Antidepressants During Pregnancy and Lactation: Pharmacokinetics and Clinical Implications

NCT ID: NCT01796132

Last Updated: 2015-07-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-31

Study Completion Date

2018-12-31

Brief Summary

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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.

Detailed Description

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see brief summary

Conditions

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Depressive Disorder Lactation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

NONE

Study Groups

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Control

Pregnant and/or nursing mothers not taking a SSRI or SNRI antidepressant are recruited in a non-exposed group (Control or no SSRI/SNRI). Control group participates only in the sub-studies related to neonatal adaptation, neurodevelopment, growth and early mother-infant relationship.

Group Type NO_INTERVENTION

No interventions assigned to this group

SSRI/SNRI exposure

Pregnant and/or nursing mothers under SSRI or SNRI treatment are recruited in an exposed group (SSRI/SNRI exposure). Drug regimen including dosage, frequency and duration is not modified by the study.

Group Type EXPERIMENTAL

SSRI/SNRI

Intervention Type DRUG

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).

Interventions

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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).

Intervention Type DRUG

Other Intervention Names

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citalopram duloxetine escitalopram fluoxetine fluvoxamine paroxetine sertraline venlafaxine

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Geneva

OTHER

Sponsor Role collaborator

Hospices Civils de Lyon

OTHER

Sponsor Role collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role collaborator

Centre Hospitalier Universitaire Vaudois

OTHER

Sponsor Role lead

Responsible Party

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Chantal Csajka

Prof PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Chantal Csajka, Prof PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Vaudois (CHUV)

Locations

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Service d'Obstétrique, Service de Néonatologie; Centre Hospitalier Universitaire Nancy

Nancy, Meurthe-et-Moselle, France

Site Status RECRUITING

Service d'Obstétrique, Service de Néonatologie; Hospices civiles de Lyon (HCL)

Lyon, Rhône, France

Site Status RECRUITING

Service d'Obstétrique, Service du Développement et de la Croissance; Hopitaux Universitaires Genevois (HUG)

Geneva, Canton of Geneva, Switzerland

Site Status RECRUITING

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, Canton of Vaud, Switzerland

Site Status RECRUITING

Service d'Obstétrique, Service de Pédiatrie; Ensemble Hospitalier de la Côte (EHC)

Morges, Canton of Vaud, Switzerland

Site Status RECRUITING

Countries

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France Switzerland

Central Contacts

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Chantal Csajka, Prof PhD

Role: CONTACT

0041 21 314 42 63

Alice Panchaud, PhD

Role: CONTACT

0041 21 314 42 76

Facility Contacts

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Jean-Michel Hascoët, Prof MD

Role: primary

Olivier Claris, Prof MD

Role: primary

Manuella Epiney, MD

Role: primary

Chantal Csajka, Prof PhD

Role: primary

Sylvie Rouiller, MD

Role: primary

References

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McNamara PJ, Abbassi M. Neonatal exposure to drugs in breast milk. Pharm Res. 2004 Apr;21(4):555-66. doi: 10.1023/b:pham.0000022401.14710.c5.

Reference Type BACKGROUND
PMID: 15139511 (View on PubMed)

Goldman AS, Hopkinson JM, Rassin DK. Benefits and risks of breastfeeding. Adv Pediatr. 2007;54:275-304. doi: 10.1016/j.yapd.2007.03.014.

Reference Type BACKGROUND
PMID: 17918475 (View on PubMed)

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. doi: 10.1089/154099903765448880.

Reference Type BACKGROUND
PMID: 12804344 (View on PubMed)

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. doi: 10.1097/01.AOG.0000116689.75396.5f.

Reference Type BACKGROUND
PMID: 15051562 (View on PubMed)

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. doi: 10.1192/bjp.bp.106.032789.

Reference Type BACKGROUND
PMID: 17978316 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 19874247 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23080479 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19563827 (View on PubMed)

Baumann P, Eap CB. Enantiomeric antidepressant drugs should be considered on individual merit. Hum Psychopharmacol. 2001 Dec;16(S2):S85-S92. doi: 10.1002/hup.336.

Reference Type BACKGROUND
PMID: 12404713 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21525869 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19385712 (View on PubMed)

Weisskopf E, Guidi M, Fischer CJ, Bickle Graz M, Beaufils E, Nguyen KA, Morisod Harari M, Rouiller S, Rothenburger S, Gaucherand P, Kassai-Koupai B, Borradori Tolsa C, Epiney M, Tolsa JF, Vial Y, Hascoet JM, Claris O, Eap CB, Panchaud A, Csajka C. A population pharmacokinetic model for escitalopram and its major metabolite in depressive patients during the perinatal period: Prediction of infant drug exposure through breast milk. Br J Clin Pharmacol. 2020 Aug;86(8):1642-1653. doi: 10.1111/bcp.14278. Epub 2020 Apr 14.

Reference Type DERIVED
PMID: 32162723 (View on PubMed)

Other Identifiers

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320030_135650

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2012-004509-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SSRI-Milk

Identifier Type: -

Identifier Source: org_study_id

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