Unveiling the hidden triad of antidepressants, benzodiazepines, and Z-hypnotics during pregnancy: A 15-year population-based study in Taiwan.

Objective: Understanding the trends and determinants of antidepressant use during pregnancy, especially when combined with sedative-hypnotics, is critical for balancing maternal mental health needs with potential fetal risks. However, the patterns of antidepressant use, both alone and with sedative-hypnotics, across different stages of pregnancy remain poorly investigated. This study aims to investigate trends in antidepressant use during pregnancy and explore the prevalence and determinants of concomitant use with BZDs or Z-hypnotics.

Methods: We conducted a retrospective cohort study using Taiwan's National Health Insurance and Birth Certificate Application databases from 2004 to 2018. The temporal trends of antidepressant use during pregnancy were reported annually, and the utilization patterns of antidepressants across different pregnancy stages were evaluated using interrupted time series analysis (ITSA). The concomitant use of antidepressants with BZDs or Z-hypnotics was defined as any overlap of prescription periods and reported annually. Logistic regression models were adopted to investigate determinants associated with the concomitant use.

Results: Among 2,930,988 pregnancies, antidepressant use increased from 0.48 % in 2004 to 1.00 % in 2018 (Annual Percent Change [APC]: 4.7 %, 95 % Confidence Interval [CI]: 4.0 % to 5.4 %). Antidepressant use decreased after pregnancy recognition (level change -0.26, 95 % CI -0.28 to -0.24) and increased postpartum (level change 0.05, 95 % CI 0.04 to 0.07). Among antidepressant users, 65 % concomitantly used BZDs and 41 % concomitantly used Z-hypnotics. Notably, alcohol abuse (OR 4.08, 95 % CI 2.13-7.81), substance abuse (OR 3.91, 95 % CI 2.15-7.12), depression (OR 3.54, 95 % CI 3.29-3.82), and insomnia (OR 3.61, 95 % CI 3.25-4.00) were significant determinants of concomitant use.

Conclusions: Antidepressant use during pregnancy increased over time, with high rates of concomitant BZD and Z-hypnotic use. The shift from BZDs to Z-hypnotics as pregnancy progressed, and the identified determinant factors for concomitant use highlight the need for tailored interventions and further research on the safety of these combinations.