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Home , Neutropenia, Thrombocytopenia

Letter to the Editor 10.5505/tjh.2012.72325

Mirtazapine-Induced and Mirtazapin İlişkili Trombositopeni ve Nötropeni

Selami K. Toprak 1, Elçin Erdogan1, Özlem Kurt Azap2 1Baskent University, School of , Department of , Ankara, Turkey 2Baskent University, School of Medicine, Department of Clinical Microbiology and Infectious Disease, Ankara, Turkey

To the Editor, /. Laboratory findings, including immu- noglobulin, , , and immunofixation lev- Neutropenia is a rare and commonly reversible side els were within normal limits. Other tests performed to effect of antidepressant treatment [1]. is a nor- determine a possible infectious etiology were negative. adrenergic and specific serotonergic antidepressant that is Peripheral smear showed thrombocytopenia and approved for use in the treatment of major depression in leucopenia/neutropenia. aspiration biopsy many countries [2]. A major hematological side effect of was performed with the permission of the patient. Bone mirtazapine is . Herein we report a patient marrow examination showed hypocellularity with dif- with depression that developed severe neutropenia-associ- ferentiation of the myeloid lineage and mildly decreased ated thrombocytopenia during treatment with mirtazapine; . There was no evidence of malign infiltra- the patient was safely treated by switching to another drug. tion. A 72-year-old Caucasian male presented to the emer- The absence of any other etiological mechanism, the gency room with and epistaxis. On presentation his patient’s unremarkable laboratory work-up, and the close white , , and counts were 3.27 temporal association between administration of mirtazap- x 109 L–1, 0.17 x 109 L–1, and 28.10 x 109 L–1, respectively. ine and the decrease in his neutrophil and thrombocyte The patient was hospitalized with neutropenic fever and counts strongly suggested that the bicytopenia was related thrombocytopenia. Complete blood cell count from 20 d to mirtazapine. As such, mirtazapine treatment was with- earlier was essentially normal. drawn due to the suspicion of its link to his symptoms. The patient had a medical history of diabetes mel- One week after discontinuation of mirtazapine escitalo- litus type 2 (regulated by diet), , and cervi- pram and alprazolam were initiated following psychiatric cal spondylosis. His medication use included isosorbide- consultation due to his labile and bad affect. The patient’s 5-monohydrate and metoprolol succinate for 5 years. He platelet count increased to 89.00 x 109 L–1, and then to had no obvious past history of hematological disorders. 100.00 x 109 L–1 on the 7th and 14th d of mirtazapine He did have a 1-month history of depressive symptoms, withdrawal, respectively. The absolute neutrophil and including low mood and alysosis. Because of his symptom platelet counts increased to 2.5 x 109 L–1 and 219.00 x 109 profile 10 d earlier he was started on mirtazapine 15 mg at L–1, respectively, 21 d after discontinuation of mirtazapine. night by the department. To the best of our knowledge like other tetracyclic On physical examination he did not have organomeg- antidepressants, mirtazapine is associated with severe aly or lymphadenopathy; nor did he have ecchymoses or neutropenia, but the mechanism of mirtazapine-associ-

Address for Correspondence: Selami K. Toprak, M.D., Başkent Üniversitesi, Tıp Fakültesi, Hematoloji Bilim Dalı, Ankara, Turkey Phone: +90 312 212 29 12 E-mail: [email protected] Received/Geliş tarihi : November 23, 2011 Accepted/Kabul tarihi : January 2, 2012 297 Toprak SK, et al: Mirtazapine-Induced Thrombocytopenia and Neutropenia Turk J Hematol 2012; 29: 297-298 ated leucopenia (neutropenia) is not well understood [3]. other than mirtazapine in the presented patient, such as and immune-mediated mechanisms have different medications and disease, supported the hypoth- been suggested, including complement-mediated toxic- esis of mirtazapine-induced thrombocytopenia, suggesting ity and drug-induced against committed stem an immune mechanism. cells, proliferating precursors, and mature blood cells [4]. While collaboration with psychiatrists is important, Mirtazapine-induced thrombocytopenia is a rare hema- clinicians (hematologist) should keep in mind that a pri- tological disorder; this serotonin reuptake inhibitor is mary care (psychiatrist) can fail to warn patients not currently accepted as a definitive or probable cause about thrombocytopenia/neutropenia or monitor throm- of thrombocytopenia [5]. In a single case report that was bocyte and total-differential counts in published in 2003 Liu and Sahud researched the immu- patients receiving mirtazapine at minimum several times nological nature of mirtazapine-induced thrombocytope- during the first year of the . As such, in patients nia [6]. The researchers identified mirtazapine-induced treated with mirtazapine —especially older adults —clini- GPIIb/IIIa reactive antibodies in the patient’s serum. cians should be aware that the drug can cause neutrope- Tests to demonstrate drug-dependent antibodies were nia/thrombocytopenia. not performed in the presented patient and therefore the Written informed consent was obtained from the drug causality assessment was based on the relationship patient. between drug intake and the onset of thrombocytopenia, as previously reported. Furthermore, the rapid increase in Conflicts of Interest Statement the patient’s platelet count after discontinuation of mir- None of the authors of this letter have any conflicts tazapine therapy further indicated that neutropenia was of interest, including specific financial interests, relation- due to mirtazapine treatment. Common causes of throm- ships, and/or affiliations, relevant to the subject matter or bocytopenia and leucopenia (neutropenia), including materials included. , were investigated using bone marrow aspira- tion biopsy and other laboratory investigations. Malig- nancy was excluded based on the clinical and histological References pattern of thrombocytopenia/neutropenia. 1. Ozcanli T, Unsalver B, Ozdemir S, Ozmen M. Sertraline and To the best of our knowledge in vitro data show that mirtazapine-induced severe neutropenia. Am J 2005; 162 (7): 1386 platelet aggregation decreases when exposed to isosorbide, but thrombocytopenia and leucopenia (neutropenia) were 2. Croom KF, Perry CM, Plosker GL. Mirtazapine: A review of not documented in clinical practice. Hematological side its use in major depression and other psychiatric disorders. CNS Drugs 2009; 23 (5): 427-452 effects, including agranulocytosis, non- and thrombocytopenic purpura have been asso- 3. Davis J, Barkin RL. Clinical pharmacology of mirtazapine: ciated with beta-blocking agents, in general. These side Revisited. Am Fam Physician 1999; 60 (4): 1101 effects occur short-medium term after initiation of meto- 4. Dholakia R, Schleifer SJ, Ahmad YJ, Narang IS. Delayed- prolol therapy. In the presented case, metoprolol was used onset mirtazapine-related leucopenia and rechallenge. J for 5 years and it was not stopped during the patient’s Clin Psychopharmacol 2010; 30 (6): 758 hospitalization. These findings showed us that metoprolol 5. Reese JA, Li X, Hauben M, Aster RH, Bougie DW, Curtis BR, and isosorbide were not the cause of thrombocytopenia/ George JN, Vesely SK. Identifying drugs that cause neutropenia. thrombocytopenia: An analysis using 3 distinct methods. Blood 2010; 116 (12): 2127-2133 Neutropenia with cross intolerance between 2 tricyclics 6. Liu X, Sahud MA. Glycoprotein IIb/IIIa complex is the has been described, and there is evidence that patients can target in mirtazapine-induced immune thrombocytopenia. be successfully treated with another class of drug after Blood Cell Mol Dis 2003; 30 (3): 241-245 such an incidence [1]. The absence of etiologic factors

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