Clinical trial NCT04597190: Sequenced Treatment Effectiveness for Posttraumatic Stress
Official title: Comparative Effectiveness PTSD Trial of Sequenced Pharmacotherapy and Psychotherapy in Primary Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: PTSD
Keywords: antidepressants
exposure therapy
primary care
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Stanford University
name: Boston University
name: Washington State University
name: Patient-Centered Outcomes Research Institute
First posted: 2020-10-22
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized to treatment sequences, stratified by site and baseline antidepressant use.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: PTSD Symptoms
timeFrame: 4 months (Hypothesis 1)
measure: PTSD Symptoms
timeFrame: 8 Months (Hypotheses 2a and 2b)
Secondary outcomes:
measure: Mental Health Related Quality of Life: SF-12V, Mental Health Component Summary Score
timeFrame: 4 months (Hypothesis 1)
measure: Mental Health Related Quality of Life: SF-12V, Mental Health Component Summary Score
timeFrame: 8 Months (Hypotheses 2a and 2b)
measure: Depression Symptoms
timeFrame: 4 months (Hypothesis 1)
measure: Depression Symptoms
timeFrame: 8 Months (Hypotheses 2a and 2b)
measure: Generalized Anxiety Symptoms
timeFrame: 4 months (Hypothesis 1)
measure: Generalized Anxiety Symptoms
timeFrame: 8 Months (Hypotheses 2a and 2b)
Other outcomes:
measure: Number of Severe and Moderate Side Effects
timeFrame: 4 months (Hypothesis 1)
measure: Number of Severe and Moderate Side Effects
timeFrame: 8 Months (Hypotheses 2a and 2b)
Locations:
city: North Little Rock
country: United States
facility: Little Rock VA Medical Center
state: Arkansas
city: West Memphis
country: United States
facility: East Arkansas Family Health Center
state: Arkansas
city: San Diego
country: United States
facility: Neighborhood Healthcare
state: California
city: San Diego
country: United States
facility: San Diego VA Medical Center
state: California
city: Aurora
country: United States
facility: VA Eastern Colorado Health Care
state: Colorado
city: Bedford
country: United States
facility: Bedford VA Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Ann Arbor VA Medical Center
state: Michigan
city: Hancock
country: United States
facility: Upper Great Lakes Family Health Center
state: Michigan
city: Temperance
country: United States
facility: Family Medical Center of Michigan
state: Michigan
city: Missoula
country: United States
facility: Partnership Health Center
state: Montana
city: Cincinnati
country: United States
facility: Cincinnati VA Medical Center
state: Ohio
city: Portland
country: United States
facility: Portland VA Medical Center
state: Oregon
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center
state: South Carolina
city: Wichita Falls
country: United States
facility: North Central Texas Community Health Center
state: Texas
city: SeaTac
country: United States
facility: Healthpoint
state: Washington
Study officials:
References: