Sertraline (Zoloft ®)
Antidepressant. Selective serotonin reuptake inhibitor (SSRI). Molecular weight:342.7
"Reproduction studies have been performed in rats and rabbits at doses up to
80 mg/kg/day and 40 mg/kg/day, respectively. These doses correspond to
approximately 4 times the maximum recommended human dose (MRHD) on a mg/m 2
basis. There was no evidence of teratogenicity at any dose level.
When pregnant rats and rabbits were given sertraline during the period of
organogenesis, delayed ossification was observed in fetuses at doses of 0.5 times
the MRHD in rats and 4 times
the MRHD in rabbits. When female rats received
sertraline at a dose of 20 mg/kg (1 times the MRHD) during the last third of
gestation and throughout lactation, there was an increase in the number of
stillborn pups and in the number of pups dying during the first 4 days after
Transplacental passage in humans has been demonstrated with a mean ratio of
cord to maternal serum concentration of 0.29 (range 0.10 to 0.66) after maternal
doses of 25 to 150 mg day .
A prospective study of women followed by The California
Teratogen Information Service found no increase in the rate of major anomalies
in the infants of 112 women who had used sertraline during pregnancy when compared to nonexposed controls. Anomalies reported in the sertraline exposed group included bilateral
choanal atresia, valvular pulmonic stenosis with an atrial septal aneurysm,
unilateral club foot, and Down syndrome in a pregnancy that was terminated.
Infants exposed to sertraline during the third trimester were more likely than
controls to have neonatal transition difficulties and were more often admitted
to a special care nursery 
Kulin NA et. al. prospectively examined 147 women
who reported use of sertraline during the first trimester pregnancy. The rates of miscarriage, stillbirth, prematurity,
mean birth weight, and major malformations in the women who used sertraline were
unexposed controls. Most of the women had taken 50 mg daily (range 25-250 mg/d)  .
Hendrick V, et. al. found no increased rate of congenital anomalies in a
group of 36 women who had received sertraline therapy at any time during
pregnancy. Reported complications included three newborns admitted to the special care nursery
because of transient tachypnea of newborn, and another infant admitted to
special care because of esophageal perforation during mouth
Sertraline and its active metabolite desmethylsertraline are excreted into
A study of fifteen nursing women taking sertraline (25-200 mg/day) found
the milk/plasma ratio to be highly variable (range, 0.42-4.81). The highest
concentrations of sertraline and desmethylsertraline were observed 8 to 9 hours
after maternal ingestion.
In another study of eight women taking sertraline the milk/plasma ratios of 1.93 and 1.64 were
estimated for sertraline and
N-desmethylsertraline respectively. Infant exposure calculated from estimated
milk production (0.15 l kg(-1) day(-1)), was estimated to be 0.90% and
1.32% for sertraline and N-desmethylsertraline respectively .
Hendrick V et. al. , found no detectable medication (parent and/or metabolite) present in the majority of (25/33) the serum samples
obtained from 30 infants exposed to sertraline through
breast-feeding. Sertraline was significantly more
likely to be detected in an infant if the mother's daily dose was 100 mg or higher
The American Academy of Pediatrics has classified sertraline as a drug
"for which the effect on nursing infants is unknown but may be of concern" .
NEONATAL SIDE EFFECTS:
Nystagmus has been observed in the newborn of a mother who had been
taking sertraline 50 mg daily for the two weeks preceding delivery. The
nystagmus resolved by 72 hours postpartum .
As previously mentioned,
Chambers CD, et. al. found infants who had been exposed to sertraline during the third
trimester were more likely than controls to have neonatal transition
difficulties and more likely to be admitted to a special care nursery .
One case report described "...agitation,
restlessness, poor feeding, constant crying, insomnia and enhanced startle
reaction." after abrupt cessation of breast feeding in an infant whose mother
had been taking the maximum recommended daily dose of 200 mg daily  throughout most of her
during lactation. Symptoms were persistent for 48 hours and subsided over next few days
In contrast to the above case report, Hendrick V et. al. did not observe
symptoms suggesting neonatal withdrawal in 11 infants after prenatal exposure to
sertraline at doses of 25 to 150 mg per day .
1. Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR;
2.Hendrick V, et. al. Placental passage of antidepressant medications.
Am J Psychiatry. 2003;160:993-6.
3. Chambers CD, et. al. Pregnancy outcome in
women who use sertraline. Teratology 1999;59:376.
4. Kulin NA, et al: Pregnancy outcome following
maternal use of the new selective serotonin reuptake inhibitors: a prospective
controlled multicenter study.
5. Hendrick V et al. Birth outcomes after prenatal exposure to
antidepressant medication. Am J Obstet Gynecol. 2003;188:812-5.MEDLINE
6. Stowe ZN, et al. The pharmacokinetics of sertraline excretion into human breast
milk: determinants of infant serum concentrations.
J Clin Psychiatry. 2003 ;64:73-80.MEDLINE
7. Kristensen JH, et al. Distribution and excretion of sertraline and
N-desmethylsertraline in human milk. Br J Clin Pharmacol. 1998;45:453-7.MEDLINE
8. Hendrick V, et al. Use of sertraline, paroxetine and fluvoxamine by nursing
women.Br J Psychiatry. 2001;179:163-6.
9.American Academy of Pediatrics Committee on Drugs: Transfer
of drugs and other chemicals into human milk. Pediatrics. 2001
10. Oca MJ, Donn SM. Association of maternal sertraline (Zoloft) therapy and
transient neonatal nystagmus.
J Perinatol. 1999;19:460-1.MEDLINE
11. Kent LS and Laidlaw JD. Suspected congenital sertraline dependence.[Letter]
Br J Psychiatry. 1995;167:412-3.
ADDITIONAL READING (Patient oriented):
Zoloft (sertraline) and Pregnancy (PDF file)
2002 Organization of Teratology Information Services
Last Update: 12/11/2003