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CLOZAPINE (CLOZARIL)

Clozapine is a medication used to treat schizophrenia and is only available with a prescription.

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    WHAT IS CLOZAPINE?

    Sometimes antipsychotic medication does not properly manage the symptoms of schizophrenia and schizoaffective disorders. When this occurs, doctors may prescribe clozapine as another form of treatment. Clozapine is a medication that can help treat mental and mood disorders.

    As an antipsychotic medication, clozapine works to re-balance neurotransmitters in the brain. By doing so, clozapine can decrease hallucinations and help prevent suicide in individuals who are at risk for self-harm. Further, this medication can help individuals think more clearly, feel more positive about themselves, and claim back control of their lives.1

    DRUG CLASS AND SCHEDULE

    Clozapine (also known as Clozaril) is a prescription-only medicine belonging to the Antipsychotics, 2nd Generation pharmacological class.2 In fact, it is the first atypical antipsychotic drug. Clozapine is not a scheduled drug; however, it is available through prescription only.

    IS IT A CONTROLLED SUBSTANCE?

    Under the Controlled Substances Act (CSA), clozapine is not a controlled substance.3 It is, however, only available through a restricted distribution program due to the risks associated with its use.4

    WHAT DOES CLOZAPINE TREAT?

    Clozapine medication is used to treat schizophrenia in patients whose symptoms are not properly managed by traditional antipsychotic medications. It is also used for people who have a history of suicidal conduct linked to schizophrenia or schizoaffective disorder. Schizophrenia is a chronic and severe mental illness characterized by cognitive, perceptual, emotional, verbal, and behavioral abnormalities.5 Several studies also support the usage of clozapine for anxiety treatment and clozapine for sleep.6

    OTHER NAMES FOR CLOZAPINE

    Clozapine is known by several brand names such as Clozaril, Fazaclo ODT, Versacloz, and Zaponex.7

    HOW SHOULD I USE CLOZAPINE?

    The use of clozapine should be closely monitored by a medical professional. Further, it is important to understand the impacts of clozapine and safe usage before taking this medication for schizophrenia or schizoaffective disorders.

    Clozapine is taken by mouth with or without food. When using the medication in liquid form, it’s important to shake the bottle before use and carefully measure the dose using a measuring device or spoon provided by the pharmacist. When taking the tablet version of clozapine, carefully remove the tablet’s packaging, place it on the tongue, and swallow immediately.

    DOSAGE FOR SCHIZOPHRENIA

    Medical professionals generally recommend taking this drug at a low dose and slowly increasing the dosage. This slow increase often reduces side effects, such as dizziness, drowsiness, and seizures. The exact dosage will be based on the individual’s medical condition, response to therapy, and medical expertise, so it is important to remain in constant communication with a medical professional.

    ARE THERE OTHER USES FOR CLOZAPINE?

    Although clozapine is commonly used to treat schizophrenia, there have been cases of clozapine being effective for non-schizophrenic individuals. For instance, it has been used to treat people with tardive dyskinesia, movement disorders, atypical borderline personality disorder, chronic psychotic symptoms, and Parkinson’s disease who also have psychotic symptoms, While it may not be the current drug of choice for these other conditions due to the risk of agranulocytosis (reduced white blood cells in the blood), more research is being conducted to discern its usefulness.8

    CLOZAPINE SIDE EFFECTS

    As with all prescription medications, clozapine may produce both short-term and long-term side effects. Although a very useful and effective drug, Clozaril has been associated with serious adverse effects after short-term and long-term use. For instance, it is associated with the onset of agranulocytosis, a condition where the body does not produce enough white blood cells.8 Clozapine side effects are discussed in more detail in the sections below.

    SHORT-TERM EFFECTS

    Common short-term clozapine side effects include:

    • Weight
    • Tremor
    • Dizziness
    • Spinning sensation
    • Headache
    • Drowsiness
    • Nausea
    • Sore throat
    • Bleeding/bruising
    • Constipation
    • Dry mouth
    • Increased salivation
    • Blurred vision
    • Fast heart rate
    • Fever
    • Increased sweating

    In addition to these effects, clozapine has also been associated with more serious effects (although they may occur less frequently). Clients should contact a medical professional if any of the below side effects are present. These less frequent Clozaril side effects include:9

    • Anxiety
    • Black, tarry stools
    • Convulsions
    • Cough or hoarseness
    • Difficult or labored breathing
    • A general feeling of tiredness or weakness
    • Hyperventilation
    • Irritability
    • Severe or continuing headache
    • Jaundice
    • Urinary complications/issues
    • Increased Prolactin levels
    • Extrapyramidal symptoms can also occur

