Is Remeron (mirtazapine) safe to use during pregnancy?

Mirtazapine (Remeron) Use in Pregnancy

Mirtazapine does not appear to increase the risk of major congenital malformations above the baseline rate of 1-3% and can be used during pregnancy when the benefits of treating maternal depression outweigh potential risks, though SSRIs like sertraline or paroxetine remain preferred first-line agents due to more extensive safety data. 1

Safety Profile During Pregnancy

Malformation Risk

• 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 1
• A prospective comparative study of 104 pregnancies found only 2 major malformations (2.6%), which does not exceed the baseline population risk 2
• Animal reproduction studies showed no teratogenic effects at doses up to 20 times the maximum recommended human dose 1

Pregnancy Complications

• Spontaneous abortion rates may be elevated (19% in mirtazapine-exposed pregnancies vs 11% in non-teratogen controls), though this difference was not statistically significant 2
• Preterm birth risk appears increased (10% vs 2% in controls, p=0.04), which is consistent with antidepressant use generally 2
• Post-implantation loss occurred in animal studies at high doses (20 times human exposure) 1

Clinical Decision-Making Algorithm

When to Use Mirtazapine

1. Patient already stable on mirtazapine pre-pregnancy: Continue if depression is well-controlled, as medication switches carry relapse risk 1
2. Treatment-resistant depression: Consider when SSRIs have failed, as untreated depression carries significant risks including poor prenatal care, preterm birth, and decreased breastfeeding initiation 3, 4
3. Severe hyperemesis gravidarum: Mirtazapine has demonstrated efficacy in case reports when standard antiemetics fail 5, 6

When to Choose Alternatives

• First-line treatment in pregnancy: SSRIs (particularly sertraline or paroxetine) have more extensive safety data and should be preferred for newly diagnosed depression 3, 7
• Mild to moderate depression: Consider whether non-pharmacologic interventions might suffice, though untreated depression itself poses risks 1

Critical Counseling Points

Risks of Untreated Depression

• Women who discontinue antidepressants during pregnancy are more likely to experience relapse than those who continue treatment, based on a prospective study of 201 pregnant women 1
• Depression during pregnancy is associated with premature birth and decreased breastfeeding initiation 3, 4

Neonatal Considerations

• Neonatal withdrawal symptoms can occur: One case report documented transient hyperarousal on days 2 and 4 postpartum after in utero mirtazapine exposure 5
• Monitor newborns for signs of poor neonatal adaptation, though this appears less common with mirtazapine than SSRIs 7

Breastfeeding Safety

• Mirtazapine is present in human milk at low levels with relative infant doses of 0.6-2.8% of the maternal weight-adjusted dose 1
• No adverse effects on breastfed infants have been reported in most cases of maternal mirtazapine use 1
• Sertraline and paroxetine remain the most commonly prescribed antidepressants during breastfeeding due to more extensive data 3

Common Pitfalls to Avoid

• Abruptly discontinuing antidepressants upon pregnancy recognition: This significantly increases relapse risk without eliminating first-trimester exposure 1
• Failing to document informed consent: Discuss both medication risks AND risks of untreated depression explicitly 1
• Not considering the limited data: While mirtazapine appears relatively safe, it should not be used as a first-line agent when alternatives with better-established safety profiles exist 7
• Ignoring the higher spontaneous abortion signal: Though not statistically significant, counsel patients about this potential association 2