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

NCT04961190 | Active Not Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 1620949-1CER-2020C1-19382
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 7

Brief Summary

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

Outcome Measures

Primary Outcomes (4)

• Change during active treatment on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

  The CAPS-5 is a structured clinical interview that assesses the presence and severity of PTSD symptoms. Twenty items are rated on a 5-point scale from 0 (absent) to 4 (extremely/incapacitating). Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity

  baseline to 14 weeks

• Change during follow-up on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

  The CAPS-5 is a structured clinical interview that assesses the presence and severity of PTSD symptoms. Twenty items are rated on a 5-point scale from 0 (absent) to 4 (extremely/incapacitating). Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity

  14 weeks to 40 weeks

• Change during active treatment on the PTSD Checklist for DSM-5 (PCL-5)

  The PCL-5 is a 20-item self-report measure examining the presence and severity of recent PTSD symptoms using a 0 (not at all) to 4 (extremely) point Likert scale. Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity.

  baseline to 14 weeks

• Change during follow-up on the PTSD Checklist for DSM-5 (PCL-5)

  The PCL-5 is a 20-item self-report measure examining the presence and severity of recent PTSD symptoms using a 0 (not at all) to 4 (extremely) point Likert scale. Total scores range from 0 to 80, with higher scores indicating greater PTSD symptom severity.

  14 weeks to 40 weeks

Secondary Outcomes (8)

• Change during active treatment on the Quick Inventory of Depressive Symptoms - clinician rated (QIDS-C)

  baseline to 14 weeks

• Change during follow-up on the Quick Inventory of Depressive Symptoms - clinician rated (QIDS-C)

  14 weeks to 40 weeks

• Change during active treatment on the Patient Health Questionnaire depression module (PHQ-9)

  baseline to 14 weeks

• Change during follow-up on the Patient Health Questionnaire depression module (PHQ-9)

  14 weeks to 40 weeks

• Change during active treatment on the Social and Occupational Functioning Assessment Scale (SOFAS)

  baseline to 14 weeks

Study Arms (3)

Prolonged Exposure Therapy

ACTIVE COMPARATOR

8-14 sessions of psychotherapy, each lasting 60-90 minutes, focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders

Behavioral: Prolonged Exposure Therapy

Pharmacotherapy

ACTIVE COMPARATOR

20-60mg of paroxetine daily, or 75-300mg of venlafaxine XR daily

Drug: Pharmacotherapy with paroxetine or venlafaxine XR

Combined treatment (Prolonged Exposure and Pharmacotherapy)

ACTIVE COMPARATOR

8-14 sessions of psychotherapy, each lasting 60-90 minutes, focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders AND 20-60mg of paroxetine daily, or 75-300mg of venlafaxine XR daily

Behavioral: Prolonged Exposure Therapy; Drug: Pharmacotherapy with paroxetine or venlafaxine XR

Interventions

Pharmacotherapy with paroxetine or venlafaxine XR DRUG

Standard dosing with paroxetine, a selectiveserotonin reuptake inhibitor that is FDA approved to treat PTSD and depression, or venlafaxine extended-release, a serotonin-norepinephrine reuptake inhibitor that is FDA approved to treat anxiety and depression

Also known as: Pharmacotherapy with Paxil or Effexor XR

Combined treatment (Prolonged Exposure and Pharmacotherapy); Pharmacotherapy

Prolonged Exposure Therapy BEHAVIORAL

A form of cognitive-behavioral psychotherapy focused on imaginal exposure to trauma memories and in vivo exposure to trauma reminders

Combined treatment (Prolonged Exposure and Pharmacotherapy); Prolonged Exposure Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Milwaukee VA Medical Center: collaborator
• North Texas Veterans Healthcare System: collaborator
• San Diego Veterans Healthcare System: collaborator
• VA Palo Alto Health Care System: collaborator
• Birmingham VA Health Care System: collaborator
• University of Pennsylvania: lead
• Corporal Michael J. Crescenz VA Medical Center: collaborator
• Coatesville VA Medical Center: collaborator
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (7)

Birmingham VA Healthcare System

Birmingham, Alabama, 35233, United States

Location

VA Palo Alto Healthcare System

Menlo Park, California, 94025, United States

Location

VA San Diego Healthcare System

San Diego, California, 92161, United States

Location

Coatesville VA Medicial Center

Coatesville, Pennsylvania, 19320, United States

Location

Corporal Michael J. Crescenz VA Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

VA North Texas Healthcare System

Dallas, Texas, 75216, United States

Location

Milwaukee VA Medical Center

Milwaukee, Wisconsin, 53295, United States

Location

Related Publications (1)

• Bredemeier K, Larsen S, Shivakumar G, Grubbs K, McLean C, Tress C, Rosenfield D, DeRubeis R, Xu C, Foa E, Morland L, Pai A, Tsao C, Crawford J, Weitz E, Mayinja L, Feler B, Wachsman T, Lupo M, Hooper V, Cook R, Thase M. A comparison of prolonged exposure therapy, pharmacotherapy, and their combination for PTSD: What works best and for whom; study protocol for a randomized trial. Contemp Clin Trials. 2022 Aug;119:106850. doi: 10.1016/j.cct.2022.106850. Epub 2022 Jul 13.

  PMID: 35842108 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Drug Therapy; Paroxetine; Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2021
• First Posted: July 14, 2021
• Study Start: May 25, 2022
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)