A 2024 meta-analysis reviewed 56 studies (totaling 2,378 patients) to evaluate the effectiveness of atropine in managing sialorrhea (excessive drooling) across diverse conditions, including brain injury, amyotrophic lateral sclerosis (ALS), cerebral palsy, clozapine- or perphenazine-induced sialorrhea, Parkinson’s disease, and terminal illness. The analysis incorporated randomized controlled trials, case reports, retrospective reviews, and systematic reviews, assessing outcomes such as reduced salivary flow rate, drooling intensity, and death rattle. Results demonstrated that atropine is efficacious across most disease states. Sublingual administration (typically using off-label atropine eye drops) was statistically superior to oral, subcutaneous, and intravenous routes in reducing salivary flow, as confirmed by generalized estimating equation (GEE) regression models controlling for dose variability (p= 0.045). This superiority is attributed to direct anticholinergic effects on sublingual salivary glands and rapid systemic absorption via the sublingual mucosa’s vascular network. Despite atropine’s widespread off-label use due to its cost-effectiveness and lower systemic side effects, limitations included heterogeneous dosing (0.3–6 mg/day), insufficient placebo-controlled data, and an inability to establish a clear dose-response relationship. A dose-response relationship was unable to be performed due to a lack of quality data. The authors concluded that sublingual atropine is a highly effective intervention for sialorrhea but called for further research to refine clinical dosing guidelines. [1]
A 2023 retrospective chart review examined the role of sublingual atropine for treating sialorrhea in pediatric patients with neurodevelopmental disabilities. The study included a cohort of 178 patients 22 years or younger with neurodevelopmental disabilities. The average initial dose was 1.5 mg/day, adjusted to about 0.09 mg/kg/day based on patient weight. Descriptive statistics from this retrospective review revealed substantial variability in prescribing practices, which lacked standardized guidance. Initial doses ranged from 1 to 3 drops, administered at varied frequencies from once daily to six times daily, with 37% of prescriptions written as "as needed." Comparatively, the study's dosage range was broader than those documented in preceding studies, though within their typical dosing strategies. Additionally, 16 patients had previously undergone more invasive treatments such as salivary gland ablation or surgery, emphasizing sublingual atropine's potential as a viable alternative in secretion management. The study highlighted the need for further evidence to support and standardize the use of sublingual atropine to ensure safe and effective practices in managing sialorrhea in children with neurodevelopmental disabilities. [2]
A 2019 systematic review evaluated the sublingual use of atropine as a potential treatment for clozapine-induced sialorrhea (CIS). The majority of literature included in this review consisted of case reports, with only one randomized controlled trial. Four case reports described either complete resolution or immediate improvement in CIS after receiving atropine 1% sublingually. Doses used in these case studies included two drops twice daily and one to two drops once daily. Case studies of sialorrhea not associated with clozapine were also included. One of these case reports of a severe head trauma patient described a 50% reduction in secretion, intraoral, and oropharyngeal accumulation of saliva. Another case report described the beneficial effects of one drop of 0.5% atropine sublingually (0.25 mg every six hours). [3]
An open-label trial including 25 children with cerebral palsy found that 0.5% atropine administered three times/day (six-hour intervals) resulted in significant improvement. Two pilot studies also showed a significant reduction in salivation. The lone randomized, controlled, cross-over trial included 22 patients receiving two drops or 0.5 mg of atropine every six hours for drooling not related to clozapine, which failed to prove the effectiveness compared to a placebo. Xerostomia was mentioned in some case reports as a potential side effect. The review authors concluded that atropine appears to be safe and effective for CIS treatment; however, large-scale randomized trials with systematic evaluation of symptoms were required to confirm the systemic absorption of atropine. [3]
