Can Risperidone (risperidone) cause leukopenia?

Risperidone and Leukopenia

Yes, risperidone can cause leukopenia as explicitly stated in the FDA drug label, which lists leukopenia as a recognized adverse effect that requires monitoring and potential discontinuation of the medication. 1

Mechanism and Evidence

Risperidone-induced leukopenia is a class effect shared among antipsychotic medications, though it occurs less frequently than with clozapine. The FDA label specifically warns about:

• Leukopenia/neutropenia temporally related to antipsychotic agents, including risperidone
• Risk factors include pre-existing low white blood cell count and history of drug-induced leukopenia/neutropenia 1

Several case reports have documented this association:

• A case of risperidone-associated leukopenia in an adolescent that developed 10 days after starting therapy (4 mg/day), with positive rechallenge at 2 mg/day 2
• A young adult who developed leukopenia specifically directed toward neutrophils while on risperidone 4 mg/day, with WBC returning to normal within one week of discontinuation 3

Monitoring Recommendations

For patients on risperidone, the FDA recommends:

• Patients with history of clinically significant low WBC or drug-induced leukopenia/neutropenia should have complete blood count (CBC) monitored frequently during the first few months of therapy
• Discontinuation should be considered at the first sign of clinically significant decline in WBC in the absence of other causative factors
• Patients with clinically significant neutropenia should be carefully monitored for fever or other signs of infection 1

Management of Risperidone-Induced Leukopenia

When leukopenia occurs:

1. For severe neutropenia (absolute neutrophil count <1000/mm³):

   • Discontinue risperidone immediately
   • Monitor WBC until recovery 1

2. For less severe cases:

   • Consider dose reduction if clinically appropriate
   • Monitor CBC closely
   • If leukopenia persists despite dose reduction, discontinuation may be necessary

3. Alternative antipsychotic options:

   • Olanzapine may represent a safe therapeutic alternative, as demonstrated in case reports where patients who developed leukopenia on risperidone tolerated olanzapine without hematological abnormalities 2, 4

Risk Factors and Special Considerations

• Ethnic background may influence risk (reported in an African adolescent) 2
• Dose-dependency has been observed with some antipsychotics causing leukopenia 5
• Patients with pre-existing low WBC are at higher risk 1

Clinical Pearls

• Leukopenia may develop within days to weeks of starting risperidone
• The effect appears to be reversible upon discontinuation in most reported cases
• Unlike clozapine, there is no mandatory hematological monitoring program for risperidone, making vigilance particularly important
• Consider baseline CBC before initiating risperidone, especially in patients with risk factors
• Rechallenge may result in recurrence of leukopenia, as demonstrated in case reports 2

While risperidone-induced leukopenia is less common than with clozapine, clinicians should remain vigilant about this potentially serious adverse effect, especially in high-risk patients.