Anti-depressants and pregnancy

- more indications of increased risk of heart malformations and persistent pulmonary hypertension of the newborn (PPHN) – but the risk is still small.

Lately, more data indicating an increased risk of both heart malformations (primarily SSRI's) and persistent pulmonary hypertension (only SSRI's) in the newborn of mothers treated with anti-depressants, has been seen.

Paroxetine should still, in general, be avoided because of an increased risk of heart malformations (1 %, NNH=100). Likewise, the newer anti-depressants (venlafaxine, duloxetine, escitalopram, mirtazapine and others), whose safety during pregnancy is, as of now, largely unknown, should not be used in general. Regarding fluoxetine, there is substantial material which gives no basis for an increased risk, but based on some newer findings, the drug should not be considered as a first line agent. The Danish Medicines Agency has, as of February 28th, 2011, described two cases of deaths in infants, after use of fluoxetine by the mothers.

Citalopram and sertraline are the two SSRIs which, to our present knowledge, are associated with the lowest risk of heart malformations. The smaller amount of background material on these cannot rule out the possibility of the existence of a similar risk, but, under all circumstances, the risk is considered very low.

Tricyclic anti-depressants (TCAs) must – based on clinical experience and available data – be regarded as the safest choice of anti-depressants, concerning the risk of malformations of the fetus. Most date arise from studies with nortriptyline, amitriptyline and clomipramine, of which a smaller reservation against clomipramine must be taken (Swedish records show a slightly increased risk). Nortriptyline is the TCA subject to the lowest risk of cardiac side effects in the mother.

In cases of low to moderate depression, there is a documented effect of cognitive and interpersonal therapy, which is why these always should be considered before drug therapy.

Pregnant women, being treated with SSRIs (and SNRIs) during pregnancy, should be oriented of the possible symptoms of pulmonary hypertension (PPHN) of the child at birth. Furthermore, at the time of birth – and earlier in pregnancy – delivery doctors (obstetricians) and midwives can, with advantage, ask about the patients’ use of SSRIs.

Both tricyclic anti-depressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are subject to a larger risk of perinatal complications such as sleep disturbances, trouble with nursing, and lability of crying, presumably as a consequence of withdrawal or abstinence symptoms.

Based on present-day data, the pros and cons of treatment should be held up against the severity of the depression, and the parents to be should be involved in the decision. The possibility of a control and scan (e.g. in week 21) should be encouraged.

Indication, ordination and control of anti-depressants during pregnancy should, according to the National Board of Health, proceed in cooperation with a specialist doctor in psychiatry. The doctor should have a particular insight in the course of treatment during pregnancy and birth.

The Institute for Rational Pharmacotherapy, April 26th, 2010.

A full version in Danish - as well as references – is available here.

Contact person in IRF according to this subject is M.Sc. Pharm. Marianne Møller, phone 44889149, e-mail mam@dkma.dk.