What are the medication options for managing increased salivation caused by antipsychotic (anti-psychotic) medication?

Management of Antipsychotic-Induced Hypersalivation

Anticholinergic medications are the first-line treatment for managing increased salivation caused by antipsychotic medications, with glycopyrrolate being the preferred agent due to its favorable efficacy and side effect profile. 1

First-Line Treatment Options

Anticholinergic Medications

Anticholinergics work by blocking acetylcholine receptors on salivary glands, thereby reducing salivation:

1. Glycopyrrolate (Glycopyrronium bromide)

   • Dosing: Start at 1 mg orally twice daily, can be titrated up as needed 2
   • Advantages:
     • Does not easily cross blood-brain barrier, minimizing cognitive side effects 2
     • Specifically targets peripheral muscarinic receptors 2
   • Administration: Take at least 1 hour before or 2 hours after meals (high-fat meals reduce bioavailability by ~78%) 2

2. Atropine

   • Can be used sublingually to reduce salivation 3
   • Less preferred than glycopyrrolate due to greater central nervous system effects

3. Benztropine (Cogentin)

   • May be used, but has more central anticholinergic effects than glycopyrrolate

Second-Line Treatment Options

Botulinum Toxin Injections

• Recommended when anticholinergic medications are ineffective or poorly tolerated 1
• IncobotulinumtoxinA (Xeomin) 100 Units is FDA-approved for this indication
• Administered into parotid and submandibular salivary glands in a 3:2 dose ratio
• Effects last for weeks to months 1
• Side effects include mild to moderate dry mouth and dysphagia 1

Other Pharmacological Options

Based on recent evidence from a network meta-analysis, the following medications have shown efficacy for clozapine-induced sialorrhea (in order of decreasing effectiveness) 4:

1. Metoclopramide (dopamine antagonist)
2. Cyproheptadine (antihistamine with anticholinergic properties)
3. Sulpiride (benzamide antipsychotic)
4. Propantheline (anticholinergic)
5. Diphenhydramine (antihistamine with anticholinergic properties)
6. Benzhexol (anticholinergic)
7. Doxepin (tricyclic antidepressant)
8. Amisulpride (benzamide antipsychotic)
9. Chlorpheniramine (antihistamine)
10. Amitriptyline (tricyclic antidepressant)

Practical Management Algorithm

1. Confirm antipsychotic causation

   • Verify timing of hypersalivation with antipsychotic initiation or dose increase
   • Rule out other causes of hypersalivation

2. Non-pharmacological approaches

   • Increase frequency of swallowing
   • Use of sugar-free chewing gum to stimulate swallowing 5

3. Antipsychotic medication adjustment

   • Consider dose reduction if clinically feasible
   • Consider splitting the daily dose 5
   • Consider switching to an antipsychotic less likely to cause hypersalivation if clinically appropriate

4. Pharmacological treatment

   • First choice: Glycopyrrolate 1 mg twice daily, titrate as needed
   • Alternative: Other anticholinergics (atropine, benztropine)
   • For nocturnal sialorrhea: Consider sublingual atropine drops at bedtime 3

5. For refractory cases

   • Consider botulinum toxin injections to salivary glands
   • Consider trial of alternative agents based on the meta-analysis findings 4

Important Considerations and Cautions

• Monitor for anticholinergic side effects:

  • Dry mouth, constipation, urinary retention, blurred vision, confusion 1
  • Anticholinergic burden may worsen cognitive function, especially in elderly patients

• Timing of medication:

  • Glycopyrrolate should be taken at least 1 hour before or 2 hours after meals 2
  • For predominantly nocturnal hypersalivation, consider evening dosing

• Contraindications:

  • Use anticholinergics with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, or significant cardiovascular disease
  • Use with caution in patients with renal impairment as glycopyrrolate is largely renally eliminated 2

• Drug interactions:

  • Be aware of potential additive anticholinergic effects when combining with other medications

By following this structured approach to managing antipsychotic-induced hypersalivation, clinicians can significantly improve patient comfort, quality of life, and medication adherence while minimizing adverse effects.