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Antidepressants During Pregnancy and Lactation: Pharmacokinetics and Clinical Implications

Information source: Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Depressive Disorder; Lactation

Intervention: SSRI/SNRI (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Centre Hospitalier Universitaire Vaudois

Official(s) and/or principal investigator(s):
Chantal Csajka, Prof PhD, Principal Investigator, Affiliation: Centre Hospitalier Universitaire Vaudois (CHUV)

Overall contact:
Chantal Csajka, Prof PhD, Phone: 0041 21 314 42 63, Email: chantal.csajka@chuv.ch


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.

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Primary outcome: Evaluate the pharmacokinetics of SSRI/SNRI antidepressant drugs in breast milk secretion

Secondary outcome:

Examine neonatal adaptation

Examine neurodevelopment

Study of growth

Examine early mother-infant relationship

Detailed description: see brief summary


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.


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.

Locations and Contacts

Chantal Csajka, Prof PhD, Phone: 0041 21 314 42 63, Email: chantal.csajka@chuv.ch

Service d'Obstétrique, Service du Développement et de la Croissance; Hopitaux Universitaires Genevois (HUG), Geneva, Switzerland; Recruiting
Manuella Epiney, MD, Email: manuella.epiney@hcuge.ch
Manuella Epiney, MD, Principal Investigator
Cristina Borradori Tolsa, MD, Principal Investigator

Service d'Obstétrique, Service de Néonatologie; Centre Hospitalier Universitaire Nancy, Nancy, Meurthe-et-Moselle, France; Recruiting
Jean-Michel Hascoët, Prof MD, Email: jm.hascoet@maternite.chu-nancy.fr
Jean-Michel Hascoët, Prof MD, Principal Investigator
Catherine Lamy, MD, Sub-Investigator

Service d'Obstétrique, Service de Néonatologie; Hospices civiles de Lyon (HCL), Lyon, Rhône, France; Recruiting
Olivier Claris, Prof MD, Email: olivier.claris@chu-lyon.fr
Olivier Claris, Prof MD, Principal Investigator
Pascal Gaucherand, Prof MD, Sub-Investigator
Etienne Beaufils, MD, Sub-Investigator
Kim NGuyen, MD, Sub-Investigator

Division de Pharmacologie Clinique, Service d'Obstétrique, Service de Néonatologie, Service de Pédopsychiatrie de liaison, Unité de Pharmacogénétique et Psychopharmacologie Clinique; Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Vaud, Switzerland; Recruiting
Chantal Csajka, Prof PhD, Email: chantal.csajka@chuv.ch
Chantal Csajka, Prof PhD, Principal Investigator
Alice Panchaud, PhD, Sub-Investigator
Chin B Eap, Prof PhD, Sub-Investigator
Jean-Francois Tolsa, Prof MD, Sub-Investigator
Yvan Vial, MD MER, Sub-Investigator
Myriam Bickle Graz, MD, Sub-Investigator
Mathilde Morisod Harari, MD, Sub-Investigator
Céline Fischer, MD, Sub-Investigator

Service d'Obstétrique, Service de Pédiatrie; Ensemble Hospitalier de la Côte (EHC), Morges, Vaud, Switzerland; Recruiting
Sylvie Rouiller, MD, Email: sylvie.rouiller@ehc.vd.ch
Sylvie Rouiller, MD, Principal Investigator

Additional Information

Related publications:

McNamara PJ, Abbassi M. Neonatal exposure to drugs in breast milk. Pharm Res. 2004 Apr;21(4):555-66. Review.

Goldman AS, Hopkinson JM, Rassin DK. Benefits and risks of breastfeeding. Adv Pediatr. 2007;54:275-304. Review.

Marcus SM, Flynn HA, Blow FC, Barry KL. Depressive symptoms among pregnant women screened in obstetrics settings. J Womens Health (Larchmt). 2003 May;12(4):373-80.

Bennett HA, Einarson A, Taddio A, Koren G, Einarson TR. Prevalence of depression during pregnancy: systematic review. Obstet Gynecol. 2004 Apr;103(4):698-709. Review. Erratum in: Obstet Gynecol. 2004 Jun;103(6):1344.

Poobalan AS, Aucott LS, Ross L, Smith WC, Helms PJ, Williams JH. Effects of treating postnatal depression on mother-infant interaction and child development: systematic review. Br J Psychiatry. 2007 Nov;191:378-86. Review.

di Scalea TL, Wisner KL. Pharmacotherapy of postpartum depression. Expert Opin Pharmacother. 2009 Nov;10(16):2593-607. doi: 10.1517/14656560903277202. Review.

Sie SD, Wennink JM, van Driel JJ, te Winkel AG, Boer K, Casteelen G, van Weissenbruch MM. Maternal use of SSRIs, SNRIs and NaSSAs: practical recommendations during pregnancy and lactation. Arch Dis Child Fetal Neonatal Ed. 2012 Nov;97(6):F472-6. doi: 10.1136/archdischild-2011-214239. Review. Erratum in: Arch Dis Child Fetal Neonatal Ed. 2013 Mar;98(2):F180.

Horstmann S, Binder EB. Pharmacogenomics of antidepressant drugs. Pharmacol Ther. 2009 Oct;124(1):57-73. doi: 10.1016/j.pharmthera.2009.06.007. Epub 2009 Jun 27. Review.

Baumann P, Eap CB. Enantiomeric antidepressant drugs should be considered on individual merit. Hum Psychopharmacol. 2001 Dec;16(S2):S85-S92.

Panchaud A, Garcia-Bournissen F, Csajka C, Kristensen JH, Taddio A, Ilett KF, Begg EJ, Ito S. Prediction of infant drug exposure through breastfeeding: population PK modeling and simulation of fluoxetine exposure. Clin Pharmacol Ther. 2011 Jun;89(6):830-6. doi: 10.1038/clpt.2011.23. Epub 2011 Apr 27.

Lobo ED, Quinlan T, O'Brien L, Knadler MP, Heathman M. Population pharmacokinetics of orally administered duloxetine in patients: implications for dosing recommendation. Clin Pharmacokinet. 2009;48(3):189-97. doi: 10.2165/00003088-200948030-00005. Erratum in: Clin Pharmacokinet. 2011 Oct 1;50(10):687-8.

Starting date: August 2012
Last updated: July 27, 2015

Page last updated: August 23, 2015

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