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
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.
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 adaptationExamine neurodevelopment Study of growth Examine early mother-infant relationship
Detailed description:
see brief summary
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
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
|