What Is Clozapine and What Does It Treat?

Author:

Emma Loker

B.S

Editor:

Ashley Pena

LCSW

Clozapine (brand name, Clozaril) is an antipsychotic medication reserved for treating people with schizophrenia who haven’t had positive results from other treatment options. Since Clozapine isn’t the first-choice option, it’s common for people to have reservations about its safety.

Whatever stage you’re at with your mental health condition, you probably have a few questions about how Clozapine works and how it might affect you. This page will explore key aspects of Clozapine; we hope to inform you as much as possible so that you have all the facts you need.

We’ll explore:

What Clozapine is used to treat
How Clozapine works in the brain
Positive and negative side effects of Clozapine
How to manage Clozapine’s side effects
How to safely withdraw from Clozapine
Clozapine FAQs

Let’s dive in!

What Is Clozapine Used to Treat?

Clozapine is used for people with treatment-resistant schizophrenia. This means that they’ve been prescribed at least two antipsychotic medications before, but they’re still experiencing moderate or persistent hallucinations or delusions.¹

Clozaril for treatment-resistant schizophrenia is guarded in this way because of its range of adverse side effects, which we’ll explore later. Clozapine is also approved to be used for suicide prevention in people with schizophrenia, as it is highly effective at reducing behaviors associated with suicidal ideation.¹

In addition, when using Clozaril for bipolar disorder, research finds it to be superior to other antipsychotics when treating people whose bipolar has been treatment-resistant so far.²

How Does Clozapine Work?

Clozapine is part of the classification of drugs known as second-generation antipsychotics (also known as AAPs or atypical antipsychotics). This group of medications works by acting on dopamine and serotonin receptors in your brain, which are key neurotransmitters involved in regulating our mood, energy, thinking, pleasure, movement, and motivation.¹ This blocking action allows Clozapine to treat hallucinations and delusions.

Similarly to other second-generation antipsychotics (such as Aripiprazole, Olanzapine, and Risperidone), Clozapine works on the parts of the brain involved with wakefulness (called histamine receptors), breathing, heart rate, and muscle contraction. The action at these sites is why we see the side effects in these areas.¹

Clozaril Side Effects

Clozapine’s side effect profile is known to be extensive and it can be serious. As a result, it’s often reserved for situations where people can be closely supervised.

Of course, its significant positive effects are that it can decrease schizophrenic relapses, improve cognition, and reduce suicidal behavior.1 However, its negative impacts must be taken into consideration to ensure your health and well-being.

Common and less serious side effects of Clozapine include sedation, dizziness, and excessive drooling.³ You might experience sexual dysfunction and urine retention, and between 15% and 60% of people who take Clozapine will experience constipation; you may need to be prescribed laxatives or stool softeners to manage this.¹

The more serious side effects to be aware of include agranulocytosis (which we’ll explain soon), seizures, and respiratory depression. However, medical vigilance and swift intervention make these mostly manageable.⁴

Let’s explore some serious side effects here:

Agranulocytosis may affect around 1% of people taking Clozapine. This is when your white blood cell count becomes dangerously low, impacting your body’s immune response.¹ Your doctor should conduct Clozaril blood monitoring throughout your treatment to ensure your body is responding well.
Seizures can occur while taking Clozapine, particularly in people with epilepsy. To manage the risk of Clozaril and seizures your doctor may also prescribe you an anti-epileptic like valproic acid.¹
Another rare but serious side effect of Clozapine is myocarditis. This is when there is inflammation of your heart, putting you at risk of flu-like symptoms, chest pain, fatigue, and heart palpitations. If you’re on Clozapine and heart problems occur, it could be because your dose has been upped too quickly or you’re also taking an SSRI. The metabolic side effects of Clozapine also put you at greater risk of myocarditis.¹
The metabolic impact of Clozapine can include weight gain, insulin resistance, type 2 diabetes, increased blood pressure, and a susceptibility to having blood clots. Weight gain is a common side effect of many antipsychotic medications, but these risks are much higher with Clozapine (and Olanzapine).1 The risks of weight gain and diabetes can be managed by giving you medication like metformin. However, you should also be counseled on proper diet and exercise practices.¹

Clozapine Sedation Effects

Sedation is a common side effect of antipsychotic medications, Clozapine included. This is because of how this medication interacts with histamine receptors in your brain, key players in your feeling of wakefulness.

While the benefits of taking Clozapine should ideally outweigh the adverse effects, you should speak to your doctor if you’re experiencing excessive sedation. It may be that your dose could be decreased, split across the day, or taken in the evening to reduce its impact on you.

How to Take Clozapine

Clozapine is available as a liquid, oral tablet, or disintegrating tablet (dissolving on your tongue without water). Unlike some other antipsychotic medications, Clozapine is not affected by food. This means you can take it with or without meals, at whatever time you prefer.

Clozapine will reach its maximum concentration in your blood within 6 hours of taking it.¹ As a result, this may be the time when you experience side effects most strongly, e.g., dizziness and drowsiness. You may choose to take your Clozapine a few hours before bed so that you’re asleep when this happens.

