To the Editor: Selective serotonin reuptake inhibitors are the most studied antidepressants in breastfeeding mothers (1). However, to date, there is only one case report regarding mirtazapine and breastfeeding (2). This study found no clinically significant levels of mirtazapine in the milk, and serum concentrations in the infant were below therapeutic concentration. Breastmilk levels, assessed 15 and 22 hours postdose, were higher in hindmilk compared with foremilk. A fully breastfed infant would ingest 0.21%–1.02% of the weight-adjusted maternal dose on a daily basis, suggesting minimal exposure of mirtazapine to the infant. However, infants may be exposed to higher levels, since serum mirtazapine concentrations peak at approximately 4 hours postdose. We report the case of evaluated mirtazapine levels in breastmilk at the time of expected maximum postdose plasma levels under the assumption that breastmilk levels peak at similar timepoints.
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.
Mirtazapine is indeed excreted in breastmilk with slightly higher hindmilk than foremilk levels. Given the minimal infant exposure to the drug and lack of adverse events in our case report, substitution of feeding did not seem necessary at that time. However, because of the scarcity of reports on mirtazapine exposure to nursed infants, interindividual differences are not known. Further research in a larger cohort and a longitudinal design assessing changes in infants’ behavior as well as behavioral problems in childhood are needed to confirm the compatibility of mirtazapine treatment during breastfeeding.
1.Weissman AM, Levy BT, Hartz AJ, Bentler S, Donohue M, Ellingrod VL, Wisner KL: Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry 2004; 161:1066–1078
2.Aichhorn W, Withworth AB, Weiss U, Stuppaeck C: Mirtazapine and breastfeeding (letter). Am J Psychiatry 2004; 161: 2325
3.Zernig G, deWit H, Telser S, Nienhusmeier M, Wakonigg G, Sturm K, Berger I, Kemmler G, Saria A: Subjective effects of slow-release bupropion vs. caffeine as determined in a quasi-naturalistic setting. Pharmacology 2004; 70:206–215
The authors report no competing interests.