The lived experiences and treatment needs of women with opioid use disorder and posttraumatic stress symptoms: A mixed methods study.

INTRODUCTION: Women show a gender-specific risk for co-occurring opioid use disorder (OUD) and posttraumatic stress disorder (PTSD). Expert groups have called for the development of integrated treatments for women with OUD/PTSD, but there remains limited information on such interventions. METHODS: This mixed-methods study interviewed and surveyed 10 women with current or past OUD and co-occurring posttraumatic stress symptoms (PTSS) and 16 providers who work with these women. Interviews and surveys queried patient participants' and providers' experiences of OUD/PTSS and how to best design an integrated, trauma-focused treatment for OUD/PTSD. RESULTS: Patient participants (90 % white, 90 % mothers, Mage = 45.70) met criteria for severe, lifetime OUD and 40 % met a provisional diagnosis for PTSD. Four themes emerged for participants' experiences of OUD/PTSS: 1) numerous stressors; 2) shame; 3) multiple motivations to use opioids; and 4) a cycle of trauma and opioid use. Four themes emerged regarding patient participants' perceptions on the development of an OUD/PTSD treatment: 1) mixed attitudes towards medications for OUD; 2) barriers to treatment (e.g., insufficient treatments and contextual factors); 3) treatment facilitators (e.g., social support); and 4) preferences in treatment (e.g., trauma-focused, gender-focused, family content, ambivalence around group therapy). Providers (Mage = 38.94) were primarily white women (76.5 %). Two themes emerged from their experiences working with women with OUD/PTSS: 1) perceiving women to use opioids to regulate emotions and 2) gender differences in trauma types. Three themes emerged for providers' perceptions on the development of an OUD/PTSD treatment: 1) barriers to treatment (e.g., chaotic lives, contextual factors, family); 2) treatment facilitators (e.g., trust and external motivations); and 3) desired treatment modifications (e.g., stabilization, early skills in therapy, flexibility in therapy, social supports, safety guidelines, and assistance in identifying an index trauma). Most participants (90.0 %) and providers (93.5 %) preferred working on OUD/PTSD symptoms simultaneously rather than separately. CONCLUSIONS: Findings demonstrate the need to modify integrated treatments to meet the preferences of providers and women with OUD/PTSS and OUD/PTSD. Treatments should consider therapeutic content, structure, contextual factors, social support, and PTSD severity to enhance uptake and reach.

Cannabis use and trauma-focused treatment for co-occurring posttraumatic stress disorder and substance use disorders: A meta-analysis of individual patient data.

High rates of cannabis use among people with posttraumatic stress disorder (PTSD) have raised questions about the efficacy of evidence-based PTSD treatments for individuals reporting cannabis use, particularly those with co-occurring alcohol or other substance use disorders (SUDs). Using a subset of four randomized clinical trials (RCTs) included in Project Harmony, an individual patient meta-analysis of 36 RCTs (total N = 4046) of treatments for co-occurring PTSD+SUD, we examined differences in trauma-focused (TF) and non-trauma-focused (non-TF) treatment outcomes for individuals who did and did not endorse baseline cannabis use (N = 410; 70% male; 33.2% endorsed cannabis use). Propensity score-weighted mixed effects modeling evaluated main and interactive effects of treatment assignment (TF versus non-TF) and baseline cannabis use (yes/no) on attendance rates and within-treatment changes in PTSD, alcohol, and non-cannabis drug use severity. Results revealed significant improvements across outcomes among participants in all conditions, with larger PTSD symptom reductions but lower attendance among individuals receiving TF versus non-TF treatment in both cannabis groups. Participants achieved similar reductions in alcohol and drug use across all conditions. TF outperformed non-TF treatments regardless of recent cannabis use, underscoring the importance of reducing barriers to accessing TF treatments for individuals reporting cannabis use.

Project harmony: A systematic review and network meta-analysis of psychotherapy and pharmacologic trials for comorbid posttraumatic stress, alcohol, and other drug use disorders.

