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.

Brief Title

Antidepressants During Pregnancy and Lactation: Pharmacokinetics and Clinical Implications

Official Title

Antidepressant Treatments During Pregnancy and Lactation: Prediction of Drug Exposure Through Breastfeeding and Evaluation of Drug Effect on the Neonatal Adaptation and the Development of the Young Child

Brief Summary

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

Detailed Description

see brief summary

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Inclusion Criteria:

  -  Patients planning to deliver in the 5 maternities involved in the study;

  -  Mothers under treatment by any SSRI/SNRI (fluvoxamine, fluoxetine, paroxetine,
     duloxetine, citalopram, escitalopram, sertraline or venlafaxine);

  -  Mothers who intent to breastfeed their child;

  -  Ability to understand and willingness to sign a written informed consent document for
     plasma and milk withdrawal and pharmacogenetic testing.

  -  For the neurodevelopment follow-up part,all babies of the Maternity of Lausanne,
     Morges or Geneva exposed to SSRI/SNRI will be enrolled. A control group of infants of
     the same socio-economic status as the subset of exposed patients will be recruited in
     the Maternity Hospital of Lausanne.

Exclusion Criteria:

  -  Mothers <18 years of age patients;

  -  Infants of gestational age < 34 weeks;

  -  Mothers giving birth to infants with major malformations;

  -  Inability to communicate due to language problems for the mother;

  -  Patients with a socio-economic context making close monitoring of the child by the
     mother or a relative not possible.