What medications can cause drooling? A guide to drug-induced sialorrhea

According to a review of psychotropic agents, excessive drooling, or sialorrhea, is a common and distressing side effect for many psychiatric patients, with clozapine being the most commonly implicated antipsychotic. This article explores what medications can cause drooling and the underlying pharmacological mechanisms.

Quick Summary

This guide covers various drug classes that can cause drooling (sialorrhea), including antipsychotics, cholinergic agents, sedatives, and anticonvulsants. It explains the mechanisms behind this side effect, such as increased saliva production or impaired swallowing, and outlines common management strategies.

Key Points

• Antipsychotics are a major cause: Clozapine is the most commonly associated antipsychotic with drug-induced drooling.

• Two main mechanisms: Drooling can result from either increased saliva production (hypersecretion) or impaired swallowing (dysphagia), with the latter being more common.

• Cholinergic drugs increase saliva: Medications that enhance cholinergic activity, such as acetylcholinesterase inhibitors, can directly cause hypersalivation.

• Sedatives cause impaired swallowing: Benzodiazepines and certain anticonvulsants can lead to drooling due to excessive sedation that affects the swallowing reflex.

• Management involves multiple strategies: Treatment options range from medication adjustment and swallowing therapy to anticholinergic drugs, botulinum toxin injections, and suction devices.

• Dose-dependency is a factor: The risk and severity of drooling from some medications, like benzodiazepines and ketamine, can depend on the dosage.

• Evaluation by a specialist is crucial: A thorough evaluation by a healthcare professional is necessary to determine the cause and best management strategy for medication-induced drooling.

Understanding Drooling (Sialorrhea)

Drooling, or sialorrhea, is the unintentional loss of saliva from the mouth. While often associated with neurological conditions, a significant number of cases are linked to medication use. Sialorrhea can be embarrassing, socially isolating, and increase the risk of complications like aspiration pneumonia. The cause of medication-induced drooling can be either hypersecretion (excessive saliva production) or, more commonly, a failure to swallow the saliva efficiently.

Causes: Increased Saliva vs. Impaired Swallowing

Two primary mechanisms explain why medications cause drooling:

• Increased Saliva Production (Hypersecretion): Some drugs directly stimulate the salivary glands, leading to an overproduction of saliva. This is often mediated by the parasympathetic nervous system, which controls saliva flow. Cholinergic agents, for example, directly mimic or potentiate the neurotransmitter acetylcholine, resulting in heightened salivary activity.
• Impaired Swallowing (Dysphagia): Many drugs do not increase saliva production but interfere with the ability to swallow effectively. This can be caused by sedation, muscle weakness, or a disruption of the swallowing reflex. This is particularly common with medications that affect the central nervous system.

Key Drug Classes That Cause Drooling

Antipsychotics and Psychotropic Medications

Antipsychotic drugs are one of the most well-documented causes of drug-induced sialorrhea, particularly certain atypical antipsychotics.

• Clozapine: This atypical antipsychotic has the strongest association with drooling, affecting a significant percentage of patients. The mechanism involves both direct agonistic effects on M3 and M4 muscarinic receptors and antagonism of α2-adrenergic receptors, which increases salivary secretion.
• Risperidone, Olanzapine, Quetiapine, and Aripiprazole: Other second-generation antipsychotics have also been reported to cause sialorrhea, though less frequently than clozapine. Risperidone's effect may be related to α2-adrenergic antagonism, while olanzapine's might involve M4 muscarinic receptor agonism.
• Haloperidol: This first-generation antipsychotic has a higher incidence of sialorrhea than some newer agents, possibly due to drug-induced parkinsonism symptoms.
• Lithium: As a mood stabilizer, lithium has been reported to cause sialorrhea, potentially by triggering chemoreceptors in the brain's emetic zone or affecting salivary gland secretion.

Cholinergic Agents

This class of drugs directly increases cholinergic activity, which in turn boosts saliva production.

• Acetylcholinesterase Inhibitors: These drugs are used to treat Alzheimer's disease and include donepezil, galantamine, and rivastigmine. They increase the amount of acetylcholine, leading to stimulation of salivary glands. While drooling is less common with these than with antipsychotics, it can occur.
• Direct Cholinergic Agonists: Medications like pilocarpine and bethanechol, which are used to treat conditions like dry mouth and urinary retention, directly stimulate muscarinic receptors to produce saliva.
• Toxic Agents: Organophosphate insecticides and nerve gases are potent, irreversible acetylcholinesterase inhibitors that can cause severe, life-threatening cholinergic toxicity, with excessive salivation being a hallmark symptom.

Sedatives and Anticonvulsants

Some sedatives and seizure medications can cause drooling by impairing neuromuscular control and depressing the swallowing reflex.

• Benzodiazepines: Drugs like alprazolam and diazepam can cause drooling, particularly at higher doses, due to excessive sedation and a subsequent reduction in the frequency of swallowing.
• Anticonvulsants: Certain anti-seizure medications, such as nitrazepam and phenobarbital, have been linked to sialorrhea. Nitrazepam, for instance, can induce swallowing coordination issues.
• Ketamine: This anesthetic and sedative agent is known to cause hypersalivation due to the overactivation of the sympathetic nervous system, leading to thick, excessive secretions.

