Project Summary Over the past decades, the use of antidepressants (ADs) as first-line treatment for both depressive and anxiety disorders has increased exponentially, with females in their reproductive years using ADs twice as often as men. Prior to conception or during pregnancy, approximately 50% of women on ADs (200,000 pregnant women in the US each year) decide to discontinue their medication. While the wish to avoid in utero AD exposure to the fetus is understandable, discontinuation of medication might lead to relapse, which can have a profound negative impact on the health of mother and child. Unfortunately, general information on relapse risks after AD discontinuation cannot be used during pregnancy and the postpartum period given the enormous changes in physiology and emotion. Further, women discontinue AD prior to or during pregnancy regardless of their mood stability, which has an impact on relapse risk. Only three small studies in highly selected populations have investigated relapse risks during pregnancy and not a single study on AD discontinuation during pregnancy has investigated the relapse risk postpartum. This study will quantify the relapse risk during pregnancy and postpartum after AD discontinuation, for the first time, in a large and representative population sample. We will use the unique Danish national longitudinal registers covering medication use since 1995 in the entire female population giving birth aged 15-49 years (N=1,098,137). With our sample size, we will be able to identify both pregnancy specific and non-pregnancy specific risk factors for relapse and timing to relapse. We will determine to which extent the perinatal period is different in terms of relapse risks after AD discontinuation compared to other periods in a woman’s life. In addition, we will explore if women with high genetic susceptibility for mood-disorders are more vulnerable for relapse after AD discontinuation. In our last aim we will determine the long-term effects (up to 24 years) of maternal relapse during pregnancy and the postpartum period on the offspring. We will conduct a sibling comparison, in which we compare the health outcomes in children exposed to maternal relapse to their siblings not exposed to maternal relapse in the perinatal period. We will explore if polygenic risk scores of the children influence the association between their exposure to maternal relapse and their long-term psychiatric outcome, considering in utero exposure to AD medication.

Project Narrative The proposed investigations have significant potential to identify women who may discontinue antidepressants with limited risk of relapse. We will identify risk factors for relapse and determine the long-term effect of relapse on the offspring.