Antidepressants in pregnancy and breastfeeding

Anne Sved Williams, Psychiatrist, Clinical Senior Lecturer, University of Adelaide, and
Director, Perinatal and Infant Mental Health Services, Children, Youth and Women's
Health Services, South Australia

Summary have increased rates of behavioural problems and learning

difficulties by the age of five years.3
Maternal depression and anxiety during
pregnancy and the early years of an infant's life Lactation
cause substantial problems to the mother, her The relationship between postnatal depression and
infant and her family. Suicide is an ever-present breastfeeding is emerging as complex. Women who develop
postnatal depression are more likely to stop breastfeeding than
risk with depression along with adverse effects
women who are not depressed. Likewise, women who establish
on infant growth and birth weight. Balancing
and maintain breastfeeding are less likely to develop depression
these risks against accumulating evidence of the than women who have difficulties with breastfeeding.
effects of selective serotonin reuptake inhibitors
on the fetus and infant presents a challenge to Harmful effects of antidepressants
the treating doctor. Careful explanation to the Antidepressant use in Australia has changed in the last two
woman and her partner of the risks of both the decades. Tricyclic antidepressants have fallen from favour and
many have been withdrawn. Their adverse effects and risk
condition and the treatment, using a biological,
of fatality from overdose make them hazardous. However,
psychological and social treatment approach, is
some doctors continue to prescribe them after considering
likely to provide the most benefit. the risks and the benefits. There have been few documented
Key words: depression, infants, lactation, selective serotonin problems arising from their use, but this is perhaps due to lack
reuptake inhibitors. of extensive research. A small study on the use of dothiepin in
(Aust Prescr 2007;30:125–7) lactation suggested better outcomes for children of depressed
Introduction mothers taking the drug compared to those whose mothers
chose no medication.4 Case reports suggest that doxepin may
Depression in pregnant and lactating women is a common
be harmful to infants and should be avoided in breastfeeding.5
problem. In attempting to find the best treatment options for
these women, doctors work with less knowledge and more risks Data on mirtazapine are sparse and therefore this drug should
than with other patients. Drug trials always exclude pregnant not be used as a first-line treatment in pregnancy. Recent
and lactating women and therefore practice is guided by data work cautiously suggests that levels of mirtazapine are low in
accumulated from clinical experience. Clinicians must consider breastfed infants.
the risk of damage from the medications and the effects of the Venlafaxine use in early pregnancy has been associated
illness itself on both the mother and the baby. with increased rates of spontaneous abortion but not fetal
abnormality. There are also now many case reports of neonatal
Harmful effects of maternal depression effects so it should be used with great caution in pregnancy.
There is increasing evidence that antenatal and postnatal Venlafaxine has the potential to accumulate in the breastfed
anxiety and depression potentially have enduring effects on baby with prolonged treatment.6
offspring. Drugs used to treat bipolar depression include sodium valproate
which is highly teratogenic and is best avoided in the first
Pregnancy trimester. However, it is probably safe to use during lactation.
Although some studies differ, most document maternal Lithium may also cause fetal abnormalities and is generally
antenatal depression as causing slightly shorter gestational advised against in early pregnancy and during lactation.
length and lower birth weight in newborns.1 Antenatal anxiety However, a recent review of its use in the first trimester has
has shown a strong association with raised cortisol levels in shown lower rates of cardiac abnormalities than previously
10-year-old offspring, with the potential for increased documented. Its use in lactation has suggested it is relatively
vulnerability to psychopathology in these children.2 Boys whose safe in compliant mothers with healthy babies.7 Infants must be
depressed mothers show ambivalence to them in early months monitored for lithium concentrations in serum as well as renal