We conducted a systematic review and network meta-analyses (NMA) of psychotherapy and pharmacologic treatments for individuals with co-occurring posttraumatic stress disorder (PTSD) and alcohol or other drug use disorder (AOD). A comprehensive search spanning 1995-2019 yielded a pool of 39 studies for systematic review, including 24 randomized controlled trials for the NMA. Study interventions were grouped by target of treatment (PTSD + AOD, PTSD-only, and AOD-only) and approach (psychotherapy or medication). Standardized mean differences (SMD) from the NMA yielded evidence that at the end of treatment, integrated, trauma-focused therapy for PTSD + AOD was more effective at reducing PTSD symptoms than integrated, non-trauma-focused therapy (SMD = -0.30), AOD-focused psychotherapy (SMD = -0.29), and other control psychotherapies (SMD = -0.43). End-of-treatment alcohol use severity was less for AOD medication compared to placebo medication (SMD = -0.36) and trauma-focused therapy for PTSD + placebo medication (SMD = -0.67), and less for trauma-focused psychotherapy + AOD medication compared to PTSD medication (SMD = -0.53), placebo medication (SMD = -0.50), and trauma-focused psychotherapy + placebo medication (SMD = -0.81). Key limitations include the small number of studies in the NMA for pharmacologic treatments and the lack of demographic diversity apparent in the existing literature. Findings suggest room for new studies that can address limitations in study sample composition, sample sizes, retention, and apply new techniques for conducting comparative effectiveness in PTSD + AOD treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mental Health Clinician Practices and Perspectives on Treating Adults with Co-Occurring Posttraumatic Stress and Substance Use Disorders.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) commonly co-occur and represent a complex, challenging clinical comorbidity. Meta-analytic studies and systematic reviews suggest that trauma-focused treatments are more efficacious than non-trauma focused interventions for co-occurring PTSD/SUD. However, relatively little is known about mental health clinicians' practices or preferences for treating co-occurring PTSD/SUD. The present study aimed to describe the current clinical practices of mental health clinicians who treat PTSD and/or SUD-related conditions and to assess interest in novel integrative treatments for PTSD/SUD. METHODS: Licensed mental health clinicians (N = 76; Mage = 39.59, SD = 8.14) who treat PTSD and/or SUD completed an anonymous online survey from April 2021 to July 2021. RESULTS: The majority (61.8%) of clinicians reported using integrative treatments for PTSD/SUD. The most commonly used trauma-focused treatments were 1) Cognitive Processing Therapy (CPT: 71.1%) and 2) Prolonged Exposure Therapy (PE: 68.4%) for PTSD. Approximately half (51.3%) of clinicians endorsed using Relapse Prevention (RP) for SUD. The vast majority (97.4%) of clinicians were somewhat or very interested in a new integrative CPT-RP intervention, and 94.7% of clinicians believed patients would be interested in a CPT-RP intervention. In the absence of an available evidence-based integrative treatment using CPT, 84.0% of clinicians reported modifying extant treatment protocols on their own to address PTSD and SUD concurrently. CONCLUSIONS: The findings demonstrate mental health clinician support of integrative treatments for PTSD/SUD. The most commonly used trauma-focused intervention was CPT and clinicians expressed strong interest in an integrative intervention that combines CPT and RP. Implications for future treatment development are discussed.

Clinician perspectives on technology-enhanced in vivo exposures during prolonged exposure therapy for PTSD.

