State of the Science: Treatment of comorbid posttraumatic stress disorder and substance use disorders.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) co-occur at high rates, with research showing that up to nearly 60% of individuals with PTSD also suffer from an alcohol and/or drug use disorder. PTSD/SUD is complex; associated with adverse health, social, and economic outcomes; and can be challenging to treat. Over the past decade, the landscape of treatment research addressing PTSD/SUD has significantly expanded. Ongoing efforts aimed at developing and evaluating novel treatments for PTSD/SUD, encompassing both psychotherapy and pharmacotherapy approaches, are steadily advancing. As such, this State of the Science paper reviews the literature on the latest scientific advances in treating PTSD/SUD. Clinical practice guidelines for the treatment of PTSD/SUD are discussed, along with evidence-based psychotherapies and emerging interventions. Rigorously conducted clinical trials demonstrate that individual, manualized, trauma-focused treatments are the most efficacious psychotherapies to use among individuals with PTSD/SUD. Moreover, patients do not need to be abstinent to initiate or benefit from evidence-based PTSD treatment. To date, no medications have been established for this comorbidity. We highlight ongoing research on novel treatments for PTSD/SUD, such as new forms of integrated trauma-focused psychotherapies, pharmacological augmentation strategies, and technology-based enhancements. Finally, promising future directions for the field are discussed.

Functional Domains of Substance Use and their Implications to Trauma: A Systematic Review of Neuroimaging Studies.

Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma-reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.

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).

Alcohol, cannabis, and nicotine use have distinct associations with COVID-19 pandemic-related experiences: An exploratory Bayesian network analysis across two timepoints.

BACKGROUND: Substance use trends during the COVID-19 pandemic have been extensively documented. However, relatively less is known about the associations between pandemic-related experiences and substance use. METHOD: In July 2020 and January 2021, a broad U.S. community sample (N = 1123) completed online assessments of past month alcohol, cannabis, and nicotine use and the 92-item Epidemic-Pandemic Impacts Inventory, a multidimensional measure of pandemic-related experiences. We examined links between substance use frequency, and pandemic impact on emotional, physical, economic, and other key domains, using Bayesian Gaussian graphical networks in which edges represent significant associations between variables (referred to as nodes). Bayesian network comparison approaches were used to assess the evidence of stability (or change) in associations between the two timepoints. RESULTS: After controlling for all other nodes in the network, multiple significant edges connecting substance use nodes and pandemic-experience nodes were observed across both time points, including positive- (r range 0.07-0.23) and negative-associations (r range -0.25 to -0.11). Alcohol was positively associated with social and emotional pandemic impacts and negatively associated with economic impacts. Nicotine was positively associated with economic impact and negatively associated with social impact. Cannabis was positively associated with emotional impact. Network comparison suggested these associations were stable across the two timepoints. CONCLUSION: Alcohol, nicotine, and cannabis use had unique associations to a few specific domains among a broad range of pandemic-related experiences. Given the cross-sectional nature of these analyses with observational data, further investigation is needed to identify potential causal links.

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.

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.

Cognitive Processing Therapy or Relapse Prevention for comorbid Posttraumatic Stress Disorder and Alcohol Use Disorder: A randomized clinical trial.

OBJECTIVE: To compare a Posttraumatic Stress Disorder (PTSD) treatment (Cognitive Processing Therapy; CPT), an Alcohol Use Disorder (AUD) treatment (Relapse Prevention; RP), and assessment-only (AO) for those meeting diagnostic criteria for both PTSD and AUD. METHOD: Participants with current PTSD/AUD (N = 101; mean age = 42.10; 56% female) were initially randomized to CPT, RP, or AO and assessed post-treatment or 6-weeks post-randomization (AO). AO participants were then re-randomized to CPT or RP. Follow-ups were at immediate post-treatment, 3-, and 12-months. Mixed effects intent-to-treat models compared conditions on changes in PTSD symptom severity, drinking days, and heavy drinking days. RESULTS: At post-treatment, participants assigned to CPT showed significantly greater improvement than those in AO on PTSD symptom severity (b = -9.72, 95% CI [-16.20, -3.23], d = 1.22); the RP and AO groups did not differ significantly on PTSD. Both active treatment conditions significantly decreased heavy drinking days relative to AO (CPT vs. AO: Count Ratio [CR] = 0.51, 95% CI [0.30, 0.88]; RP vs. AO: CR = 0.34, 95% CI [0.19, 0.59]). After re-randomization both treatment conditions showed substantial improvements in PTSD symptoms and drinking between pre-treatment and post-treatment over the 12-month follow-up period, with RP showing an advantage on heavy drinking days. CONCLUSION: Treatments targeting one or the other aspects of the PTSD/AUD comorbidity may have salutary effects on both PTSD and drinking outcomes. These preliminary results suggest that people with this comorbidity may have viable treatment options whether they present for mental health or addiction care. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT01663337).

