Antidepressant continuation and adherence in pregnancy, and risk of antenatal hospitalization for unipolar major depressive and/or anxiety disorders

Background: Knowledge about the effectiveness of antidepressants in pregnancy is limited. We aimed to evaluate the association of antidepressant continuation in pregnancy and adherence with the risk of antenatal hospitalization for depression/anxiety. Methods: In a population-based study based on the healthcare databases of the Lombardy region, Italy (2010–2020), we included 17,033 live-birth pregnancies within 16,091 women with antidepressant use before pregnancy. Antidepressant exposure was classified as continued in pregnancy versus discontinued proximal to pregnancy. Outcome measure was antenatal hospitalization for depression/anxiety. Propensity score matching analysis was performed to control for measured confounding. Stratification by pre-pregnancy antidepressant adherence based on the proportion of days covered (PDC) with antidepressants served to address confounding by disease severity. We applied 60 days lag-time for antidepressant exposure to minimize the risk of protopathic bias. Results: There were 362 (2.1 %) antenatal hospitalizations for depression/anxiety. Among the matched pairs, the cumulative incidence was 3.5 (continued antidepressant) versus 2.1 (discontinued antidepressant) per 1000 person-months, yielding a hazard ratio (HR) of 1.76 (95 % confidence interval (CI): 1.34–2.33)). The HR declined to the null (1.02, 95 % CI: 0.62–1.69) in the stratified analysis of pregnancies with moderate-high adherence pre-pregnancy. Moderate-high adherence in pregnancy was associated with 85 % greater risk of the antenatal outcome, but the HR decreased with the 60 days lag-time (HR: 1.40, 95 % CI: 0.79–2.50). Limitations: Lack of information regarding antidepressant dosage. Conclusion: We found no difference in risk for antenatal hospitalization for depression/anxiety with antidepressant continuation or higher adherence in pregnancy, relative to discontinuation or lower adherence.