Is Remeron (Mirtazapine) Secure to Use During Pregnancy? Recent Data 

Mirtazapine (Remeron) is an atypical antidepressant FDA-approved for the treatment of major depressive disorder but commonly prescribed off-label for generalized anxiety disorder, panic disorder, post-traumatic stress disorder and other mental health and medical indications. Along with its antidepressant and anxiolytic effects, mirtazapine’s sedating and antiemetic properties make this medication an appealing selection for patients who struggle with comorbid insomnia, nausea, and appetite suppression. As these are symptoms which commonly occur while pregnant, this medication could potentially play a very important role inside perinatal psychiatry. Nonetheless, reproductive safety data on the medication has been limited.

Mirtazapine use in pregnancy has previously been evaluated in a single systematic review of 390 exposed pregnancies and two register-based Scandinavian studies. While the systematic review was more reassuring, one register-based study found an associated risk of miscarriage (Kjaersgaard et al, 2013) and the opposite an

associated risk of elective termination of pregnancy for fetal anomalies in mirtazapine-exposed pregnancies (Kieler et al, 2015). Questions surrounding confounding by indication remain; in other words, how does the underlying mental illness within the mother influence risk for these adversarial outcomes?

Largest Study To Date Examines Reproductive Safety of Mirtazapine

But adding to this existing literature, in 2022, a register-based Danish nationwide cohort study from Ostenfeld and colleagues, now serves as the most important study thus far on mirtazapine exposure inside pregnancy.

Using Danish national register data, 1,945 mirtazapine exposed pregnancies were compared with mirtazapine unexposed pregnancies. The mirtazapine exposure group consisted of those women who filled not less than one prescription of mirtazapine while pregnant. Mirtazapine exposure groups were subdivided based on collected medication dose, into higher and lower dosage groups, on condition that the medication assumes different properties depending on its dose.

Propensity rating matching was performed to manage for potentially confounding variables such as confounding by indication.

Study Results

Whatever the collected dose, there was no association found between mirtazapine exposure inside pregnancy and the next outcomes:

1) major congenital malformations

2) spontaneous abortion (pregnancy loss between 6-22 weeks’ gestation)

3) stillbirth (pregnancy loss after 22 weeks’ gestation)

4) neonatal death (lack of an infant 0-27 days after birth)

Clinical Implications

This study provides reassuring data on the usage of mirtazapine while pregnant, demonstrating no association between mirtazapine exposure and 4 adversarial outcomes: major malformations, miscarriage, stillbirth, and neonatal death. As is the case with most studies exploring the reproductive safety of medicines, one limitation of the present study is that it’s unknown if the ladies studied were actually taking the medication and/or taking the medication as prescribed. Nonetheless, this study, taken along with previous studies, indicates that mirtazapine is unlikely to be a significant teratogen.

What stays to be studied on the usage of mirtazapine inside pregnancy is whether or not mirtazapine exposure could also be related to other adversarial pregnancy and delivery outcomes, which weren’t evaluated inside this study–corresponding to poor neonatal adaptation (related to other antidepressants) and long-term neurodevelopmental outcomes in exposed children.

Decisions surrounding continuing mirtazapine inside pregnancy or initiating mirtazapine in pregnancy must be thoughtfully considered by the patient and her provider on a person basis. As with all medication decisions inside pregnancy, patient and provider should fastidiously weigh the risks of untreated illness against each the known and unknown risks of the psychiatric medication.

Rebecca Leval, MD, MPH

References

Kieler H, Malm H, Artama M, Engeland A, Furu K, Gissler M, Nørgaard M, Stephansson O, Valdimarsdottir U, Zoega H, Haglund B. Use of antidepressants and association with elective termination of pregnancy: population based case-control study. BJOG. 2015 Nov;122(12):1618-24. doi: 10.1111/1471-0528.13164. Epub 2014 Nov 14. PMID: 25395328.

Kjaersgaard MI, Parner ET, Vestergaard M, Sørensen MJ, Olsen J, Christensen J, Bech BH, Pedersen LH. Prenatal antidepressant exposure and risk of spontaneous abortion – a population-based study. PLoS One. 2013 Aug 28;8(8):e72095. doi: 10.1371/journal.pone.0072095. PMID: 24015208; PMCID: PMC3756033.

Ostenfeld A, Petersen TS, Pedersen LH, Westergaard HB, Løkkegaard ECL, Andersen JT. Mirtazapine exposure in pregnancy and fetal safety: A nationwide cohort study. Acta Psychiatr Scand. 2022 Jun;145(6):557-567.