Study finds higher SSRI dose increases bleeding risk

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Dive into the research finding increased risks of postpartum hemorrhage and anemia among women who use higher doses of selective serotonin re-uptake inhibitors during pregnancy.

Study finds higher SSRI dose increases bleeding risk | Image Credit: © Dragana Gordic - © Dragana Gordic - stock.adobe.com.

Study finds higher SSRI dose increases bleeding risk | Image Credit: © Dragana Gordic - © Dragana Gordic - stock.adobe.com.

Bleeding complications in pregnant women may be managed utilizing the dose-dependent relationship between selective serotonin re-uptake inhibitors (SSRIs) and complications, according to a recent study published in the European Journal of Obstetrics & Gynecology and Reproductive Biology.

Takeaways

  1. The study highlights a dose-dependent relationship between selective serotonin re-uptake inhibitors (SSRIs) and bleeding complications in pregnant women. This suggests that managing SSRIs' dosage could help mitigate the risk of such complications.
  2. The findings underscore the critical importance of managing psychiatric illnesses during pregnancy and postpartum depression. Untreated mental health issues not only pose risks to the mother's well-being but also impact pregnancy outcomes.
  3. SSRIs may deplete serotonin in platelets, affecting initial coagulation activation and increasing the risk of bleeding. Understanding this mechanism is crucial for managing the medication's usage during pregnancy.
  4. Since serotonin plays a role in myometrial contractions, SSRIs may contribute to atonic postpartum hemorrhage. This suggests a need for careful consideration of SSRI use in pregnant women to prevent such complications.
  5. The study suggests that using the lowest effective dose of SSRIs could help reduce the risk of bleeding complications in pregnant women. This finding has significant implications for clinical practice in managing mental health conditions during pregnancy.

Management of psychiatric illnesses during pregnancy and postpartum depression is crucial, as suicide has been reported as the most prevalent indirect cause of maternal death in England. Untreated mental health issues during pregnancy are also associated with low birth weight, preterm birth, and other adverse pregnancy outcomes.

SSRIs are used to manage depression and anxiety disorders in 1% to 5% of pregnancies. However, SSRIs may deplete serotonin in platelets, leading to suboptimal initial coagulation activation and increasing the risk of bleeding.

Postpartum hemorrhage (PPH) rates have increased over time since the 1990s. Since PPH is often prevented by myometrial contractions partly mediated by serotonin, SSRIs may contribute to atonic PPH.

Investigators conducted a study to determine the dose-dependent association between SSRI use and postpartum bleeding complications. Participants included 40,094 women who gave birth from January 2007 to December 2011, 1.2% of whom used SSRIs.

SSRI use was determined by manual evaluation of medical charts. Participants with twin or cesarean delivery were excluded from the analysis, leading to 334 women with SSRI use and 31,929 women without SSRI use included in the analysis.

Data about health and drug intake was obtained through interviews conducted by midwives at participants’ first antenatal care visit. SSRIs included paroxetine, citalopram, fluoxetine, escitalopram, and sertraline. Moderate vs high dose was determined by each drug’s recommended dosage.

Routine measurements of blood loss were performed by the assisting midwife at delivery. This included blood absorbed by cloths and swabs. Hemoglobin under 100 g/l on the second day after delivery indicated postpartum anemia (PPA), while blood loss over 1000 ml in the first 24 hours after pregnancy indicated PPH.

A higher maternal age, body mass index, odds of smoking, and use of epidural analgesia during delivery were observed among SSRI users vs non-users. Additionally, users had a shorter gestational age than non-users, at 274 and 277 days, respectively. Delivering preterm was reported among 8.1% and 5.3%, respectively.

The mean blood loss among controls was 406 ml, vs 483 ml among median-dose SSRI users and 482 among high-dose users. The risks of PPA and PPH were also increased among moderate- and high-dose users vs controls.

Median hospitalization lengths when compared to controls were increased by 20.3 and 28.8 hours among median- and high-dose users, respectively. Preterm delivery was reported among 4.4% of sertraline users, 11.1% of citalopram users, 8% of escitalopram users, 10.6% of fluoxetine users, and 10% of paroxetine users.

These results indicated a dose-dependent association between SSRI use and bleeding complication risk among pregnant women. Investigators concluded the lowest dose of SSRI should be used to mitigate these risks.

Reference

Öndemark M, Nordström L, Lindqvist PG. Dose-dependent increase in risk of bleeding and bleeding complications in relation to SSRI use at delivery. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2024;226:265-269. doi:10.1016/j.ejogrb.2024.02.051

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