Treatment resistant schizophrenia (TRS) explained

Magnitude and impact of schizophrenia

Schizophrenia affects roughly 23 million people or 1 in 345 people worldwide. This rate is 1 in 233 people among adults.

Schizophrenia is frequently associated with significant distress and impairment in personal, family, social, educational, occupational, and other important areas of life.

Onset is most often during late adolescence and the twenties, and tends to happen earlier among men than among women.

Treatment resistant schizophrenia

TRS is the name for schizophrenia that has not responded to at least two medicines used to treat the condition. Around one-third of schizophrenia patients have the treatment resistant form of the disease.

Symptoms of schizophrenia

Schizophrenia is characterised by significant impairments in the way reality is perceived and changes in behaviour related to:

  • Persistent delusions: the person has fixed beliefs that something is true, despite evidence to the contrary
  • Persistent hallucinations: the person may hear, smell, see, touch, or feel things that are not there
  • Experiences of influence, control or passivity: the experience that one’s feelings, impulses, actions, or thoughts are not generated by oneself, are being placed in one’s mind or withdrawn from one’s mind by others, or that one’s thoughts are being broadcast to others
  • Disorganised thinking, which is often observed as jumbled or irrelevant speech
  • Highly disorganised behaviour e.g. the person does things that appear bizarre or purposeless, or the person has unpredictable or inappropriate emotional responses that interfere with their ability to organise their behaviour
  • Negative symptoms” such as very limited speech, restricted experience and expression of emotions, inability to experience interest or pleasure, and social withdrawal
  • Extreme agitation or slowing of movements, maintenance of unusual postures

Management and support of schizophrenia

A range of effective care options for people with schizophrenia exist, and these include medication, psychoeducation, family interventions, cognitive-behavioural therapy and psychosocial rehabilitation (e.g., life skills training). Facilitated assisted living, supported housing and supported employment are essential care options that should be available for people with schizophrenia. A recovery-oriented approach – giving people agency in treatment decisions – is essential for people with schizophrenia and for their families and/or caregivers as well.

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What is clozapine?

Clozapine is one of a number of antipsychotic medicines called second-generation (or atypical) antipsychotic medicines. You may have been prescribed Clozaril®, which is the same medicine as clozapine. Medicines normally have two names, one is the generic name (in this case, clozapine) and the other is the brand name chosen by the pharmaceutical company that markets the medicine (in this case Clozaril®).

People with schizophrenia have too much chemical activity in their brain. Clozapine interacts with receptors in the brain to decrease the chemical activity.

What is Clozapine

Clozapine is used to treat people with schizophrenia in whom other medicines have not worked. A patient should only use this medicine if they have already tried at least two other antipsychotic medicines, including one of the newer atypical antipsychotics, to treat schizophrenia, and these medicines did not work, or caused severe side effects that cannot be treated.

To help reduce the risk of side-effects, the doctor will start the patient on a low dose of clozapine. This will be increased slowly so that the doctor can examine how the patient reacts. The aim is to find the lowest effective dose for the patient: the dose that has the best effect with the fewest side-effects.

Clozaril® (clozapine) is taken in tablet form. The medicine is taken once or twice a day as directed by the doctor. As doses are increased, the dose can be divided unevenly, with the larger portion taken at bedtime. The patient should follow their doctor’s advice about dividing the dose.

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Managing schizophrenia

It is important that patients take their clozapine medication as directed by their doctor to achieve the best possible outcomes. For patients with TRS treated with clozapine, it is important that:

  • Patients take their medicine as directed by their doctor and/or nurse

Patients who do not take clozapine as instructed by their doctor are more likely to find the treatment less effective. The patient’s doctor or nurse will be able to provide more information about how to take clozapine if needed.

  • Side-effects are managed by your doctor and/or nurse

All medicines can have side-effects. The doctor can explain the possible side-effects and will monitor the patient so they can be spotted early. The doctor will know how to manage any side-effects should they occur.

This will include monitoring of: the effectiveness of Clozaril® (clozapine), the results of regular blood tests for blood-related side effects and any other side-effects.

Side-effects with medicines for schizophrenia

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side-effects not listed in the package leaflet.

Please continue to report suspected side effects to the MHRA through the Yellow Card Scheme. Please report all suspected side effects that are serious or result in harm. Serious reactions are though that are fatal, life-threatening, disabling or incapacitating, those that cause congenital abnormality or result in hospitalisation, and those that are considered medically significant for any reason. It is easiest and quickest to report side effects online via the Yellow Card website: www.yellowcard.mhra.gov.uk or via the YellowCard app available from the Apple App Store or GooglePlay Store.

