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

Nhung TH Trinh,1 Hedvig ME Nordeng,1,2 Gretchen Bandoli,3,4 Kristin Palmsten,5 Malin Eberhard-Gran,6,7 Angela Lupattelli1 1PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway; 2Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway; 3Department of Pediatrics, University of California San Diego, La Jolla, CA, USA; 4Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA; 5HealthPartners Institute, Minneapolis, MN, USA; 6Norwegian Research Centre for Women’s Health, Women’s and Children’s Division, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 7Institute for Clinical Medicine, University of Oslo, Oslo, NorwayCorrespondence: Nhung TH Trinh, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Post box 1068 Blindern, Oslo, 0316, Norway, Email [email protected]: 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.Keywords: longitudinal k-means trajectory modelling, antidepressant fill trajectories, depression, anxiety, pregnancy, drug utilizatio

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. PROSPERO, CRD42016035711