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Rapid response to:


Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study

BMJ 2009; 339 doi: (Published 23 September 2009) Cite this as: BMJ 2009;339:b3569

Rapid Response:

Neonatal Serotonin Syndrome, cardiac outcomes and SSRIs in pregnancy.

We should not fret about the several limitations of yet another
cohort study and instead concentrate on recognising the findings of
existing studies and maintain caution about prescribing SSRIs in

In the Israeli study, Rachel Levinson-Castiel et al used the Finnegan
scoring to assess neonatal abstinence syndrome (NAS)(1). Almost a third
of these neonates exposed to SSRIs in-utero (either through the entire
pregnancy or at least during the third trimester) had symptoms of NAS.
Four SSRIs were compared (Paroxetine, Fluoxitine, Sertraline and
Citalopram) with the greatest risk of NAS correlating to a higher dose of
Paroxetine. In this study, 3 out of 60 infants with prolonged in-utero
exposure to SSRIs developed congenital anomalies including ventricular
septal defects.

Pedersen et al confirm a similar risk of cardiac malformations but
provided fair assurance that no specific SSRI was associated with major
malformation. The association of septal heart defects was greater with
Sertraline and Citalopram but not, in this study, with Paroxetine (OR
1.99) (2).

A six-fold greater risk of persistent pulmonary hypertension in
newborns with in-utero exposure to SSRIs after the 20th week of gestation
was found by Chambers et al (3). The risk was not, however, increased if
SSRI use was restricted to the first trimester.

Associations are also found with SSRI use and decreased gestational
age, spontaneous abortion (4), reduced APGAR score (5) and decreased birth
weight (5,6,7,8).

Salvatore Gentile draws attention to the possible risk to long term
neurocognitive development of children exposed to SSRIs in-utero (9).
Results however are conflicting. The Stanford Study found significantly
lower scores on neurobehavioral functions and psychomotor indices in
children exposed to SSRIs in-utero compared to children of women with
major depression who were treated with psychotherapy (10). On the other
hand, a study conducted at the University of Toronto showed no differences
in well established neurobehavioural indices between exposed and unexposed
children (11) and prospective studies on Fluoxetine usage during pregnancy
could find no effect on global IQ, language development or behavioural
development in preschool children (12). Untreated depression was
associated with poorer cognitive and language achievement (13).

Clearly, further research is warranted and the clinician should
assess the risk-benefit ratio of continuing SSRIs in pregnancy, consider
the long term harm that may be caused by relapse and promote the
potentially safer modality of psychotherapy.


Levinson-Castiel R, Merlob P, Linder N, et al. Neonatal abstinence
syndrome after in utero exposure to selective serotonin reuptake
inhibitors in term infants. Arch PediatrAdolesc Med. 2006;160:173-176.

Lars Henning Pedersen et al. Selective serotonin reuptake inhibitors
in pregnancy and congenital malformations: population based cohort study.
BMJ 2009; 339: b3569

Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al. Selective
serotonin-reuptake inhibitors and risk of persistent pulmonary
hypertension of the newborn. N Engl J Med. 2006;354:579-587.

Hemels ME, Einarson A, Koren G, et al. Antidepressant use during
pregnancy and the rates of spontaneous abortions: a meta-analysis. Ann
Pharmacother 2005;39:803-9.

Hallberg, P., &Sjoblom, V. (2004). The use of selective serotonin
reuptake inhibitors during pregnancy and breast-feeding: A review and
clinical aspects. Journal of Clinical Psychopharmacology, 25, 59–73.

Gentile S. The safety of newer antidepressants in pregnancy and
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Simon GE, Cunningham ML, Davis RL: Outcomes of prenatal
antidepressant exposure. Am J Psychiatry 2002; 159:2055–2061.

Oberlander, TF, Warburton, W, Misri, S, et al. Neonatal outcomes
after prenatal exposure to selective serotonin reuptake inhibitor
antidepressants and maternal depression using population-based linked
health data. Arch Gen Psychiatry 2006; 63:898.

Gentile S. SSRIs in pregnancy and lactation: emphasis on
neurodevelopmental outcome. CNS Drugs 2005; 19(7): 623-33.

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Nulman I et al.(1997) NEJM 336:258

Nulman I, et al.. Child development following exposure to tricyclic
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Competing interests:
None declared

Competing interests: No competing interests

15 October 2009
Meghana Godbole
Specialty Trainee (ST4)
Malcolm Hawthorne (consultant Psychiatrist), Shubha Rao (ST3)
Surrey & Borders Partnership NHS Trust, c/o Liaison Psychiatry, Frimley Park Hospital, Surrey.