Positive Processes and Transition to Health

Not Applicable

Completed

Conditions: Post Traumatic Stress Disorder
Major Depressive Disorder

Interventions: Behavioral: Positive Processes and Transition to Health (PATH)

Registration Number: NCT04678232

Lead Sponsor: Case Western Reserve University

Brief Summary: The R61 will be an open trial to determine if Positive Processes and Transition to Health (PATH) engages the proposed targets: unproductive processing, avoidance, and reward deficits in a sample of 45 adults who have experienced a destabilizing life event involving profound loss or threat, report persistent stressor-related symptoms of PTSD and/or depression, and are elevated on symptoms related to 2 of the 3 therapeutic targets. Additionally, will examine whether patients perceive PATH as helpful and complete/adhere to treatment, and therapist fidelity. Patients will receive 6 sessions of PATH (with 2 boosters, if partial responders). Primary targets will be assessed at pre-treatment, week 4, post-treatment, and at 1- and 3-month follow-up; secondary targets at pre-treatment, weekly during treatment, post-treatment, and at 1- and 3-month follow-ups.

Detailed Description: Evidence-based psychotherapies for posttraumatic stress disorder (PTSD) and depression consistently produce strong, clinically meaningful effects for many individuals. However, these interventions also have significant dropout rates, a large minority of individuals continue to have debilitating symptoms, and even those who respond may be vulnerable to relapse upon future stressors. More efficient and mechanistically precise interventions are needed. Consistent with the cross-cutting theme of studying the role of the environment in the NIMH Strategic Plan, the etiological role of exposure to destabilizing, stressful life events is common to both PTSD and depression. Not only do they share common distress-related triggers, symptoms, and maintaining processes, but they also commonly co-occur (upwards of 60%). Current PTSD and depression treatments typically focus on their respective disorders rather than on common processes that maintain psychopathology; and, importantly, they do not explicitly target positive adaptive processes associated with resilience. Decades of experimental studies, prospective studies, and psychotherapy trials have identified interconnected maladaptive and adaptive processes associated with persistent psychopathology after stressful, destabilizing events. These maladaptive processes include: 1) unproductive event processing; 2) avoidance; and 3) reward sensitivity and processing deficits. These processes prolong negative mood, interfere with adaptive coping and processing of emotional material, and increase sensitivity to future stressful life events. PATH (Positive Processes and Transition to Health) directly targets these maladaptive processes while also teaching parallel adaptive skills (constructive processing, approach, and positive emotion processing and reward seeking). Six, 90-min sessions target individuals who have experienced a destabilizing life event and have persistent stressor-related symptoms. PATH utilizes life event processing (revisiting, meaning making), focusing repeatedly on an identified destabilizing life event, positive life events, and future events as a framework to identify maladaptive processes and teach constructive processing skills. PATH has the potential to reduce dropout, improve treatment engagement and outcomes, identify potential treatment mechanisms, and ultimately reduce the costly human and economic burden of stressor-related psychopathology.

For the open trial's "Go" to be achieved and to proceed to the R33, two criteria must be met. The first is that at least 2 of the 3 primary targets must change via PATH. A moderate effect size (d = 0.60) was chosen to reflect evidence of clinically meaningful target engagement (see Gold et al., 2017), in line with NIMH guidelines for a preliminary signal of target engagement/efficacy in intervention trials. Second, at least one of the secondary measures must show a moderate effect (d = 0.50) from pre- to post-treatment. We included measures of each of the targets, as they are conceptualized as interrelated parts of a "stuck" system. For "Go" to an R01 after the R33, in addition to target engagement, primary outcomes of PTSD and depression must show clinically meaningful gains (e.g., Barth et al., 2016; Cusak et al., 2016).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 45

Inclusion Criteria

Destabilizing life event involving profound loss or threat, with a minimum duration of 12 weeks since the event, but occurred within the last 5 years.
Between the ages of 18 and 65.
Elevated target: Scores of at least moderate (1 or higher) on at least 2 of the 3 target mechanisms: re- experiencing or ruminative processing of the destabilizing event (PSS-I items: 1, 2, 3, 4 or QIDS-C item 11), avoidance (PSS-I items 6, 7, 8), or reward deficits (PSS-I items 12, 13, or QIDS-C item 13).

Exclusion Criteria

Current diagnosis of schizophrenia, delusional disorder, or organic mental disorder as defined by DSM-5.
Current diagnosis of bipolar disorder, depression with psychotic features, or depression severe enough to require immediate psychiatric treatment (i.e., serious suicide risk with intent and plan).
Severe self-injurious behavior or suicide attempt within the previous three months.
Unwilling or unable to discontinue current cognitive behavioral psychotherapy.
No clear memory of the destabilizing event or event occurred before age 3.
Unstable dose of psychotropic medications in prior 3 months.
Ongoing intimate relationship with the perpetrator (in assault related event).
Current diagnosis of a substance use disorder (DSM-5).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
receive PATH therapy	Positive Processes and Transition to Health (PATH)	PATH includes six 60-90 min, weekly sessions, with two booster sessions for partial responders. Session 1 provides the PATH rationale and a review of life events (PATH of life: negative and positive). A rationale for an explicit focus on positive events/emotions will be provided. Sessions 2-4 focus on a verbal narrative of the destabilizing life event, reminiscence and processing of a major positive life event, and real-life practice to enact what was taught. Sessions 5 focuses on constructive processing and provides opportunity for integration and consolidation of learning. Session 6 focuses on future negative and positive events to promote application of new learning and resilience. Booster sessions focus on positive and negative life events since the last session and adaptive processes (constructive processing, approach, and reward). All sessions will include cultivation and elaboration of positive emotions to promote engagement and to build on the benefits of positive emotions.

