Sialorrhea Explained: What Drugs Cause Excess Saliva?

October 7, 2025 •

4 min read

Sialorrhea, or excessive salivation, is a side effect reported by 30% to 80% of patients taking the antipsychotic drug clozapine [1.3.2, 1.8.1]. Understanding what drugs cause excess saliva is the first step toward managing this often embarrassing and uncomfortable condition.

Quick Summary

Certain medications, particularly antipsychotics like clozapine and Alzheimer's drugs such as donepezil, can lead to excessive saliva production (sialorrhea) by stimulating the body's cholinergic system.

Key Points

Sialorrhea: The medical term for excessive saliva production, a notable side effect of certain drugs like antipsychotics and cholinergic agents [1.8.1, 1.2.1].
Primary Culprits: Atypical antipsychotics, especially clozapine, and cholinesterase inhibitors used for Alzheimer's are the most common drug classes to cause hypersalivation [1.2.3].
Cholinergic System: Most drugs causing this side effect work by over-activating the body's cholinergic system, which directly controls salivation via muscarinic receptors [1.2.1, 1.5.5].
Clozapine's High Incidence: Clozapine is linked to sialorrhea in 30-80% of patients due to a complex mechanism involving muscarinic and adrenergic receptors [1.3.2, 1.8.1].
Management is Crucial: Patients should never stop medication on their own; instead, they should consult a doctor about management options like dose changes, anticholinergic treatments, or behavioral strategies [1.6.3, 1.8.1].
Treatment Options: Management can range from chewing sugar-free gum to promote swallowing to medical interventions like glycopyrrolate, atropine drops, or botulinum toxin injections [1.6.5, 1.6.1].

Understanding Sialorrhea: More Than Just Drooling

Sialorrhea, the medical term for excessive saliva production or hypersalivation, is a condition where there is an excess of saliva in the mouth that may result in drooling [1.8.1]. While saliva is essential for functions like digestion, lubrication, and oral health, its overproduction can lead to significant physical and psychosocial complications [1.2.1, 1.3.1]. These can include skin irritation around the mouth, difficulty with speech, social stigma, and even an increased risk of aspiration pneumonia, particularly at night [1.4.2, 1.8.1]. It's important to distinguish true sialorrhea, which is the hypersecretion of saliva, from issues with swallowing that lead to saliva pooling [1.2.3]. This article focuses on true sialorrhea induced by medications.

The Pharmacology Behind Excess Saliva

The production of saliva is primarily controlled by the autonomic nervous system, specifically the parasympathetic branch [1.3.1, 1.4.2]. This system uses a neurotransmitter called acetylcholine (ACh) to signal salivary glands to produce saliva [1.5.3]. Many drugs that cause sialorrhea do so by increasing the activity of this system. They are often classified as cholinergic or muscarinic agonists, meaning they directly or indirectly stimulate the muscarinic receptors (specifically M1 and M3 receptors) in the salivary glands, leading to increased saliva flow [1.2.1, 1.5.5]. Other mechanisms include the blockade of alpha-2 adrenergic receptors, which also plays a role in regulating saliva production [1.4.2].

Common Classes of Drugs That Cause Excess Saliva

Several major medication groups are known to be associated with sialorrhea. The most prominent are antipsychotics and medications used to treat dementia [1.2.3].

Antipsychotics

Atypical antipsychotics are a major cause of drug-induced sialorrhea [1.2.3].

Clozapine: This is the medication most notoriously linked to hypersalivation, with incidence rates reported between 30% and 80% of patients [1.3.2, 1.8.1]. The mechanism is complex, involving agonism at M4 muscarinic receptors and antagonism of alpha-2 adrenergic receptors [1.3.1, 1.4.2]. Its metabolite, norclozapine, is a potent M1 agonist, which also contributes significantly to drooling [1.3.6].
Olanzapine, Risperidone, and Quetiapine: While less frequent than with clozapine, other atypical antipsychotics like olanzapine, risperidone, and quetiapine have also been reported to cause sialorrhea [1.3.1]. In one study, sialorrhea was found in less than 12% of patients on these drugs, compared to 38% for clozapine [1.7.3]. The mechanism for risperidone-induced sialorrhea is thought to be related to its potent antagonism of α2-adrenergic receptors [1.4.1].

Cholinesterase Inhibitors

These drugs work by increasing the amount of acetylcholine available, which can stimulate salivary glands. They are primarily used to treat the symptoms of Alzheimer's disease [1.2.1].

Donepezil, Rivastigmine, and Galantamine: As the main clinical acetylcholinesterase inhibitors, these medications can increase saliva flow as a side effect of their intended mechanism [1.2.1].

Direct Cholinergic Agonists

These drugs directly mimic the action of acetylcholine, stimulating muscarinic receptors.

Pilocarpine and Cevimeline: These medications are often prescribed to treat xerostomia (dry mouth), a condition associated with Sjögren's syndrome or radiation therapy [1.9.3, 1.2.1]. Paradoxically, their mechanism of action directly stimulates saliva production, and an excessive dose can lead to sialorrhea [1.2.1, 1.9.2].

