When schizophrenia symptoms don’t improve with standard treatments, it can feel discouraging and frustrating. Finding the right treatment isn’t always simple. Clozapine is often prescribed for treatment-resistant schizophrenia and may help when other medications haven’t worked.

For some people, clozapine can help reduce symptoms and improve daily functioning, but it also requires regular monitoring. In this article, we’ll explain why clozapine is prescribed, how it works, and what to expect while taking it.

When Is Clozapine Prescribed for Schizophrenia?

Clozapine is the only medication approved by the U.S. Food and Drug Administration (FDA) to treat treatment-resistant schizophrenia. It belongs to a drug class called atypical antipsychotics.

Healthcare providers often prescribe clozapine for people with treatment-resistant schizophrenia. This means that a person has tried at least two other antipsychotic medications but didn’t get enough symptom relief.

Clozapine may also be used to lower the risk of repeated suicidal behavior in people with schizophrenia or schizoaffective disorder.

Think of your brain as a network of chemical messages sent between nerve cells. In schizophrenia, the balance of certain brain chemicals — especially dopamine and serotonin — may be disrupted.

Clozapine helps balance these chemicals. This can help reduce psychosis symptoms, such as hallucinations (sensing things that aren’t there) and delusions (false beliefs), and it may also help prevent symptom relapses (return of symptoms).

For many people with treatment-resistant schizophrenia, clozapine can work when other medications haven’t provided enough relief.

What Are the Side Effects of Clozapine?

Like many medications, clozapine can cause side effects. Not everyone experiences them, but it’s helpful to know what to watch for. Your healthcare provider can help manage side effects so you get the most benefit out of your medication.

Common Side Effects

Some of the most common side effects of clozapine include:

• Drowsiness and fatigue (extreme tiredness that’s doesn’t improve with rest)
• Increased saliva production or drooling
• Increased appetite, weight gain, and high blood sugar
• Nausea, vomiting, and constipation
• Low blood pressure

Having side effects doesn’t necessarily mean clozapine isn’t right for you. Many side effects can be managed with dose adjustments, lifestyle changes, or other treatments recommended by your healthcare provider.

Always talk with your healthcare provider about new or bothersome side effects rather than stopping the medication on your own.

Rare but Serious Side Effects

Most people taking clozapine don’t experience serious side effects. However, it’s important to know the warning signs and when to contact your healthcare provider.

Low White Blood Cell Count

A rare but serious side effect of clozapine is agranulocytosis, a condition in which neutrophils (a type of white blood cell) drop to very low levels.

When white blood cell levels become too low, your body may have a harder time fighting infections. Regular blood tests help healthcare providers detect this problem early.

Clozapine-induced agranulocytosis is most likely to develop during the first few months of treatment. Your doctor will order blood tests to monitor your absolute neutrophil count and check for changes in neutrophil levels.

If your blood counts drop to dangerously low levels, your doctor may stop clozapine to reduce the risk of infection.

Fever

A fever can sometimes occur during the first few weeks of clozapine treatment. Although it may be harmless, fever can also be a sign of an infection. Contact your healthcare provider if you develop a fever, especially if you also have chills or flu-like symptoms.

Chest Pain

In rare cases, clozapine can affect the heart and cause serious complications. Contact a healthcare provider right away if you have chest pain or a fast heart rate. These symptoms may be a sign of myocarditis (inflammation of the heart muscle), which can occur during the first month of treatment.

Seizures

Clozapine may increase the risk of seizures, especially at higher doses or in people with a history of seizures. This is a rare side effect, but it can occur at any point during treatment. Seek medical attention right away if you experience a seizure or lose consciousness.

If a seizure occurs, your healthcare provider may adjust your clozapine dose or prescribe medication to help prevent future seizures.

Constipation and Slowed Digestion

Clozapine can slow down movement through the digestive tract. This can cause constipation, which can sometimes become severe or dangerous if it’s not treated.

Contact your healthcare provider right away if you have:

• Severe constipation
• Stomach pain
• Nausea
• Bloating
• Vomiting
• Trouble passing stool

What Should You Expect When Taking Clozapine?

Starting clozapine can feel overwhelming, especially when you learn about the possible side effects and ongoing monitoring it requires. Although these safety guardrails are important, clozapine is often the most effective treatment for people with treatment-resistant schizophrenia.

With close monitoring, many people on clozapine are satisfied with the results and choose to continue taking it. Knowing what to expect — from how the medication is taken to when you may notice symptom relief — can help you feel more confident as you begin treatment.

Clozapine is available as an oral suspension (Versacloz), tablets (Clozaril), and orally disintegrating tablets. This medication is usually taken once or twice a day, with or without food.

It’s important to take the dose as prescribed by your healthcare provider. If you miss two or more days of treatment, talk with your doctor before restarting. You may need to begin with a lower dose and increase it again gradually.

Dose Titration

Clozapine is started at a low dose that’s increased slowly over several days or weeks. This process is called dose titration. Increasing the dose gradually gives your body time to adjust to the medication and may help reduce the risk of side effects.

Your healthcare provider will decide how quickly to increase the dose based on your symptoms and blood test results.

Blood Test Requirements

Regular blood tests are an important part of clozapine treatment. These tests help your healthcare provider monitor your white blood cell levels to make sure they remain high enough to fight infections safely. In some cases, your healthcare provider may also check clozapine levels to help guide treatment.

In the past, people who prescribed and dispensed clozapine had to report ANC results to the FDA through a risk evaluation and mitigation strategy (REMS) program. The REMS program was designed to monitor ANC levels but also made it harder for some people to access treatment.

The clozapine REMS program is no longer required for prescribers or pharmacies. However, regular blood monitoring is still recommended. Your healthcare provider may order blood tests:

• Weekly during the first six months of treatment
• Every two weeks during the next six months if your blood counts remain stable
• Monthly after one year if your blood counts remain stable

Your healthcare provider will explain your blood test schedule before you start treatment.

How Long Does Clozapine Take To Work?

It may take time before you notice your symptoms improving. Some people notice a boost in overall well-being within the first weeks of treatment. Hallucinations and delusions often take longer to get better.

Because clozapine is started at a low dose and increased gradually, try to be patient if you don’t notice immediate results. Many people continue to improve over time and may not experience the full benefits for several months.

Other Important Considerations

Clozapine can interact with many prescribed and over-the-counter medications. Make sure your healthcare provider knows about all the medications and supplements you take.

Clozapine passes into breast milk, so breastfeeding while taking clozapine may not be recommended. If you are pregnant, planning to become pregnant, or breastfeeding, talk to your healthcare provider before starting or continuing clozapine.

Your healthcare team will work with you throughout treatment to make sure clozapine is safe and effective for you.

Join the Conversation

On MySchizophreniaTeam, people share their experiences with schizophrenia, get advice, and find support from others who understand.

Have you or someone you know taken clozapine for schizophrenia? Let others know in the comments below.