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October 31, 2025
Clozapine is a highly effective atypical antipsychotic, but it’s not without drawbacks (Table 1). Historically, patients, prescribers and pharmacies were required to enroll in the Clozapine REMS program due to the drug’s potential to cause agranulocytosis. The REMS program was officially eliminated on June 13th, 2025, though the FDA still recommends that prescribers monitor absolute neutrophil counts (ANC) according to clozapine’s prescribing information.[1]
Table 1: Advantages and disadvantages of clozapine
| Advantages | Disadvantages |
|---|---|
| May provide benefit when other antipsychotics have failed (i.e., treatment resistant cases) | Adverse effects, including agranulocytosis (rare), anticholinergic effects, orthostasis, dizziness, hypersalivation, hyperglycemia |
| Lowest risk of extrapyramidal symptoms among antipsychotics, so considered safe to use in patients with Parkinson disease psychosis (PDP) or dementia with Lewy bodies (DLB) | Lack of clinician familiarity |
| More effective than quetiapine and significantly more cost-effective than pimavanserin when treating PDP |
Notably, before the REMS program was eliminated, there was a “carve out” for hospice patients that reduced ANC monitoring requirements to at baseline, then every 6 months, which is still a reasonable recommendation.[1] Prior to starting clozapine, ANC should be ≥ 1,500/μL for patients without benign ethnic neutropenia (BEN; a condition observed in certain ethnic groups whose average ANC values are lower than standard laboratory ranges) and ≥ 1,000/μL for patients with BEN.
Clozapine is prescribed for a variety of indications. Outside of the hospice setting, it’s most commonly prescribed for treatment-resistant schizophrenia, but is also reported to be effective for treatment-resistant agitation in dementia and PDP.[2-4] Initial doses for treating PDP or dementia-related agitation are lower than those used for schizophrenia or bipolar disorder (Table 2). In most cases, clozapine won’t be a first-line antipsychotic, so switching from another antipsychotic is involved and it usually requires cross-tapering (Table 3). If clozapine discontinuation is indicated (e.g., due to lack of efficacy or as a periodic attempt to discontinue), then gradual tapering is recommended.
Table 2: Clozapine dosing for select indications
| Indication | Initial Dosing*∆ | Titration*∆ | Final Dose |
|---|---|---|---|
| Agitation, aggression, psychosis associated with dementia | 6.25 to 12.5mg QHS | Increase by 12.5mg every 3 to 5 days based on response and tolerability | 60mg/day is most common dose studied |
| Parkinson disease psychosis | 6.25mg QHS | Increase by 6.25 to 12.5mg every 3 to 7 days based on response and tolerability | Maximum dose is 50mg/day |
* Often requires halving or quartering tablets, as lowest available strengths are 25mg tablet and 12.5mg disintegrating tablet and oral suspension is prohibitively expensive. If disintegrating tablets are split, discard the half that is not immediately taken.[5-6]
∆ Once nightly dosing is preferred to minimize daytime sedation and to simplify the regimen, though doses can be divided BID.
Table 3: Switching from other oral antipsychotics to clozapine[7-8]
| Direct switch permissible | Cross taper recommended | |
|---|---|---|
| Aripiprazole | Chlorpromazine | Quetiapine |
| Brexpiprazole | Haloperidol | Risperidone |
| Pimavanserin | Olanzapine |
For more information, including information on switching from antipsychotics not listed, visit: Australian Prescriber Antipsychotic Switching Tool
Clozapine isn’t a first-line player in hospice, but it could come to the rescue when other options fail. And with the elimination of Clozapine REMS, the pathway to using it just got simpler.
Written by: OnePoint Patient Care Clinical Team
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