Sequenced Treatment Effectiveness for Posttraumatic Stress

NCT04597190 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: STUDY00011185
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 15

Brief Summary

Individuals with PTSD are more likely to engage in unhealthy behaviors such as tobacco use, drug use, alcohol misuse, and have high rates of morbidity/mortality. PTSD negatively impacts marriages, educational attainment, and occupational functioning. Some patients with PTSD can be successfully referred to specialty mental health clinics, but most patients with PTSD cannot engage in specialty care because of geographical, financial and cultural barriers and must be treated in primary care. However, policy makers do not know the best way to treat PTSD in primary care clinics, especially for patients who do not respond to the initial treatment choice. There are effective treatments for PTSD that are feasible to deliver in primary care. These treatments include commonly prescribed antidepressants and brief exposure-based therapies. However, because there are no head-to-head comparisons between pharmacotherapy and psychotherapy in primary care settings, primary care providers do not know which treatments to recommend to their patients. In addition, despite high treatment non-response rates, very few studies have examined which treatment should be recommend next when patients do not respond well to the first, and no such studies have been conducted in primary care settings. This trial will be conducted in Federally Qualified Health Centers and VA Medical Centers, where the prevalence of both past trauma exposure and PTSD are particularly high. The investigators will enroll 700 primary care patients. The investigators propose to 1) compare outcomes among patients randomized to initially receive pharmacotherapy or brief psychotherapy, 2) compare outcomes among patients randomized to treatment sequences (i.e., switching and augmenting) for patients not responding to the initial treatment and 3) examine variation in treatment outcomes among different subgroups of patients. Telephone and web surveys will be used to assessed outcomes important to patients, like self-reported symptom burden, side-effects, health related quality of life, and recovery outcomes, at baseline, 4 and 8 months. Results will help patients and primary care providers choose which treatment to try first and which treatment to try second if the first is not effective.

Conditions

PTSD

Keywords

antidepressants; exposure therapy; primary care

Outcome Measures

Primary Outcomes (2)

• PTSD Symptoms

  Self reported burden of PTSD symptoms (PCL-5) (range 0-80, higher scores are worse)

  4 months (Hypothesis 1)

• PTSD Symptoms

  Self reported burden of PTSD symptoms (PCL-5) (range 0-80, higher scores are worse)

  8 Months (Hypotheses 2a and 2b)

Secondary Outcomes (6)

• Mental Health Related Quality of Life: SF-12V, Mental Health Component Summary Score

  4 months (Hypothesis 1)

• Mental Health Related Quality of Life: SF-12V, Mental Health Component Summary Score

  8 Months (Hypotheses 2a and 2b)

• Depression Symptoms

  4 months (Hypothesis 1)

• Depression Symptoms

  8 Months (Hypotheses 2a and 2b)

• Generalized Anxiety Symptoms

  4 months (Hypothesis 1)

Other Outcomes (2)

• Number of Severe and Moderate Side Effects

  4 months (Hypothesis 1)

• Number of Severe and Moderate Side Effects

  8 Months (Hypotheses 2a and 2b)

Study Arms (3)

SSRI Then Augmentation by WET

ACTIVE COMPARATOR

Prescribers will prescribe one of three SSRIs (sertraline, fluoxetine or paroxetine). Patients who do not respond to treatment by four months will have their treatment augmented by Written Exposure Therapy (WET) delivered by an integrated behavioral health consultant.

Drug: Selective serotonin reuptake inhibitor; Behavioral: Written Exposure Therapy

SSRI Then Switch to SNRI

ACTIVE COMPARATOR

Prescribers will prescribe one of three SSRIs (sertraline, fluoxetine or paroxetine). Patients who do not respond to treatment by four months will have their treatment switched to the SNRI (serotonin-norepinephrine reuptake Inhibitor) venlafaxine.

Drug: Selective serotonin reuptake inhibitor; Drug: Serotonin-norepinephrine reuptake inhibitor

WET Then Switch to SSRI

ACTIVE COMPARATOR

Integrated behavioral health consultants will deliver WET. Patients who do not respond to treatment by four months will be switched to one of three SSRIs (sertraline, fluoxetine or paroxetine).

Drug: Selective serotonin reuptake inhibitor; Behavioral: Written Exposure Therapy

Interventions

Selective serotonin reuptake inhibitor DRUG

Prescribers and patients choose among three selective serotonin reuptake inhibitors (SSRI), sertraline, paroxetine, or fluoxetine based on patient's treatment history (i.e., failed SSRI trials due to side-effects or lack of efficacy) and preference. If a patient experiences problematic side effects after taking their choice of SSRI, the provider may switch them to another of the SSRI options during the first 8 weeks of follow-up. Patients on any antidepressant (including SSRIs) at enrollment will be cross-tapered over four weeks to either fluoxetine, sertraline or paroxetine (i.e., the old drug will be tapered down while the new drug is tapering up).

