Granulocytopenia With Clozapine and Quetiapine

Ms. A, a 53-year-old woman with a history of schizophrenia that was refractory to treatment for more than 20 years, had been treated with several typical antipsychotics. Subsequent trials of both risperidone and olanzapine for at least 8 weeks, respectively, had little effect on her mental status. Trials of mood stabilizers targeted unpredictable aggressiveness and were discontinued after demonstrating no further improvement.

Ms. A had a baseline neutrophil level of 1,800/mm³ before she began clozapine treatment. Clozapine was titrated up to 400 mg/day and maintained at that dose for a year, which effected a partial treatment response. Ms. A’s neutrophil levels fluctuated between 1,800/mm³ and 2,200/mm³ during this period. Her partial response to clozapine over 12 months and persistently low neutrophil count suggested a trial with another atypical neuroleptic, and quetiapine was initiated with the intention of gradually tapering the clozapine dose.

During Ms. A’s first week of taking quetiapine, 200 mg b.i.d., her neutrophil count dropped to 1,400/mm3, and clozapine was discontinued. She continued taking quetiapine, 250 mg b.i.d., for 4 more weeks, during which time significant clinical deterioration occurred. Her neutrophil count remained less than 1,500/mm3 for the entire period she took quetiapine and did not return to normal (>2,000/mm3) until 3 days after she discontinued quetiapine.