Drug use during pregnancy with focus on antidepressants

Abstract: Background: More than half of pregnant women use at least one prescribed medication during pregnancy, and almost all pregnant women use some kind of over-the-counter medication. Depression is one of the most common diseases in the world today, also during the peripartum period. The prevalence of pregnant women using antidepressant medication is increasing. General knowledge about the use of medication during pregnancy needs to improve. The overall aim of the studies on which this thesis is based is therefore to examine different aspects of medication use during pregnancy, with a focus on antidepressants.Material and methods: Study I was a questionnaire study where 850 pregnant women were asked about their perceptions on medication use during pregnancy. In Study II, plasma samples from 200 women were obtained at gestational weeks 10-12 and 25, and screened for drugs. The results of the analysis were compared with medication use noted in antenatal medical care records. Study III was a national register‐based cohort study including 262,329 pregnant women, and their first child born in 2012-2015. Maternal obstetric and neonatal outcomes were studied in three groups: women diagnosed with depression and who had redeemed an antidepressant before becoming pregnant and women who were diagnosed with depression and who had redeemed an antidepressant both before and during pregnancy, were compared with each other and with women who had neither been diagnosed with depression nor been prescribed antidepressants. Study IV was a pharmacokinetic study that included 81 pregnant women with ongoing antidepressant medical treatment. Antidepressant drug and metabolite concentrations were measured throughout pregnancy. Participants were genotyped for enzymes involved in antidepressant drug metabolism, i.e. CYP2D6 and CYP2C19. Results and conclusions: The majority of pregnant women in our study considered the use of medication during pregnancy as either “probably harmful” or “harmful”, and this perception was associated with non-use of medication. The women had high confidence in health care professionals when seeking advice about medication.There was a good coherence between reported drug intake in antenatal care records and presence of the drug in the pregnant women’s blood. For drugs prescribed for continuous use the coherence was 100%; thus, the reported use of medication in antenatal records is reliable. Women with major depressive disorder and antidepressant medication prior to becoming pregnant were at increased risk for adverse obstetric and neonatal outcomes compared with women without major depressive disorder. Continuation of antidepressant medication during pregnancy somewhat increased the risk of adverse obstetric and neonatal outcomes. The dose-adjusted concentrations of sertraline and citalopram and their metabolites, did not change significantly throughout pregnancy. Observed concentrations of escitalopram, mirtazapine and venlafaxine did not appear to change.