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) is an oral atypical antipsychotic 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. Here, we’ll cover nine clozapine side effects you should know about.

1. Sleepiness

Between 21% and 46% of people noticed feeling more sleepy after starting clozapine in clinical trials. 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 our guide for sleep hygiene for tips on how to improve your rest.

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

• Are you taking other medications that cause sleepiness? Your provider 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.

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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 healthcare provider.

2. Constipation

Clozapine makes food move through your digestive tract more slowly. The result: you might poop less often. In fact, studies show that up to 60% of people taking clozapine experience constipation. Fortunately, there are a lot of things you can do to help keep things moving.

Make sure you’re staying well hydrated and getting regular exercise. Eating fiber-rich foods, such as fruits and vegetables, can also help. You can also ask your healthcare provider or pharmacist to recommend an over-the-counter laxative or stool softener.

Constipation can be uncomfortable. And, in rare cases, it can lead to serious complications. Make sure to tell your provider right away if you have severe constipation, stomach pain, or trouble eating.

3. Excess saliva

Another common clozapine side effect is hypersalivation (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, talk with your healthcare provider. They may recommend a treatment change. There are also some medications they might consider for you that can help lower the amount of saliva you produce.

4. Neutropenia

About 3% of 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 usually occurs during the first 4 to 6 months of treatment.

In rare cases, your neutrophil count might fall so low that life-threatening infections become possible. The FDA requires clozapine products to have a boxed warning (the FDA’s most serious type of warning) for this risk. For added safety, clozapine is only available through the FDA’s Risk Evaluation and Mitigation Strategies (REMS) program.

Your healthcare provider will check your blood counts before you start clozapine and throughout the treatment. Make sure to tell your healthcare provider if you have any signs of an infection, such as fever, cough, or skin wounds.

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 fainting. Your risk of this side effect is higher if you have existing heart problems or take medications for high blood pressure. In rare cases, people on 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 provider if you experience dizziness or changes in your heart rate.

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

Antipsychotics can cause changes in your metabolism. This can lead to increases in your blood glucose (sugar), body weight, and cholesterol. Over time, metabolic changes can raise your risk of developing Type 2 diabetes and heart disease. They can also make these conditions more difficult to manage if you already have them.

Talk to your healthcare provider about what you can do to help limit these clozapine side effects. They’ll likely suggest following a healthy diet and exercising regularly. Depending on your situation, however, they may also recommend certain medications to help combat 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 provider know if you notice muscle movements you can’t control.

8. Heart inflammation

Clozapine also has a boxed warning for myocarditis (heart inflammation). This side effect is estimated to happen in less than 3% of people taking clozapine. In rare cases, it may lead to cardiomyopathy, a serious condition that makes it hard for your heart to pump blood.

The risk for myocarditis is highest during the first 2 months of treatment. Make sure your healthcare provider knows if you or anyone in your family has a history of heart conditions. And if you experience chest pain or shortness of breath, get medical care right away.

9. Higher risk of death in older adults with dementia

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 is possible. The FDA issued a boxed warning for this risk with all antipsychotic medications. Clozapine shouldn’t be used to treat dementia symptoms.

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).

Although other antipsychotic medications may have a lower risk of certain serious side effects than clozapine, they may be less effective for TRS. Currently, clozapine is the only medication that’s FDA-approved for TRS. The American Psychiatric Association recommends clozapine for TRS because, for many people, the treatment benefits outweigh the risk of side effects.

When should I contact my healthcare provider about clozapine side effects?

In between appointments with your healthcare provider, it’s important to let them know if you’re noticing any unusual changes since your last check-in.

Some side effects, however, require immediate attention. Get medical help right away if you experience any of the following:

• Severe dizziness or fainting

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

• Chest pain

• Trouble breathing

• Severe constipation

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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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