Risk Factor: CM
Class: Central nervous system drugs/ Antidepressants
Fetal Risk Summary
Mirtazapine is a tetracyclic antidepressant that is chemically unrelated to selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors. Although the exact mechanism of action is unknown, the antidepressant effect is thought to result from an increase in central noradrenergic and serotonergic activity (1). Mirtazapine is also a potent inhibitor of histamine (H1) inhibitors, a property that probably explains the marked sedation often seen with this agent.
No teratogenic effects were observed in rats given doses up to 100 mg/kg or in rabbits given doses up to 40 mg/kg, 20 and 17 times the maximum recommended human dose on a mg/m2 basis, respectively (1). Toxicity observed in rats at the maximum dose (but not at 15 mg/kg) included an increase in postimplantation losses, increased pup deaths during the first 3 days of lactation, and lower pup birth weights.
It is not known whether mirtazapine crosses the placenta to the fetus. Because of its low molecular weight (about 265), however, transfer to the fetus in measurable amounts should be anticipated.
Mirtazapine was approved by the FDA for use in the United States in June 1996. No published reports describing the use of this drug in human pregnancy have been located. Moreover, no reports of adverse pregnancy outcomes related to mirtazapine have been reported to the FDA (F. Rosa, personal communication, FDA, 1996).
Breast Feeding Summary
It is not known whether mirtazapine is excreted into human milk. No reports describing the use of the drug during lactation have been located. Because other antidepressants are excreted into milk (see Maprotiline, another tetracyclic antidepressant) and because of its relatively low molecular weight (about 265), the passage of mirtazapine into milk should be expected. Moreover, the long-term effects on neurobehavior and development from exposure to this class of agents during a period of rapid central nervous system development have not been studied. The American Academy of Pediatrics considers the effects of other antidepressants to be unknown, although they may be of concern (2).
- Product information. Remeron. Organon, 1997.
- Committee of Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.