Mirtazapine (Remeron) Use in Pregnancy
Mirtazapine does not appear to increase the baseline risk of major birth defects above 1-3% and can be used during pregnancy when clinically indicated, though it is associated with neonatal adaptation syndrome in approximately 25% of third-trimester exposures.
Safety Profile for Major Malformations
Prolonged experience with mirtazapine in pregnant women has not reliably identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, according to the FDA drug label based on published observational studies and postmarketing reports 1.
A prospective comparative study of 104 pregnancies found 2 major malformations among 77 live births (2.6%), which does not exceed the baseline population risk of 1-3% 2.
Multiple systematic reviews confirm no increased risk of major congenital malformations associated with mirtazapine exposure during pregnancy 3, 4.
Spontaneous Abortion Risk
The rate of spontaneous abortion may be elevated in women taking mirtazapine (19-20%) compared to non-teratogen controls (11%), though this difference did not reach statistical significance and is likely attributable to underlying depression rather than the medication itself 2, 3.
Depression itself increases the risk of adverse pregnancy outcomes, and women who discontinue antidepressants during pregnancy are more likely to experience relapse of major depression 1.
Neonatal Adaptation Syndrome (Third Trimester Exposure)
Approximately 25.9% of infants exposed to mirtazapine in the third trimester develop poor neonatal adaptation syndrome (PNAS), which is similar to rates seen with other antidepressants 5.
PNAS typically presents as self-limiting symptoms including respiratory distress, jitteriness, irritability, and feeding difficulties in the first days of life 4.
Breastfeeding significantly reduces the incidence of PNAS (18.6% in breastfed infants versus 54.5% in non-breastfed infants, p=0.024), suggesting gradual weaning from the medication through breast milk may be protective 5.
Preterm Birth
- One study found a statistically significant increase in preterm births (<37 weeks) in the mirtazapine group (10%) compared to non-teratogen controls (2%, p=0.04), though this may reflect underlying maternal depression rather than medication effect 2.
Clinical Decision-Making Algorithm
When depression requires treatment during pregnancy:
Assess severity of maternal depression - untreated depression carries its own risks including poor prenatal care, substance use, preterm birth, low birth weight, and in severe cases, suicide or infanticide 1, 6.
First trimester exposure (organogenesis period): Mirtazapine appears safe with no increased malformation risk; 95% of exposures in studies occurred during this critical period without adverse outcomes 2, 3.
Third trimester considerations: Anticipate possible PNAS in approximately 25% of exposed neonates; plan for neonatal monitoring in the first 48-72 hours after delivery 5, 4.
Delivery planning: Consider initiating or continuing breastfeeding to reduce PNAS severity through gradual medication weaning 5.
Lactation Safety
Mirtazapine is present in breast milk at low levels with relative infant doses ranging from 0.6-2.8% of the maternal weight-adjusted dose 1.
No adverse effects on breastfed infants have been reported in most cases, though data remain limited 1, 3.
The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for mirtazapine 1.
Important Caveats
Animal studies showed increased post-implantation loss and pup deaths at doses 20 times the maximum recommended human dose, though no teratogenic effects were observed 1.
The overall quality of evidence is low, consisting primarily of observational studies, case series, and case reports rather than randomized controlled trials 4.
There is a pregnancy exposure registry available for monitoring outcomes; healthcare providers should register patients by calling 1-844-405-6185 1.
Results on spontaneous abortion remain conflicting across studies, making it difficult to separate medication effects from disease effects 3, 4.