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and thyroid function. Specialist advice is highly recommended be high. For a woman whose depression has receded, a trial
with lithium. This is also the case for lamotrigine. of slow cessation of medication before conception may be
successful, but her mental state should be monitored in case
SSRIs during pregnancy of a relapse.
First trimester: Early prospective trials on SSRIs suggested they Unplanned conceptions for women on antidepressants can
were safe with no teratogenic effects. However, recent data have cause alarm and some women will abruptly cease their
challenged this and suggest a small increase in birth defects. medication. Unfortunately, up to 75% of women who do so
These results were not statistically significant and should be may develop a recurrence of their depression before delivery.13
interpreted with caution.8,9 Paroxetine has been associated Careful reassessment of relative risks will reassure many
with cardiovascular abnormalities10, although recent analysis women that continuation of their medication is appropriate.
suggests this risk is only at doses greater than 25 mg per day.11 If a pregnant woman decides to continue taking the drug,
Second and third trimesters: Recent studies show a small but doctors should be aware that pharmacokinetics change during
significant risk of shorter gestational length and lower birth pregnancy. In the event of a relapse, a woman might need
weight in infants of mothers who used SSRIs in later pregnancy higher doses of many drugs including SSRIs to maintain clinical
even compared to babies of untreated mothers with depression.1 improvement.
Third trimester: Increases in mild respiratory distress, irritability Later in pregnancy, concerns over neonatal toxicity and
and feeding problems have been observed in infants of mothers withdrawals guide some doctors to lower SSRI doses until
taking SSRIs in late pregnancy. Some but not all research after delivery. Anecdotally, many women can manage this well,
suggests that paroxetine may cause more neonatal difficulties.12 provided good psychosocial support is available. Some women
These effects are self-limiting and have generally settled by 14 will choose to continue on current doses with support, and
days. It is unclear whether these neonatal effects are withdrawal appropriate management of the neonate.
or toxic effects.13 There have also been reports of persistent
pulmonary hypertension of the newborn14 and possibly
Which antidepressant to use?
intraventricular haemorrhage.12 Experts differ in their assessments of the relative risks of the
antidepressants, but in general, SSRIs are preferred to tricyclic
SSRIs during lactation antidepressants, combined serotonin and noradrenaline
Many SSRIs are highly protein bound and little drug is reuptake inhibitors and mirtazapine. Every antidepressant
transferred from the mother to the infant during lactation. has been associated with some neonatal effects, and different
We can therefore be more confident in prescribing SSRIs in studies show differing results. The data on paroxetine in higher
lactation.5 However, there is individual variability in infant doses cause concern.11 While some perinatal psychiatrists
levels of SSRIs and there are occasional case reports describing prefer fluoxetine with its longer half-life and potential for slower
adverse effects.15 Less data are available on the use of other neonatal withdrawal effects, many prefer the shorter-acting
antidepressant drugs during lactation. SSRIs, either citalopram, fluvoxamine or sertraline as the
maternal response may be faster.
So what is a doctor to do?
Useful sources of information
When a woman presents early in pregnancy with depression
It is essential to frequently update information about best
a very careful assessment should be made, preferably with
practice in this area as new information rapidly changes
her partner or other family member as additional historian. An
practice. Reliable websites such as the Organisation of
assessment of risk of self-harm or suicide is vital. Other risks
Teratology Information Specialists (OTIS) (www.otispregnancy.
such as poor antenatal care are increased with depression.
org) and the Canadian www.motherisk.org are valuable to both
Once safety issues and general self-care have been addressed,
doctors and patients. Most large Australian obstetric facilities
a biological, psychological and social treatment plan should
also provide a pharmacy information service (see box), and if
be explored relating to the patient's needs and wishes, and
in doubt, a telephone call is appropriate. Telephone advice
the severity of the depression. Sufficient information should
from a psychiatrist can be obtained privately or through
be provided to the patient so they can make an informed
GP PsychSupport on 1800 200 588. Pharmaceutical companies
decision about their treatment. Careful documentation of these
may have additional data about the effects of antidepressants
discussions is important for medicolegal reasons.
on pregnancy and lactation.
Pre-conception counselling for women already taking
antidepressants must explore the relative risks of the depression Conclusion
itself compared to the risks of using antidepressants in The risks of the depression and its consequences must be
pregnancy. Anxiety about medication use in pregnancy may weighed against the risks of the medications to both mother and

