Preventing Postpartum Depression With Intranasal Oxytocin (IN-OXT)

The purpose of this study is to test a new treatment for preventing childbirth-related mental illness in postpartum mothers. The treatment is aimed at enhancing maternal bonding, reducing postpartum depression (PPD) and anxiety in mothers at risk, and promoting child development. To this end, the investigators will test the clinical utility of intranasal (IN) oxytocin (OXT) administered to mothers during the first postpartum days.

Postpartum depression (PPD) is a debilitating disorder which imposes a threat to mother and infant health. An estimated 600,000 American women suffer from PPD annually, making it one of the most frequent complications of pregnancy. Available secondary preventive interventions are often ineffective, which calls for identifying novel means for prevention. Impaired mother-infant bonding is a hallmark of PPD. Depressed mothers may have difficulties developing maternal feelings and providing sensitive care. In turn, impaired bonding may worsen mother's depression. Conventional pharmacotherapy does not help with bonding impairment. This study will attempt to fill in the current gap in effective preventive interventions for pregnant mothers at risk. Evidence in postpartum mothers indicates that high peripartum OXT levels are associated with enhanced maternal behavior and low levels with depression. Data also indicates that in depressed mothers, OXT levels may decrease during the first days following childbirth rather than increase as is the norm. Therefore, the investigators will test the therapeutic effects of OXT in women at risk for PPD. It is hypothesized that administration of IN-OXT (total daily dose 48 IU) over the course of four days from as early as day one postpartum in comparison to placebo will 1) enhance mother-infant bonding, 2) reduce depressive and anxiety symptoms at 5 days postpartum, and 3) facilitate child development.

Day 5 postpartum: Self-report assessment of maternal bonding 2 months postpartum: Quantitative observational assessment of mother-infant bonding and repeat of self-reports

Inclusion Criteria: Third-trimester pregnant women being followed at the MGH Obstetrics Program At risk of postpartum depression (PPD) Exclusion Criteria: Failure to participate in regular prenatal check-ups Current diagnosis DSM-5 mental disorder pertaining to psychosis or substance abuse Suicidality Obstetric complication (e.g., preeclampsia, excessive hemorrhaging) Use of potentially confounding or interacting medications Complicating pediatric medical condition in the newborn

Mah BL, Bakermans-Kranenburg MJ, Van IJzendoorn MH, Smith R. Oxytocin promotes protective behavior in depressed mothers: a pilot study with the enthusiastic stranger paradigm. Depress Anxiety. 2015 Feb;32(2):76-81. doi: 10.1002/da.22245. Epub 2014 Feb 12.

Skrundz M, Bolten M, Nast I, Hellhammer DH, Meinlschmidt G. Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression. Neuropsychopharmacology. 2011 Aug;36(9):1886-93. doi: 10.1038/npp.2011.74. Epub 2011 May 11.

Fewtrell MS, Loh KL, Blake A, Ridout DA, Hawdon J. Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants. Arch Dis Child Fetal Neonatal Ed. 2006 May;91(3):F169-74. doi: 10.1136/adc.2005.081265. Epub 2005 Oct 13.

Riem MM, Bakermans-Kranenburg MJ, Pieper S, Tops M, Boksem MA, Vermeiren RR, van Ijzendoorn MH, Rombouts SA. Oxytocin modulates amygdala, insula, and inferior frontal gyrus responses to infant crying: a randomized controlled trial. Biol Psychiatry. 2011 Aug 1;70(3):291-7. doi: 10.1016/j.biopsych.2011.02.006. Epub 2011 Apr 5. Erratum In: Biol Psychiatry. 2012 Apr 1;71(7):660.

Jobst A, Krause D, Maiwald C, Hartl K, Myint AM, Kastner R, Obermeier M, Padberg F, Brucklmeier B, Weidinger E, Kieper S, Schwarz M, Zill P, Muller N. Oxytocin course over pregnancy and postpartum period and the association with postpartum depressive symptoms. Arch Womens Ment Health. 2016 Aug;19(4):571-9. doi: 10.1007/s00737-016-0644-2. Epub 2016 Jun 20.

Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022 Feb 10;2(2):CD013443. doi: 10.1002/14651858.CD013443.pub2.