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.

Estimating posttraumatic stress disorder severity in the presence of differential item functioning across populations, comorbidities, and interview measures: Introduction to Project Harmony.

Multiple factor analytic and item response theory studies have shown that items/symptoms vary in their relative clinical weights in structured interview measures for posttraumatic stress disorder (PTSD). Despite these findings, the use of total scores, which treat symptoms as though they are equally weighted, predominates in practice, with the consequence of undermining the precision of clinical decision-making. We conducted an integrative data analysis (IDA) study to harmonize PTSD structured interview data (i.e., recoding of items to a common symptom metric) from 25 studies (total N = 2,568). We aimed to identify (a) measurement noninvariance/differential item functioning (MNI/DIF) across multiple populations, psychiatric comorbidities, and interview measures simultaneously and (b) differences in inferences regarding underlying PTSD severity between scale scores estimated using moderated nonlinear factor analysis (MNLFA) and a total score analog model (TSA). Several predictors of MNI/DIF impacted effect size differences in underlying severity across scale scoring methods. Notably, we observed MNI/DIF substantial enough to bias inferences on underlying PTSD severity for two groups: African Americans and incarcerated women. The findings highlight two issues raised elsewhere in the PTSD psychometrics literature: (a) bias in characterizing underlying PTSD severity and individual-level treatment outcomes when the psychometric model underlying total scores fails to fit the data and (b) higher latent severity scores, on average, when using DSM-5 (net of MNI/DIF) criteria, by which multiple factors (e.g., Criterion A discordance across DSM editions, changes to the number/type of symptom clusters, changes to the symptoms themselves) may have impacted severity scoring for some patients.

Frontal Alpha Asymmetry in Children with Trauma Exposure.

The purpose of the current study was to investigate differences in frontal alpha asymmetry (FAA) between children (5-17 years) with or without histories of trauma exposure. EEG data were obtained from 165 children who participated in the Healthy Brain Network Initiative during rest with eyes open and closed. FAA during resting-state electroencephalography was significantly more negative in the trauma-exposed group, suggesting greater left lateralized FAA and avoidance-oriented motivation. Moreover, alpha suppression (difference in alpha amplitude between eyes open and eyes closed conditions) was marginally greater in the trauma-exposed group. The results suggest that early exposure to trauma may be associated with trait-level avoidance of environmental stimuli, which ultimately may be predictive of psychopathology, including posttraumatic stress disorder (PTSD). Study findings thus provide preliminary evidence of brain-based mechanisms that may confer risk for PTSD in the wake of early trauma exposure.

What's in a name? A data-driven method to identify optimal psychotherapy classifications to advance treatment research on co-occurring PTSD and substance use disorders.

Background/Objective: The present study leveraged the expertise of an international group of posttraumatic stress and substance use disorder (PTSD+SUD) intervention researchers to identify which methods of categorizing interventions which target SUD, PTSD, or PTSD+SUD for populations with both PTSD+SUD may be optimal for advancing future systematic reviews, meta-analyses, and comparative effectiveness studies which strive to compare effects across a broad variety of psychotherapy types. Method: A two-step process was used to evaluate the categorization terminology. First, we searched the literature for pre-existing categories of PTSD+SUD interventions from PTSD+SUD clinical trials, systematic and literature reviews. Then, we surveyed international trauma and substance use subject matter experts about their opinions on pre-existing intervention categorization and ideal categorization nomenclature. Results: Mixed method analyses revealed that a proliferation of PTSD+SUD treatment research over the last twenty years brought with it an abundance of ways to characterize the treatments that have been evaluated. Results from our survey of experts (N = 27) revealed that interventions for PTSD+SUD can be classified in many ways that appear to overlap highly with one another. Many experts (11/27; 41%) selected the categories of 'trauma-focused and non-trauma focused' as an optimal way to distinguish treatment types. Although several experts reinforced this point during the subsequent meeting, it became clear that no method of categorizing treatments is without flaws. Conclusion: One possible categorization (trauma-focused/non-trauma focused) was identified. Revised language and nomenclature for classification of PTSD+SUD treatments are needed in order to accommodate the needs of this advancing field.

