GlaxoSmithKline ( GSK ) conducted a retrospective epidemiologic study of major congenital malformations in infants born to women taking antidepressants during the first trimester of pregnancy.

A preliminary analysis has recently been conducted which yielded adjusted odds ratios of 2.20 (95% Confidence interval [CI]: 1.34-3.63) for congenital malformations as a whole, and 2.08 (CI: 1.03-4.23) for cardiovascular malformations alone, for Paroxetine as compared to the other antidepressants in the database.
The prevalence of congenital malformations as a whole and cardiovascular malformation alone was approximately 4% and 2%, respectively.
Of the cardiovascular malformations reported in infants whose mothers were dispensed Paroxetine, the majority were ventricular septal defects.

It is important to note that because the GSK study was designed to evaluate the relative risk of congenital malformations in infants born to women exposed to antidepressants, the study did not include a comparison to infants who were not exposed to any antidepressant. Therefore, these data should be viewed within the context of the overall prevalence of congenital malformations in the general population, which is estimated in the US to be approximately 3% for any malformation and approximately 1% for cardiovascular malformations alone ( Honein 1999 ).

Previous epidemiological studies of pregnancy outcome following first trimester exposure to selective serotonin reuptake inhibitors ( SSRIs ), including Paroxetine, have not provided evidence for an increased risk of major malformations for SSRI medications.

In the most recent publication based on the Swedish Medical Birth Registry ( Hallberg 2005 ), which unlike the GSK study above, included a comparison to infants not of malformations was 3.4%.

In addition to the data by Hallberg et al, there are three published reports of small, epidemiologic case-control studies based on prospectively gathered data in women exposed to Paroxetine during their first trimester ( Kulin, 1998; Unfred, 2001; Diav-Citrin, 2002). The number of Paroxetine-exposed pregnancies reported in the three studies ranged from 89 to 97, and all studies found no major teratogenic risk.
A small study ( 19 Paroxetine-exposed pregnancies ) based on medical records review found congenital anomaly rates in accord with the general population ( Hendrick, 2003 ).

More recently, Alwan et al ( 2005 ) have reported data obtained from the National Birth Defects Prevention Study of infants delivered from 1997-2001.
Adjusted analyses showed that women who took an SSRI were more likely than those who were not exposed to have an infant with omphalocoele ( n=161 ) ( odds ratio [OR] 3.0 ).
The strongest effect was reported to be with Paroxetine, which accounted for 36% of all SSRI exposures ( OR 6.3 ).
The authors also found an association of exposure to any SSRI and having an infant with craniosynostosis ( n=372 ) ( OR 1.8 ).

A second abstract, from Wogelius et al, just presented at the 21 st International Conference on Pharmacoepidemiology and Therapeutic Risk Management ( August 21-24, 2005 ), reported an adjusted OR of 1.4 for congenital malformations overall and 1.6 for congenital cardiac malformations in women who redeemed a prescription for SSRIs ( Paroxetine-specific data were not presented ) from 30 days before conception to the end of the first trimester compared to women with no SSRI prescriptions during this period.

Source: GlaxoSmithKline, 2005


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