OBJECTIVE: To investigate clinicians' perceptions regarding the use of mobile technology tools during prolonged exposure (PE) therapy to allow for monitoring and enhancing in-vivo exposures (IVEs). METHODS: Clinicians with training in PE therapy (N = 32; average of 9 years of practice) completed surveys asking about their perspectives on the utility of virtually attending IVEs with patients while simultaneously having access to real-time subjective and physiological data (i.e., heart rate, galvanic skin conductance) to guide exposure exercises and assure optimal stimulus engagement. RESULTS: Findings showed clinicians to have a favorable view of applying technology devices and systems to enhance IVEs of PE therapy. Most clinicians (93.8%) believed that real-time monitoring of IVEs-particularly monitoring patients' subjective distress and completion of and duration of time in the IVE-would be useful and significantly enhance PE therapy. CONCLUSION: The positive perceptions toward integrating technology into IVEs in this study have important implications for the development and implementation of technology-enhanced PE therapy. A mobile technology system that incorporates real-time indicators of engagement (i.e., both subjective and physiological) during IVEs and allows clinicians to review recordings of, or virtually accompany, patients during IVEs has the potential to innovate and transform PE and other exposure-based treatments. Clinicians also believed that technology-enhanced IVEs may help reduce early termination from PE.

A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD.

BACKGROUND: PTSD may involve oxidative stress, and N-acetylcysteine (NAC) may reduce the impact of oxidative stress in the brain. This study aims to investigate the efficacy of adjuvant NAC in people with treatment-resistant PTSD. METHODS: A multicentre, randomised, double-blind, placebo-controlled trial for adults with PTSD unresponsive to first-line treatment. The intervention was either oral NAC 2.7 g/day or placebo for 12 weeks. The primary outcome was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks compared with baseline. Secondary outcomes included depression and substance craving. Follow-up measures were obtained at 16 and 64-weeks. RESULTS: 133 patients were assessed, with 105 randomised; 81 participants completed the 12-week trial, 79 completed week-16 follow-up, and 21 completed week-64 follow-up. There were no significant differences between those taking NAC and those taking placebo in CAPS-5 scores at week 12, nor in secondary outcomes. Significant between-group differences were observed at week 64 in craving duration (Cohen's d = 1.61) and craving resistance (Cohen's d = 1.03), both in favour of NAC. CONCLUSION: This was the first multicentre, double-blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. No benefit of NAC was observed in this group beyond that provided by placebo at end of the trial. TRIAL REGISTRATION: ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004.

DSM-5 criterion-a-based trauma types in service members and veterans seeking treatment for posttraumatic stress disorder.

OBJECTIVE: In posttraumatic stress disorder (PTSD), the assumption of the equipotentiality of traumas ignores potentially unique contexts and consequences of different traumas. Accordingly, Stein et al. (2012) developed a reliable typing scheme in which assessors categorized descriptions of traumatic events into six "types": life threat to self (LTS), life threat to other, aftermath of violence (AV), traumatic loss, moral injury by self (MIS), and moral injury by other (MIO). We extended this research by validating the typing scheme using participant endorsements of type, rather than assesor-based types. We examined the concordance of participant and assesor types, frequency, and validity of participant-based trauma types by examining associations with baseline mental and behavioral health problems. METHOD: Interviewers enrolled military personnel and veterans (N = 1,443) in clinical trials of PTSD and helped them select the most currently distressing Criterion-A trauma. Participants and, archivally, assessors typed the distressing aspect(s) of this experience. RESULTS: AV was the most frequently participant-endorsed type, but LTS was the most frequently rated worst part of an event. Although participants endorsed MIS and MIO the least frequently, these were associated with worse mental and behavioral health problems. The agreement between participants and assessors regarding the worst part of the event was poor. CONCLUSION: Because of discrepancies between participant and assessor typologies, clinical researchers should use participants' ratings, and these should trump assessor judgment. Differences in pretreatment behavioral and mental health problems across some participant-endorsed trauma types partially support the validity of the participant ratings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Childhood Maltreatment and Use of Aggression among Veterans with Co-occurring PTSD and Alcohol Use Disorder: The Mediating Role of Hostile Cognitions.

