Thursday, February 08, 2007

Ask a Scientist: Antidepressants and Pregnancy (5)

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/ postnatal adaptation problems
    • Muscle stiffness
    • Breathing distress at birth
    • Neurological withdrawal symptoms
  5. Breastfeeding risks
    • Infant weight gain
    • Infant serotonin levels
    • Long-term neurologic development
  6. Maternal risks of going without treatment
    • Relapses
    • Infant failure to thrive
    • Parenting problems, attachment, child behavior
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.

5. Breastfeeding risks
Okay, folks, there are a LOT of articles about this. If you want to see them, search 'breastfeeding antidepressants' on Pubmed. As far as I can tell, they largely come to the same conclusions. So here's a summary of the first 50 or so.

Did you know there's a Journal of Human Lactation??? They have an excellent 2001 review of various ADs in lactation.

Motherisk has a lovely patient-oriented summary about drugs and breastfeeding. (Thanks, Aurelia.)


Use of SSRIs and TCAs (except doxepin) is considered safe. Occasional adverse events are reported. They generally resolve once either breastfeeding is stopped, the schedule is altered to minimize infant exposure, or the mother stops taking the drug.

Of the SSRIs, sertraline and paroxetine have very low numbers of adverse events. Mild adverse events are associated with fluoxetine and citalopram (colic, crying, etc.).

Antipsychotics and lithium are not recommended in breastfeeding.

5a. Infant weight gain

A study comparing the 5 most common SSRIs and venlafaxine shows absolutely normal weights in all infants. They note, however, that maternal depression of >2 months DOES make the babies gain less weight.

Paroxetine in 27 mothers has no effect on weight gain or developmental milestones. A meta-analysis of SSRIs (other than fluoxetine) and TCAs also showed no effect on weight gain.

One study on 26 breastfed infants whose mothers took fluoxetine, however, showed an average 1-pound difference in weight gain over 6 months. The JHL review notes that none of the weights, even the lower ones, were below the national mean. Another study notes lower birth weights in fluoxetine usage, but only studies five exposed infants (i.e., not enough to say).

5b. Infant serotonin levels

Unsurprisingly, this isn't exactly studied a lot. One editorial (pdf) summarizes a few studies on the matter: rats exposed to fluoxetine had a 50% occupancy of their serotonin reuptake protein (5-HTT); however, apparently about 80% is necessary for an AD effect. (Also, nobody's quite sure exactly what 5-HTT does or how it relates to depression.)

A human study on fluoxetine says that "most infants may continue to breastfeed without experiencing meaningful changes in" serotonin uptake and metabolism. A small study that lumps together three ADs seems to suggest that newborn serotonin levels are changed by maternal AD use, but stabilize within one month. They go on to suggest that it could have terrible! developmental! consequences but I think they're full of beans (and hand-waving).

5c. Long-term neurologic development

You'll be shocked (shocked!) to learn that basically, nobody has a clue. In infants followed for up to a year, they're perfectly normal. After that, well, neurology is complicated and poorly understood anyways. The best that can be said is that SSRIs and other ADs don't appear to do anything either a) really nasty b) quick or c) much of the time.

Reported infant exposures in breastfeeding

The medical literature says that infant exposure of <10% is largely considered safe. In addition, some data indicate that breastfeeding can alleviate neonatal abstinence syndromes (here in, for example, methadone exposure. Think how much more innocuous sertraline is.).

These exposures and reported adverse effects in lactation are taken from the JHL article and a review in Drug Safety. Both studies note that changing dosage time and breastfeeding times can significantly reduce/ minimize infant exposure.

A modeling study notes that the total infant yearly dose (of fluoxetine) is generally about 1 or 1.5 of the mother's daily dose. This isn't very much. Another meta-analysis summarizes overall exposures for many psychoactive drugs.

Fluoxetine: Infants may receive up to 20% of maternal daily dose (MD). Some reports of extreme infant fussiness which resolve on maternal drug or breastfeeding discontinuation. Other studies indicate no complications in infants. Labelling recommends not using in breastfeeding, but is generally considered low-risk.

Paroxetine: Infant exposure ~3% MD.

Fluvoxamine: May be contraindicted in infants who are taking caffeine (i.e. for apnea). Infant breastmilk dose 0.75%-1.4% MD. Alternatively, undetectable in infant serum.

Citralopram: 0.4%-1.8% MD. No adverse effects reported.

Sertraline: 0.5-2% MD; sometimes undetectable in infant. No known adverse effects. Considered safe and well-studied.

Nefadozone: Adverse event in preterm infant receiving 0.45% of maternal dose; attributed to reduced hepatic function. Calculated to be safe if infant is confirmed to receive less than 10%.

Bupropion: ~0.02% MD; therefore considered very safe in lactating mothers. One case report of seizures; may be avoided if family history of seizure.

Venlafaxine: up to 7.6% MD; metabolized well by infants. No apparent effect on weight. Well-tolerated.

  • Being depressed affects infant weight gain.
  • SSRIs and TCAs in breastmilk don't.
  • There are no data on long-term neurological consequences.
  • In any case, infant AD dosage through breastmilk is very low.
  • On the other hand, infant/child exposure to maternal depression definitely has bad effects on weight gain, "emotional and behavioural development", maternal-infant bonding, cognitive development, and children's levels of fear and anxiety.
  • Many ADs are well-studied in lactating mothers; few-to-no adverse events are reported. Most are widely considered to be safe.