Both citalopram and escitalopram are antidepressants belonging to the SSRI class.  While escitalopram (marketed in the U.S. as Lexapro) contains only the S-stereoisomer (or enantiomer) of the drug citalopram, Celexa or generic citalopram is a racemic mixture of the S-citalopram and its mirror image, R-citalopram, which is less effective as an antidepressant.

Thus far, there have been three studies published on the safety of citalopram use during pregnancy.  The first two reported no serious adverse outcomes among infants exposed to citalopram; however, a third study using a different methodology reported a small increase in risk for cardiovascular septal defects (odds ratio [OR] of 2.52). (This study relied upon data derived from a prescription database, where it could not be confirmed whether or not the women actually took the drug.)

It has generally been assumed that the reproductive safety of escitalopram would be similar to that of the parent drug citalopram, as S-citalopram is one component of this racemic mixture.  A recent study, a collaborative effort from three teratogen information services, is the first to specifically assess the reproductive safety of escitalopram.

In this observational multicenter cohort study, data was collected prospectively from the Motherisk Program in Toronto, the Swiss Teratogen Information Service, and the Florence Teratogen Information Service.  During the initial telephone contact with participants, demographic information, medical and obstetrical histories, and details of drug exposure were gathered using a standardized questionnaire.  Each participant was matched to a woman who subsequently contacted the teratogen information services with exposure to (1) other antidepressants (SSRIs, venlafaxine, bupropion, trazodone, nefazodone, and mirtazapine) and (2) nonteratogenic exposures to drugs such as acetaminophen, antibiotics, antihistamines, etc.  Approximately 2 to 3 months following expected date of delivery, researchers contacted each woman and obtained oral completed a questionnaire regarding details of drug exposures during pregnancy.

Malformations were counted only if exposure took place in the first trimester, during organogenesis, and neonatal adverse effects were only counted if the drug was taken close to delivery (within 1 week).

Among the 213 escitalopram-exposed infants (including one pair of twins), there were 172 (81%) live births, 32 (15%) spontaneous abortions, 3 (1.8%) stillbirths, and 19 (11%) premature births.  As seen in several previous studies, spontaneous abortion rates were higher in both antidepressant groups (15% and 16% compared to unexposed controls, although this finding was not statistically significant.

The mean ± SD birth weight of escitalopram-exposed infants was 3198 ± 594 g, and mean gestational age at delivery was 38.6 weeks. The rate of low birth weight (<2500 g) was higher in the escitalopram group (9.9%) than in the other antidepressant group (3.6%) and in the nonteratogen group (2.1%).

There were 3 (1.7%) major malformations in the escitalopram group.  There were no differences in the rates of major malformations, premature births, stillbirths, or NICU admissions among the three groups.

Escitalopram does not appear to be associated with an increased risk for major malformations. The major strength of this study is that information on drug exposure was collected prospectively.  One of its limitations, however, was its relatively small size.  It is estimated that at least 750 participants in each group would be required to detect a 2-fold increase in more common malformations.

As seen in other studies of antidepressants, escitalopram was associated with higher rates of low birth weight (<2500 mg).  Without a comparison group of women diagnosed with depression who are not taking an antidepressant, it is difficult to determine whether this adverse effect is due to the depression itself or exposure to the drug.  This is particularly relevant given the multiple studies that have associated low birth weight with untreated depression and anxiety.

Ruta Nonacs, MD PhD

 

References:

Ericson A, Källén B, Wiholm B.  Delivery outcome after the use of antidepressants in early pregnancy.  Eur J Clin Pharmacol. 1999; 55(7):503-8.

Klieger-Grossmann C, Weitzner B, Panchaud A, Pistelli A, Einarson T, Koren G, Einarson A.  Pregnancy Outcomes Following Use of Escitalopram: A Prospective Comparative Cohort Study. J Clin Pharmacol. 2011; Nov 11.

Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH. Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study. BMJ 2009;339:b3569.

Sivojelezova A, Shuhaiber S, Sarkissian L, Einarson A, Koren G. Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome. Am J Obstet Gynectol 2005;193:2004-9.