Antidepressant Fill and Dose Trajectories in Pregnant Women with Depression and/or Anxiety: A Norwegian Registry Linkage Study

Abstract

Background: Few studies investigated longitudinal antidepressant exposure during pregnancy and included dosage in the assessment. Methods: We conducted a nationwide, registry-linkage study in Norway using data on antidepressant prescription fills in pregnancies lasting ≥32 weeks in women with a delivery between 2009 and 2018 who had a depression/anxiety diagnosis and antidepressant fills prior to pregnancy. Information on antidepressant exposure by week (measured by filled prescriptions) and prescribed average daily dose was used in longitudinal k-means trajectory modelling for a 108-week time window from six months prior to pregnancy to one year after delivery. Factors associated with trajectory group membership were examined using multinomial logistic regression models. Results: We included 8,460 pregnancies in 8,092 women. Four antidepressant fill trajectories were identified based on filled antidepressant prescriptions: two distinct discontinuing patterns, one at around the start of pregnancy (30.4%) and one around the end of pregnancy (33.8%); one continuing pattern (20.6%); and one interrupting pattern (15.2%). Using average usual daily dose, we identified low dose discontinuing (60.3%), medium dose reducing (20.6%) and high dose continuing (15.2%) patterns. The multinomial logistic regressions showed that the fill trajectory group membership was strongly associated with: antidepressant type and dose prior to pregnancy and co-medication prior to pregnancy, maternal age, marital status, parity, previous pregnancy loss, and pregnancy planning. Conclusion: Longitudinal trajectory modelling revealed distinct antidepressant fill and dosage patterns in the period around pregnancy. Knowledge about factors associated with utilization trajectories might be useful for health-care personnel counselling women about antidepressant use in pregnancy.

Switching pattern and dose adjustment of antidepressants before and during pregnancy

“…This study also spans a longer study period to analyze AD prescriptions’ switching patterns and dose adjustments over time. Lastly, the observed trends in current study were comparable to findings from other studies in France and four Nordic countries (Zoega et al 2015 ; Bénard-Laribière et al 2018 ; Trinh et al 2022 ), indicating external validity of the study outcomes.…”

“…The absolute difference in the mean DDDs for all ADs studied was less than 10% change before and during pregnancy for all ADs studied, indicating that the observed DDD adjustment was meager, mostly comparable, and considered to be clinically irrelevant. A similar result of slight difference (<10%) in the mean DDDs before and during pregnancy among AD continuers has been reported in Norway (Trinh et al 2022 ). The only exception AD with a significant adjustment of DDD is sertraline.…”

Partner support for women’s antidepressant treatment and its association with depressive symptoms in pregnant women, mothers, and women planning pregnancy

“…Women planning pregnancy constitute an understudied population group (Barker et al 2020 ), and most research to date has focused on depression during and after pregnancy (Tuohy and McVey 2008 ; Putnam et al 2017 ). Women being unsupported by their partner may discontinue their antidepressant treatment also at the phase of preconception, thereby entering the pregnancy with clinically relevant symptoms of anxiety, which may increase the risk of multiple negative outcomes for both mother and child (Trinh et al 2022 ). Future studies of larger sample size are needed to better understand the role of partner support on the mental health of women planning pregnancy.…”

“…In moderate-to-severe cases of perinatal depression and/or anxiety, or if first-line psychotherapy has been ineffective, antidepressant medication, mainly selective serotonin reuptake inhibitors (SSRIs), is the preferred pharmacological choice. About 2–3% of women in Europe and 4–10% in North America receive SSRIs during pregnancy (Yonkers et al 2009 ; Battle et al 2013 ; Zoega et al 2015 ).Pregnancy remains a major driver of antidepressant discontinuation (Trinh et al 2022 ), and interruption of treatment may have negative implications for maternal perinatal mental health outcomes (Trinh et al 2023 ).…”