History of childhood maltreatment is common among military veterans, particularly those with posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Childhood maltreatment is associated with negative psychosocial outcomes, including use of aggression during adulthood. Prior research has identified maladaptive cognitions as a key mediating variable in the association between early life trauma and aggression. Given the high rates of comorbid PTSD and AUD among veterans and the increased risk of aggression when these conditions co-occur, it is critical to examine malleable intervention targets, such as maladaptive cognitions, for this population. The current secondary analyses examined the mediating role of hostile cognitions on the associations between childhood maltreatment and adulthood aggression in a sample of dually diagnosed veterans. Participants were veterans with co-occurring PTSD and AUD (N = 73) who were enrolled in a larger randomized controlled laboratory trial. Participants completed self-report measures of childhood maltreatment, hostile cognitions, and aggressive behavior. Three models were tested to examine the mediating effect of hostility on the associations between childhood maltreatment, abuse, and neglect on aggression. Results indicated that hostility fully mediated the effect of maltreatment on aggression and partially mediated the effect of childhood abuse on aggression. The effect of childhood neglect on aggression was nonsignificant. Hostile cognitions may be a critical intervention target for veterans with co-occurring PTSD and AUD and history of childhood maltreatment, particularly for those who have experienced higher levels of childhood abuse.

A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans.

Objective: The aim of this study was to determine the efficacy of doxazosin, an α1-adrenergic antagonist, for the treatment of co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD).Methods: This 12-week, double-blind, randomized controlled trial of doxazosin (16 mg/d) was conducted between June 2016 and December 2019 at the Ralph H. Johnson VA Medical Center in Charleston, South Carolina. Participants were military veterans (N = 141) who met DSM-5 criteria for current PTSD and AUD and were randomly assigned to receive doxazosin (n = 70) or placebo (n = 71). Primary outcome measures were the Clinician Administered PTSD Scale (CAPS-5), the PTSD Checklist for DSM-5 (PCL-5), and the Timeline Follow-Back (TLFB).Results: Findings from the intent-to-treat analyses revealed that participants in both groups demonstrated statistically significant reductions in CAPS-5 and PCL-5 scores (P < .0001), but, contrary to hypotheses, no significant differences were observed between groups. Percent drinking days and percent heavy drinking days also decreased significantly during treatment, but there were no differences between groups (P < .0001). Abstinence during treatment was significantly higher in the doxazosin versus the placebo group (22% vs 7%, P = .017); however, participants in the doxazosin group consumed a greater number of drinks on drinking days (6.15 vs 4.56, P = .0096). A total of 74.5% of the sample completed the treatment phase, and there were no group differences in retention or adverse events.Conclusions: Doxazosin was safe and tolerable but was not more effective than placebo in reducing PTSD or AUD severity in this dually diagnosed sample. Clinical considerations such as heterogeneity of PTSD and AUD presentation and potential moderators are discussed in the context of future research directions.Trial Registration: ClinicalTrials.gov Identifier: NCT02500602.

Differential symptom weighting in estimating empirical thresholds for underlying PTSD severity: Toward a "platinum" standard for diagnosis?

OBJECTIVE: Symptom counts as the basis for Post-Traumatic Stress Disorder (PTSD) diagnoses in the DSM presume each symptom is equally reflective of underlying disorder severity. However, the "equal weight" assumption fails to fit PTSD symptom data when tested. The present study developed an enhanced PTSD diagnosis based on (a) a conventional PTSD diagnosis from a clinical interview and (b) an empirical classification of full PTSD that reflected the relative clinical weights of each symptom. METHOD: Baseline structured interview data from Project Harmony (N = 2658) was used. An enhanced diagnosis for full PTSD was estimated using an empirical threshold from moderated nonlinear factor analysis (MNLFA) latent PTSD scale scores, in combination with a full conventional PTSD diagnosis based on interview data. RESULTS: One in 4 patients in the sample had a PTSD diagnosis that was inconsistent with their empirical PTSD grouping, such that the enhanced diagnostic standard reduced the diagnostic discrepancy rate by 20%. Veterans, and in particular female Veterans, were at greatest odds for discrepancy between their underlying PTSD severity and DSM diagnosis. CONCLUSION: Psychometric methodologies that differentially weight symptoms can complement DSM criteria and may serve as a platform for symptom prioritization for diagnoses in future editions of DSM.