Other Substances

Lithium: Used as a mood stabilizer, lithium has been reported to cause sialorrhea, possibly by irritating salivary glands or triggering central chemoreceptors [1.3.1].
Certain Toxins and Heavy Metals: Exposure to organophosphate insecticides, nerve gases, mercury, and arsenic can cause profuse drooling by irreversibly blocking the acetylcholinesterase enzyme [1.2.1, 1.2.3].

Comparison of Key Medications Causing Sialorrhea


Drug Name	Drug Class	Primary Use	Common Mechanism of Sialorrhea
Clozapine	Atypical Antipsychotic	Treatment-resistant schizophrenia	M4 muscarinic agonism & α2-adrenergic antagonism [1.3.1, 1.4.2]
Risperidone	Atypical Antipsychotic	Schizophrenia, Bipolar disorder	Potent α2-adrenergic antagonism [1.4.1]
Donepezil	Cholinesterase Inhibitor	Alzheimer's disease	Increases acetylcholine levels, stimulating muscarinic receptors [1.2.1]
Pilocarpine	Cholinergic Agonist	Dry mouth (Xerostomia)	Direct stimulation of muscarinic receptors [1.2.1, 1.9.2]

Managing Drug-Induced Sialorrhea

It is crucial never to stop taking a prescribed medication without consulting a healthcare provider [1.6.3]. If sialorrhea is causing distress, a doctor can explore several management strategies.

Dose Adjustment: In some cases, reducing the medication dosage may alleviate the side effect, although this is not always effective, especially with clozapine [1.6.3, 1.8.1].
Switching Medications: A doctor might suggest switching to a different antipsychotic less associated with sialorrhea, such as paliperidone instead of risperidone [1.4.1].
Behavioral Techniques: Simple strategies like chewing sugar-free gum can promote more frequent swallowing [1.6.5]. Elevating the head during sleep and using a towel on the pillow can manage nocturnal drooling [1.8.1].
Pharmacological Treatment: Several off-label medications can be used to counteract sialorrhea. Anticholinergic agents like glycopyrrolate, scopolamine patches, or sublingual atropine drops work to reduce saliva production [1.6.1, 1.6.3]. However, these can have their own side effects, such as constipation and blurred vision [1.6.1].
Botulinum Toxin Injections: For severe, refractory cases, injections of botulinum toxin (Botox) directly into the parotid and submandibular glands can effectively reduce saliva production for several months at a time [1.6.1, 1.6.4].

Conclusion

Drug-induced sialorrhea is a common and distressing side effect, primarily associated with antipsychotics like clozapine and cholinesterase inhibitors. It results from the overstimulation of the salivary glands, often through the body's cholinergic pathways. While it can significantly impact a person's quality of life, it is a manageable condition. Open communication with a healthcare provider is essential to find the most suitable strategy, whether it involves adjusting medication, trying behavioral techniques, or using targeted treatments to reduce saliva flow.

For more in-depth information on the management of medication side effects, a valuable resource is the National Institute of Mental Health (NIMH) website. (https://www.nimh.nih.gov/health/topics/mental-health-medications)

Frequently Asked Questions

The atypical antipsychotic medication clozapine is the drug most frequently associated with causing excessive salivation (sialorrhea), affecting up to 80% of patients who take it [1.3.1, 1.8.1].

Clozapine causes hypersalivation through a complex mechanism. It is believed to act as an agonist at M4 muscarinic receptors and an antagonist at alpha-2 adrenergic receptors, both of which can increase saliva flow. Additionally, its metabolite, norclozapine, is a potent M1 muscarinic agonist, further contributing to the effect [1.3.1, 1.3.6].

Yes, medications used to treat Alzheimer's disease, such as donepezil, rivastigmine, and galantamine, can cause excess saliva. These drugs are cholinesterase inhibitors, which increase the levels of acetylcholine in the brain, a neurotransmitter that also stimulates saliva production [1.2.1].

You should never stop your medication without consulting your doctor. Management strategies include dose reduction, switching to another medication, using anticholinergic drugs like glycopyrrolate, or behavioral techniques like chewing sugar-free gum. In severe cases, botulinum toxin injections may be an option [1.6.3, 1.6.1, 1.6.5].

While often just socially embarrassing, severe sialorrhea can have dangerous complications. It can cause skin breakdown around the mouth and, more seriously, lead to choking or aspiration pneumonia if excess saliva is inhaled into the lungs, especially during sleep [1.4.2, 1.8.1].

Yes, chewing sugar-free gum can be a helpful behavioral intervention. It doesn't reduce the amount of saliva produced, but it promotes more frequent swallowing, which helps manage the excess saliva in the mouth and can reduce drooling [1.6.5].

While dry mouth is a more common side effect of antidepressants, some, like sertraline, have been reported to cause sialorrhea in rare cases [1.3.1]. However, it is not a widely reported or common side effect for this class of drugs.