What medications are used to treat hypersalivation?

Medications for Hypersalivation

Start with oral glycopyrrolate as first-line pharmacological therapy for hypersalivation, continuing only if benefits outweigh side effects. 1

First-Line Pharmacological Treatment: Oral Anticholinergics

Oral anticholinergic medications are the recommended initial approach because they are relatively inexpensive, readily available, and allow straightforward assessment of individual patient response versus adverse effects. 1

Specific Agent Selection:

• Glycopyrrolate (oral solution): Dosed at 1 mg/5 mL, this is now approved within the EU specifically for pediatric hypersalivation and represents the preferred first-line agent. 2, 3 The FDA-approved formulation provides standardized dosing with predictable pharmacokinetics. 4

• Atropine: Can be used as an alternative inexpensive oral anticholinergic when glycopyrrolate is unavailable or not tolerated. 1

• Scopolamine (transdermal patch): Provides more convenient, potentially longer-acting delivery but at higher cost compared to oral agents. 1 This may be particularly useful for patients with compliance issues or those who cannot tolerate oral medications.

Critical Dosing Considerations for Glycopyrrolate:

• Must be administered at least one hour before or two hours after meals, as high-fat meals reduce oral bioavailability by approximately 74-78%. 4
• Bioavailability is low (approximately 3%) and highly variable among patients (range 1.3-13.3%), necessitating individualized dose titration. 4
• Use with caution in patients with renal impairment, as glycopyrrolate is largely renally eliminated. 4

Common Anticholinergic Side Effects to Monitor:

• Dry mouth, blurred vision, urinary retention, constipation, and potential cognitive effects in elderly patients. 1, 4
• In overdose situations, peripheral anticholinergic symptoms predominate (hyperthermia, ileus) rather than central effects, as glycopyrrolate does not easily cross the blood-brain barrier. 4

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

• Botulinum toxin injections into the salivary glands (parotid and submandibular) are safe, effective, with long-lasting saliva reduction lasting approximately four months per treatment cycle. 1, 2
• Ultrasound-guided injections improve accuracy and safety of the procedure. 5
• Incobotulinumtoxin A has completed phase III trials and is now FDA-approved in the United States for treatment of chronic hypersalivation in adults. 2, 3
• This approach is particularly useful for neurogenic sialorrhea in conditions such as Parkinson's disease, ALS, and post-stroke patients. 1
• Injections are relatively simple to perform and not overly uncomfortable for patients. 1

Third-Line Treatment: Radiation Therapy

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

• Provides long-lasting, potentially permanent relief from hypersalivation. 1
• Associated with irreversible xerostomia (dry mouth), viscous saliva, and mild to moderate pain. 1
• Modern 3D radiation techniques minimize tissue damage compared to older approaches. 2, 5
• Reserved mainly for neurodegenerative diseases where other options have failed. 5
• Cancer induction risks must be discussed with patients before proceeding. 5

Alternative Pharmacological Agents (Off-Label, Limited Evidence)

For drug-induced hypersalivation (particularly clozapine-induced), additional agents have been described in case reports and small studies: 6

• Alpha-2-adrenergic agonists: Clonidine patch can increase adrenergic tone and reduce saliva production. 6, 7
• Dopamine antagonists: Amisulpride has been reported effective in some cases. 6
• Other agents: Terazosin, moclobemide, bupropion, and N-acetylcysteine have isolated case reports of efficacy. 6

These agents should only be considered when standard anticholinergics and botulinum toxin have failed, and the risk-benefit assessment must be carefully weighed. 6

Important Diagnostic Consideration

Dysphagia can cause apparent hypersalivation due to reduced clearance rather than increased saliva production, particularly in Parkinson's disease and post-stroke conditions. 1

• Proper diagnosis should differentiate between true hypersalivation and impaired swallowing with normal saliva production before initiating antisialagogue therapy. 1
• Fiberoptic endoscopic evaluation of swallowing (FEES) generates important data on therapy selection and control. 2, 5
• Acetylcholinesterase inhibitors (used for Alzheimer's disease) commonly increase saliva production and may need dose adjustment or discontinuation. 1

Non-Pharmacological Approaches (Adjunctive)

• Swallowing therapy programs should be initiated as first-line approach before or alongside pharmacological treatment to activate compensation mechanisms. 2, 5
• In children with hypotonic oral muscles, oral stimulation plates can induce relevant symptom relief through improved lip closure. 2, 3
• Increasing frequency of swallowing with chewing gum may provide symptomatic benefit. 6

Common Pitfalls to Avoid

• Do not use anticholinergics without first ruling out dysphagia as the primary cause, as reducing saliva in patients with swallowing dysfunction may worsen aspiration risk. 1
• Avoid systemic anticholinergics in elderly patients with cognitive impairment or urinary retention without careful risk-benefit analysis. 4
• Do not proceed to surgical interventions (salivary duct relocation) given the availability of effective medical options with lower morbidity. 5
• Monitor for respiratory infections from saliva aspiration, which justifies more aggressive treatment. 5