(124) A case of olanzapine-induced neutropenia

Abstract: Background:

Clozapine is an antipsychotic highly effective in treating symptoms of schizophrenia, but limited in its use to treatment-resistant schizophrenia due to potential agranulocytosis. Olanzapine is structurally similar to clozapine but much less associated with agranulocytosis. We present a case that adds to a limited body of evidence of olanzapine-induced neutropenia and explore its implications.



Case:

A 23-year-old African American male with no known psychiatric history presented with delusions, hallucinations, and disorganized speech, in the context of self-reported substance abuse, notably methamphetamine 3-4 days prior to admission. He was seen by our psychiatry service and started on Olanzapine 5mg daily. Two days after olanzapine was started, patient’s blood work showed a white blood cell count (WBC) of 2.4x10⁹/L and absolute neutrophil count (ANC) of 0.6x10⁹/L, significant for neutropenia. Patient had normal vital signs was not showing any signs of active infection. Olanzapine was switched to paliperidone 6mg daily. One week following the switch, WBC improved to 3.1x10⁹/L and ANC to 1.2x10⁹/L.



Discussion:

Clozapine-induced agranulocytosis has been readily recognized and relatively well-studied, leading to a more judicious use of an otherwise effective antipsychotic. Olanzapine, despite its structural similarity to clozapine, has been reported much less frequently to induce agranulocytosis. A recent in vitro study showed that inflammasome-dependent signaling, a hypothesized mechanism of drug-induced agranulocytosis, was seen in human cells with clozapine but not with olanzapine (Sernoskie et al., 2022). We report a case of olanzapine-induced neutropenia that improved quickly following discontinuation of the agent. This adds to the limited number of existing reports of olanzapine-induced neutropenia as well as thrombocytopenia, which, like our case, improved quickly following discontinuation of olanzapine (Malhotra et al., 2015, Malik et al., 2018). This may suggest olanzapine may be a rare cause of drug-induced neutropenia, albeit in a mechanism different from that of clozapine.



Conclusion:

Drug-induced neutropenia is a potentially dangerous but reversible side effect of some psychotropics. Clinicians should be aware that in patients taking olanzapine, unexplained neutropenia should warrant concern for olanzapine-induced causes. In such cases, early discontinuation of olanzapine should be considered. More study is needed to understand the mechanism of olanzapine-induced hematologic effects.



References:

Sernoskie, S. C., Lobach, A. R., Kato, R., Jee, A., Weston, J. K., & Uetrecht, J. (2022). Clozapine Induces an Acute Proinflammatory Response That Is Attenuated by Inhibition of Inflammasome Signaling: Implications for Idiosyncratic Drug-Induced Agranulocytosis. Toxicological sciences, 186(1), 70–82. https://doi.org/10.1093/toxsci/kfab154

Malhotra, K., Vu, P., Wang, D. H., Lai, H., & Faziola, L. R. (2015). Olanzapine-Induced Neutropenia. Mental illness, 7(1), 5871. https://doi.org/10.4081/mi.2015.5871

Malik, Y. K., Sahoo, S., & Avasthi, A. (2018). Olanzapine-induced leucopaenia and thrombocytopaenia in an elderly patient: a case report and review of the evidence. General psychiatry, 31(2), e000013. https://doi.org/10.1136/gpsych-2018-000013