A 2020 retrospective analysis reviewed the use of sublingual atropine sulfate in managing sialorrhea in pediatric patients. Thirty-five pediatric patients with recorded prescriptions of sublingual atropine sulfate were identified; however, only 20 had complete records with documented Teacher Drooling Scale (TDS) scores. These patients, aged between 3 to 78 months, primarily required care for complications related to neuromuscular dysfunction, with 80% on invasive mechanical ventilation. A significant reduction in TDS scores was observed, with median scores decreasing from 5 to 3 by the second day of atropine sulfate administration. The treatment entailed administering atropine ampoules, dosed at 20 µg/kg, four to six times daily for seven days. Statistical analysis confirmed the change in drooling severity as significant (p <0.001), with notable improvements in secretion management. Importantly, the study reported no side effects, thereby indicating the short-term safety and efficacy of sublingual atropine sulfate in this cohort. However, the authors emphasized the need for further randomized, placebo-controlled trials and long-term follow-up to consolidate these preliminary findings and assess the practicality of home administration by caregivers. [4]
A 2021 systematic review aimed to evaluate the effectiveness of anticholinergic medications for managing sialorrhea in children. The review included 27 studies, among which atropine, scopolamine (also referred to as hyoscine), and other anticholinergics were evaluated. Two prospective clinical trials assessed sublingual administration of atropine eye drops and demonstrated improvement in drooling symptoms using the Visual Analog Scale (VAS) and Drooling Impact Scale (DIS). Evidence suggested reported improvement across all studies evaluating scopolamine transdermal patches, though efficacy was reported for all medications, including reduction in sialorrhea symptoms, albeit with a high incidence of adverse side effects like behavioral changes, constipation, and visual disturbances. Reported adverse event rates ranged from 12 to 42% for atropine and 46 to 76% for scopolamine. However, no direct head-to-head studies comparing sublingual atropine with scopolamine or hyoscyamine in terms of efficacy, safety, or cost were identified. The review noted substantial heterogeneity in dosing regimens and study designs, highlighting the need for standardized outcome measures to enable better comparisons across future studies. Despite these challenges, the review underscored the critical need for further research to refine treatment protocols and optimize patient outcomes. [5]
In a 1957 study published in the journal Anesthesia, researchers compared the antisialogogue effects of atropine, scopolamine, and l-hyoscyamine (then marketed as “Bellafoline”) in healthy volunteers using a precise method where salivary flow was stimulated with intravenous (IV) carbachol (0.12 mg) and epinephrine (0.06 mg), and measured directly from the parotid duct via suction. Each belladonna agent was administered intravenously at a dose of 0.2 mg, with atropine also tested at 0.4 mg. Results showed that scopolamine was the most potent, reducing secretion by 97%, followed by l-hyoscyamine (87%), and atropine (51% at 0.2 mg, 84% at 0.4 mg). Scopolamine and l-hyoscyamine had faster onset and longer duration of effect than atropine, which showed a more variable response across individuals. Side effects included drowsiness (scopolamine), dizziness, choking, tachycardia, and arrhythmia (l-hyoscyamine), with atropine being better tolerated but less potent. Notably, individual responses to atropine varied more than with the other two agents, highlighting its less consistent effect as an antisialogogue. The study underscored the enhanced potency of scopolamine and l-hyoscyamine, which could have clinical implications in pre-anesthetic settings where reduction of secretions is crucial. [6], [7]
A 2015 systematic review provides an extensive examination of treatment options for managing sialorrhea in patients with amyotrophic lateral sclerosis (ALS), including the use of anticholinergic medications such as atropine, hyoscyamine, and transdermal scopolamine. Anticholinergic medications, such as atropine, glycopyrrolate, and scopolamine, are frequently utilized but often deliver limited results and present significant side effects like sedation and mucous thickening. The review highlights that, despite their widespread use, these drugs have not been systematically evaluated for effectiveness in ALS, rendering their widespread application somewhat speculative. However, studies cited in the review suggest that scopolamine patches may be the most effective anticholinergic medication for the management of sialorrhea in ALS, with an 85% positive response rate, though 20% of patients discontinued due to adverse skin reactions. Notably, sublingual atropine and hyoscyamine were discussed among various options, but without head-to-head comparisons or cost analyses. Overall, the review concluded that while these agents are commonly employed, further research to establish standardized treatment protocols and clarify their comparative benefits and tolerability in ALS-related sialorrhea is necessary. [8]