Thursday, February 01, 2007

Ask a Scientist: Antidepressants and Pregnancy (3)

Series: Antidepressants, Pregnancy, Risks

  • Introduction
  1. Spontaneous abortion
  2. Premature birth
  3. Congenital or teratogenic defects; that is, malformations in utero
    • Cardiac defects
  4. Antenatal adaptation problems
    • Muscle stiffness
    • Breathing distress at birth
    • Neurological withdrawal symptoms
  5. Breastfeeding risks
    • Infant weight gain
    • Long-term neurologic development
  6. Maternal risks of going without treatment
    • Relapses
    • Infant failure to thrive
    • Parenting problems, attachment, child behavior

[Disclaimer: I am not a medical professional; this is an academic summary of the evidence available and not a medical opinion. I do not offer medical advice. If you require medical opinions or treatment, please consult your physician.]

This information is drawn from published articles in medical journals, some of which are compiled here, and from public databases. (See also: summaries on Motherisk, FDA registries for pregnant women, this excellent Medscape article, and the FDA's index by drug name.) Information is also available through PubMed by searching various terms; I suggest starting with 'antidepressants and pregnancy'.

A list of generic and trade names is here.

3. Congenital or teratogenic defects; that is, malformations in utero
  • All defects; cardiac defects
There is a lot of very good data tracking birth defects (and post-natal events) in SSRIs and several other antidepressants. These studies have used large numbers of study subjects, and have characterized the various possible adverse effects. I would say that these data are reliable and believable.

These studies are often reported as odds ratios (ORs): the chance that X will happen under condition Y, divided by the rate of X without condition Y. Sometimes ORs are high: 2-fold, 4-fold. Remember that the basal rate is important; does it increase from 1% to 2% or 10% to 20%? Is the basal rate noisy; that is, is it small enough that there is doubt what the basal rate really is; could it be 1-3% in reality? So a high OR is not always cause for alarm. (Moral: Read articles carefully.)

It is believed that first-trimester exposure has the most impact on congenital (i.e. pre-birth) deformities; for an example, see this; this is why many of these studies focus on women who took ADs in the first trimester.

For comparison, the CDC runs a long-term birth defect database called the MACDP. Its latest report, from 2004, reports 1.2% cardiac defects and 2.3% all birth defects (including trisomies) among all births in the study.

The same large Finnish database mentioned in Part 1 investigated rate of birth defects among women with SSRI purchases in 1st, 2nd, 3rd, or all trimesters. About 1400 women bought SSRIs in the first trimester, being: citalopram, fluoxetine, paroxetine, sertraline, and fluvoxamine. Most SSRIs had no effect on birth defect incidence. There was a questionable association between 1st-trimester fluoxetine exposure and cardiac defects: 2.3% vs. a reported rate of 0.8% in Finland. After the authors adjusted for other factors, however(they don't specify, but probably things like smoking, family history, cocaine use, etc.), they found no association.

A study of 150 women on venlafaxine (Effexor) detected no defects above the basal level of 1-3% in the general population. A literature review of many other studies says that fluoxetine, sertraline (SSRIs), bupropion, and low doses of paroxetine are not associated with birth defects. A few isolated cases are reported with venlafaxine.

A large study/database (pdf) by Glaxo-Smith-Kline tracking reported defects (incident reporting), especially in bupropion use for all purposes, finds the following incidences (selected data):

All congenital defects:
Bupropion: 3.4%
All other ADs: 2.5%

1st trimester use (smaller cohorts), all defects:
Paroxetine: 4%
Citralopram: 3.2%
Trazodone: 5%
Venlafaxine: 1.9%
Sertraline: 1.4%

Bupropion is associated with a 1.9% incidence of cardiac defects (CDC: 1.2%).

A recent study on the Quebec pregnancy registry also reports that 7% of infants in 1403 women taking paroxetine had congenital defects, and 1.7% had cardiac defects.

  • SSRIs (except for paroxetine) are probably not associated with increased risk of birth defects, including cardiac defects. Neither is venlafaxine.
  • Paroxetine and trazodone are associated with increased risk of birth defects.
  • The Quebec study indicates that low doses of paroxetine are NOT associated with increased risk.
  • Bupropion may slightly increase cardiac defects; however, the effect is small and therefore not certain.