COPE and oxytocin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in U.S. military veterans.

BACKGROUND: A significant proportion of individuals with alcohol use disorder (AUD) also meet criteria for posttraumatic stress disorder (PTSD). Military veterans are at increased risk for developing co-occurring AUD/PTSD, with prevalence rates 2-4 times higher than the general population. Research is needed to develop more effective treatments for this common comorbidity. The current investigation addresses this need by examining the synergistic effects of a novel pharmacotherapy combined with psychotherapy for co-occurring AUD/PTSD among veterans. Accumulating evidence suggests that the neuropeptide oxytocin (OT) is a promising pharmacotherapy to augment psychotherapy for AUD/PTSD. OT targets neurobiological and behavioral dysregulation common to both AUD and PTSD, in particular, corticolimbic connectivity. Human and animal studies show OT reduces alcohol self-administration, tolerance, and withdrawal; enhances fear extinction; and promotes prosocial behaviors. The current study builds on previous work by examining OT among veterans with AUD/PTSD receiving Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE), an evidence-based integrated treatment. METHODS: This paper describes the rationale, design, and methodology of a Stage II, 12-week, double-blind, randomized clinical trial of intranasal OT (40 IU) versus placebo combined with COPE among veterans (N = 180) with current AUD/PTSD. In addition, the effects of treatment on corticolimbic connectivity will be examined using functional magnetic resonance imaging (fMRI) at pre- and post-treatment. CONCLUSIONS: The proposed study will provide new knowledge and mechanistic insights to accelerate research in this understudied area and may lead to improved treatment outcomes for co-occurring AUD/PTSD. CLINICALTRIALS: gov: NCT04523922.

Enhancing Prolonged Exposure therapy for PTSD using physiological biomarker-driven technology.

Prolonged Exposure (PE) therapy is one of the most efficacious, evidence-based treatments for posttraumatic stress disorder (PTSD). A key component of PE involves in vivo exposures (IVEs) during which patients approach situations or activities in "real life" that are safe but avoided because they elicit a fear response. Despite their critical role in treatment, little research has focused on IVEs. This gap in knowledge is primarily due to the fact that IVEs are typically conducted by patients in between therapy sessions, leaving clinicians reliant upon patient self-report. This approach has numerous shortcomings, which the current study addresses by leveraging technology to develop an innovative device that allows for physiological, biomarker-driven, therapist-guided IVEs. The new system enables clinicians to virtually accompany patients during IVEs and provides real-time physiological (heart rate, skin conductance) and self-report (subjective units of distress) data that clinicians can use to modify the exposure and optimize therapeutic value. This Small Business Innovation Research (SBIR) Phase I project aims to: (1) integrate physiological sensors and live audio/visual streaming into a system for clinicians to guide patients during IVEs; (2) determine feasibility and acceptability of the system; and (3) conduct a pilot randomized clinical trial among veterans with PTSD (N = 40) to evaluate the preliminary efficacy of the system in reducing PTSD symptoms during PE. This paper describes the rationale, design, and methodology of the Phase I project. The findings from this study have the potential to innovate clinical practice, advance the science of exposure therapy, and improve clinical outcomes.

Concurrent treatment of substance use disorders and PTSD using prolonged exposure: A randomized clinical trial in military veterans.

OBJECTIVE: A substantial amount of individuals with substance use disorders (SUD) also meet criteria for posttraumatic stress disorder (PTSD). Prolonged Exposure (PE) is an effective, evidence-based treatment for PTSD, but there is limited data on its use among individuals with current alcohol or drug use disorders. This study evaluated the efficacy of an integrated treatment that incorporates PE (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure or COPE) among veterans. METHOD: Military veterans (N = 81, 90.1% male) with current SUD and PTSD were randomized to 12 sessions of COPE or Relapse Prevention (RP). Primary outcomes included the Clinician Administered PTSD Scale (CAPS), PTSD Checklist-Military version (PCL-M), and the Timeline Follow-back (TLFB). RESULTS: On average, participants attended 8 out of 12 sessions and there were no group differences in retention. Intent-to-treat analyses revealed that COPE, in comparison to RP, resulted in significantly greater reductions in CAPS (d = 1.4, p < .001) and PCL-M scores (d = 1.3, p = .01), as well as higher rates of PTSD diagnostic remission (OR = 5.3, p < .01). Both groups evidenced significant and comparable reductions in SUD severity during treatment. At 6-months follow-up, participants in COPE evidenced significantly fewer drinks per drinking day than participants in RP (p = .05). CONCLUSIONS: This study is the first to report on the use of an integrated, exposure-based treatment for co-occurring SUD and PTSD in a veteran sample. The findings demonstrate that integrated, exposure-based treatments are feasible and effective for military veterans with SUD and PTSD. Implications for clinical practice are discussed.