Agranulocytosis (a white blood cell abnormality) is uncommon in patients taking clozapine

One of the side-effects of clozapine, agranulocytosis is when not enough white blood cells are produced in the body. Although this condition can be serious if left untreated, the doctor will monitor the number of white blood cells in the patient’s blood and will adjust the treatment if necessary. Agranulocytosis is uncommon (this affects less than 1 in 100 patients but is reported in more than 1 in every 1000 patients) in patients taking clozapine.

Weight gain with clozapine

Patients taking clozapine may experience weight gain. Weight gain is a common side-effect seen in most drugs that treat schizophrenia. Please talk to your doctor, pharmacist or nurse if weight gain begins to be an issue.

Tips to help you lose weight:

  1. Try being active for 150 minutes a week – you can break this up into shorter sessions
  2. Try to include five portions of fruit and vegetables in your daily diet. Each portion can be 80 grams of fresh, canned, or frozen produce
  3. Aim to lose 0.5 to 1 kg per week
  4. Read food labels – products with more green colour coding than amber and red are often a healthier option
  5. Replace sugary drinks with water. If plain water isn’t appealing, try adding a few slices of lemon or lime for a refreshing twist
  6. Reduce your intake of foods high in added sugars and unhealthy fats. A simple first step is to switch from sugary breakfast cereals to wholegrain options, which provide more fibre and help support steady blood sugar levels
  7. Talk to someone you trust about your weight loss goals. Having support can make a big difference - especially on days when motivation is low. You do not have to do everything at once, try one thing at a time and find what works for you

For more help and advice, click here

Clozapine and constipation

Constipation may occur in patients taking drugs for schizophrenia, including clozapine.

Everyone has their own normal bowel habit, and this will differ from person to person. Symptoms of constipation include:

  • You've had fewer than three bowel movements in the past week or if you are going less often than is normal for you
  • The stools are unusually large or small and is dry, hard or lumpy
  • You are straining or in pain during a bowel movement
  • You feel like you have not fully emptied your bowels

Generally, a few simple changes to your lifestyle and diet will relieve your constipation. However, you should talk to your doctor, pharmacist or nurse if constipation becomes an issue.

Tips to manage constipation include:

  1. Eat a healthy balanced diet and include fruits that contain sorbitol. These include apples, apricots, grapes, raisins, raspberries and strawberries
  2. Drink plenty of water and avoid alcohol
  3. Increase the amount of fibre in your diet:
    • Wholemeal bread
    • Brown rice
    • Fruits and vegetables
    • Beans
    • oats
  4. Become more active:
    • Do a daily walk or run

Keep to a regular time and place and give yourself plenty of time to use the toilet. Do not delay if you feel the urge to open your bowels. To make it easier to poo, try resting your feet on a low stool while going to the toilet. If possible, raise your knees above your hips.
For more help and advice on constipation and how to manage it, click here to visit the NHS website on digestive health.

It is important that the patient’s blood is monitored for abnormalities while receiving clozapine therapy

Blood monitoring will help the doctor detect and quickly treat any blood related side-effects if they occur.

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The active ingredient and instructions for use are the same for Clozaril® and Clozapine Mylan. Any mention of Clozaril® would also apply to Clozapine Mylan.

This website is owned and managed by Viatris. This website is intended for patients prescribed Clozaril.

We recommend that you read the full Clozaril 25 mg Patient Information Leaflet or the Clozaril 100 mg Patient Information Leaflet carefully before using Clozaril®. If you are a healthcare professional, please click here.

Clozaril is indicated in treatment-resistant schizophrenic patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics. Treatment resistance is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotic agents, including an atypical antipsychotic agent, prescribed for adequate duration.

Clozaril is also indicated in psychotic disorders occurring during the course of Parkinson's disease, in cases where standard treatment has failed.

© Copyright 2025 Viatris Inc. All rights reserved. Viatris UK Healthcare Limited (company registration number 09189103), an English company with a registered office address at 20 Station Close, Potters Bar, Hertfordshire, EN6 1TL (VAT - 421 623 781)

Reporting of side effects : If you get any side effects or have a device failure, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in the package leaflet. Please report side effects or device failures with any medicine or vaccine to the medicines regulator MHRA through the Yellow Card Scheme. It is easiest and quickest to report side effects and device failures online via the Yellow Card website: https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. Alternatively, prepaid Yellow Cards for reporting are available by writing to FREEPOST YELLOW CARD (no other address details necessary), by emailing yellowcard@mhra.gov.uk, by telephoning the Commission on Human Medicines (CHM) free phone line: 0800-731-6789, or by downloading and printing a form from the Yellow Card section of the MHRA website.

You should also report any side effects to Viatris at email address: cpms@viatris.com.