Psychometric Properties of the Self-Injurious Thoughts and Behaviors Interview-Short Form Among U.S. Active Duty Military Service Members and Veterans.

We assessed the interrater reliability, convergent validity, and discriminant validity of the Self-Injurious Thoughts and Behaviors Interview-Short Form (SITBI-SF) in a sample of 1,944 active duty service members and veterans seeking services for posttraumatic stress disorder (PTSD) and related conditions. The SITBI-SF demonstrated high interrater reliability and good convergent and discriminant validity. The measurement properties of the SITBI-SF were comparable across service members and veterans. Approximately 8% of participants who denied a history of suicidal ideation on the SITBI-SF reported suicidal ideation on a separate self-report questionnaire (i.e., discordant responders). Discordant responders reported significantly higher levels of PTSD symptoms than those who denied suicidal ideation on both response formats. Findings suggest that the SITBI-SF is a reliable and valid interview-based measure of suicide-related thoughts and behaviors for use with military service members and veterans. Suicide risk assessment might be optimized if the SITBI-SF interview is combined with a self-report measure of related constructs.

COPE and oxytocin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in U.S. military veterans.

BACKGROUND: A significant proportion of individuals with alcohol use disorder (AUD) also meet criteria for posttraumatic stress disorder (PTSD). Military veterans are at increased risk for developing co-occurring AUD/PTSD, with prevalence rates 2-4 times higher than the general population. Research is needed to develop more effective treatments for this common comorbidity. The current investigation addresses this need by examining the synergistic effects of a novel pharmacotherapy combined with psychotherapy for co-occurring AUD/PTSD among veterans. Accumulating evidence suggests that the neuropeptide oxytocin (OT) is a promising pharmacotherapy to augment psychotherapy for AUD/PTSD. OT targets neurobiological and behavioral dysregulation common to both AUD and PTSD, in particular, corticolimbic connectivity. Human and animal studies show OT reduces alcohol self-administration, tolerance, and withdrawal; enhances fear extinction; and promotes prosocial behaviors. The current study builds on previous work by examining OT among veterans with AUD/PTSD receiving Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE), an evidence-based integrated treatment. METHODS: This paper describes the rationale, design, and methodology of a Stage II, 12-week, double-blind, randomized clinical trial of intranasal OT (40 IU) versus placebo combined with COPE among veterans (N = 180) with current AUD/PTSD. In addition, the effects of treatment on corticolimbic connectivity will be examined using functional magnetic resonance imaging (fMRI) at pre- and post-treatment. CONCLUSIONS: The proposed study will provide new knowledge and mechanistic insights to accelerate research in this understudied area and may lead to improved treatment outcomes for co-occurring AUD/PTSD. CLINICALTRIALS: gov: NCT04523922.

Patient- and therapist-rated alliance predict improvements in posttraumatic stress disorder symptoms and substance use in integrated treatment.

OBJECTIVE: Concurrent Treatment of Posttraumatic Stress Disorder (PTSD) and Substance Use Disorders Using Prolonged Exposure (i.e., COPE) is an efficacious, integrated, psychotherapy that attends to PTSD and substance use disorders simultaneously. No study has examined how therapeutic alliance functions during the provision of COPE and how this compares to non-integrated treatments, such as relapse prevention (RP) for substance use disorders. Understanding the role of alliance in COPE versus RP could inform treatment refinement and ways to enhance treatment outcomes. METHODS: Participants (N = 55 veterans) were randomized to 12, individual, weekly sessions of COPE or RP in a randomized clinical trial. Piecewise linear mixed effect models examined how mid-treatment (1) patient-rated alliance, (2) therapist-rated alliance, and (3) the convergence between patient- and therapist-rated alliance as measured by a difference score predicted reductions in PTSD symptoms and substance use across treatment and follow-up periods. RESULTS: Both patient- and therapist-rated alliance predicted reductions in PTSD symptoms in COPE. Higher patient-rated alliance predicted lower percent days using substances in RP. Difference score models showed higher patient-rated alliance relative to therapist-rated alliance scores predicted symptom reductions in COPE whereas higher therapist-rated alliance scores relative to patient-rated alliance scores predicted symptom reductions in RP. DISCUSSION: Preliminary findings show a unique relationship between the rater of the alliance and treatment modalities. Patient-rated alliance may be important in trauma-focused, integrated treatments whereas therapist-rated alliance may be more important in skills-focused, substance use interventions.

