Pilocarpine Drops for Xerostomia in Patients With a Life-Limiting Condition or Frailty: A Double-Blind Placebo-Controlled Randomized Clinical Trial

OBJECTIVES: To assess the effectiveness and acceptability of oral pilocarpine drops for the treatment of xerostomia in patients with a life-limiting condition and/or frailty. DESIGN: Double-blind, placebo-controlled randomized clinical trial, comparing topical pilocarpine with placebo. SETTINGS AND PARTICIPANTS: This randomized controlled trial was conducted from June 2023 to April 2025 at 2 hospitals and 3 nursing homes in the Netherlands, involving 92 adults with xerostomia [Numeric Rating Scale ≥5 (NRS, 0-10)] and a life-limiting condition and/or frailty. METHODS: Participants received 4 weeks of either topical pilocarpine or placebo drops. The primary outcome was the mean change in xerostomia severity at 4 weeks. One hundred twenty participants were required to detect a meaningful difference between groups. Secondary outcomes included proportion of responders, xerostomia severity, oral health-related quality of life global perceived effect, side effects, medication changes, adherence, and medical costs at baseline, 2, and 4 weeks. Regression analyses were performed. RESULTS: Of 299 patients screened, 92 were randomized (placebo, n = 48, pilocarpine, n = 44). Linear regression showed no significant between-group difference at week 2 or week 4 [adjusted β = 0.35; (95% CI, -0.44 to 1.15) and β = -0.37; (95% CI, -1.31 to 0.58), respectively]. Both groups showed a significant decrease in mean NRS from baseline to week 2 (placebo, -1.4; pilocarpine, -1.5), but the NRS decreased further only for pilocarpine between week 2 and week 4 [-0.86 (95% CI, -1.56 to -0.15)]. Oral health-related quality-of-life score significantly improved for pilocarpine compared with placebo at 2 weeks [adjusted β = 2.8 (95% CI, 0.91, 4.65)]. Other secondary outcomes showed no significant between-group differences. Adverse effects were limited. CONCLUSIONS AND IMPLICATIONS: Topical pilocarpine did not significantly reduce xerostomia severity compared with placebo. However, only pilocarpine showed continuation of reduction in xerostomia severity over 4 weeks, with good tolerability. As the current study was underpowered, the potential clinical benefit of pilocarpine should be further investigated in adequately powered trials.