Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor-Treated Women.

Objective: Tracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum. Methods: This is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers (N = 85) and a single rural health center (N = 3) from 2016 to 2020. Pregnant women had at least one prior episode of major depressive disorder, were not in a current episode, and were treated with sertraline, fluoxetine, citalopram, or escitalopram. Of 192 women screened, 88 (46%) women enrolled, and 77 (88%) women completed the postpartum follow-up. Symptom trajectories were generated with scores from the Edinburgh Postnatal Depression Scale, the Quick Inventory of Depressive Symptoms, the Generalized Anxiety Disorder Scale, 7-item, and the Patient-Reported Outcomes Measurement Information System Global Health measure. A semi-parametric, group-based mixture model (trajectory analysis) was applied. Results: Three relatively stable depression trajectories emerged, described as Minimal, Mild, and Subthreshold, in each group across pregnancy. Two of the four anxiety trajectories were stable, including Asymptomatic and Minimal, while the third, termed Breakthrough, was ascending with increasing symptoms and the fourth trajectory, described as Mild, had descending symptoms. Conclusions: Screening for anxiety with depression for pregnant women will yield a comprehensive view of psychiatric symptoms and treatment targets in perinatal women.

Changes in Sertraline Plasma Concentrations Across Pregnancy and Postpartum.

Major depressive disorder (MDD) is a common disorder in pregnancy. Although sertraline is the most frequently prescribed antidepressant for pregnant people in the United States, limited information about its pharmacokinetics in pregnancy is available. Our objectives were to characterize plasma sertraline concentration to dose (C/D) ratios across pregnancy and postpartum and investigate the effect of pharmacogenetic variability on sertraline elimination. We performed a prospective observational cohort study in people with a singleton pregnancy ≤ 18 weeks gestation and a lifetime diagnosis of MDD at the 3 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)-funded Obstetrical-Fetal Pharmacology Research Center sites. Subjects (N = 47) were receiving maintenance sertraline therapy and chose to continue it during pregnancy. Blood samples were obtained 24-hours postdose every 4 weeks across pregnancy and twice postpartum for measurement of plasma concentrations of sertraline and desmethylsertraline. Overall mean sertraline C/D ratios were decreased at study onset and remained consistently low until after delivery. During the last 4 weeks of pregnancy the mean sertraline C/D ratio (95% confidence interval (CI)), 0.25 (95% CI, 0.19, 0.3) ng/mL/dose (mg/day), was smaller than the mean ratio at ≥ 8 weeks after delivery, 0.32 (95% CI, 0.27, 0.37) ng/mL/dose (mg/day), a 22% difference. Mean sertraline/desmethylsertraline ratios were highest after birth, which confirmed increased sertraline elimination during pregnancy. Sertraline C/D ratios in participants with functional CYP2C19 activity did not change significantly during pregnancy, whereas ratios in participants with poor or intermediate CYP2C19 activity decreased by 51%. Exploratory pharmacogenomic analysis indicated that pregnant people with poor or intermediate CYP2C19 activity are at risk for subtherapeutic sertraline concentrations during pregnancy.

Treatment Integrity Failures during Timeout from Play.

Timeout is an effective behavior-reduction strategy with considerable generality. However, little is known about how timeout is implemented under natural conditions, or how errors in implementation impact effectiveness. During Experiment 1, we observed teachers implementing timeout during play to evaluate how frequently the teachers implemented timeout following target behavior (omission errors) and other behaviors (commission errors) for four children. Teachers rarely implemented timeout; thus, omission errors were frequent, but commission errors rarely occurred. During Experiment 2, we used a reversal design to compare timeout implemented with 0% omission integrity, 100% integrity, and the level of omission integrity observed to occur during Experiment 1 for two of the participants. Timeout implemented with reduced-integrity decreased problem behavior relative to baseline, suggesting that infrequent teacher implementation of timeout may have been sufficient to reduce problem behavior.

A common clinical conundrum: Antidepressant treatment of depression in pregnant women.

Depression during pregnancy is associated with adverse maternal, pregnancy, and infant outcomes. Treatment during pregnancy requires a balanced discussion of the risks of both drug exposure and untreated depression. An updated review of the epidemiology, outcomes, and management of maternal depression is presented. Adverse outcomes are associated with both maternal depression and antidepressants. Research gaps include data on the longitudinal developmental trajectory of offspring exposed to antidepressants compared to depression, with assessment of in utero symptom exposure and environmental exposures. Additionally, neonatal syndrome associated with antidepressant use during pregnancy has no consensus definition or mechanistic explanation. With sophisticated large-scale epidemiologic studies, there has been progress in distinguishing the impact of depression processes from medication used for treatment. Optimal treatment of perinatal depression includes close symptom monitoring and medication adjustments to maintain symptom remission. This evolving field requires frequent consultation with reproductive data sources included in this article.