Primary Outcome Measures

Name	Time	Method
Affective Updating Task (Pe et al., 2013; Pe, Raes, et al., 2013)	Score at 6 weeks (immediately post treatment)	The Affective Updating task (Pe et al., 2013; Pe, Raes, et al., 2013) measures updating of affective information in working memory. The task requires participants to continuously monitor and modify relevant affective information in working memory. Performance is inhibited by rumination. Forty-seven positive and 49 negative words are included. Under high levels of stress, deficits in affective updating predict more depressive symptoms over one year (Pe et al., 2016) and efficiency of reappraisal (Pe et al., 2013). Affective updating in contrast, predicts subjective well-being (Pe et al., 2013). The AUT is scored using the mean proportion of correct responses across 4 types of stimulus sets (positive-positive-positive words, negative-negative-negative, positive-negative-positive, negative-positive-negative). Scores for the AUT range from 0 to 1. Lower scores reflect greater deficits in affecting updating, while higher scores indicate greater abilities with affective updating.
Idiographic Behavioral Approach Task	Score at 6 weeks (immediately post treatment)	The Idiographic Behavioral Approach Task (BAT; Mori \& Aermendariz, 2001; Haynes, 2001) will use in vivo confrontation with feared or avoided stimuli measuring avoidance behavior. Each BAT is unique to each participant (e.g., news/videos of similar events, pictures of loved one). A general list of idiographic stimuli will be developed with participants, who will then approach the stimuli. The task requires participants to rate their subjective units of distress (SUDs) on a scale of 0-100 (0 = no distress, 100 = extreme distress). The primary outcome measured is mean peak SUDs. The mean peak SUDs is calculated by averaging together all of the participant's reported SUDs measured at their highest level of distress. Higher scores indicate a higher average level of distress across all items, and lower scores indicate less distress on average across all items.
Probabilistic Reward Task (Pizzagalli et al., 2005)	Score at 6 weeks (immediately post treatment)	The Probabilistic Reward Task (PRT) assesses reward responsivity (e.g., Der-Avakian et al. 2013; Pizzagalli et al., 2005, 2008, 2008). In each trial, participants choose which of 2 difficult-to-differentiate stimuli was presented. Stimuli are groups of bunnies or dogs (diameter: 25 mm; eyes: 7 mm). Unknown to them, correct identification of the "rich stimulus" is rewarded 3 times more frequently ("Correct! You won 20 cents"). Reward propensity is calculated by increase in response bias during the final block relative to the first. Degree of response bias toward the frequently reinforced alternative is a robust measure of reward sensitivity (Pizzagalli et al., 2005, 2008; Vrieze et al., 2013). The PRT is administered online through Inquisit Lab on Millisecond. PRT scores range between -.75 to .65 (-.75 = lower reward sensitivity, .65 = greater reward sensitivity).

Secondary Outcome Measures

Name	Time	Method
Posttraumatic Cognitions Inventory (Foa et al., 1999)	Score at 6 weeks (immediately post treatment)	The Posttraumatic Cognitions Inventory (PTCI; Foa et al., 1999) is a self-report that measures negative posttraumatic stressor-related thoughts that can contribute to the development and maintenance of PTSD. The measure includes 33 items grouped into three subscales. The 21-item Negative Cognitions about Self scale measures negative self-perception since the traumatic event. The 7-item Negative Cognitions about the World subscale evaluates mistrust of others and perceptions of danger. The 5-item Self Blame scale measures self-blame since the traumatic incident. All items are measured on a scale from 1-7 with 1 indicating "totally disagree" and 7 indicating "totally agree." The total score for the PTCI ranges from 33 to 231 and is determined by summing the scores of each subscale. Higher scores reflect more rigid negative cognitions. Total scores were used.
Behavioral Activation for Depression Scale (Kanter et al., 2006)	Score at 6 weeks (immediately post treatment)	Behavioral Activation for Depression Scale (Secondary Measure; BADS; Kanter et al., 2006) is a 25- item self-report of approach and avoidance in cognitive and behavioral domains not specific to depression. Items are rated from 0 = Not at all to 6 = Completely. The measure contains four subscales which include Activation, Avoidance/Rumination, Work/School Impairment, and Social Impairment. Total scores, which range from 0-150 are calculated by summing the four subscales. A higher score indicates higher behavioral activation and lower scores indicate more depressive symptoms. The BADS has good factor structure, internal consistency, construct, and predictive validity (Kanter et al., 2009; Manos et al, 2011) and sensitivity to change (d =.86; CBT for depression, O'Mahen et al., 2017).
Snaith-Hamilton Pleasure Scale (Snaith et al., 1995)	Score at 6 weeks (immediately post treatment)	Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al., 1995). The SHAPS is a 14- item self-report measuring the capacity to experience pleasure. On a four-point scale (1 = Strongly Agree to 4 = Strongly Disagree), varying statements are rated (e.g., "I would find pleasure in small things"; "I would find pleasure in a telephone call from a friend"). The measure has good convergent and discriminant validity and reflects a unidimensional construct of anhedonia (Leventhal et al., 2006; Nakonezny et al., 2010). Total scores are measured on a scale from 14 to 56 (14 = severe anhedonia, 56 = no anhedonia).

Trial Locations

Locations (3): Case Western Reserve University
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Cleveland, Ohio, United States
University of Washington
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Seattle, Washington, United States
University of Delaware
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Newark, Delaware, United States