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 6. Ilett KF, Kristensen JH, Hackett LP, Paech M, Kohan R,
Pregnancy drug information centres Rampono J. Distribution of venlafaxine and its O-desmethyl
metabolite in human milk and their effects in breastfed
New South Wales infants. Br J Clin Pharmacol 2002;53:17-22.
MotherSafe 7. Viguera AC, Newport DJ, Ritchie J, Stowe Z, Whitfield T,
Tel: (02) 9382 6539 / 1800 647 848 (toll free for NSW callers) Mogielnicki J, et al. Lithium in breast milk and nursing
infants: clinical implications. Am J Psychiatry 2007;164:342-5.
Queensland
8. Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM;
Queensland Drug Information Centre (health professionals)
National Birth Defects Prevention Study. Use of selective
Tel: (07) 3636 7098 serotonin-reuptake inhibitors in pregnancy and the risk of
South Australia birth defects. N Engl J Med 2007;356:2684-92.
9. Louik C, Lin AE, Werler MM, Hernandez-Diaz S, Mitchell AA.
Women's and Children's Hospital
First-trimester use of selective serotonin-reuptake inhibitors
Tel: (08) 8161 7222
and the risk of birth defects. N Engl J Med 2007;356:2675-83.
Victoria 10. Wogelius P, Norgaard M, Gislum M, Pedersen L, Munk E,
Royal Women's Hospital Mortensen PB, et al. Maternal use of selective serotonin
Tel: (03) 9344 2277 reuptake inhibitors and risk of congenital malformations.
Epidemiology 2006;17:701-4.
Western Australia 11. Berard A, Ramos E, Rey E, Blais L, St-Andre M, Oraichi D.
Women's & Newborn Health Service First trimester exposure to paroxetine and risk of cardiac
Tel: (08) 9340 2723 malformations in infants: the importance of dosage. Birth
Defects Res B Dev Reprod Toxicol 2007;80:18-27.
12. Nordeng H, Spigset O. Treatment with selective serotonin
infant during the different phases of pregnancy and lactation. reuptake inhibitors in the third trimester of pregnancy:
Careful history taking, close monitoring and good psychosocial effects on the infant. Drug Saf 2005;28:565-81.
care may be sufficient for many women with depression 13. Austin MP. To treat or not to treat: maternal depression, SSRI
use in pregnancy and adverse neonatal effects. Psychol Med
during pregnancy. When antidepressants are needed, the baby
2006;36:1663-70.
should be monitored postnatally for feeding, neurological and
14. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM,
respiratory difficulties. Prescription of SSRIs postnatally appears Louik C, Jones LK, et al. Selective serotonin-reuptake
less hazardous than in antenatal use, and potentially of benefit inhibitors and risk of persistent pulmonary hypertension of
to mother and child. the newborn. N Engl J Med 2006;354:579-87.
15. Lattimore KA, Donn SM, Kaciroti N, Kemper AR, Neal CR,
Acknowledgement: T
  hanks to Mr Neil Hotham, Pharmacist, Vazquez DM. Selective serotonin reuptake inhibitor (SSRI)
Children, Youth and Women's Health Service, South Australia, use during pregnancy and effects on the fetus and newborn:
and Associate Professor Marie-Paule Austin, University of a meta-analysis. J Perinatology 2005;25:595-604.
New South Wales.
Further reading
References Maternal SSRI use and neonatal effects. Aust Adv Drug React Bull
2003;22:14.
1. Oberlander TF, Warburton W, Misri S, Aghajanian J,
Hertzman C. Neonatal outcomes after prenatal exposure
Dr Sved Williams has received financial assistance for
to selective serotonin reuptake inhibitor antidepressants
and maternal depression using population-based linked educational activities from Pfizer, Wyeth, Bristol-Myers Squibb,
health data. Arch Gen Psychiatry 2006;63:898-906. Solvay, Eli Lilly, GlaxoSmithKline and Lundbeck.
2. van den Bergh BR, Mulder EJ, Mennes M, Glover V.
Antenatal maternal anxiety and stress and the
neurobehavioural development of the fetus and child: links
and possible mechanisms. A review. Neurosci Biobehav Rev
2005;29:237-58.
3. Weinberg K, Tronick E. Emotional characteristics of infants
associated with maternal depression and anxiety. Pediatrics Self-test questions
1998;102 Suppl 5:1298-304.
The following statements are either true or false
4. Buist A, Janson H. Effect of exposure to dothiepin and
(answers on page 135)
northiaden in breast milk on child development.
Br J Psychiatry 1995;167:370-3. 3. It is safe to prescribe sodium valproate during early
5. Eberhard-Gran M, Eskild A, Opjordsmoen S. Use of pregnancy.
psychotropic medications in treating mood disorders
4. Generally, SSRIs are safe to use during lactation.
during lactation: practical recommendations. CNS Drugs
2006;20:187-98.

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