Dear Editor:
Several earlier case reports have suggested that olanzapine (Zyprexa®) may present a safe alternative for patients who develop hematologic side effects from other antipsychotics, especially clozapine.1,2 However, a number of more recent cases imply a possible association between olanzapine use and hematopoetic suppression. We now report a case of an elderly woman who developed severe neutropenia and thrombocytopenia shortly after starting olanzapine.
Case report. Ms. A was an 83-year-old Italian woman with a history of major depression and dementia. She had been clinically stable on doxepin (Adapin®)100mg nightly for many years. Eighteen months after her husband's death, she was admitted to the geriatric psychiatry unit for increasing agitation, depression, anxiety, and somatic preoccupation. We restarted her current medications, which included lansoprazole (Prevacid®), indapamide (Lozal®), mirtazapine ( Zispin®), and clonazepam (Klonopin®). On Hospital Day 2, olanzapine 2.5mg orally at bedtime was initiated for her somatic delusions, related agitation, and insomnia. Olanzapine was the only new medication given. On the morning after her first dose of olanzapine, she developed a fever of 39.0 degrees celsius but was otherwise asymptomatic. On Hospital Day 3, her leukocyte count decreased to 1.9x109 cells/liter (c/L) with an ANC of 0.91x109c/l and her platelets decreased to 145x109c/L. On admission, her complete blood count was entirely within normal limits.
A fever work-up was initiated at this time. On Hospital Day 4, her ANC decreased further to 0.52x109c/L. Chest radiographs, urinalyses and cultures, and blood cultures were obtained and they were all negative for infection.
Ms. A. was then transferred to the internal medicine service for further management and was placed on neutropenia precautions. All of her psychotropic medications were discontinued secondary to a suspicion of drug reaction. Intravenous hydration and IV cefipime for infection prophylaxis were begun. On Hospital Day 6, her fever remitted but her labs revealed a leukocyte count of 1.6x109c/L with an ANC of 0.54x109c/L, and platelet count of 107x109c/L.
At this point, she was administered one dose of granulocyte-cell stimulating factor (G-CSF). The following day, her leukocyte count increased to 6.0x109c/L and her ANC improved to 4.76x109c/L. She was transferred back to the psychiatry unit.
Upon a review of the literature, we found at least 11 reports linking olanzapine use with hematologic side effects. Our case is unique in many ways. In some of the reported cases,3 the adverse effect was dose dependent, while in Ms. A's case, the effect started shortly after the first dose. Although our patient had been on mirtazepine and clonazepam at the time of admission, she had been taking these agents for weeks to months, without adverse effects in the past.
Cordes, et al.,4 and Steinwachs, et al.,5 reported that their patients' cell counts increased after discontinuing olanzapine, but Ms. A required treatment with G-CSF in order to stimulate neutrophil recovery. The presence of sudden onset of fever preceding leukopenia was also a unique feature of our case (in contrast with the report of Steinwachs, et al.,5 where no signs of infection were noted).
The onset of olanzapine-related leukopenia has been reported to vary from one day to 18 months.4 This case and the others cited argue for the consideration of hematologic monitoring guidelines in all patients on olanzapine, regardless of dosage or length of treatment course. Whether or not this is a class-wide effect of the atypical antipsychotics remains unclear. We suggest that patients on olanzapine and the patients' families be counseled about the signs and symptoms of bacterial infection, as is part of the informed consent process with the use of clozapine. Additionally, it may be prudent to avoid the use of olanzapine with other medications that have known potential for hematologic side effects (e.g., clonazepam and mirtazepine).
With regards,
Aditi Mehta, MD
PGY3 Resident, University
Hospitals of Cleveland
John Sanitato, MD
Assistant Professor of
Psychiatry, Case Western
School of Medicine, Medical
Director, Inpatient
Geropsychiatry, University
Hospital of Cleveland
Contributor Information
Aditi Mehta, PGY3 Resident, University Hospitals of Cleveland.
John Sanitato, Assistant Professor of Psychiatry, Case Western School of Medicine, Medical Director, Inpatient Geropsychiatry, University Hospital of Cleveland.
References
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