A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD

Description

Posttraumatic Stress Disorder (PTSD) remains a salient and debilitating problem, in the general population and for military veterans in particular. Several psychological and pharmacological treatments for PTSD have evidence to support their efficacy. However, the lack of comparative effectiveness data for PTSD treatments remains a major gap in the literature, which limits conclusions that can be drawn about which of these treatments work best. The current study will compare the effectiveness of PTSD treatments with the strongest evidentiary support - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine - as well as the combination of these two treatments. A randomized trial will be conducted with a large, diverse sample of veterans with PTSD (N = 300) recruited from 6 VA Medical Centers throughout the US. Participants will complete baseline assessments, followed by an active treatment phase (involving up to 14 sessions of PE and/or medication management) with mid (7 week) and posttreatment (14 week) assessments, and follow-up assessments at 27 and 40 weeks. Study outcomes will include PTSD severity, depression, quality of life and functioning, assessed via clinical ratings and self-report measures. Further, a range of demographic and clinically relevant variables (e.g., trauma type/number, resilience) will be collected at baseline and examined as potential predictors or moderators of treatment response, addressing another gap in the PTSD treatment literature. These data will be used to develop algorithms from predicting the optimal treatment for individual patients (i.e., "personalized advantage indices"; PAIs). Effectiveness of the treatments will be compared using multilevel modeling. PAIs will be developed by conducting bootstrapped analyses to select variables that predict or moderate outcomes (clinician rated PTSD severity at Week 14), followed by jacknife analyses to determine the magnitude of the predicted difference (representing an individual's "predicted advantage" of one treatment over the others).

Conditions

Posttraumatic Stress Disorder

Study Overview

Study Details

Study overview

Posttraumatic Stress Disorder (PTSD) remains a salient and debilitating problem, in the general population and for military veterans in particular. Several psychological and pharmacological treatments for PTSD have evidence to support their efficacy. However, the lack of comparative effectiveness data for PTSD treatments remains a major gap in the literature, which limits conclusions that can be drawn about which of these treatments work best. The current study will compare the effectiveness of PTSD treatments with the strongest evidentiary support - Prolonged Exposure (PE) therapy and pharmacotherapy with paroxetine or venlafaxine - as well as the combination of these two treatments. A randomized trial will be conducted with a large, diverse sample of veterans with PTSD (N = 300) recruited from 6 VA Medical Centers throughout the US. Participants will complete baseline assessments, followed by an active treatment phase (involving up to 14 sessions of PE and/or medication management) with mid (7 week) and posttreatment (14 week) assessments, and follow-up assessments at 27 and 40 weeks. Study outcomes will include PTSD severity, depression, quality of life and functioning, assessed via clinical ratings and self-report measures. Further, a range of demographic and clinically relevant variables (e.g., trauma type/number, resilience) will be collected at baseline and examined as potential predictors or moderators of treatment response, addressing another gap in the PTSD treatment literature. These data will be used to develop algorithms from predicting the optimal treatment for individual patients (i.e., "personalized advantage indices"; PAIs). Effectiveness of the treatments will be compared using multilevel modeling. PAIs will be developed by conducting bootstrapped analyses to select variables that predict or moderate outcomes (clinician rated PTSD severity at Week 14), followed by jacknife analyses to determine the magnitude of the predicted difference (representing an individual's "predicted advantage" of one treatment over the others).

A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD: What Works Best, and for Whom

A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD

Condition
Posttraumatic Stress Disorder
Intervention / Treatment

-

Contacts and Locations

Menlo Park

VA Palo Alto Healthcare System, Menlo Park, California, United States, 94025

San Diego

VA San Diego Healthcare System, San Diego, California, United States, 92161

Coatesville

Coatesville VA Medicial Center, Coatesville, Pennsylvania, United States, 19320

Philadelphia

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, United States, 19104

Dallas

VA North Texas Healthcare System, Dallas, Texas, United States, 75216

Milwaukee

Milwaukee VA Medical Center, Milwaukee, Wisconsin, United States, 53295

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * DSM-5 diagnosis of Posttraumatic Stress Disorder
  • * military veteran
  • * fluent in English
  • * willing to participate in PE, pharmacotherapy, or both
  • * capable of providing informed consent
  • * suicidal ideation with intent and/or plan, or suicidal behavior in the past month
  • * active psychosis
  • * history of manic episode(s)
  • * a failed trial of Prolonged Exposure therapy or paroxetine and venlafaxine XR
  • * ongoing medical conditions or treatments that would contraindicate initiating these treatments (e.g., medications that have potential interactions with paroxetine and venlafaxine such as MAO inhibitors)

Ages Eligible for Study

18 Years to 75 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

University of Pennsylvania,

Study Record Dates

2026-02-15