Project Summary

What is the research about?

Posttraumatic stress disorder, or PTSD, is a mental health problem that can occur after a life-threatening or dangerous event. People with PTSD often have a heightened sense of danger, causing them to feel stressed or fearful, even when they’re safe. Doctors can treat PTSD in one of several ways. One way is with medicine. Another way is prolonged exposure therapy, in which patients work with a therapist to learn how to confront their fears. Both ways are effective, but questions remain about how they compare to each other.

In this study, the research team is comparing three ways to treat PTSD:

  • Medicine
  • Prolonged exposure therapy
  • Both medicine and prolonged exposure therapy

Who can this research help?

Results may help patients and doctors when considering ways to treat PTSD.

What is the research team doing?

The research team is enrolling 450 veterans with PTSD who are receiving treatment at one of 6 Veterans Affairs, or VA, medical centers across the United States. The team is assigning patients by chance to one of three groups. Each group is receiving active treatment at the VA for 14 weeks.

Patients in the first group are receiving medicine and meeting with their doctors to talk about how well the medicine is working and make changes to the dose if needed.

Patients in the second group are receiving between 8 and 14 prolonged exposure therapy sessions. During the sessions, patients recount the event that caused their PTSD multiple times. The therapist records each session and encourages patients to listen to the recordings between visits. Patients also work with their therapist to develop a plan to confront their fears outside of the therapy sessions.

Patients in the third group are receiving both prolonged exposure therapy and medicine.

After active treatment, patients are encouraged to continue taking the medicine and to use the skills they learned in therapy on their own.

The research team is interviewing and surveying patients at the start of the study and again 7, 14, 27, and 40 weeks later. The interviews and surveys ask patients about symptoms of PTSD and depression and quality of life. Doctors are checking patients’:

  • Symptoms of PTSD
  • Symptoms of depression
  • Ability to look after their health and well-being
  • Ability to successfully perform tasks at work and interact with others at home and in the community

Patients with PTSD and doctors are helping to design the study.

Research methods at a glance

Design Element Description
Design Randomized controlled trial
Population 450 veterans with PTSD receiving treatment at 1 of 6 VA Medical Centers across the United States
  • Medicine (paroxetine or venlafaxine)
  • Prolonged exposure therapy
  • Medicine (paroxetine or venlafaxine) plus prolonged exposure therapy


Primary: PTSD severity

Secondary: depression symptoms, quality of life, social and occupational functioning

Timeframe Timeframe Length of follow-up for collecting data on primary outcomes. View Glossary 40-week follow-up for primary outcome

Project Information

Keith Bredemeier, PhD, BA
Michael Thase, MD
University of Pennsylvania Perelman School of Medicine
A Comparison of Prolonged Exposure Therapy, Pharmacotherapy, and Their Combination for PTSD: What Works Best and For Whom

Key Dates

November 2020
April 2026

Study Registration Information


Award Type
Health Conditions Health Conditions These are the broad terms we use to categorize our funded research studies; specific diseases or conditions are included within the appropriate larger category. Note: not all of our funded projects focus on a single disease or condition; some touch on multiple diseases or conditions, research methods, or broader health system interventions. Such projects won’t be listed by a primary disease/condition and so won’t appear if you use this filter tool to find them. View Glossary
Populations Populations PCORI is interested in research that seeks to better understand how different clinical and health system options work for different people. These populations are frequently studied in our portfolio or identified as being of interest by our stakeholders. View Glossary
Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: March 15, 2024