Safety of selective serotonin reuptake inhibitors in pregnancy

Selective serotonin reuptake inhibitors (SSRIs) are recommended by the National Institute for Clinical Excellence as first-line drugs for the treatment of depression, but there is emerging evidence that they might not be entirely safe in pregnancy. We reviewed the literature in this area.

RESULTS

Some data indicate an association between first-trimester SSRI exposure, particularly with paroxetine, and an increased risk of some major congenital malformations. Stronger evidence supports an association with small reductions in gestational age and neonatal withdrawal symptoms.

CLINICAL IMPLICATIONS

Risks and benefits of using SSRIs during pregnancy should be discussed with the patient, and a joint decision made between prescriber and patient regarding treatment. Limited data suggest that other SSRIs are safer than paroxetine in pregnancy.

Risks and benefits of using SSRIs during pregnancy should be discussed with the patient, and a joint decision made between prescriber and patient regarding treatment. Limited data suggest that other SSRIs are safer than paroxetine in pregnancy.

Depression is common in women of child-bearing age with an annual prevalence of approximately 10% (World Health Organization, 2001). Women who develop depression during pregnancy may be less likely to care for themselves, placing their own health and that of their unborn child at risk. For those who have an established diagnosis of depression and who are taking antidepressant drugs when they conceive, the risk of relapse on stopping their antidepressant is high. Cohen et al (2006) found that 44 of 65 women (68%) who discontinued their antidepressant relapsed compared with 21 of 82 women (26%) who continued their treatment. Women with a history of depression, particularly post-partum, are at a high risk of post-partum relapse. For those with bipolar disorder this may be up to 50% (Cohen et al, 1995). These figures suggest that most psychiatrists who work with adults of working age are likely to be faced with making decisions about prescribing antidepressants for women who are pregnant or who wish to conceive.

The National Institute for Clinical Excellence (NICE) recommends selective serotonin reuptake inhibitors (SSRIs) as first-line treatment for moderate to severe depression (National Institute for Clinical Excellence, 2004). There have been a number of recent publications reporting on the safety of SSRIs in pregnancy and these studies are reviewed here.

Assessing the effects of drugs on pregnancy outcome

It is obviously unethical to conduct randomised controlled trials in pregnant women as this would involve the intentional exposure of the foetus to a potential teratogen. Other methods commonly used to detect congenital malformations associated with drugs include pre-licensing studies in laboratory animals, and post-licensing observational studies in humans. Extrapolation of animal data to humans is complex and studies of this type will not be considered further here. Human data can originate from prospective or retrospective studies, all of which have limitations. Examples of prospective studies include cohort studies such as those conducted through teratology information services; women who contact these services may not be representative of pregnant women as a whole. Examples of retrospective studies are cohort and case-control studies; these types of study usually utilise administrative data from healthcare databases that have been set up for an entirely different purpose. Assumptions are made, such as every woman who is prescribed an antidepressant drug will actually take it. People cannot be directly questioned or physically examined.