SSRI Then Augmentation by WET; SSRI Then Switch to SNRI; WET Then Switch to SSRI

Serotonin-norepinephrine reuptake inhibitor DRUG

Prescribers will prescribe venlafaxine.

SSRI Then Switch to SNRI

Written Exposure Therapy BEHAVIORAL

Written Exposure Therapy will be delivered during six 30 minute sessions. The first session includes psychoeducation about symptoms of PTSD, provides a treatment rationale for approaching the trauma memory, and discusses the use of writing as a means of doing so. In sessions 2-6, patients will write about the memory of their worst traumatic event for 20 minutes, with a focus on details of the event and thoughts and feelings that occurred during the event. Patients are directed to write about the same trauma memory during each session. The session ends with the therapist instructing the patient to allow themselves to experience any trauma-related memories, images, thoughts, and feelings in the interval between sessions. The therapist reads the narrative between sessions to make sure instructions were followed. Feedback about the narrative is provided to the patient at the beginning of sessions 3-6. This feedback is used to prompt the patient for writing in the current session.

SSRI Then Augmentation by WET; WET Then Switch to SSRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Screen positive for PTSD (PC-PTSD\>=3 AND PCL\>=33)
• Screen positive for trauma (Brief Trauma questionnaire)

You may not qualify if:

• Diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder or dementia
• Current prescription of venlafaxine
• Change in any psychotropic prescription in the past 2 months
• A scheduled specialty mental health appointment or preference for specialty mental health care
• Pregnant
• Terminally ill
• Prisoner
• Unable to communicate in English or Spanish
• \<18 years of age
• Impaired decision making capacity

Sponsors & Collaborators

• University of Washington: lead
• Stanford University: collaborator
• Boston University: collaborator
• Washington State University: collaborator
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (15)

Little Rock VA Medical Center

North Little Rock, Arkansas, 72214, United States

Location

East Arkansas Family Health Center

West Memphis, Arkansas, 72301, United States

Location

Neighborhood Healthcare

San Diego, California, 92025, United States

Location

San Diego VA Medical Center

San Diego, California, 92161, United States

Location

VA Eastern Colorado Health Care

Aurora, Colorado, 80045, United States

Location

Bedford VA Medical Center

Bedford, Massachusetts, 01730, United States

Location

Ann Arbor VA Medical Center

Ann Arbor, Michigan, 49109, United States

Location

Upper Great Lakes Family Health Center

Hancock, Michigan, 49930, United States

Location

Family Medical Center of Michigan

Temperance, Michigan, 48182, United States

Location

Partnership Health Center

Missoula, Montana, 59802, United States

Location

Cincinnati VA Medical Center

Cincinnati, Ohio, 45220, United States

Location

Portland VA Medical Center

Portland, Oregon, 97239, United States

Location

Ralph H. Johnson VA Medical Center

Charleston, South Carolina, 29401, United States

Location

North Central Texas Community Health Center

Wichita Falls, Texas, 76301, United States

Location

Healthpoint

SeaTac, Washington, 98188, United States

Location

Related Publications (1)

• Fortney JC, Kaysen DL, Engel CC, Cerimele JM, Nolan JP Jr, Chase E, Blanchard BE, Hauge S, Bechtel J, Taylor A, Acierno R, Nagel N, Sripada RK, Painter JT, DeBeer BB, Zimberoff A, Bluett EJ, Teo AR, Morland LA, Grubbs K, Sloan DM, Marx BP, Heagerty PJ. Pragmatic Comparative Effectiveness of Primary Care Treatments for Posttraumatic Stress Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Dec 1;82(12):1203-1215. doi: 10.1001/jamapsychiatry.2025.2962.

  PMID: 41091477 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Selective Serotonin Reuptake Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs

Results Point of Contact

• Title: John Fortney
• Organization: University of Washington

fortneyj@uw.edu

2066856955

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The survey team members will be masked to which arm the study participant has been randomized. The PI, Co-PIs, and Co-Is will not have access to the outcomes until the primary data collection phase has been completed. The statistician will present outcomes by arm to the Data Safety Monitoring Board (DSMB) members during closed sessions of DSMB meetings.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, School of Medicine

Model Details: Patients will be randomized to treatment sequences, stratified by site and baseline antidepressant use.

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 22, 2020
• Study Start: June 1, 2020
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: May 8, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (15)