Mirtazapine-Induced Thrombocytopenia and Neutropenia

Abstract

Neutropenia is a rare and commonly reversible side effect of antidepressant treatment [1]. Mirtazapine is a noradrenergic and specific serotonergic antidepressant that is approved for use in the treatment of major depression in many countries [2]. A major hematological side effect of mirtazapine is agranulocytosis. Herein we report a patient with depression that developed severe neutropenia-associated thrombocytopenia during treatment with mirtazapine; the patient was safely treated by switching to another drug.A 72-year-old Caucasian male presented to the emergency room with fever and epistaxis. On presentation his white blood cell, neutrophil, and platelet counts were 3.27 x 10 9 L -1 , 0.17 x 10 9 L -1 , and 28.10 x 10 9 L -1 , respectively. The patient was hospitalized with neutropenic fever and thrombocytopenia. Complete blood cell count from 20 d earlier was essentially normal.The patient had a medical history of diabetes mellitus type 2 (regulated by diet), hypertension, and cervical spondylosis. His medication use included isosorbide-5-monohydrate and metoprolol succinate for 5 years. He had no obvious past history of hematological disorders. He did have a 1-month history of depressive symptoms, including low mood and alysosis. Because of his symptom profile 10 d earlier he was started on mirtazapine 15 mg at night by the neurology department.On physical examination he did not have organomegaly or lymphadenopathy; nor did he have ecchymoses or petechia/purpura. Laboratory findings, including immunoglobulin, vitamin B12, folate, and immunofixation levels were within normal limits. Other tests performed to determine a possible infectious etiology were negative. Peripheral blood smear showed thrombocytopenia and leucopenia/neutropenia. Bone marrow aspiration biopsy was performed with the permission of the patient. Bone marrow examination showed hypocellularity with differentiation of the myeloid lineage and mildly decreased megakaryocytes. There was no evidence of malign infiltration.

Mirtazapine induced neutropenia: A case report and systematic review

“…There was no specific age predisposition with age ranging from 29 to 72. Three cases (12,14,16 ) presented with febrile neutropenia, while other cases were asymptomatic. There was concomitant new onset thrombocytopenia in two cases (12,15) .…”

“…Three cases (12,14,16 ) presented with febrile neutropenia, while other cases were asymptomatic. There was concomitant new onset thrombocytopenia in two cases (12,15) . Before attributing neutropenia to medication, other potential causes of neutropenia should be excluded, Case 3.…”

“…Testing for anti-drug antibodies may be unnecessary, as the anti-drug antibodies may either be the cause or result of immune mediated injury (25) . The onset of mirtazapine induced neutropenia ranged from 1 day to 8 months after initiation of the drug with majority of cases occurring within 1 month after initiation of mirtazapine (2,12,13,16,18) . In two cases, there was a rapid drop of ANC within few days of exposure to mirtazapine.…”

“…Huber (20) first including but not limited to viral infection, vitamin B12, folate, autoimmune workup and ideally a bone marrow biopsy. Such investigations were performed only in 3 cases (12,14,15) which included bone marrow biopsy in 2 cases (12,14) . Other cases were presumed to be mirtazapine induced neutropenia given the temporal relationship and improvement of counts after discontinuation of the drug (13,16,17).…”

“…Alternate antidepressants from other classes have been reported to be safely initiated in patients with mirtazapine induced neutropenia. There are reports of patients who subsequently tolerated sertraline, escitalopram and venlafaxine well (12,13,16) . However, there was one episode of cross reactivity between tricyclic and tetracyclic antidepressants (27) .…”