How should I transition, taper or discontinue an existing antipsychotic medication when starting clozapine?

When starting clozapine, if a patient is taking an antipsychotic medication and they are tolerating it, it should be continued until the clozapine begins to be effective. For oral antipsychotic medications, one can often start to taper an existing antipsychotic medication when the clozapine dosage is between 100 mg and 200 mg per day. In general, the dosage of the prior medication can be reduced as indicated by clozapine response. A typical approach can be a 25% dose reduction per week. According to Stahl’s cross-titration guidelines, certain antipsychotic medications can be stopped immediately once clozapine is at medium dose: aripiprazole, brexpiprazole, cariprazine, paliperidone. Other antipsychotic medications can be tapered while clozapine is slowly titrated up to avoid severe sedation: iloperidone, lurasidone, risperidone, ziprasidone, asenapine, olanzapine, quetiapine. Closely monitor for psychotic symptoms and antipsychotic side effects, and adjust the speed of taper as indicated. If the patient has been on a long-acting injectable antipsychotic medication, no further injections should be given after starting clozapine. If needed for symptom control, oral antipsychotic medication can be given during the transition to clozapine. If the patient is in a hospital setting, both the up-titration of clozapine and the down-titration of existing antipsychotic medications can occur more quickly. Ensure that the non-clozapine antipsychotic medication is titrated off completely over time, do not stop with antipsychotic polypharmacy. Later, after clozapine has been maximized, augmenting strategies can be tried.

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