Early intervention using written exposure therapy for PTSD and AUD symptoms following sexual assault: Description of design and methodology.

The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common following sexual assault and associated with more severe symptomology and increased likelihood of sexual revictimization. Integrated interventions aimed at reducing PTSD and AUD symptoms following recent sexual assault are needed and should address barriers to care and early treatment termination. The proposed study will test a novel, brief (5 to 7 sessions) intervention that integrates Written Exposure Therapy for PTSD and Cognitive Behavioral Therapy for AUD, and is initiated within the first six weeks post-assault. In Phase 1, qualitative analysis of content gathered during focus groups with treatment providers will be conducted to inform intervention development. In Phase 2, a proof-of-concept pilot study (n = 10) of the intervention, Substance Use Skills Training and Exposure Post-Sexual Assault (STEPS), will be conducted. In Phase 3, a pilot randomized controlled trial (RCT) among 54 recent sexual assault survivors will be implemented using the updated manualized STEPS intervention to evaluate feasibility and preliminary efficacy in reducing PTSD and AUD symptoms. Ecological momentary assessments will be used to assess daily alcohol use, craving, affect, intrusions and avoidance. The effects of STEPS on commonly associated symptoms (e.g., depression, substance use) will be examined. The proposed study has the potential to make a significant public health impact by advancing knowledge on the link between sexual assault and co-occurring PTSD and AUD and informing early intervention efforts for this high-risk population.

Project Harmony: A Meta-Analysis With Individual Patient Data on Behavioral and Pharmacologic Trials for Comorbid Posttraumatic Stress and Alcohol or Other Drug Use Disorders.

OBJECTIVE: Treatment efficacy for co-occurring posttraumatic stress disorder (PTSD) and substance use disorders is well established, yet direct evidence for comparative effectiveness across treatments is lacking. The present study compared the effectiveness of several behavioral and pharmacological therapies for adults with co-occurring PTSD and alcohol or other drug use disorders. METHODS: A systematic search of PsycINFO, MEDLINE, and ClinicalTrials.gov was conducted through December 2020 for trials targeting PTSD, alcohol or other drug use disorders, or both disorders (36 studies, N=4,046). Primary outcomes were severity scores for PTSD, alcohol use, and drug use, estimated via moderated nonlinear factor analysis. Propensity score weight-adjusted multilevel models were used. Model-predicted effect sizes were estimated for each treatment, and comparative effect sizes for each active arm against treatment as usual, at end of treatment and at 12-month follow-up. RESULTS: Compared with treatment as usual, combining trauma-focused therapy and pharmacotherapy for substance use disorders showed the largest comparative effect sizes for PTSD severity (d=-0.92, 95% CI=-1.57, -0.30) and alcohol use severity (d=-1.10, 95% CI=-1.54, -0.68) at end of treatment. Other treatments with large comparative effect sizes included pharmacotherapies for alcohol or other drug use disorders, trauma-focused integrated therapies, and trauma-focused nonintegrated therapies. Reductions in outcomes for PTSD symptoms and alcohol use were observed for nearly all treatments. CONCLUSIONS: The findings provide support for treating comorbid PTSD and substance use disorders using a variety of approaches, with alcohol-targeted pharmacotherapies and trauma-focused behavioral therapies as a combination of treatments that lead to early and sustained improvements in PTSD and alcohol use severity. Further treatment development is indicated for combining behavioral and pharmacological treatments for synergized impact and understanding the mechanisms of action and conditions under which each treatment type is optimized.

