Mirtazapine is a benzazepine tetracyclic antidepressant licensed for use in the treatment of depression and mood disorders. It is also used off-licence in the treatment of anxiety and as an antiemetic. Its mechanism of action is related to that of selective-serotonin reuptake inhibitors (SSRIs).
The data regarding exposure to mirtazapine in human pregnancy comprise around 1,300 exposures derived from case reports, case series and observational cohort studies.
The available data, although limited and conflicting for some outcomes, do not currently indicate that mirtazapine use in pregnancy increases the risk of malformation, preterm delivery, or an impact upon fetal growth. The available data regarding miscarriage, intrauterine death, neonatal complications and neurodevelopmental impairment risks do not currently provide evidence of an association with mirtazapine use in pregnancy, but are too limited to allow definitive conclusions to be drawn.
In utero SSRI exposure has been associated with a small increase in the occurrence of persistent pulmonary hypertension of the newborn (PPHN) and neonatal withdrawal. No epidemiological studies have investigated the risk of PPHN for mirtazapine specifically. Owing to the pharmacological similarities between mirtazapine and SSRI antidepressants, and given that cases of poor neonatal adaptation syndrome, neonatal withdrawal features and PPHN have been described in uncontrolled case reports/series, neonatal monitoring is recommended following mirtazapine exposure in the later stages of pregnancy.
Infants exposed to antidepressants in utero should ideally be delivered in a unit with adequate neonatal support and the delivery team made aware of the exposure. In non-pregnant adults, mirtazapine has an elimination half-life of 20 to 40 hours which is extended in cases of liver or renal impairment.[SmPC] Due to immature metabolic capabilities, neonatal clearance of mirtazapine following in utero exposure may also be prolonged, and as such neonatal effects may be delayed.
It is important to ensure that maternal mental health is treated appropriately. As such, mirtazapine use in pregnancy may be clinically indicated, but the risks and benefits must be carefully considered on a case-by-case basis. Where possible, non-pharmaceutical management of depression and/or anxiety is preferable in pregnancy. Where a patient is stabilised on mirtazapine, either prior to conception or during pregnancy, any perceived benefits of altering the treatment should be carefully weighed against the risk of maternal relapse either during pregnancy or post-partum. In cases where treatment with mirtazapine is continued in pregnancy, the lowest effective dose should be used.
Exposure to mirtazapine at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.