Evaluating the Discontinuation of Clozapine Due to Serious Side Effects: A Retrospective Cohort Study

Clozapine remains underutilized due to its serious side effects, leading to negative prescriber attitudes. We aim to elaborate on serious side effects and discontinuation of clozapine in patients followed up in our center for 12 years.

We retrospectively reviewed the medical records of patients admitted to the tertiary inpatient psychiatry service between 2010 and 2022. The cohort included patients with psychotic disorders (PD) or bipolar affective disorders (BAD), who discontinued clozapine during their hospitalization due to serious side effects. Rechallenge attempts and clinical outcomes after discontinuation were recorded.

Among 2298 patients, 568 (178 clozapine users, prescribing rate: 31.3%) were diagnosed with PD, and 420 (21 clozapine users, prescribing rate: 5%) were diagnosed with BAD. Fourteen patients with PD and 3 patients with BAD had a serious side effect of clozapine, which resulted in discontinuation in 15 patients (7.53%). The most frequent serious side effects were myocarditis or suspected myocarditis (5.02%) and agranulocytosis (1.50%). There was no sudden death, cardiac arrest, or need for intensive care. Of serious side effects, 88.2% occurred within 6 months after clozapine initiation. The most switched antipsychotic was olanzapine (57.1%) after discontinuation. Among those whose clozapine was discontinued, 20% of the patients were rechallenged, of which 66.6% were successful.

Twelve years of observation shows that even life-threatening side effects of clozapine can be managed successfully. Our findings support that physicians should not miss patients' opportunities to benefit from clozapine due to their concern about serious side effects. Lastly, rechallenge is an option even if serious side effects occur in certain conditions.