Antecedentes/Objetivo: El presente estudio aprovechó la experticia de un grupo internacional de investigadores de intervención en trastorno de estrés postraumático y trastorno por uso de sustancias (TEPT+TUS) para identificar qué métodos de categorización de las intervenciones con foco en TUS, TEPT y TEPT+TUS para poblaciones con ambos TEPT+TUS serían óptimos para avanzar en futuras revisiones sistemáticas, meta-análisis y estudios comparativos de efectividad que busquen comparar efectos en una amplia variedad de tipos de psicoterapia.Método: Se utilizó un proceso de dos etapas para evaluar la terminología de categorización. Primero, buscamos en la literatura categorías pre-existentes de intervenciones para TEPT+TUS en ensayos clínicos de TEPT+TUS, revisiones sistemáticas y de la literatura. Después, entrevistamos a expertos internacionales en la materia de trauma y uso de sustancias sobre su opinión de la categorización pre-existente de las intervenciones y la nomenclatura ideal de categorización.Resultados: Métodos de análisis mixtos revelaron que una proliferación de investigación de tratamientos para TEPT+TUS en los últimos veinte años trajo consigo una abundancia de formas de categorizar los tratamientos que han sido evaluados. Los resultados de nuestra encuesta de expertos (N = 27) revelaron que las intervenciones para TEPT+TUS pueden ser clasificadas en muchas formas que parecen sobreponerse altamente entre sí. Muchos expertos (11/27; 41%) seleccionaron las categorías de 'centrados en el trauma y no centrados en el trauma' como una forma óptima de distinguir los tipos de tratamiento. Aunque varios expertos reforzaron este punto en la reunión subsecuente, quedó claro que ningún método de categorización de los tratamientos está libre de defectos.Conclusión: Se identificó una posible categorización (centrado en el trauma/No centrado en el trauma). Se necesita lenguaje y nomenclatura revisada para la clasificación de tratamientos de TEPT+TUS a fin de acomodar las necesidades de este campo en desarrollo.

Graded response item response theory in scaling suicidal thoughts and behaviors among trauma-exposed women with substance use disorders.

Objective: The co-occurrence of substance use disorders (SUD) and trauma-exposure is a risk factor for suicidal thoughts and behaviors (STB). However, traditional methods of measurement for suicidal thoughts and behaviors are limited by an overreliance on dichotomous (i.e., yes or no) and averaged/summed scale score measurements. Further, among trauma-exposed individuals with SUD, it remains unclear which specific demographic factors, types of SUDs, and trauma sequelae (e.g., posttraumatic stress disorder [PTSD] symptom clusters) may be associated with elevated STB. The present study utilized item response theory to (a) generate empirically derived STB severity scores and, (b) examine which demographic factors, SUD diagnoses, and DSM-IV PTSD symptom clusters are associated with suicidality in a trauma-exposed sample with SUDs. Method: Female trauma-exposed participants with SUDs (N = 544) were recruited from community substance use treatment facilities in the National Drug Abuse Treatment Clinical Trials Network (CTN). Clinician-administered interviews assessed STB, SUDs, and PTSD symptoms. Results: Results indicated that the unidimensional item response theory (IRT) model used to estimate latent STB severity scores fit well, with strong local reliability at higher levels of latent STB severity. Regression predictors of elevated STB severity included younger age, opioid dependence, and higher PTSD reexperiencing symptoms. Conclusions: Clinicians are advised to screen for and target opioid use disorders and reexperiencing symptoms when addressing suicidal thoughts and behavior in trauma-exposed individuals with SUDs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Seeing the forest for the trees: Predicting attendance in trials for co-occurring PTSD and substance use disorders with a machine learning approach.

Objective: High dropout rates are common in randomized clinical trials (RCTs) for comorbid posttraumatic stress disorder and substance use disorders (PTSD + SUD). Optimizing attendance is a priority for PTSD + SUD treatment development, yet research has found few consistent associations to guide responsive strategies. In this study, we employed a data-driven pipeline for identifying salient and reliable predictors of attendance. Method: In a novel application of the iterative Random Forest algorithm (iRF), we investigated the association of individual level characteristics and session attendance in a completed RCT for PTSD + SUD (n = 70; women = 22 [31.4%]). iRF identified a group of potential predictor candidates for the total trial sessions attended; then, a Poisson regression model assessed the association between the iRF-identified factors and attendance. As a validation set, a parallel regression of significant predictors was conducted on a second, independent RCT for PTSD + SUD (n = 60; women = 48 [80%]). Results: Two testable hypotheses were derived from iRF's variable importance measures. Faster within-treatment improvement of PTSD symptoms was associated with greater session attendance with age moderating this relationship (p = .01): faster PTSD symptom improvement predicted fewer sessions attended among younger patients and more sessions among older patients. Full-time employment was also associated with fewer sessions attended (p = .02). In the validation set, the interaction between age and speed of PTSD improvement was significant (p = .05) and the employment association was not. Conclusions: Results demonstrate the potential of data-driven methods to identifying meaningful predictors as well as the dynamic contribution of symptom change during treatment to understanding RCT attendance. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Evaluating treatments for posttraumatic stress disorder, alcohol and other drug use disorders using meta-analysis of individual patient data: Design and methodology of a virtual clinical trial.

