9 Clozapine Side Effects You Should Know About

Schizophrenia is a serious mental health condition. Living with schizophrenia or loving someone who has this condition can make everyday life challenging. But with treatment and support, symptoms can be managed so that you can live a healthy and full life. Medications are an important part of treatment.

Clozapine (Clozaril, Versacloz) is an oral atypical antipsychotic that’s FDA approved to treat severe schizophrenia. It mainly works by balancing the activity of chemical messengers in the brain, such as serotonin and dopamine.

By balancing these chemicals, clozapine can help reduce symptoms of schizophrenia. But it can also cause a number of side effects, including some serious ones. Because of these risks, clozapine is typically prescribed only when other medications aren’t working well enough.

Clozapine side effects at a glance

Not everyone taking clozapine will notice side effects or experience the same ones. Still, it’s a good idea to know what clozapine side effects are possible. It’s also good to know when it’s time to reach out for help.

Common or mild clozapine side effects include:

• Sleepiness

• Mildly elevated heart rate

• Constipation

• Dizziness

• Mildly low or high blood pressure

• Excess saliva or drooling

• Headache

• Nausea or vomiting

• Tremor (shakiness)

• Sweating

• Dry mouth

• Stomach upset or heartburn

• Nightmares

• Restlessness or feeling like you can’t sit still

• Trouble sleeping

• Diarrhea

• Weight gain

Rare but serious clozapine side effects and risks include:

• Dangerously high heart rate

• Dangerously high or low blood pressure

• Fainting or falls

• Fever

• High blood glucose (blood sugar), which can lead to Type 2 diabetes

• High cholesterol

• Paralytic ileus (paralyzed intestines)

• Liver damage

• Blood clots

• Stroke

• Heart rhythm problems

• Tardive dyskinesia (a type of movement disorder)

• Neuroleptic malignant syndrome (when there’s not enough dopamine in the body)

• Severe allergic reaction or rash, such as drug reaction with eosinophilia and systemic symptom (DRESS) syndrome

This medication also has a few boxed warnings. This is the FDA’s strictest warning for medications. While rare, these side effects can be life-threatening. Clozapine has the following boxed warnings:

• Severe neutropenia (low white blood cells)

• Dangerously low blood pressure, which could cause fainting or falls

• Heart inflammation or certain heart pumping problems

• Seizures

• Increased risk of death in older adults with dementia

 Here, we’ll cover nine clozapine side effects you should know about.

1. Sleepiness

Sleepiness is one of the most common clozapine side effects. Until you know how clozapine affects you, be careful about doing tasks that require alertness, such as driving.

Here are a few things to consider if clozapine is making you sleepy:

• Are you getting enough sleep? If you’re waking up tired, check out this guide for sleep hygiene for tips on how to improve your rest.

• Are you taking your clozapine in the morning? If so, ask your prescriber if it’s OK to take your dose at night instead. Or, if you’re taking clozapine twice daily, ask them if you can take a larger portion of your daily dose in the evening.

• Are you taking other medications that cause sleepiness? Your prescriber or pharmacist can help you answer this question. Taking more than one medication that causes drowsiness can worsen this side effect. If this is a concern, your healthcare team might suggest changing one of your other medications.

As your body adjusts to clozapine, the sleepiness may become less severe. But if you continue feeling tired, or if you’re having trouble staying awake during the day, tell your prescriber.

2. Constipation

Clozapine can slow down how quickly food moves through your digestive tract, which can cause constipation. You’re more likely to have trouble staying regular if you’re a woman, age 65 or older, or take other constipating medications. But anyone taking clozapine should watch for this side effect.

Drinking plenty of fluids, eating more fiber-rich foods, and moving your body more may help. Your prescriber may also recommend an over-the-counter laxative or stool softener to keep things moving.

Constipation can be uncomfortable. But even if it doesn’t bother you much, tell your prescriber about it. In rare cases, constipation can be a symptom of paralyzed intestines (a serious clozapine side effect). Treating constipation early can help you avoid this emergency situation.

3. Excess saliva

Another common clozapine side effect is excess saliva, which can cause drooling. Besides being annoying, it can sometimes cause a rash around your mouth. It also raises your risk of aspiration pneumonia. This is when the contents of your mouth or stomach enter your lungs and cause an infection.

To prevent skin irritation from drooling, try applying a thin layer of petroleum jelly around your mouth, especially at bedtime. During the day, chewing sugar-free gum might help you swallow more saliva. But if excess saliva continues to be a problem, tell your prescriber. They may recommend a medication to help lower the amount of saliva you produce.

4. Neutropenia

Some people taking clozapine develop neutropenia — a condition in which your number of neutrophils (a type of white blood cell) gets too low. This is serious because neutrophils help protect against germs that cause illness.

