Sequenced Treatment Effectiveness for Posttraumatic Stress (STEPS)

Comparative Effectiveness PTSD Trial of Sequenced Pharmacotherapy and Psychotherapy in Primary Care

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.

Study Overview

• Status: Completed
• Conditions: PTSD
• Intervention / Treatment: Drug: Selective serotonin reuptake inhibitor; Behavioral: Written Exposure Therapy; Drug: Serotonin-norepinephrine reuptake inhibitor

Detailed Description

Background: In primary care settings, PTSD frequently goes undetected and untreated. When PTSD is diagnosed in primary care, treatment is usually inadequate and outcomes are poor. This is highly problematic because many patients with PTSD prefer receiving care in primary care settings, and less than half are successfully referred to the specialty mental health setting. This is especially a concern for safety net primary settings such as Federally Qualified Health Centers and VA Medical Centers, where the prevalence of both past trauma exposure and PTSD are particularly high. However, there are effective pharmacotherapy and psychotherapy treatments for PTSD that are feasible to deliver in primary care.

Objective: Because there are no head-to-head comparisons of pharmacotherapy and psychotherapy for PTSD among 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.

Methods: This multi-site trial will enroll 700 patients meeting clinical criteria for PTSD from 7 Federally Qualified Health Centers and 8 VA Medical Centers. The pharmacotherapy treatments are sertraline, fluoxetine, paroxetine and venlafaxine. The psychotherapy treatment is Written Exposure Therapy. Telephone and web surveys will be used to assessed outcomes (patient treatment engagement, self-reported symptom burden, health related quality of life, and recovery outcomes) at baseline, 4 and 8 months. Patients will be the unit of the intent-to-treat analysis. Multiple imputation will be used for missing data. Mixed-models will be used to test hypotheses.

Significance: Due to a lack of head-to-head comparisons between pharmacotherapy and psychotherapy protocols, clinical practice guidelines for PTSD provide contradictory recommendations about pharmacotherapy and psychotherapy. In particular, PTSD clinical practice guidelines have little to offer primary care providers because so few trials have been conducted in this setting. The proposed large pragmatic trial will compare, head-to-head, FDA approved PTSD medications with a brief trauma-focused psychotherapy that is evidence-based and feasible to deliver in primary care. In addition, despite high treatment non-response rates, very few trials have examined treatment sequencing and none have done so in the primary care setting. For patients not responding to the initial treatment, the proposed research is powered to compare, head-to-head, alternative treatment sequences that are feasible to deliver in primary care.

• Study Type: Interventional
• Enrollment (Actual): 700
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • North Little Rock, Arkansas, United States, 72214
      • Little Rock VA Medical Center
    • West Memphis, Arkansas, United States, 72301
      • East Arkansas Family Health Center
  • California
    • San Diego, California, United States, 92161
      • San Diego VA Medical Center
    • San Diego, California, United States, 92025
      • Neighborhood Healthcare
  • Colorado
    • Aurora, Colorado, United States, 80045
      • VA Eastern Colorado Health Care
  • Massachusetts
    • Bedford, Massachusetts, United States, 01730
      • Bedford VA Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 49109
      • Ann Arbor VA Medical Center
    • Hancock, Michigan, United States, 49930
      • Upper Great Lakes Family Health Center
    • Temperance, Michigan, United States, 48182
      • Family Medical Center of Michigan
  • Montana
    • Missoula, Montana, United States, 59802
      • Partnership Health Center
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Cincinnati VA Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Portland VA Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson VA Medical Center
  • Texas
    • Wichita Falls, Texas, United States, 76301
      • North Central Texas Community Health Center
  • Washington
    • SeaTac, Washington, United States, 98188
      • Healthpoint

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SSRI Then Augmentation by WET; 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; 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).; Behavioral: Written Exposure Therapy; 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.
Active Comparator: SSRI Then Switch to SNRI; 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; 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).; Drug: Serotonin-norepinephrine reuptake inhibitor; Prescribers will prescribe venlafaxine.
Active Comparator: WET Then Switch to SSRI; 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; 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).; Behavioral: Written Exposure Therapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mental Health Related Quality of Life: SF-12V, Mental Health Component Summary Score	SF-12V, Mental Health Component Summary Score (range 0-100, higher scores are better)	4 months (Hypothesis 1)
Mental Health Related Quality of Life: SF-12V, Mental Health Component Summary Score	SF-12V, Mental Health Component Summary Score (range 0-100, higher scores are better)	8 Months (Hypotheses 2a and 2b)
Depression Symptoms	Self reported burden of depression symptoms (PHQ-9) (range 0-27, higher scores are worse)	4 months (Hypothesis 1)
Depression Symptoms	Self reported burden of depression symptoms (PHQ-9) (range 0-27, higher scores are worse)	8 Months (Hypotheses 2a and 2b)
Generalized Anxiety Symptoms	Self reported burden of anxiety symptoms (GAD-7) (range 0-21, higher scores are worse)	4 months (Hypothesis 1)
Generalized Anxiety Symptoms	Self reported burden of anxiety symptoms (GAD-7) (range 0-21, higher scores are worse)	8 Months (Hypotheses 2a and 2b)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Severe and Moderate Side Effects	Self reported severity of specific side-effects	4 months (Hypothesis 1)
Number of Severe and Moderate Side Effects	Self reported severity of specific side-effects	8 Months (Hypotheses 2a and 2b)

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Patient-Centered Outcomes Research Institute; Boston University; Washington State University; Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: October 1, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: primary care; exposure therapy; antidepressants
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Uptake Inhibitors; Serotonin Agents; Sympathomimetics; Vasoconstrictor Agents; Serotonin Receptor Agonists; Norepinephrine; Serotonin; Selective Serotonin Reuptake Inhibitors
• Other Study ID Numbers: STUDY00011185

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A public use dataset will be hosted by the Patient-Centered Outcomes Research Institute Data Repository hosted by Inter-university Consortium for Political and Social Research (ICPSR), the University of Michigan's Institute for Social Research.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No