Q. I have taken Paxil for about six years for depression and obsessive-compulsive disorder. I have tried several times to stop the medication but the symptoms come back within a few weeks of stopping the medication. My husband and I are now planning a pregnancy, and my obstetrician tells me that I cannot take Paxil during pregnancy. Are there any other options?

A. Several recent studies have raised concerns regarding the use of paroxetine (Paxil) during pregnancy. (These studies have been reviewed in detail in the Winter 2005 Newsletter.) In an unpublished report from GlaxoSmithKline, the manufacturer of paroxetine as Paxil (see communication, GlaxoSmithKline, December 2005), data derived from an HMO claims database demonstrated a 1.8-fold increase in overall risk of malformations and a trend toward an increased risk for cardiovascular malformations (odds ratio of 1.54) in paroxetine-exposed infants. A recent report from the Swedish Medical Birth Registry, including 822 infants exposed to paroxetine, also demonstrated a 1.8-fold increased risk of cardiovascular malformation in paroxetine-exposed children. Infants exposed to other SSRIs did not have an increased risk of cardiac or other defects (Hallberg 2005).

In a case control study, investigators from the University of British Columbia, Vancouver analyzed data from the National Birth Defects Prevention study (Alwan et al, 2005) and found an association between exposure to an SSRI during the first trimester and a three-fold increased risk of omphalocele. The strongest effect was observed with paroxetine, which was associated with a 6.4-fold increase in risk for this defect. (Omphalocele, an abnormality in which the infant’s intestines or other abdominal organs protrude from the navel, occurs in approximately 1 out of every 4,000 births.)

These recent findings of increased risk with prenatal paroxetine exposure are inconsistent with earlier findings. While there is clearly a need for more thorough analysis of the existing data, these reports, taken together, may signal an increase in risk of malformations in children exposed to paroxetine. However, it is important to put this risk in perspective. Even if we assume the associations from the new case-control study are true, a 6.4-fold increase in risk for omphalocele translates into an absolute risk of only 0.16% (approximately 2 out of every 1,200 births). The overall risk of cardiovascular malformation is estimated to be about 1.5%. Absolute risk is of far greater clinical value than relative risk and should be taken into consideration when making decisions regarding the use of antidepressants during pregnancy.

Patients who are planning to conceive and are at significant risk for depressive relapse in the setting of antidepressant discontinuation may benefit from switching to an antidepressant for which there is more information supporting reproductive safety. These include fluoxetine and citalopram, as well as the older tricyclic antidepressants. However, some women may not be able to tolerate or may have an inadequate response to these alternative treatments; under these circumstances, they may elect to continue treatment with paroxetine, acknowledging that, while there may be some concerns regarding its use during pregnancy, the relative risk remains small. And this risk should be weighed against the risks associated with untreated illness in the mother.

Ruta Nonacs, MD PhD

Communication: “Dear Doctor” Letter from GlaxoSmithKline, December 2005

New FDA Guidelines concerning paroxetine during pregnancy (Issued September 2005)

Einarson TR, Einarson A. Newer antidepressants in pregnancy and rates of major malformations: a meta-analysis of prospective comparative studies. Pharmacoepidemiol Drug Saf 2005; 14(12 ): 823-827.

Alwan S, Reefhuis J, Rasmussen S, et al. Maternal use of selective serotonin re-uptake inhibitors and risk for birth defects, (abstract). Birth Defects Research (Part A): Clinical and Molecular Teratology 2005;73:291.

Hallberg P, Sjoblom V. The use of selective serotonin reuptake inhibitors during pregnancy and breast- feeding: a review and clinical aspects. Journal of Clinical Psychopharmacology 2005; 25 (1): 59-73.

*This post was originally published as an article in our Spring 2006 Newsletter.

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