Other Medications and Substances

• Medications Irritating the Esophagus: Some oral antibiotics, such as doxycycline and tetracycline, can cause irritation that leads to excessive salivation.
• Illegal Drugs: Certain illicit substances, like phencyclidine (PCP) and arecoline found in betel nut, can cause drooling through various mechanisms, including muscarinic agonism.
• Heavy Metal Poisoning: Toxicity from heavy metals like mercury, thallium, and arsenic can induce drooling.

Managing Medication-Induced Drooling

Effective management requires a comprehensive approach, often starting with non-pharmacological methods before considering other options.

1. Review and Adjust Medications: The first and most critical step is to consult with a healthcare provider. If possible, the dose of the offending medication may be reduced, or a different drug may be substituted. In cases of clozapine, switching to another antipsychotic might be considered.
2. Behavioral and Swallowing Therapy: A speech and language therapist can provide training to improve posture, head control, and swallowing techniques to handle saliva more effectively. Visual cues and reminders can also be helpful for some patients.
3. Use of Oral Devices and Suction: Portable suction machines are available to help remove excess saliva from the mouth, which can be especially useful at night.
4. Pharmacological Treatments: Several medications can be used to treat drooling, often by reducing saliva production. These include:
   • Anticholinergics: Drugs like glycopyrrolate or scopolamine (via transdermal patch) can reduce saliva flow by blocking cholinergic receptors.
   • Alpha-2 Adrenergic Agonists: Clonidine can help manage drooling, especially that caused by antipsychotics like risperidone.
   • Tricyclic Antidepressants: Amitriptyline, which has anticholinergic properties, can help reduce saliva production.
5. Botulinum Toxin Injections: For severe cases unresponsive to other treatments, injections of botulinum toxin into the salivary glands can temporarily paralyze the muscles responsible for squeezing out saliva.
6. Surgical Intervention: In rare, severe, and persistent cases, surgical options might be considered, such as removing salivary glands or rerouting ducts.

Comparison of Drooling-Causing Medications

Drug Class/Example	Mechanism of Action	Drooling Risk	Management Considerations	Relevant Source
Clozapine	M4 partial agonism, α2 antagonism, impaired swallowing reflex	High	Adjusting dose, anticholinergics, or switching to alternative antipsychotics
Cholinergic Agonists	Direct stimulation of muscarinic receptors	Variable	Dose reduction or discontinuation if drooling is problematic
Benzodiazepines	Excessive sedation, impaired swallowing	Moderate (dose-dependent)	Dose reduction, behavioral therapy for swallowing
Anticonvulsants (e.g., Nitrazepam)	Impaired swallowing coordination	Low-Moderate	Dose reduction, swallowing therapy
Ketamine	Sympathetic overactivation leading to thick secretions	Moderate (dose-dependent)	Administering ketamine slowly; suction
Risperidone	Adrenergic antagonism, some muscarinic activity	Moderate	Dose reduction, switching, or using alpha-2 agonists

Conclusion

While a variety of medications can cause drooling, the phenomenon is particularly associated with certain antipsychotics, cholinergic agents, and sedatives. The underlying cause can stem from either increased saliva production or, more often, an impaired swallowing mechanism. For anyone experiencing this side effect, it is essential to consult a healthcare provider. Management options range from dose adjustment and behavioral therapy to pharmacological interventions and, in rare cases, surgical procedures. By understanding which medications can cause drooling and their mechanisms, healthcare providers can offer appropriate, individualized strategies to mitigate this distressing side effect and improve a patient's quality of life.

Frequently Asked Questions

Which antipsychotics are most likely to cause drooling?

Clozapine is the antipsychotic most frequently associated with drooling (sialorrhea). Other antipsychotics like risperidone, olanzapine, and quetiapine can also cause this side effect, though with a lower incidence.

Can Alzheimer's medication cause excessive saliva?

Yes, medications for Alzheimer's disease, specifically acetylcholinesterase inhibitors like donepezil, galantamine, and rivastigmine, increase acetylcholine, which can stimulate salivary flow.

How do sedatives cause drooling?

Sedatives such as benzodiazepines often cause drooling by inducing excessive sedation. This reduces the frequency of swallowing, leading to an accumulation of saliva in the mouth and subsequent drooling.

Is it possible for antibiotics to cause drooling?

Yes, some antibiotics, like doxycycline and tetracycline, can cause drooling by irritating the esophagus, which in turn can trigger excessive salivation.

What is the difference between drug-induced drooling and normal drooling?

Drug-induced drooling can be caused by either increased saliva production or impaired swallowing due to a medication's effect. Normal drooling can stem from other conditions like neurological disorders or oral infections.

What should I do if my medication is causing me to drool?

You should consult your healthcare provider. They can determine if adjusting your dosage, switching to an alternative medication, or adding another drug to manage the side effect is appropriate.

Can botulinum toxin injections be used for drug-induced drooling?

Yes, botulinum toxin injections into the salivary glands are a treatment option for severe, persistent cases of drooling that do not respond to other interventions.