Women with Severe Mental Illness Benefit from Continuing Antidepressant Use During Pregnancy

Women with severe mental illness who are on stable antidepressant treatment when they become pregnant may benefit from continuing pharmacotherapy during pregnancy, according to new research from Scandinavia that analyzed national register data from approximately 60 000 pregnancies.

Writing in JAMA Psychiatry, Nhung Trinh, PhD, of the PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, at the University of Oslo and colleagues note that approximately one-half of women who are being treated for an affective disorder elect to stop antidepressant therapy during pregnancy, a decision that may have benefits but that also poses the risk for relapse after giving birth.

“The treatment of pregnant women with antidepressants must balance possible risks of untreated mental disorders against fetal drug exposure,” the authors wrote. “While psychiatric disorders before and during pregnancy are known to be associated with postpartum mental health, few studies have addressed how antidepressant use before and during pregnancy influences postpartum psychiatric outcomes.” The small number of studies that have been conducted have yielded conflicting results, they add.

“While psychiatric disorders before and during pregnancy are known to be associated with postpartum mental health, few studies have addressed how antidepressant use before and during pregnancy influences postpartum psychiatric outcomes.”

Trinh and colleagues from Denmark, Australia, New York, and the Netherlands investigated further, analyzing the associations between longitudinal antidepressant prescription fill trajectories during pregnancy and postpartum psychiatric outcomes in a large Scandinavian cohort.

For the study data, investigators tapped population-based registers in Denmark and Norway including both prescription and medical birth registers. They identified 41 475 live-born singleton pregnancies in Denmark between 1997-2016 and 16 459 live-born singleton pregnancies in Norway between 2009-2018 for women who filled at least 1 antidepressant prescription within 6 months prior to pregnancy. Mean maternal age was 30.7 years in Denmark and 29.9 years in Norway, the authors report.

The team obtained data on antidepressant prescription fills from the Norwegian Prescription Database and the Danish National Prescription Register and in each country applied the k-means for longitudinal (KmL) data trajectory modeling method to antidepressant treatment from 6 months prior to pregnancy through gestational week 37 to cluster the cohort into groups.

The researchers’ primary outcomes of interest were initiation of psycholeptics, psychiatric emergencies, or records of self-harm within 1-year post-partum.

Using the 4 antidepressant fill trajectories identified (at right), Trinh et al found the following distribution for included pregnancies in Denmark and Norway, respectively:

• Early discontinuers: 31.3% and 30.4%
• Late discontinuers (previously stable users) 21.5% and 27.8%
• Late discontinuers (short-term users) 15.9% and 18.4%
• Continuers: 31.3% and 23.4%

Overall, their analyses found a lower probability of initiating psycholeptics and having postpartum psychiatric emergencies in the early discontinuer and late discontinuer groups compared to the continuers.

The investigators observed a moderately increased probability of initiating psycholeptics among late discontinuers compared to continuers (hazard ratio [HR] 1.13, 95% CI, 1.03-1.24), which was more pronounced among participants with previous affective disorders (HR 1.28, 95% CI, 1.12-1.46).

They also reported finding no association between antidepressant fill trajectories and postpartum self-harm.

Among limitations mentioned the authors include that the analysis of risk of self-harm relied solely on Danish data so an accurate conclusion based on the small sample size was not possible. Also, residual confounding by treatment indications may persist despite the inclusion of several variables as proxy of disease severity.

“Based on pooled data from Denmark and Norway, a moderately elevated probability of initiation of psycholeptics in late discontinuers (previously stable users) vs continuers was found,” the authors wrote. “These findings suggest that women with severe mental illness who are currently on stable treatment may benefit from continuing antidepressant treatment and personalized treatment counseling during pregnancy.”

Reference: Trinh NTH, Munk-Olsen T, Wray NR, et al. Timing of antidepressant discontinuation during pregnancy and postpartum psychiatric outcomes in Denmark and Norway. JAMA Psychiatry. Published online March 08, 2023. doi:10.1001/jamapsychiatry.2023.0041