The role of posttraumatic guilt and anger in integrated treatment for PTSD and co-occurring substance use disorders among primarily male veterans.

OBJECTIVE: PTSD and substance use disorders (SUD) frequently co-occur among veterans. Integrated exposure-based treatments, such as Concurrent Treatment of PTSD and SUD Using Prolonged Exposure (COPE), are efficacious in reducing PTSD and SUD symptoms and posttraumatic emotions. This study examines whether guilt and anger (a) decreased in a randomized clinical trial comparing COPE with Relapse Prevention (RP) therapy for SUD and (b) mediated PTSD and SUD symptom reductions or vice versa. METHOD: Veterans (90.1% men) diagnosed with PTSD and SUD were randomized to 12 sessions of COPE (n = 54) or RP (n = 27). Guilt and anger were assessed at 10 time points during treatment. Multilevel linear models assessed changes in guilt and anger across treatments and lagged multilevel mediation analyses assessed within-subject change in guilt and anger predicting PTSD and percent days of substance use, and vice versa. RESULTS: Guilt (B = -.12, SE = .02, p < .001) and anger (B = -.13, SE = .02, p < .001) improved in both treatments, however guilt was significantly lower in Sessions 7 through 11 among veterans receiving COPE. Improvement in guilt mediated PTSD symptom improvement in both treatment groups (B = -.08, SE = .04, 95% CI [-.16, -.01]), and PTSD symptom improvement mediated anger reduction in COPE (B = -.03, SE = .01, 95% CI [-.06, -.01]). The substance use models were insignificant. CONCLUSIONS: Among veterans, integrated, trauma-focused treatments may be associated with greater guilt (directly) and anger (indirectly) reductions due to processing trauma. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Technology-enhanced in vivo exposures in Prolonged Exposure for PTSD: A pilot randomized controlled trial.

In vivo exposures (IVEs) are a key component of exposure-based treatments, during which patients approach fear-provoking, yet safe, situations in "real life." This pilot study assessed the use of a wearable technology (Bio Ware) during IVEs to enhance Prolonged Exposure (PE) therapy for PTSD. Bio Ware provides a clinician dashboard with real-time physiological and subjective data for clinicians to use for virtually guided IVEs. Participants (N = 40) were randomized to a Guided group that received standard PE and virtual, clinician-guided IVEs with the Bio Ware device, or a Non-Guided group that received standard PE and used the Bio Ware device on their own for IVEs. Multilevel linear models with bootstrapping were completed on the intent-to-treat (ITT; N = 39) and per-protocol samples (PP; n = 23), defined as completing at least eight sessions of PE and using the Bio Ware system during ≥ 1 IVEs. In the PP sample, there were significant effects of treatment condition (b = -14.55, SE = 1.47, 95% CI [-17.58, -11.78], p < .001) and time (b = -1.98, SE = 0.25, 95% CI [-2.47, -1.48], p < .001). While both groups showed reductions in PTSD symptoms, the Guided group evidenced significantly greater reductions than the Non-Guided group. These findings demonstrate the feasibility and safety of leveraging Bio Ware for virtual, clinician-guided IVEs during PE therapy for PTSD and suggest that virtual, clinician-guided exposures may enhance treatment outcomes. CLINICAL TRIAL REGISTRATION: NCT04471207.

Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind, randomized, sham-controlled pilot study.