    LONG-TERM EFFECTS

    Tardive dyskinesia (TD) is a Clozaril side effect that commonly develops after long-term treatment with second-generation antipsychotic drugs. Nevertheless, it has been demonstrated to have a lower risk of TD compared to older antipsychotics like haloperidol. Symptoms of TD could include:

    • Grimacing
    • Sucking
    • Smacking of lips
    • Other uncontrollable motions

    Other long-term effects associated with usage include:

    • Increased risk of diabetes (due to high blood sugar)
    • Weight gain
    • High cholesterol
    • Stroke

    Second-generation antipsychotics have also been associated with an increased risk of cardiac problems and dementia, especially in older patients.10 In addition, high clozapine dosage or long-term use can induce a severe movement problem that is not always reversible. The risks of developing this movement disorder are further elevated for women and elderly patients. High doses can also increase the risk of seizures significantly.11

    CAN CLOZAPINE BE DANGEROUS?

    When Clozapine is taken as directed by a medical professional, it can help restore the balance of neurotransmitters in the brain. Nonetheless, similar to other medications, misuse can lead to negative side effects, including clozapine overdose and clozapine withdrawal.

    CLOZAPINE OVERDOSE

    Clozapine overdose usually involves symptoms such as drowsiness, confusion, fast heartbeats, delirium, weak or shallow breathing, drooling, choking, or seizure.11 Unconsciousness and death could occur if there is no immediate medical intervention.

    CLOZAPINE WITHDRAWAL

    Studies on clozapine discontinuation suggest that withdrawal-associated psychosis occurs within one to two weeks of stopping the drug. However, there is an indication of an increased risk of relapse several months after stopping the drug, implying that neural adaptations persist.12 Because no studies have directly evaluated the effects of different withdrawal regimens, there is a lack of data on how Clozaril should be terminated to lower the risk of withdrawal-associated psychosis.

    PROS AND CONS OF TAKING CLOZAPINE

    When deciding whether or not to start a new medication, it’s important to consider the pros and cons. Here are some of the benefits of taking clozapine:

    • Can effectively treat schizophrenia when other medications have failed
    • Can lower the risk of suicidal behavior
    • Can lower cravings for drugs of abuse
    • Available at a lower cost as a generic
    • Available as a tablet that can dissolve on the tongue without water

    Here are some of the potential cons of using clozapine:

    • May cause high blood sugar, cholesterol, and weight gain
    • May not be the best option for those with a history of seizures
    • Not all pharmacies are registered to provide it
    • Associated with lower white blood cell count and seizures
    • Requires blood work to be done every time a new prescription is filled

    CLOZAPINE REVIEWS

    Clozapine has several positive reviews, and those who use the prescription drug generally report positive effects. Especially if an individual starts using clozapine due to ineffective medications for schizophrenia, finding that clozapine works to reduce symptoms can be a positive experience.13

    STATISTICS ON CLOZAPINE’S EFFECTIVENESS

    According to a meta-analysis completed in 2017, researchers found that clozapine is the most effective antipsychotic for the 25% to 33% of individuals with schizophrenia who have been classified as treatment-resistant. While not every individual who uses clozapine will have a reaction, researchers found a 40% response rate to the medication. This means that the use of clozapine to treat schizophrenia can reduce the percentage of treatment-resistant individuals to between 12% to 20%.14

    PRECAUTIONS OF CLOZAPINE

    Clozapine may not be the best medication for every individual with schizophrenia. There are some medications that individuals should avoid and some precautions that should be considered.

    WHAT MEDICATIONS TO AVOID

    Clozapine can interact with medications and supplements. It is important to let doctors know about other medications or supplements that a client may be taking. It is not recommended to take clozapine with any of the following medications:

    • Bepridil
    • Bromopride
    • Cisapride
    • Dronedarone
    • Droperidol
    • Fluconazole
    • Ketoconazole
    • Mesoridazine
    • Metoclopramide
    • Nelfinavir
    • Pimozide
    • Piperaquine
    • Posaconazole
    • Saquinavir
    • Sparfloxacin
    • Terfenadine
    • Thioridazine
    • Ziprasidone

    WHO SHOULD NOT USE CLOZAPINE?

    Not everyone is a candidate for clozapine. For example, those who have heart problems, high blood pressure, have ever had a heart attack, seizures, and high cholesterol may be advised against this medication. Additionally, individuals who fall into any of the following categories should not use clozapine:

    • Older adults with dementia-related psychosis
    • Individuals with allergies to clozapine
    • Pregnant women
    • Breastfeeding women
    • Individuals under the age of eighteen

    HOW LONG DOES ONE USE CLOZAPINE?

    Typically, clozapine treatment is continued for at least six months; however, if an individual develops side effects, medical professionals may decide to discontinue treatment. It can take a few weeks for clozapine to start improving symptoms, so a medical professional should continually monitor those using this medication to keep track of their health and symptoms.15

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