Clozapine

Clozapine, one of the first atypical agents to be developed, carries a significant risk of agranulocytosis and full blood count monitoring is therefore essential during treatment. For this reason, clozapine should only be used in patients resistant to other antipsychotic medication. The BNF states:

Clozapine should be introduced if schizophrenia is not controlled despite the sequential use of two or more antipsychotic drugs (one of which should be a second-generation antipsychotic drug), each for at least 6-8 weeks.

Adverse effects of clozapine

• agranulocytosis (1%), neutropaenia (3%)
• reduced seizure threshold - can induce seizures in up to 3% of patients
• constipation
• myocarditis: a baseline ECG should be taken before starting treatment
• hypersalivation

Remember ‘C’s - Cell count, C(s)eizures, myoCarditis, Constipation, C(s)alivation

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Smoking cessation can cause a significant rise in clozapine levels, and so it should be discussed with a psychiatrist before stopping smoking. Starting smoking, or smoking more, can reduce clozapine levels. Stopping drinking can also reduce levels, as alcohol binges can increase the level.

Therefore, dose adjustment of clozapine is necessary if smoking is just started or stopped during treatment.

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