Neutropenia from clozapine is most likely to happen in the first 18 weeks (4 months) of treatment. After the first 6 months, the risk becomes much lower, but it never completely goes away. To keep this side effect in check, your healthcare team will monitor your blood counts before you start clozapine and should regularly do so during treatment.

In rare cases, your neutrophil count might fall so low that life-threatening infections become possible. Contact your prescriber if you develop signs or symptoms of an infection, such as:

• Fever (body temperature of 100.4°F or greater)

• Cough or flu-like symptoms

• Skin wounds

• Unusual vaginal discharge, odor, or itching

• Pain or burning when peeing

• Severe fatigue

5. Changes in heart rate and blood pressure

Clozapine can cause changes in your heart rate and blood pressure, especially early on or after a dose increase. Some people experience a drop in blood pressure after changing positions. This can cause a racing heart or even fainting.

For most people, heart rate or blood pressure changes are small and symptom-free. But it’s possible to experience more severe changes, too. Your risk of this clozapine side effect may be higher if you have existing heart problems or take medications for high blood pressure. In rare cases, people taking clozapine have experienced cardiac arrest (when the heart suddenly stops).

Staying well hydrated and moving slowly when you get up from sitting or lying down can help protect you from fainting or falling. Reach out to your healthcare team if you experience dizziness or changes in your heart rate.

6. Weight gain, high blood sugar, and raised cholesterol

Antipsychotics can slow your metabolism. This can increase your blood sugar, body weight, and cholesterol levels. Over time, these metabolic changes can raise your risk of developing Type 2 diabetes and heart disease — or make these conditions harder to manage if you already have them.

Before you start clozapine, your healthcare team will review your overall metabolic health and suggest any helpful changes to your medications or lifestyle habits, including maintaining a nutritious diet and exercising regularly. During treatment, they should check in on you regularly. If your body weight, blood sugar, or cholesterol start to move outside of your target ranges, steps can be taken early.

Your prescriber might recommend a diabetes medication, such as metformin, or a weight-lowering glucagon-like peptide-1 (GLP-1) receptor agonist, such as Wegovy (semaglutide). There’s evidence that these medications can help manage these metabolic side effects.

7. Movement problems

Like all antipsychotic medications, clozapine can cause movement-related side effects. These can include feeling like you can’t sit still, painful muscle spasms, and tremors.

In rare cases, antipsychotics can cause a condition called tardive dyskinesia (TD). But the risk of TD is lower with clozapine than with many other antipsychotics. Symptoms of TD include uncontrollable muscle movements, typically in the face and mouth. TD can be irreversible in some cases. And your risk of developing it goes up the longer you take clozapine. Let your healthcare team know if you notice muscle movements you can’t control.

8. Heart inflammation

In rare cases, clozapine can cause certain types of heart inflammation. This includes myocarditis (heart muscle inflammation) and pericarditis (inflammation of the tissue surrounding the heart). The risk for this side effect is highest during the first 2 months of treatment.

Possible symptoms of heart inflammation may include:

• Fatigue or difficulty exercising

• Shortness of breath

• Fever

• Chest pain

• Rapid or irregular heartbeat

• Fainting

• Flu-like symptoms, such as body aches or sore throat

Your prescriber might order a blood test called high sensitivity C-reactive protein (hs-CRP) to check for inflammation.

In rare cases, clozapine may lead to cardiomyopathy, a condition that makes it hard for your heart to pump blood. Make sure your prescriber knows if you or anyone in your family has a history of heart conditions. And if you experience chest pain, body swelling, or shortness of breath, get medical care right away.

9. Higher risk of death in older adults with dementia

Some studies show a lower risk of death overall for people with severe schizophrenia who are treated with clozapine. But for one particular group — older adults with dementia — a higher risk of dying might be possible.

Reviews of multiple studies have found that older adults with dementia have a higher risk of experiencing many of clozapine’s side effects. This includes life-threatening ones, such as strokes. And this risk seems to be present for all antipsychotics, not just clozapine.

Clozapine shouldn’t be used to treat dementia-related psychosis. But it can be a helpful option for older adults living with schizophrenia. If you or a loved one is taking clozapine later in life, your prescriber may recommend a lower dose, increase the dose more slowly, and monitor more closely for side effects. These steps can help limit clozapine side effects.

Is there a safer alternative to clozapine?

Not for its recommended use. Clozapine is reserved for people whose schizophrenia symptoms haven’t gotten better with other medications. This type of schizophrenia is known as treatment-resistant schizophrenia (TRS). Clozapine is also approved to lower the risk of suicidal behavior among people with schizophrenia or schizoaffective disorder.

Although other antipsychotic medications may have a lower risk of certain serious side effects than clozapine, they may be less effective for these uses. Currently, clozapine is the only medication that’s FDA approved for TRS. What’s more, the American Psychiatric Association recommends clozapine as the first‑choice treatment for TRS. For many people, its benefits outweigh the risks of side effects.

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Written by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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