo, n=2)