Mirtazapine and Breastfeeding: Maternal and Infant Plasma Levels

A 35-year-old, 60 kg, primiparous, breastfeeding woman who was prescribed mirtazapine (22.5 mg/day) approached our outpatient service for concerns about her 6-week-old child’s possible exposure to mirtazapine through her breastmilk. After description of the study procedure to the patient, written informed consent was obtained for herself and her child. We examined breastmilk levels following 14 days of mirtazapine therapy to ensure that steady state was reached. At the time of assessment, the mother was breastfeeding exclusively. Breastmilk was collected at 4 and 10 hours postdose, foremilk and hindmilk were collected separately. Because of nighttime medication intake, maternal and infant plasma could not be obtained until 12.5 hours postdose. Mirtazapine levels (mass transition, 266 >165) were determined by tandem mass spectrometry, as described previously (2), with an interday imprecision of 12%. Mass transition characterizes the mirtazapine molecule. In tandem mass spectrometry, the mother molecule is broken into fragments, and 165-dalton fragment is taken to characterize and quantify mirtazapine. Although considerably higher levels were found in the milk 4 hours postdose (130 ng/ml foremilk, 145 ng/ml hindmilk) compared with 10 hours postdose (61ng/ml foremilk, 90ng/ml hindmilk), the weight-adjusted maternal dose was still relatively low, ranging from 3.9%–4.4% at 4 hours to 1.8%–2.7% at 10 hours. Infant plasma levels were not detectable at 12.5 hours postdose. Weekly follow-ups showed no abnormalities of the infant, especially regarding sedation or weight gain. The infant’s weight at 6 months was 6.3 kg, i.e. consistently below the 25 percentile even before mirtazapine therapy.