Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway

Nhung T.H. Trinh*, Trine Munk-Olsen, Naomi R. Wray, Veerle Bergink, Hedvig M.E. Nordeng, Angela Lupattelli, Xiaoqin Liu


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IMPORTANCE Approximately one-half of women treated for affective disorders discontinue antidepressant use during pregnancy, yet this discontinuation could lead to relapse post partum. OBJECTIVE To investigate the associations between longitudinal antidepressant fill trajectories during pregnancy and postpartum psychiatric outcomes. DESIGN, SETTING, AND PARTICIPANTS This cohort study used nationwide registers in Denmark and Norway. The sample included 41 475 live-born singleton pregnancies in Denmark (1997-2016) and 16 459 in Norway (2009-2018) for women who filled at least 1 antidepressant prescription within 6 months before pregnancy. EXPOSURES Antidepressant prescription fills were obtained from the prescription registers. Antidepressant treatment during pregnancy was modeled using the k-means longitudinal method. MAIN OUTCOMES AND MEASURES Initiation of psycholeptics, psychiatric emergencies, or records of self-harm within 1 year post partum. Between April 1 and October 30, 2022, hazard ratios (HRs) for each psychiatric outcome were estimated using Cox proportional hazards regression models. Inverse probability of treatment weighting was used to control for confounding. Country-specific HRs were pooled using random-effects meta-analytic models. RESULTS Among 57 934 pregnancies (mean [SD] maternal age, 30.7 [5.3] years in Denmark and 29.9 [5.5] years in Norway), 4 antidepressant fill trajectories were identified: early discontinuers (31.3% and 30.4% of the included pregnancies in Denmark and Norway, respectively), late discontinuers (previously stable users) (21.5% and 27.8%), late discontinuers (short-term users) (15.9% and 18.4%), and continuers (31.3% and 23.4%). Early discontinuers and late discontinuers (short-term users) had a lower probability of initiating psycholeptics and having postpartum psychiatric emergencies vs continuers. A moderately increased probability of initiation of psycholeptics was found among late discontinuers (previously stable users) vs continuers (HR, 1.13; 95% CI, 1.03-1.24). This increase in late discontinuers (previously stable users) was more pronounced among women with previous affective disorders (HR, 1.28; 95% CI, 1.12-1.46). No association between antidepressant fill trajectories and postpartum self-harm risk was found. CONCLUSIONS AND RELEVANCE 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. 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.

TidsskriftJAMA Psychiatry
Udgave nummer5
Sider (fra-til)441-450
StatusUdgivet - 3. maj 2023

Bibliografisk note

Funding Information:
This study was supported by grant 288696 from the Norwegian Research Council (Drs Trinh and Lupattelli), internationalization support from UiO: Life Science (Dr Trinh), Marie Skłodowska-Curie grant 891079 from the European Union's Horizon 2020 research and innovation programme (Dr Liu), and grant R01MH122869 from the National Institute of Mental Health (Drs Munk-Olsen and Bergink). Norwegian data access costs and costs to handle and store the Norwegian data in Tjeneste for Sensitive Data (TSD) were covered by the PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, University of Oslo.


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