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Clozapine is an antipsychotic drug that may be used to treat patients with schizophrenia whom are unresponsive to, or intolerant of, conventional neuroleptics. It causes few extra-pyramidal adverse effects and may be effective in combatting the negative symptoms of schizophrenia.

Clozapine has a relatively low affinity for D2 receptors and a much higher affinity for D4 receptors. Furthermore it has some affinity for 5HT2 receptors. It is not clear exactly which aspects are responsible for its superior antipsychotic effect in treatment-resistant schizophrenia (1).

The major side effect is neutropaenia which is not dose-related and occurs in 1-2% of patients. For this reason, clozapine is contra-indicated in patients with a past history of neutropaenia. There has also been a recent update to information for prescribers regarding cardiac disease and clozapine and information regarding this is linked in the menu below.

One third of patients with chronic intractable schizophrenia will respond within 6 weeks; about two-thirds within a year.

Inadequate response to antipsychotic treatment in schizophrenia and use of clozapine (1)

  • clozapine should be be used if symptoms have not responded adequately despite sequential use of at least two different antipsychotics, one of which should be a non-clozapine second-generation antipsychotic
    • if symptoms have not responded adequately to an optimised dose of clozapine, review the diagnosis, adherence to treatment, engagement with and use of psychological treatments, other possible causes of non-response and measure therapeutic drug levels before offering a second antipsychotic to augment clozapine. The second drug should not compound the common side effects of clozapine. An adequate trial of augmentation may need to be up to 8-10 weeks

The summary of product characteristics should be consulted before prescribing this drug.


Last reviewed 06/2021