This paper describes Project Harmony, a Virtual Clinical Trial (VCT) funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to harmonize and analyze data from over 40 independent psychological, pharmacologic and/or combined pharmacological treatment studies for posttraumatic stress disorder and comorbid alcohol and other drug use disorders (PTSD/AOD). The study attends to three distinct analysis challenges: (1) variation in measurement of PTSD/AOD across studies, time, populations and reporters, (2) cross-study variation in treatment effect sizes and (3) non-randomized, cross-study variation in the classification of treatments (despite within-study randomization of treatment arms). To address these challenges, the study combines meta-analysis of individual patient data (MIPD), integrative data analysis (IDA) and propensity score weighting (PSW) to integrate raw data from these clinical trials. This protocol shows how this VCT analytic framework was used to (1) develop commensurate scale scores of PTSD and AOD severity when measures vary across studies, (2) compare the efficacy of evidence-based treatment models for PTSD/AOD, (3) test for potential mediators of treatment effects on AOD and PTSD across treatment models, and (4) explore individual- and study-level moderators to inform for whom each of the treatment models works best. The advantages of the general VCT approach are juxtaposed against the limitations of single randomized controlled trials and conventional meta-analysis.

A unifying translational framework to advance treatment research for comorbid PTSD and substance use disorders.

We provide a unifying translational framework that can be used to synthesize extant lines of human laboratory research in four neurofunctional domains that underlie the co-occurrence of posttraumatic stress and substance use disorders (PTSD+SUD). We draw upon the Alcohol and Addiction Research Domain Criteria (AARDOC) to include executive functioning, negative emotionality, reward, and added social cognition from the National Institute of Mental Health (NIMH) Research Domain Criteria into our framework. We review research findings across each of the four domains, emphasizing human experimental studies in PTSD, SUD, and PTSD+SUD for each domain. We also discuss the implications of research findings for treatment development by considering new ways of conceptualizing risk factors and outcomes at the level of the individual patient, which will enhance treatment matching and advance innovations in intervention.

Putting the Patient Back in Clinical Significance: Moderated Nonlinear Factor Analysis for Estimating Clinically Significant Change in Treatment for Posttraumatic Stress Disorder.

The present study introduced a modernized approach to Jacobson and Truax's (1991) methods of estimating treatment effects on individual-level (a) movement from the clinical to the normative range and (b) reliable change on posttraumatic stress disorder (PTSD) severity. Participants were 450 trauma-exposed women (M age = 39.2 years, SD = 8.9, range: 18-65 years) who presented to seven geographically diverse community mental health and substance use treatment centers. Data from 53 of these women, none of whom met the criteria for full or subthreshold PTSD, were used to establish the normative range. Using moderated nonlinear factor analysis (MNLFA) scale scoring, which weights symptoms by their clinical relevance, a significantly larger proportion of participants moved into the normative range for PTSD severity scores and/or exhibited reliable changes after treatment compared to the same individuals' movement when using symptom counts. Further, approximately 24% of the participants showed discrepant judgments on reliable change indices (RCI) between MNLFA scores and symptom counts, likely due to the false assumption that the standard error of measurement is equal for all levels of underlying PTSD severity when estimating RCIs with symptom counts. An MNLFA approach to estimating underlying PTSD severity can provide clinically meaningful information about individual-level change without the de facto assumption that PTSD symptoms have equivalent weight. Study implications are discussed with regard to a joint emphasis on (a) measurement models that highlight differential symptom weighting and (b) treatment-arm differences in individual-level outcomes rather than the current overemphasis of treatment-arm differences on group-averaged trajectories.

Response-to-Treatment for Comorbid Post-Traumatic Stress and Substance Use Disorders: The Value of Combining Person- and Variable-Centered Approaches.

Optimizing treatment for co-occurring post-traumatic stress disorder and substance use disorder (PTSD+SUD) is critically important. Whereas treatments have been designed that target PTSD+SUD with some success, these treatments do not benefit all. Data-driven approaches that combine person- and variable-centered methods, such as parallel process latent class growth analysis (PP-LCGA) can be used to identify response-to-treatment trajectories across both PTSD symptoms and substance use. The current study employed PP-LCGA separately in two randomized clinical trials (study 1 n = 81, Mean age = 40.4 years, SD = 10.7; study 2 n = 59, Mean age = 44.7 years, SD = 9.4) to examine PTSD symptom response and percentage of days using substances across treatment trials comparing Concurrent Treatment of PTSD and SUD using Prolonged Exposure and Relapse Prevention. Results revealed four PTSD+SUD profiles for study one and three PTSD+SUD profiles for study two. For PTSD symptoms, response trajectories could be broadly classified into treatment responders and non-responders across both studies. For substance use, response trajectories could be broadly classified into declining, moderately stable, and abstaining profiles. When considering PTSD symptoms and substance use trajectories together, profiles emerged that would have been missed had these treatment outcomes been considered separately.