# Enhancing Prolonged Exposure Therapy for PTSD with Oxytocin

> **NIH VA I01** · RALPH H JOHNSON VA MEDICAL CENTER · 2020 · —

## Abstract

Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S.
military Veterans. PTSD is a chronic disorder that is associated with significant morbidity, mortality,
disability, and costly health care expenditures. The clinical impairment associated with PTSD among Veterans
is severe and associated with comorbid depression, suicidality, substance abuse, physical health
problems, interpersonal violence, and neuropsychiatric impairment. Despite these pervasive health
consequences, the current treatment services offered to Veterans do not adequately address PTSD.
Several promising psychosocial interventions, including Prolonged Exposure (PE) therapy, have been
developed for the treatment of PTSD. Although PE is one of the most widely used evidence-based
treatments for PTSD, there is substantial room for improvement in outcomes and retention rates. For example,
approximately one-third of patients dropout of PE treatment prematurely, and the highest dropout rates occur
among Veterans. Consistent with the VA Office of Research and Development initiative to develop effective
treatments for PTSD, identifying pharmacotherapies to enhance PTSD treatment retention and outcomes is
critical. Accumulating data from our group and others suggests that oxytocin is a promising candidate to
achieve this goal. Oxytocin is known to promote prosocial behaviors associated with successful
psychosocial treatment outcomes (e.g., trust, safety, social cognition) and has demonstrated positive effects
on extinction learning in animal and human stress models. Furthermore, recent neuroimaging studies show
that oxytocin has the ability to ameliorate dysregulation of the corticolimbic brain circuitry, which is a central
component of the pathophysiology and maintenance of PTSD. In the only study to date examining the
feasibility, acceptability, and preliminary efficacy of augmenting PE with oxytocin, our group found that
participants randomized to the oxytocin condition demonstrated lower PTSD and depression symptoms
during PE, and had higher working alliance scores compared to participants randomized to the placebo
condition. Therefore, the primary objective of the proposed two-site Phase II study is to examine the ability of
oxytocin (vs. placebo) combined with PE therapy to (1) reduce PTSD symptom severity, (2) improve
rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To
accomplish these objectives, we will employ a randomized, double-blind, placebo-controlled trial and use
standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of
treatment, and 3 and 6 month follow-up). The proposed study directly addresses the mission of the Veterans
Health Administration Blueprint for Excellence in that it seeks to advance personalized and proactive mental
health care opportunities for Veterans. Findings from this study will provide critical new information regarding
the ef...

## Key facts

- **NIH application ID:** 9890048
- **Project number:** 1I01CX001962-01A1
- **Recipient organization:** RALPH H JOHNSON VA MEDICAL CENTER
- **Principal Investigator:** JULIANNE Christina Flanagan
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890048

## Citation

> US National Institutes of Health, RePORTER application 9890048, Enhancing Prolonged Exposure Therapy for PTSD with Oxytocin (1I01CX001962-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9890048. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*