An antipsychotic for treatment-resistant schizophrenia
Clozapine
The most effective medicine for schizophrenia that has not responded to other treatments — powerful but requiring regular blood tests because it can rarely lower a key type of white blood cell.
What is Clozapine?
Clozapine is used for schizophrenia that has not responded to at least two other antipsychotics ("treatment-resistant"), where it is the most effective option. Its use is tightly controlled because, rarely, it can cause a dangerous fall in a type of white blood cell (neutrophils) that fights infection — so everyone on it has regular blood monitoring through a registered scheme. It can be transformative when other treatments have failed.
Education and reference only. This is a plain-language guide to Clozapine — it deliberately contains no doses. Doses depend on the person, the brand and the reason for treatment, and belong with your prescriber. Always check the BNF, the product labelling (SmPC) and follow medical advice.
What it is
Clozapine is a distinctive antipsychotic reserved for schizophrenia that has not improved with other treatments, and for some people who cannot tolerate the movement side effects of other antipsychotics. It is the most effective medicine available for treatment-resistant schizophrenia and can dramatically improve lives where other drugs have failed — but it carries specific risks that mean its use is carefully monitored. It is dispensed only through registered monitoring schemes, with regular blood tests, and is taken as a daily tablet or liquid.
How it works
Clozapine acts on a broad range of brain receptors — including dopamine and serotonin receptors — in a pattern different from other antipsychotics. This unusual profile is thought to explain both why it works when other antipsychotics do not, and why it causes very few of the movement side effects (stiffness, restlessness) typical of the group. The same broad action also underlies its wider range of other side effects.
What it treats
Conditions Clozapine is used for
Practical use
How to take Clozapine
General, dose-free guidance — always follow your prescriber's and the leaflet's specific instructions.
- Attend all blood-monitoring appointments — clozapine is only supplied when the blood count is confirmed safe; this is non-negotiable.
- Report fever, sore throat, mouth ulcers or any sign of infection promptly (possible low white cells).
- Take it exactly as prescribed; if you miss more than a couple of days’ doses, do not just restart — contact your team, as it must be re-titrated slowly.
- Report severe constipation, which can become serious; keep well hydrated and mention any gut symptoms.
- Tell your team if you start or stop smoking, or become unwell, as this changes clozapine levels.
Weighing it up
Advantages & disadvantages of Clozapine
Advantages
- The most effective treatment for schizophrenia that has not responded to other antipsychotics.
- Causes very few movement side effects compared with other antipsychotics.
- May reduce suicidal behaviour in schizophrenia.
Disadvantages
- Requires lifelong regular blood monitoring (risk of low neutrophils).
- Range of side effects: sedation, weight gain, excess saliva, constipation, and rare heart effects.
- Complex to start and restart; strongly affected by smoking changes.
Practical use
Good to know
Clozapine’s benefits come with a strict safety framework. Rarely it can cause a sharp drop in neutrophils (a white blood cell that fights infection), which can be dangerous, so everyone on it has regular blood tests through a registered scheme — frequently at first, then less often — and the medicine is only supplied if the blood count is safe. Report any fever, sore throat or signs of infection promptly. Other important points: it is started slowly and increased gradually (a missed run of doses means restarting slowly); it can cause drowsiness, excess saliva, weight gain, constipation (which can become serious) and, rarely, effects on the heart. Smoking and stopping smoking significantly change clozapine levels, so tell your team if this changes.
Who should not take it / use with caution
- People who cannot or will not have the required regular blood monitoring, or who have had a serious blood reaction to it.
- People with certain active heart, bowel (severe constipation/obstruction) or bone-marrow conditions.
- Used with great care in epilepsy and heart disease; pregnancy and breastfeeding are considered individually by a specialist.
Monitoring
- Regular full blood count (neutrophils) through a registered scheme — the cornerstone of safe use
- Heart (for myocarditis early on), weight, blood sugar and lipids
- Bowel function; clozapine level where relevant
Side effects
- Common: drowsiness, excess saliva (especially at night), weight gain, constipation, dizziness and a fast heartbeat.
- Important: a rare but serious fall in infection-fighting white cells (hence blood monitoring), and serious constipation that can lead to bowel blockage.
- Rarely, inflammation of the heart muscle (myocarditis) — report chest pain, breathlessness or palpitations, especially in the first weeks; and a raised seizure risk at higher amounts.
Key interactions
- Medicines that also suppress the bone marrow are avoided together.
- Fluvoxamine, ciprofloxacin and some others raise clozapine levels (via the CYP1A2 enzyme, the same one affected by smoking); enzyme inducers lower them.
- Other sedating medicines add to drowsiness; care with medicines affecting the heart’s rhythm and with strong constipating drugs.
Available as: Tablets and an oral liquid (suspension), supplied through registered monitoring schemes.
Answers
Clozapine: frequently asked questions
Why do I need regular blood tests on clozapine?
Rarely, clozapine can cause a dangerous fall in neutrophils, a white blood cell that fights infection. Regular blood tests — frequent at first, then less often — catch this early, and the medicine is only supplied when your count is safe. This monitoring is why clozapine can be used safely, and it is a required part of treatment.
What should I report straight away?
Contact your team urgently if you develop a fever, sore throat, mouth ulcers or other signs of infection (possible low white cells); chest pain, breathlessness or palpitations (rare heart inflammation, especially early); or severe constipation, which can become a serious bowel problem on clozapine.
Why does smoking matter with clozapine?
Chemicals in cigarette smoke speed up the breakdown of clozapine, so smokers often need more. Importantly, if you stop smoking (or cut down), your clozapine level can rise significantly and cause side effects — so always tell your team if your smoking changes, as the dose may need adjusting.
Why is clozapine only used when other medicines have failed?
Because of its need for blood monitoring and its range of side effects, clozapine is reserved for schizophrenia that has not responded to at least two other antipsychotics — but in that situation it is the most effective option available, and can help significantly where other treatments have not.
The wider class
About Second-generation (atypical) antipsychotic
Clozapine belongs to the second-generation (atypical) antipsychotic class. For how the class as a whole works, its shared safety principles and monitoring, see the full guide.
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Authoritative sources
- BNF: Clozapine.
- electronic Medicines Compendium (SmPC): Clozapine (Clozaril).
- NICE CG178: Psychosis and schizophrenia in adults.
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