A 35-year-old patient with schizophrenia is started on clozapine after failing two adequate trials of antipsychotics. Which of the following is the MOST life-threatening absolute contraindication to continuing clozapine therapy?
- A QTc prolongation to 490 ms
- B Fasting blood glucose of 180 mg/dL
- C Absolute neutrophil count of 900/mm³ ✓
- D Serum prolactin elevation
Correct answer: C. Absolute neutrophil count of 900/mm³
Explanation
Clozapine causes agranulocytosis in approximately 1% of patients; an absolute neutrophil count (ANC) below 1000/mm³ (severe neutropenia) requires immediate discontinuation. An ANC of 900/mm³ constitutes severe neutropenia (below the 1000 threshold for clozapine, with absolute discontinuation required below 500/mm³ for agranulocytosis). QTc prolongation is concerning but is a relative rather than absolute contraindication at 490 ms. Clozapine has minimal dopaminergic blockade and does not significantly elevate prolactin.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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