Fluoxetine: possible small risk of congenital cardiac defects

Recent epidemiological evidence suggests a possible small increased risk of congenital cardiac defects in association with fluoxetine in early pregnancy, similar to that seen with paroxetine. There are insufficient data to draw conclusions on whether there is a similar risk for other SSRIs. The potential risks should be considered in the context of the benefits of treatment

From:
Medicines and Healthcare products Regulatory Agency
Published
11 December 2014
Therapeutic area:
Paediatrics and neonatology, Psychiatry

Article date: March 2010

Fluoxetine (brand leader Prozac) is a commonly used antidepressant belonging to the selective serotonin reuptake inhibitor (SSRI) class of medicines. Depressive symptoms and major depressive disorders occur in pregnant women with prevalence rates ranging from 7% to 20%.[footnote 1] [footnote 2] Untreated depression in pregnancy is associated with a variety of adverse outcomes, including low birth weight, preterm delivery, and lower Apgar scores. [footnote 3] [footnote 4] It is estimated that 2.3% of pregnant women per year are exposed to SSRI antidepressant therapy. 4

An analysis of epidemiological data from seven cohort studies[footnote 5] [footnote 6] [footnote 7] [footnote 8] [footnote 9] [footnote 10] [footnote 11] provided a risk estimate of 1·08 (0·84–1·39) for all congenital malformations with fluoxetine use. Analysis of data from five studies 5,7–8, 10–11 out of the seven gave a risk estimate of 1·43 (0·83–2·47) for congenital cardiac defects (data are odds ratios and 95% confidence intervals). The results suggest that fluoxetine is not associated with a risk of non-cardiac defects, and that any increased risk of malformations appears to be driven by a possible excess cardiac risk. The cardiac defects reported in the studies included in the meta-analysis were varied, and ranged in severity from reversible ventricular septal defects to transposition of the great vessels.

The background incidence of congenital cardiac defects is approximately 1/100. The meta-analysis results for fluoxetine are consistent with an increased absolute risk to less than 2/100 pregnancies. The current evidence indicates that the risk of congenital cardiac defects for fluoxetine is similar to that for paroxetine. The mechanism is unknown and it is possible that the effects may be a class-related phenomenon, however data are insufficient at present to issue advice about the risk with other SSRIs.

The current Summary of Product Characteristics (SPCs) and Patient Information Leaflets (PILs) are being revised to reflect this information for fluoxetine-containing products.

Advice for healthcare professionals

When prescribing fluoxetine to treat depression during pregnancy, prescribers should be aware that there may be a small increased risk of congenital cardiac defects in infants exposed in early pregnancy, similar to that seen with paroxetine.
There are insufficient data to draw conclusions on the risk of congenital anomalies with other SSRIs, but the possibility of a class effect cannot be excluded.
The potential increased risk should be considered in the context of the benefits of treating depression in pregnancy.

Article citation: Drug Safety Update March 2010, vol 3 issue 8: 4.

  1. Bennett H, et al. Obstet Gynecol 2004; 103:698–709 ↩

  2. Marcus S, et al. J Womens Health. 2003; 12(4): 373–380 ↩

  3. Kessler RC, et al. JAMA 2003 289: 3095–3105 ↩

  4. Reefhuis J, et al. N Engl J Med 2006; 354(20): 2188–2190 ↩

  5. Diav-Citrin O, et al. Br J Clin Pharmacol; 2008; 66: 695–705 ↩

  6. Einarson A, et al. Can J Psychiatry 2009; 54: 242–246 ↩

  7. Chambers CD, et al. N Engl J Med 1996; 335: 1010–1015 ↩

  8. Kallen and Otterblad Olaussen. Birth Defects Res Clin Mol Teratol 2007; 79: 301–308 ↩

  9. Malm H, et al. Obstet Gynecol. 2005; 106: 1289–1296 ↩

  10. Oberlander TF, et al. Early Hum Dev 2008; 84: 689–697 ↩

  11. Pastuszak A, et al. JAMA 1993; 269: 2246–2248 ↩

Published 11 December 2014

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