Antidepressant
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Moderate Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Phenelzine is a monoamine oxidase (MAO) inhibitor used in the treatment of depression. Other agents in this subclass are iproniazid, isocarboxazid, nialamide, and tranylcypromine. The human pregnancy experience is too limited to assess the embryo–fetal risk. (See also Tranylcypromine.)
FETAL RISK SUMMARY
Phenelzine has been found to be effective in depressed patients clinically characterized as atypical, nonendogenous, or neurotic. It is extensively metabolized to apparently inactive metabolites. Plasma protein binding was not reported by the manufacturer, but the mean elimination half-life after a single 30-mg dose was 11.6 hours (1).
In reproduction studies with mice at doses above the maximum recommended human dose, a significant decrease in the number of viable offspring per mouse was observed (1).
It is not known if phenelzine crosses the human placenta. The molecular weight of the sulfate form (about 234) and elimination half-life suggest that exposure of the embryo–fetus should be expected.
The Collaborative Perinatal Project monitored 21 mother–child pairs exposed to MAO inhibitors during the 1st trimester, 3 of which were exposed to phenelzine (2). Three of the 21 infants had malformations (relative risk 2.26). Details of the three cases with phenelzine exposure were not specified (2).
A 1995 report described a 25-year-old woman who had been treated for depression with phenelzine (45 mg/day) for 6 years before becoming pregnant (3). The drug was continued throughout gestation. Because labor failed to progress, a cesarean section was performed to give birth to a healthy male infant with Apgar scores of 9 at 1 and 5 minutes (3).
A 31-year-old white female with severe recurrent major depression took phenelzine 45 mg/day before and throughout her pregnancy (4). Attempts to taper her dose were unsuccessful and the patient declined to change to other depression therapy. An ultrasound at 10 weeks’ gestation revealed nonidentical twins. A repeat examination at 16 weeks’ showed resorption of one fetus, an event that was considered spontaneous and not related to the patient’s drug therapy. Because of worsening depression in the 2nd trimester, her daily dose was increased to 52.5 mg. At 37 weeks’, she gave birth to a normal healthy 2.651-kg male infant with Apgar scores of 6, 8, and 9 at 1, 5, and 10 minutes, respectively. The infant was discharged home on day 3 and growth and development were normally at 16 months of age (4).
A 2014 case study described the use of phenelzine (105 mg/day), lithium (900 mg/day), and quetiapine (600mg/ day) in a 31-year-old woman with bipolar affective disorder (5). She was also taking metformin (1 g/day) for polycystic ovarian syndrome with oligomenorrhea. Despite her oligomenorrhea, a pregnancy was confirmed at 17 weeks’ gestation. A glucose tolerance test was negative at 26 weeks’. Lithium was suspended 24–48 hours before induction of labor at 39 weeks’ Because of obstructed labor, a cesarean section was performed to give birth to a 4.2-kg male infant with Apgar scores of 5 and 9 at 1 and 5 minutes, respectively. The baby required initial resuscitation during the first 10 minutes. The baby was discharged home with the mother at 5 days. At 10 weeks of age, the baby’s growth and development were normal (5).
BREASTFEEDING SUMMARY
No reports describing the use of phenelzine during breastfeeding have been located. The molecular weight (about 234) and moderately long elimination half-life (11.6 hours) suggest that the drug will be excreted into breast milk. If the drug is used during breastfeeding, the infant should be monitored for the most common adverse reactions observed in adults (dizziness, headache, drowsiness, sleep disturbances, fatigue, weakness, tremors, twitching, myoclonic movements, hyperreflexia, constipation, dry mouth, and edema).
References
1.Product information. Nardil. Parke-Davis, 2000.
2.Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:336–7.
3.Pavy TJG, Kliffer AP, Douglas MJ. Anaesthetic management of labour and delivery in a woman taking long-term MAOI. Can J Anaesth 1995;42:618–20.
4.Gracious BL, Wisner KL. Phenelzine use throughout pregnancy and the puerperium: case report, review of the literature, and management recommendations. Depress Anxiety 1997;6:124–8.
5.Frayne J, Nguyen T, Kohan R, De Felice N, Rampono J. The comprehensive management of pregnant women with major mood disorders: a case study involving phenelzine, lithium, and quetiapine. Arch Womens Ment Health 2014;17:73–5.