Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition that disproportionately affects Veterans. Prolonged Exposure (PE) therapy is a "gold standard" treatment for PTSD. However, approximately one-third of Veterans fail to receive an adequate dose of treatment because they prematurely drop out of PE therapy. There is also room to improve PE treatment outcomes. Consistent with the VA Office of Research and Development initiative to develop effective treatments for PTSD, the proposed randomized clinical trial will examine the ability of oxytocin (as compared with placebo) combined with PE to reduce PTSD symptom severity, improve the rate of PTSD symptom reduction, and to enhance PE treatment retention and adherence. This two-site study will leverage the investments made in the nationwide rollout off PE therapy and has the potential to significantly improve mental health care among Veterans, advance the science in this area, and identify mechanisms underlying positive PTSD treatment response. Participants may choose to complete this research study via home-based telemedicine (HBT) care (i.e. service delivery to patients in their homes using consumer friendly, video-conferencing technology). HBT sessions will be delivered via standard desk, laptop computer, tablet, or smartphone using VA approved applications. All procedures that take place via telemedicine will be performed and completed as though they were in-person/in-office

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 the investigators' 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, the investigators' 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, the investigators 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 efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the neurobiological mechanisms underlying PTSD and positive treatment response. Participants may choose to complete this research study via home-based telemedicine (HBT) care (i.e. service delivery to patients in their homes using consumer friendly, video-conferencing technology). HBT sessions will be delivered via standard desk, laptop computer, tablet, or smartphone using VA approved applications. All procedures that take place via telemedicine will be performed and completed as though they were in-person/in-office

Inclusion Criteria:

• Veteran

• Any race or ethnicity

• Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of the assessment instruments (> 26 on the Mini Mental Status Exam)

• Meet DSM-5 diagnostic criteria for current (i.e., past 6 months) PTSD (assessed via the CAPS-5)

  • participants may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria)
  • anxiety disorders (e.g. panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive disorder)

• Participants taking psychotropic medications will be required to be maintained on a stable dose for at least four weeks before study initiation

Exclusion Criteria:

• Meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, or with current suicidal or homicidal ideation and intent

  • those participants will be referred clinically

• Participants who present a serious suicide risk or are likely to require hospitalization during the study

• Participants on maintenance anxiolytic, antidepressant, or mood stabilizing medications, which have been initiated during the past 4 weeks

• Pregnancy or breastfeeding for women

From baseline through 10 week treatment phase and through 6 month follow up phase.