What is the evidence for the association of mirtazapine and neutropenia/agranulocytosis? Should whi

Fråga: What is the evidence for the association of mirtazapine and neutropenia/agranulocytosis? Should white blood cell count (WBC) be followed during therapy? Are there any known risk factors for bone marrow suppression in treatment with mirtazapine?

Sammanfattning: Neutropenia and bone marrow suppression are known side effects of mirtazapine. The fact that several cases have occurred upon dose increase indicate that it may be a concentration dependent effect, though actual serum concentrations are lacking. Thus mirtazapine may not be the drug of choice for depression in patients on concomitant therapy with other drugs with myelosuppressive activity, or for patients with incipient bone marrow failure. Though awareness of myelosuppression as a possible side effect of mirtazapine is mandated. In our view, available evidence does not indicate routine monitoring of WBC in asymtomatic patients on mirtazapine.

Svar: Bone marrow depression and agranulocytosis are listed as a rare side effect in FASS (The Swedish catalogue of approved medical products). It is also recommended that medication be discontinued pending analysis of WBC in case of fever, sore throat, stomatitis or other possible signs of neutropenia. The basis for this recommendation is that three patients developed agranulocytosis (neutrophil count <0.5 million/mL) during pre-marketing clinical trials comprising 2796 patients. All three recovered upon discontinuation of mirtazapine (1). This makes for an incidence of 11/10000. The onset of neutropenia was between 9-61 days after initiation of therapy and was associated with increased dosage (2). The literature contains several reports of neutropenia (neutrophils <1.8 million/mL) and agranulocytosis in mirtazapine treated patients, generally with recovery following discontinuation. One review estimates the incidence of neutropenia with mirtazapine to 1.9%, which is compared with 1.1% for placebo, 1.2% for clomipramine and 0.4% for amitryptiline (3). The Swedish adeverse drug reaction register contains two reports of agranulocytosis, two reports of neutropenia, two reports of leucopenia and two reports of thrombocytopenia out of a total of 328 reports.

The information in the available case was not sufficient for a more rigorous analysis of possible risk factors for mirtazapine-related myelosuppression. Mirtazapine. Drugdex(R) System; Micromedex, Inc., Englewood, Colorado (Edition expires Ahmed A. Neutropenia associated with mirtazapine use: is a drop in the neutrophil count in asymptomatic older adults a cause for concern? J Am Geriatr Soc 2002;50(8):1461-3. Hutchison LC. Mirtazapine and bone marrow suppression: a case report. J Am Geriatr Soc 2001;49(8):1129-30.