Atropine Drops for Sialorrhoea Management
Start with an initial trial of inexpensive oral anticholinergic agents, including sublingual atropine drops, as first-line therapy for sialorrhoea, continuing use only if benefits outweigh side effects. 1
First-Line Approach: Anticholinergic Therapy
The American College of Chest Physicians (CHEST) 2023 guidelines explicitly recommend anticholinergic medications as the initial treatment for sialorrhoea in neuromuscular disease, emphasizing their relative affordability and ready availability. 1 The balance of benefits and risks for anticholinergics is considered neutral because some patients experience symptomatic relief while others do not tolerate them well. 1
Why Anticholinergics Work
Atropine blocks muscarinic receptors in salivary glands, directly reducing saliva production through competitive antagonism of acetylcholine at postganglionic cholinergic nerve sites. 2 This mechanism specifically targets the exocrine glands responsible for excessive salivation. 2
Sublingual Atropine: The Preferred Route
Sublingual administration of atropine is superior to oral and subcutaneous routes for reducing salivary flow. 3 A 2024 meta-analysis of 2,378 patients demonstrated that sublingual delivery provides better efficacy across multiple disease states including stroke, cerebral palsy, amyotrophic lateral sclerosis, and clozapine-induced sialorrhoea. 3
Specific Dosing Recommendations
- Standard dose: 1-2 drops of 1% atropine eye drops sublingually, 2-3 times daily 4
- Pediatric dose: 20 µg/kg/dose (minimum 0.25 mg, maximum 0.03 mg/kg) 5
- Stroke patients: One drop of 1% atropine eye drops sublingually 3 times daily reduced sialorrhoea scores from 5.12 to 3.94 (p<0.01) 6
Evidence for Sublingual Atropine
A 2024 randomized controlled trial in 100 stroke patients demonstrated that sublingual 1% atropine eye drops three times daily significantly reduced sialorrhoea severity compared to routine rehabilitation training alone, with no significant difference in adverse events between groups. 6 In pediatric patients, sublingual atropine reduced Teacher Drooling Scale scores from a median of 5 to 3 within two days (p<0.001) without observed side effects. 5
Clinical Impact on Morbidity and Quality of Life
Sialorrhoea significantly reduces quality of life and increases the risk of aspiration pneumonia due to impaired swallowing, airway protection, and cough effectiveness. 1 The CHEST guidelines emphasize that untreated sialorrhoea in neuromuscular disease, particularly ALS, causes substantial distress and functional impairment. 1
Side Effects and Monitoring
Common Adverse Effects
- Dry mouth 4
- Unpleasant taste 4
- Short duration of action requiring multiple daily doses 4
- Tachycardia (particularly concerning with systemic absorption) 7
Important Precautions
Doses less than 0.5 mg may paradoxically slow heart rate due to parasympathomimetic response. 8 Atropine's effects on heart rate are delayed by 7-8 minutes after intravenous administration and are non-linearly related to drug levels in the peripheral compartment. 2
The pharmacokinetics of atropine are nonlinear, with plasma protein binding of approximately 44% that is saturable at concentrations of 2-20 mcg/mL. 2 The elimination half-life is more than doubled in children under two years and elderly patients (>65 years) compared to other age groups. 2
Treatment Algorithm
- Initiate sublingual atropine drops: 1-2 drops of 1% atropine eye drops sublingually 2-3 times daily 4
- Assess response within 2 days: Use objective measures like drooling scales or sialometry 6, 5
- Continue if benefits exceed side effects: Individual tolerance varies significantly 1
- Escalate if inadequate response: Consider anticholinergic patches or subcutaneous glycopyrrolate formulations 1
- Reserve botulinum toxin or radiation therapy: For refractory cases with significant debility 1
Evidence Quality and Limitations
The certainty of evidence for anticholinergic management of sialorrhoea is low to very low across all interventions. 1 However, the 2024 systematic review and meta-analysis of 56 studies with 2,378 patients provides the most comprehensive recent evidence supporting atropine's efficacy. 3
Of 24 patients treated with sublingual atropine for clozapine-induced sialorrhoea, 21 (87.5%) experienced beneficial effects. 4 Among 67 patients treated for sialorrhoea of other etiologies, generally beneficial effects with few side effects were reported. 4
Critical Pitfalls to Avoid
Do not use atropine in combination with fixed-dose diphenoxylate preparations (Lomotil) for diarrhea management, as this combination has been associated with adverse outcomes in specific contexts. 1 This is irrelevant to sialorrhoea management but highlights the importance of avoiding inappropriate atropine formulations.
Avoid inadvertent overdose: The risk of imprecise dosing with eye drops led to discontinuation in one case despite efficacy. 7 Developing micro-dosing devices could enhance precision and reduce side effects. 7
Monitor for tachycardia: Systemic absorption can cause cardiovascular effects, particularly in patients with underlying cardiac conditions. 7