Antidepressants During Pregnancy and Lactation: Pharmacokinetics and Clinical Implications

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.

Conditions

• Depressive Disorder
• Lactation

Interventions

DRUG

SSRI/SNRI

Exposed group of mothers taking one of the mentioned antidepressant drugs of the class of selective serotonin reuptake inhibitors (SSRI) or serotonin/noradrenalin reuptake inhibitors (SNRI).

Sponsors & Collaborators

• University Hospital, Geneva

  collaborator OTHER

• Hospices Civils de Lyon

  collaborator OTHER

• Central Hospital, Nancy, France

  collaborator OTHER

• Centre Hospitalier Universitaire Vaudois

  lead OTHER

Principal Investigators

• Chantal Csajka, Prof PhD · Centre Hospitalier Universitaire Vaudois (CHUV)

Study Design

Allocation

NON_RANDOMIZED

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-08-31

Primary Completion

2016-12-31

Completion

2018-12-31

Countries

• France
• Switzerland

Study Locations