The Efficacy and Adverse Effects of Pilocarpine and Cevimeline in Patients with Hyposalivation: A Retrospective Cohort Study

Abstract

Objective: The efficacy and side effects vary among cholinergic receptor agonist medications that stimulate salivary flow. This retrospective cohort investigation primarily aimed to compare the efficacy of pilocarpine (Pilo) and cevimeline (Cev) in stimulating salivary flow among patients with hyposalivation. The secondary aim was to compare the medications' side effects,discontinuation rates, and reasons for discontinuations, along with subjective changes in xerostomia, subjective perception, fungal recurrence, and the frequent usage of over-the-counter (OTC) oral lubricant products among the two drugs. Patients were further categorized into subgroups based on the underlying causes of hyposalivation, including Sjögren’s disease/Sicca Syndrome, polypharmacy, and radiotherapy. Method: A retrospective chart review was conducted for all patients seen at the Oral Medicine Clinic at Tufts University School of Dental Medicine (TUSDM) from January 1990 to January 2025 and prescribed Pilo or Cev. Patient demographics, medical history, and medications were collected. Changes in xerostomia perception over time (at 3, 6, 12, and 24 months) were evaluated using mixed linear regression. VAS scores were compared between medication groups at each time point using independent sample t-tests, while the Mann-Whitney U test was applied for non-normally distributed data. Categorical variables such as medication dosage/frequency changes, reported side effects, and drug discontinuation rates were analyzed using Fisher’s exact test. Descriptive statistics were used to summarize patient demographics, baseline characteristics, and polypharmacy profiles. Significance was set at P<0.05.

Result: This retrospective cohort study evaluated 326 patients with hyposalivation treated with Pilo or Cev at Tufts University School of Dental Medicine from 1990 to 2025. Both medications significantly improved unstimulated whole saliva (USW) and reduced subjective oral dryness measured by visual analogue scale (VAS) scores at 3 and 6 months. Cev demonstrated more sustained benefits. USW stimulated whole saliva (SWS) showed modest, time-variable improvements with both agents. There is no statistically significant difference between Cev and Pilo regarding USW, SWS, and VAS through 24 months. Adherence rates favored Cev at baseline significantly, with higher continuation rates and fewer discontinuations observed across all follow-up periods. Although overall fungal infection recurrence was low, a statistically significant association was identified between Cev use and a higher recurrence rate. No significant difference in OTC oral lubricant use was observed between the two groups. Baseline adverse effects were infrequent and mild, and both medications exhibited a strong long-term safety profile. A statistically significant association between female gender prevalence and four etiologies of hyposalivation was observed, with Sjögren’s disease being predominantly female. Conclusion: Both Pilo and Cev are effective and well-tolerated treatments for hyposalivation. However, Cev may offer superior long-term adherence, more consistent improvements in salivary flow, and greater relief of subjective dryness. Pilo showed a lower fungal recurrence rate.