Can Clozapine (Clozaril) increase White Blood Cell (WBC) count?

From the Guidelines

No, clozapine typically causes white blood cell (WBC) counts to decrease, not increase. Clozapine is an antipsychotic medication that carries a significant risk of agranulocytosis, a dangerous condition where the body produces very few neutrophils (a type of white blood cell) [ 1 ]. This decrease in WBCs occurs in approximately 1% of patients taking clozapine, as noted in the practice parameter for the assessment and treatment of children and adolescents with schizophrenia [ 1 ]. Due to this risk, patients on clozapine require regular blood monitoring, with guidelines recommending weekly blood cell counts during the first 6 months of treatment, then every 2 weeks thereafter [ 1 ].

Key Points to Consider

• The risk of agranulocytosis associated with clozapine use necessitates careful monitoring of WBC counts [ 1 ].
• If a patient on clozapine shows a significant decrease in WBC count, the medication must be stopped immediately, and the patient monitored for infection [ 1 ].
• An increased WBC count in a patient taking clozapine would not be attributed to the medication itself and could indicate an underlying infection, inflammation, or other medical condition that should be evaluated.
• The mechanism behind clozapine's effect on white blood cells involves the drug or its metabolites causing direct toxicity to developing neutrophils in the bone marrow or triggering an immune response against these cells.

Monitoring and Management

• Weekly blood cell counts are crucial during the initial 6 months of clozapine treatment [ 1 ].
• The American Academy of Child and Adolescent Psychiatry guidelines provide specific recommendations for managing decreased WBC counts in patients on clozapine, including immediate cessation of the medication if the WBC drops below 2,000/mm3 or the absolute neutrophil count (ANC) drops below 1,000/mm3 [ 1 ].

From the FDA Drug Label

The fever can be associated with an increase or decrease in WBC count The FDA drug label mentions that clozapine can cause a fever that may be associated with an increase or decrease in WBC count.

• This suggests that clozapine may increase the WBC count in some cases, although the exact mechanism and frequency of this effect are not specified.
• It is essential to closely monitor patients taking clozapine for any changes in their WBC count, especially during the first few weeks of treatment.
• If a patient experiences a fever while taking clozapine, it is crucial to carefully evaluate them to rule out severe neutropenia or infection 2.

From the Research

Effect of Clozapine on White Blood Cell Count

• The study published in 2011 3 found that changing the timing of complete blood count (CBC) sampling for clozapine patients from early morning to after a minimum two-hour period of wakefulness/movement may have potential to improve WBC and ANC values, with a marginal increase in WBC values (mean increase=667/mm3, p=.07).
• However, other studies have reported that clozapine is associated with a risk of agranulocytosis, a potentially life-threatening decrease in white blood cell count, with an incidence of 0.9% to 2% in patients treated with clozapine 4, 5, 6.
• A study published in 1992 4 noted that granulocytopenia can be expected in approximately 3% of patients during clozapine treatment, and regular white blood cell count monitoring is necessary to minimize the risk of serious sequelae.
• Another study published in 1993 5 found that the cumulative incidence of agranulocytosis was 0.80% at 1 year and 0.91% at 1 1/2 years, with the risk increasing with age and being higher among women.
• A case report published in 2002 7 described a patient who suddenly developed agranulocytosis after 89 months of nearly continuous clozapine therapy, highlighting the need for ongoing monitoring of white blood cell counts even after long-term treatment.

Monitoring of White Blood Cell Count

• Regular monitoring of white blood cell counts is crucial to minimize the risk of agranulocytosis in patients treated with clozapine 4, 5, 6.
• The Australian Clozaril Patient Monitoring System (CPMS) central database review published in 1998 6 found that monitoring white blood cell counts ensures minimal risk to patients who develop agranulocytosis.
• The study published in 2011 3 suggested that changing the timing of CBC sampling may help improve WBC and ANC values, but this finding needs to be validated in larger and more ethnically diverse samples.