A lesson in labelling: SSRIs and birth defects

Date published

18/10/2017

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According to the World Health Organisation, depression is a leading cause of death worldwide and is on the rise globally.

Clinical depression is reported to affect 8-20% of women, with approximately 10% to 15% of pregnant women being affected by depression. Depression is considered particularly serious during pregnancy, and treating physicians are increasingly prescribing selective serotonin-reuptake inhibitors (SSRIs), to expectant mothers.

What are SSRIs?

SSRIs appeared as a new class of antidepressants in the 1980s. Today they are widely accepted and commonly prescribed. SSRIs operate by blocking a neurotransmitter in the brain from reabsorbing serotonin. Serotonin affects mood, and increased levels of serotonin can improve the mood and the feeling of happiness in the user. Some of the medications in this class include:

  • Zoloft (Sertraline)
  • Lexapro (Escitalopram)
  • Prozac and Sarafem (Fluoxetine)
  • Celexa (Citalopram)
  • Paxil (Paroxetine)
  • Effexor (Venlafaxine)
  • Pristiq (Desvenlafaxine)

Conflicting studies

In December 2005, the FDA issued a Public Health Advisory based upon US and Swedish epidemiologic studies showing that exposure to certain antidepressants in the first trimester of pregnancy may be associated with an increased risk of cardiac birth defects. The majority of the heart related defects observed in these studies were conditions in which the wall between the right and left sides of the heart is not completely developed.

In July 2006, the FDA issued a Public Health Advisory for SSRIs, including Celexa (citalopram), Fluvoxamine, Lexapro (escitalopram), Symbyax (olanzapine and fluoxetine) and Zoloft (sertraline) based on a New England Journal of Medicine study that suggests there may be additional risks of SSRI medications during pregnancy. In this study, Persistent pulmonary hypertension of the newborn (PPHN)  was six times more common in babies whose mothers took an SSRI antidepressant after the 20th week of the pregnancy, compared to babies whose mothers did not take an antidepressant.

Further studies followed. These concluded that the chance of birth defects arising in babies exposed to SSRIs was “rare” and risks “small”. In 2011, the FDA released an updated safety communication indicating that more studies were needed to confirm an association between SSRIs and PPHN, as some trials have yielded conflicting results.

Research studies have continued in this area. In January 2017, a Université de Montréal study was published in the British Medical Journal, revealing that antidepressants prescribed to pregnant women could increase the chance of having a baby with birth defects. The study found the risk was 6 to 10 %, against 3 to 5 % in women who do not take SSRIs. The study only considered the first trimester when all of the organ systems are developed and said that any disturbance of the the serotonin signaling process has the potential to result in a wide variety of malformations. One of the SSRIs studied taken in the first trimester, showed a rise from 5% to 8% in birth defects.

Associated birth defects

A wide-ranging spectrum of birth defects, which have been potentially linked to SSRIs from the various studies to date, include:

  • PPHN
  • Abdominal Birth Defects/Omphalocele
  • Anal atresia (complete or partial closure of the anus)
  • Autism Spectrum Disorders
  • Cardiac (heart) defects
  • Cleft lip and cleft palate
  • Clubfoot (one or both feet turn downward and inward)
  • Craniosynostosis (skull defect)
  • Limb Defects
  • Neural-tube defects (brain and spinal cord, spina bifida)
  • Atrial septal defects (ASD)
  • Ventricular septal defects (VSD)
  • TOF (tetralogy of fallot) with pulmonary atresia
  • Low fetal birth weight and low APGAR score

Lessons

In order for pregnant women to make a choice as to whether or not they want to remain on an SSRI during their pregnancy, they need to be fully informed of the potential risks to the baby and be allowed to weigh those risks against the potential risks of discontinuing the SSRI.

All patients have a legal right to be fully-warned of all potential complications and problems that a drug can cause, so that they can make an informed choice and provide informed consent to any medical prescription.

SSRI manufacturers who fail to provide adequate warning of these risks may end up facing liability for any injury that their drugs may cause to the newborns.

To determine if a product is defective, a “reasonable safety expectation” test applies under Art.6 of the EU Product Liability Directive 85/374/EC. A product is deemed to be defective if it does not provide the safety that consumers generally are entitled to expect taking all of the circumstances into account, including the:

  • Presentation (including get-up and warnings) of the product.
  • Product’s use that could be reasonably expected.
  • Time when the product was put into circulation.

Comment

Manufacturers of SSRIs and their insurers must ensure that their product labelling provides adequate warning to pregnant women and their treating physicians about all the potential risks associated with taking SSRIs whilst pregnant/breast-feeding.

Drug companies who do not test their drugs properly and do not warn their consumers about the potential risks could end up facing substantial financially liability and reputational damage.

Read other items in the Healthcare Brief - November 2017