Antidepressants During Pregnancy and Lactation: Pharmacokinetics and Clinical Implications
Status:
Unknown status
Trial end date:
2018-12-01
Target enrollment:
Participant gender:
Summary
Background: The childbearing years are a time of increased vulnerability to the onset of mood
disorders in women and a high prevalence of exposure to antidepressant drugs during pregnancy
and postpartum has been reported. However, the lack of information regarding the milk
transfer and the safety of these drugs in breastfed infants and the related fear of adverse
events for the sucking infant are some of the factors responsible for stopping prematurely
breast-feeding or avoiding drug therapy. Selective serotonin reuptake inhibitors (SSRI) and
selective serotonin and noradrenaline reuptake inhibitors (SNRI) are the most frequently
prescribed antidepressant drugs during pregnancy and the post-partum period. They exhibit a
wide interpatient variability in their concentration profiles that has been related to
numerous environmental, stereochemical, demographic and genetic influences that might alter
the level of exposure of breastfed newborns. Limited information is available regarding the
safety of use of these antidepressant drugs during lactation, and is generally derived from
small studies. A comprehensive description of their distribution and quantification in milk
in a larger cohort of patients under various influences and the resulting impact on milk
concentrations is lacking.
Objectives: The current proposal addresses the primary objectives of quantifying the range of
concentration to citalopram, escitalopram, sertraline, fluoxetine, paroxetine, fluvoxamine,
duloxetine and venlafaxine in mother plasma and breast milk in relation to genetic
polymorphisms, stereochemistry, demographics and environmental factors in a large cohort of
depressive mothers. This will enable to derive the exposure to the breast-fed child taking
into account this variability and therefore better adjust treatment to potential influences.
As secondary objectives, we will examine the neurodevelopmental outcome of a sub-set of
infants subjected to SSRI/SNRI in utero and/or during breastfeeding at birth, 6, 18 and 36
months, and compared to that of a control population of infants not subjected to this
treatment.
Expected Results: The proposed strategy will offer new information regarding the expected
level of drug exposure associated with each or with a combination of risk factors and help
for optimizing the security and rationalizing the use of antidepressant treatment in
lactating women. Hence, research on the safety of use of these drugs for the developing child
is an area of great public health significance.
Phase:
Phase 4
Details
Lead Sponsor:
Centre Hospitalier Universitaire Vaudois
Collaborators:
Central Hospital, Nancy, France Hospices Civils de Lyon University Hospital, Geneva