Postpartum haemorrhages are serious birth complications that represent one of the leading causes of maternal mortality and morbidity.

While incidences of postpartum haemorrhages have risen steadily in the past decades (in the US alone, numbers increased from 2.3% to 2.9% from 1994 to 2006), there is little evidence as to why.

Antidepressants – especially selective serotonin reuptake inhibitors (SSRIs) – have been associated with increased bleeding and poor wound healing, which, together with increasing prescription rates, renders them a potential explanation.

Methods

Antidepressant treatment is estimated at 7-13% in pregnant women and is therefore quite common (Cooper et al., 2007). In order to provide clinicians with information to gauge risk-benefit prescription decisions, a cohort study by Palmsten et al. (2013) takes a closer look at the topic.

Relying on Medicaid data on live births from 2000-7, the authors assessed 106,000 pregnant women aged 12-55 who had been diagnosed with a mood or anxiety disorder for antidepressant consumption and occurrence of postpartum haemorrhage.

Results

• 

  15.1% of pregnant women received antidepressant treatment that overlapped with their delivery date

• Current SSRI treatment was associated with 1.26% higher risk of postpartum haemorrhages (95% CI: 0.9 to 1.62%), while non-SSRIs antidepressant conferred 1.03% excess risk (95% CI: 0.07 to 1.99%) compared to non-exposure
• Exposure to SSRIs (1.19, 95% CI: 1.03 to 1.38) and non-serotonin reuptake inhibitors (1.17, 95% CI: 0.8 to 1.7) one month before delivery resulted in increased relative risk of haemorrhage
• SSRI treatment 1 to 5 month pre-delivery was not associated with higher risk (0.93, 95% CI: 0.82 to 1.06), but non-SSRI drugs approached significance (1.26, 95% CI: 1.00 to 1.59)
• For every 80 (SSRI) or 97 (non-SSRI) pregnant women, exposure to antidepressants close to delivery is estimated to cause one additional case of haemorrhage (assuming a causality)

Conclusions

The authors conclude:

While potential confounding by unmeasured factors cannot be ruled out, these findings suggest that patients treated with antidepressants during late pregnancy are more likely to experience postpartum hemorrhage.

Limitations

Due to the study design, it is not possible to establish causal relationships between antidepressant drugs and postpartum haemorrhage.

What is more, there are a myriad of alternative explanations and confounding factors that prevent straightforward interpretation. For instance, associations between antidepressants and haemorrhages could be mediated by nutritional or lifestyle choices that often accompany mood or anxiety disorders, such as tobacco use or alcohol consumption (Stewart, 2011). Also, women exposed to antidepressant drugs were on average older than their non-exposed counterparts.

Because of vastly differing individual pharmacokinetics and antidepressant pharmacodynamics, it is quite problematic that Palmsen et al. had no means of assessing treatment adherence. Due to low prescription rates, less common antidepressants such as mirtazapine or trazodone could not be taken into consideration.

In general, it should be kept in mind that these inferences are based on low-income women and therefore do not necessarily generalise to other socioeconomic strata.

Summary

All SSRIs, venlafaxine (a serotonin-noradrenaline reuptake inhibitor) and tricyclic antidepressants were associated with significantly heightened risk of postpartum haemorrhage. Even though risk increases might seem small, these results stress the need to inform pregnant women about the risks of post-delivery bleeding when treated with antidepressant drugs.

Links

Palmsten, K., Henandez-Diaz, S., Huybrechts, K.F., Williams, P.L., Michels, K.B., Achtyes, E.D., et al. (2013). Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States. BMJ, 347, f4877.

Cooper, W.O., Willy, M.E., Pont, S.J., & Ray, W.A. (2007). Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol, 196, 544. [PubMed abstract]

Stewart, D. (2011). Clinical Practice. Depression during pregnancy. N Engl J Med, 365, 1605-1611.