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Br J Clin Pharmacol. 2008 Apr;65(4):600-6. Epub 2007 Oct 22.

Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands.

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EUROCAT registration of congenital anomalies, Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.



* Recently, the use of selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, in pregnancy has been associated with an increased risk on specific birth defects or other adverse pregnancy outcomes. * However, the extent of SSRI use in pregnancy is largely unknown.


* In the last decade the use of SSRIs in the year preceding delivery has increased twofold. * This increase runs parallel with the increase in use of SSRIs among women of fertile age. * Paroxetine is one of the most commonly used SSRIs. * Only recently have sufficient data become available on the use of paroxetine to detect moderate increased risks for specific malformations. * The safety of SSRIs which are less frequently used is not yet established. * Case-control birth defect-monitoring systems may be helpful in providing safety and risk estimates that become more precise as data accumulate for these drugs.


Recent case-control studies suggest a relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and the occurrence of birth defects and other adverse pregnancy outcomes. The aim was to determine the extent of the use of SSRIs before and during pregnancy and its trend over the years 1995-2004 in the Netherlands.


The study was performed with data from a population-based prescription database. Within this database, women giving birth to a child between 1995 and 2004 were identified. The exposure rate and 95% confidence interval (CI) were calculated as the number of pregnancies per 1000 that were exposed to an SSRI in a defined period (per trimester or in the year preceding delivery). Exposure rates were calculated for 2-year periods: 1995/1996, 1997/1998, 1999/2000, 2001/2002 and 2003/2004. Trends in exposure rates were analysed using the chi(2) test for trend.


Included were 14,902 pregnancies for which complete pharmacy records were available from 3 months before pregnancy until delivery. A total of 310 pregnancies were exposed to an SSRI in the year preceding delivery. The exposure rate increased from 12.2 (95% CI 7.0, 19.8) in 1995/1996 to 28.5 (95% CI 23.0, 34.9) in 2003/2004.


There has been a significant increase in the use of SSRIs among pregnant women in the Netherlands over the last 10 years, parallel with the increase in exposure in women of fertile age. In light of the recent warnings about the use of SSRIs in pregnancy, healthcare professionals should be careful in prescribing SSRIs to women planning a pregnancy.

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