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Re: Antidepressant use and pregnancy: promoting risk minimisation for all teratogens is overdue

Sir, Kolding et al. must be commended for including terminations for abnormality within their methods and for providing the numbers needed to harm (NNH) when analysing the risk of cardiac malformations with antidepressant use, particularly during the first trimester of pregnancy. However, further comments regarding policy implications are warranted. First, Denmark seems to be a beacon of cautious prescribing: whereas the international prevalence estimate of selective serotonin reuptake inhibitor (SSRI) use during pregnancy is 3.0%, and increasing, in this series the prevalence of first-trimester exposure to antidepressants was only 1.1%. Could Kolding and colleagues suggest explanations for this difference in order to improve affairs for pregnant women worldwide through benchmarking? Second, this comprehensive retrospective analysis of 2007–2014 data from the Danish National Patient Registry, Medical Birth Register and Prescription Database begs a question as to why regulatory agencies internationally have not already required the systematic recording of teratogen prescriptions during pregnancy, especially when we have more powerful data linkage than ever before. Given that the first warning letters to prescribers about antidepressants were issued 16 years ago, why are we not measuring, and minimising, use via specific unified clinical databases to closely monitor prescriptions and clinical outcomes? Inertia in pharmacovigilance systems is neither acceptable nor understandable when serious adverse effects have accumulated over time: (i) observational studies report developmental disorders in line with experimental studies, and human infant magnetic resonance imaging (MRI) studies indicate that SSRI exposure has an association with changes in brain structure, white matter microstructure, brain connectivity and cerebral metabolism, particularly in brain regions that are critical to emotional processing; and (ii) SSRIs increase the risk of postpartum haemorrhage. Third, prescribers should be aware that antidepressants are not risk free for women during pregnancy: the fetal harms of SSRIs are well documented, as well as the limited effectiveness of antidepressants in the general population, and no controlled trials have been performed during pregnancy. The antidepressant versus placebo trials that have been published are short term (6–8 weeks), so although the decreases in depression scores are statistically significant, their clinical relevance versus that of psychotherapy is doubtful. Many patients with depression respond to judicious ‘watchful waiting’ and psychotherapies successfully treat most episodes of even persistent depression. These interventions are evidence based in real-life settings, are favoured by patients and must be the preferred initial option to treat depression, especially in women of childbearing age. Regulatory agencies must implement and monitor adequate risk minimisation measures for antidepressants, as for other teratogens, including: (i) an assessment of each woman’s potential to become pregnant and an explanation about the need for effective contraception throughout treatment, given that many pregnancies are unintended; (ii) supported decision making about the risks of antidepressant treatment in general, and specifically during pregnancy, by providing the NNH; (iii) informed pregnancy testing before and during treatment, as needed; and (iv) a ‘risk acknowledgement form’, in which the woman and the prescriber confirm that appropriate counselling has been given and understood.