BACKGROUND: Opioid Use Disorder (OUD) is a serious public health problem, and the behavioral and physiological effects of opioid withdrawal can be a major impediment to recovery. Medication for OUD is currently the mainstay of treatment; however, it has limitations and alternative approaches are needed. OBJECTIVE: The purpose of this study was to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on behavioral and physiological manifestations of acute opioid withdrawal. METHODS: Patients with OUD undergoing acute opioid withdrawal were randomly assigned to receive double blind active tcVNS (N = 10) or sham stimulation (N = 11) while watching neutral and opioid cue videos. Subjective opioid withdrawal, opioid craving, and anxiety were measured using a Visual Analogue Scale (VAS). Distress was measured using the Subjective Units of Distress Scale (SUDS), and pain was measured using the Numerical Rating Scale (NRS) for pain. Electrocardiogram signals were measured to compute heart rate. The primary outcomes of this initial phase of the clinical trial (ClinicalTrials.gov NCT04556552) were heart rate and craving. RESULTS: tcVNS compared to sham resulted in statistically significant reductions in subjective opioid withdrawal (p = .047), pain (p = .045), and distress (p = .004). In addition, tcVNS was associated with lower heart rate compared to sham (p = .026). Craving did not significantly differ between groups (p = .11). CONCLUSIONS: tcVNS reduces behavioral and physiological manifestations of opioid withdrawal, and should be evaluated in future studies as a possible non-pharmacologic, easily implemented approach for adjunctive OUD treatment.

Measurement Error-Corrected Estimation of Clinically Significant Change Trajectories for Interventions Targeting Comorbid PTSD and Substance Use Disorders in OEF/OIF Veterans.

In randomized control trials (RCTs), a focus on average differences between treatment arms often limits our understanding of whether individuals show clinically significant improvement or deterioration. The present study examined differences in individual-level clinical significance trajectories between Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) and Relapse Prevention (RP). Eighty-one treatment-seeking veterans with a comorbid PTSD/SUD diagnosis were randomized to COPE or RP; data from an additional n = 48 patients who did not meet criteria for both disorders was used to establish a normative threshold. A newly developed, modernized approach to the Jacobson and Truax (1991) clinically significant change framework, using (a) moderated nonlinear factor analysis (MNLFA) scale scoring and (b) measurement error-corrected multilevel modeling (MEC-MLM) was used; this approach was compared to other approaches using conventional total scores and/or assuming no measurement error. Using a conventional approach to estimating the Reliable Change Index (RCI) yielded no differences between COPE and RP in the percentage of patients achieving statistically significant improvement (SSI; 88.9% for both groups). However, under MNLFA/MEC-MLM, higher percentages of patients receiving COPE (75.0%) achieved SSI compared to RP (40.7%). Findings suggest that, even though COPE and RP appear to reduce the same number of PTSD symptoms, MNLFA scoring of outcome measures gives greater weight to interventions that target and reduce "hallmark" PTSD symptoms.

Enhancing Prolonged Exposure therapy for PTSD using physiological biomarker-driven technology.

Prolonged Exposure (PE) therapy is one of the most efficacious, evidence-based treatments for posttraumatic stress disorder (PTSD). A key component of PE involves in vivo exposures (IVEs) during which patients approach situations or activities in "real life" that are safe but avoided because they elicit a fear response. Despite their critical role in treatment, little research has focused on IVEs. This gap in knowledge is primarily due to the fact that IVEs are typically conducted by patients in between therapy sessions, leaving clinicians reliant upon patient self-report. This approach has numerous shortcomings, which the current study addresses by leveraging technology to develop an innovative device that allows for physiological, biomarker-driven, therapist-guided IVEs. The new system enables clinicians to virtually accompany patients during IVEs and provides real-time physiological (heart rate, skin conductance) and self-report (subjective units of distress) data that clinicians can use to modify the exposure and optimize therapeutic value. This Small Business Innovation Research (SBIR) Phase I project aims to: (1) integrate physiological sensors and live audio/visual streaming into a system for clinicians to guide patients during IVEs; (2) determine feasibility and acceptability of the system; and (3) conduct a pilot randomized clinical trial among veterans with PTSD (N = 40) to evaluate the preliminary efficacy of the system in reducing PTSD symptoms during PE. This paper describes the rationale, design, and methodology of the Phase I project. The findings from this study have the potential to innovate clinical practice, advance the science of exposure therapy, and improve clinical outcomes.