A 30-year-old man with treatment-resistant schizophrenia (failed two adequate antipsychotic trials) is started on clozapine. After 3 weeks he presents with a fever of 39.5°C, sore throat, and malaise. His white cell count is 1,200/mm³ with an absolute neutrophil count of 400/mm³. What is the most appropriate immediate action?

• A Reduce the dose of clozapine by half and recheck CBC in 1 week
• B Discontinue clozapine immediately and do not rechallenge ✓
• C Add lithium to boost white cell count and continue clozapine
• D Switch to olanzapine and continue current dose monitoring

Explanation

Clozapine-induced agranulocytosis (ANC < 500/mm³) is a life-threatening complication occurring in approximately 1% of patients and is the primary reason for mandatory hematological monitoring. When agranulocytosis is detected, clozapine must be stopped immediately and permanently — rechallenge is contraindicated due to very high risk of recurrence with potentially fatal outcome. Supportive care with G-CSF and infectious precautions are required. Lithium can increase WBC as prophylaxis but cannot reverse established agranulocytosis.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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