Health Considerations Before Taking Clozapine

Before prescribing Clozapine, your doctor will ask about your liver and kidney health. If either of these are in some way impaired, your dose may be reduced. In addition, there are serious effects on infants who are exposed to Clozapine through pregnancy and breastfeeding, so this should be avoided.¹

Withdrawing From Clozapine

It may not always be medically advisable, but you have the right to withdraw from Clozapine if you want to. Tapering off Clozapine gradually is generally advised as it will reduce the impact of withdrawal symptoms, which can be worse if you stop taking your medication abruptly.

You might experience symptoms of psychosis and delirium when withdrawing Clozapine, this is sometimes called a ‘rebound’ of your previous symptoms. If these are severe, they can be quickly resolved by taking a low dose of Clozapine.⁵

In terms of non-psychotic Clozapine withdrawal symptoms, about 20% of people discontinuing Clozapine will experience some of the following:

Restlessness
Fast heart rate and high blood pressure
Sweating
Headache
Muscle rigidity
Shivering and goosebumps
Confusion
Anxiety
Extra pyramidal symptoms (involuntary muscle movements and tremors)
Catatonia
Insomnia
Sudden onset of obsessive-compulsive symptoms (in people who didn’t have OCD before taking Clozapine)
Neuroleptic malignant syndrome (NMS)

How intensely you experience these symptoms will depend on how abruptly you come off your medication, so stopping Clozapine safely is really crucial.⁴ If you can taper your withdrawal as gradually as possible, this should minimize the side effects you experience.

Clozapine FAQs

What Are the Signs Clozaril Is Working?

Since Clozapine is a second-generation antipsychotic, this means it treats both ‘positive’ (hallucinations and delusions) and ‘negative’ (being withdrawn or ambivalent) symptoms of schizophrenia.⁶ Your Clozaril will be working effectively if your symptoms of psychosis have mostly or completely disappeared. You should feel less agitated and that your thoughts are more organized.

How Long Does Clozaril Take to Work?

Even though Clozaril will reach maximum concentration in your blood within 6 hours of taking it, it might take a few weeks until you feel it’s truly working for you. On the whole, the most significant improvement in symptoms is usually seen within the first two weeks of antipsychotic treatment. However, clinicians usually give it 4 to 6 weeks to monitor whether a medication is working, so you should know after this long.⁷

How Much Weight Do You Gain on Clozapine?

Some research has found that over 50% of patients who take Clozapine will become substantially overweight, with most of the weight being gained in the first 6 to 12-months of treatment.⁸ Other research found 70% of patients gained an average of 7.5 kg over a 12-month period, with men gaining more than women.⁹

Why Is Clozapine a High Risk Drug?

Clozapine is reserved for people who have already tried other antipsychotic medications because of its extensive profile of side effects. While some of Clozapine’s side effects can result in serious health conditions, even its ‘less serious’ impacts can significantly affect your ability to carry out normal activities and be integrated into society (i.e., extreme fatigue).

Find Out More About Clozapine Today

If you have any more questions about Clozapine or your mental health condition, reach out to us here at Mission Connection. We treat people with schizophrenia, bipolar, depression, and psychosis.

Our antipsychotic treatments can include talking therapies, whether it’s online, in person, or both. We offer cognitive behavioral therapy, trauma-focused therapy, exposure therapy, mindfulness therapy, dialectical behavior therapy, and many more approaches.

Call us today to ask any questions or request a consultation, or get started online here.

References

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Delgado, A., Velosa, J., Zhang, J., Dursun, S., Kapczinski, F., & de Azevedo Cardoso, T. (2020). Clozapine in bipolar disorder: A systematic review and meta-analysis. Journal of Psychiatric Research, 125. https://doi.org/10.1016/j.jpsychires.2020.02.026
Lieberman, J. A., & Safferman, A. Z. (1992). Clinical profile of clozapine: Adverse reactions and agranulocytosis. Psychiatric Quarterly, 63(1), 51–70. https://doi.org/10.1007/bf01064682
Yee, B. K., Jeffrey Cl Looi, Agaciak, M., Allison, S., Kit, S., & Tarun Bastiampillai. (2023). Non-Psychosis Symptoms of Clozapine Withdrawal: a Systematic Review. PubMed, 33(2), 44–64. https://doi.org/10.12809/eaap2261
Stanilla, J. K., José de León, & Simpson, G. M. (1997). Clozapine Withdrawal Resulting in Delirium With Psychosis. The Journal of Clinical Psychiatry, 58(6), 252–255. https://doi.org/10.4088/jcp.v58n0603
Chokhawala, K., & Stevens, L. (2023, February 26). Antipsychotic Medications. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK519503/
Ofer Agid, Seeman, P., & Kapur, S. (2006). The “delayed onset” of antipsychotic action — an idea whose time has come and gone. Journal of Psychiatry & Neuroscience, 31(2), 93. https://pmc.ncbi.nlm.nih.gov/articles/PMC1413955/
Umbricht, D. S., Pollack, S., & Kane, J. M. (1994). Clozapine and weight gain. The Journal of Clinical Psychiatry, 55 Suppl B, 157–160. https://pubmed.ncbi.nlm.nih.gov/7961563/
Briffa, D., & Meehan, T. (1998). Weight Changes during Clozapine Treatment. Australian & New Zealand Journal of Psychiatry, 32(5), 718–721. https://doi.org/10.3109/00048679809113128