What medications can be used to treat hypersalivation?

Medications to Reduce Hypersalivation

Start with an oral anticholinergic medication (glycopyrrolate or atropine) as first-line therapy, continuing only if benefits outweigh side effects; if ineffective or poorly tolerated, escalate to botulinum toxin injections into the salivary glands. 1

First-Line Treatment: Anticholinergic Medications

Oral anticholinergics are the recommended initial pharmacological approach because they are relatively inexpensive, readily available, and allow easy assessment of individual patient benefits versus adverse effects. 1

Glycopyrrolate (Preferred Agent)

• Glycopyrrolate oral solution is FDA-approved for chronic severe drooling in patients aged 3-16 years with neurologic conditions. 2
• Dosing: Start at 0.02 mg/kg three times daily, titrate in increments of 0.02 mg/kg every 5-7 days based on response and tolerability, up to maximum 0.1 mg/kg three times daily (not exceeding 1.5-3 mg per dose based on weight). 2
• Critical administration requirement: Must be given at least one hour before or two hours after meals, as high-fat meals reduce bioavailability by approximately 78%. 2
• Mechanism: Competitive inhibitor of acetylcholine receptors on salivary glands, reducing salivation rate. 2
• Advantages: Does not easily cross the blood-brain barrier (quaternary amine), minimizing central nervous system side effects. 2

Alternative Oral Anticholinergics

• Atropine can be used as an alternative inexpensive oral anticholinergic. 1
• Scopolamine (transdermal patch) provides more convenient, potentially longer-acting delivery but at higher cost. 1, 3
• Ipratropium (sublingual spray) offers more localized anticholinergic effect. 4

Common Anticholinergic Side Effects

• Dry mouth (paradoxically), constipation, urinary retention, blurred vision, flushing, nasal congestion. 2
• Constipation is the most common dose-limiting adverse reaction, requiring assessment within 4-5 days of initial dosing or dose increases. 2
• Use with caution in patients with renal impairment, as glycopyrrolate is largely renally eliminated. 2

Second-Line Treatment: Botulinum Toxin Injections

If anticholinergics provide inadequate response or are not tolerated, botulinum toxin (BT) therapy to salivary glands is recommended. 1

• Injection sites: Parotid and submandibular glands. 4, 3
• Advantages: Safe, effective, with long-lasting saliva reduction; injections are relatively simple and not overly uncomfortable. 1
• Limitations: Effects fade after several months, requiring repeat injections; doses are not standardized across studies. 1, 3
• Particularly useful for: Neurogenic sialorrhea in conditions such as Parkinson's disease, ALS, and post-stroke patients. 5
• Recent development: Incobotulinumtoxin A has completed phase III trials and is FDA-approved in the U.S. for chronic hypersalivation in adults. 6, 7

Third-Line Treatment: Radiation Therapy

Radiation therapy (RT) to salivary glands should be reserved for experienced centers and patients with significant debility from sialorrhea who have failed other interventions. 1

• Advantages: Provides long-lasting, potentially permanent relief. 1
• Significant concerns: Associated with irreversible dryness, viscous saliva, and mild to moderate pain; harm may outweigh benefits in some patients. 1
• Modern technique requirement: Use 3D radiation techniques to minimize tissue damage. 6, 7

Additional Pharmacological Options (Limited Evidence)

Alpha-2 Adrenergic Agonists

• Clonidine patch increases adrenergic tone to reduce salivation. 4, 8

Dopamine Antagonists

• Amisulpride has been described as clinically effective in case reports. 8

Other Agents

• Terazosin, moclobemide, bupropion, and N-acetylcysteine have isolated case reports of efficacy. 8

Important Clinical Considerations

Contraindications to Anticholinergics

• Glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon, myasthenia gravis. 2
• Concomitant use with solid oral potassium chloride formulations (may arrest GI passage). 2

Drug Interactions with Glycopyrrolate

• Digoxin tablets: May increase digoxin levels; monitor and consider alternative digoxin formulations. 2
• Amantadine: May increase glycopyrrolate effects; consider dose reduction. 2
• Atenolol or metformin: Glycopyrrolate may increase their serum levels; consider dose reduction. 2
• Haloperidol or levodopa: Glycopyrrolate may decrease their levels; consider dose increase. 2

Distinguishing True Hypersalivation from Apparent Hypersalivation

• Dysphagia can cause apparent hypersalivation due to reduced clearance rather than increased production, particularly in Parkinson's disease and post-stroke conditions. 1, 5
• Proper diagnosis should differentiate between true hypersalivation and impaired swallowing with normal saliva production. 5

Medications That Cause Hypersalivation

• Acetylcholinesterase inhibitors (used for Alzheimer's disease) commonly increase saliva production. 1, 5
• Clozapine is the most frequently implicated antipsychotic, with other psychotropics (risperidone, quetiapine, aripiprazole) also causing this adverse effect. 4, 8