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

Morgan-López A.A., McDaniel H.L., Bradshaw C.P., Saavedra L.M., Lochman J.E., Kaihoi C.A., Powell N.P., Qu L., Yaros A.C.

As suicide rates have risen in the last decade, there has been greater emphasis on targeting early risk conditions for suicidality among youth and adolescents as a form of suicide "inoculation". Two particular needs that have been raised in this nascent literature are a) the dearth of examination of early intervention effects on distal suicide risk that target externalizing behaviors and b) the need to harmonize multiple existing intervention datasets for greater precision in modeling intervention effects on low base rate outcomes such as suicidal behaviors. This project, entitled "Integrative Data Analysis of Coping Power (CP): Effects on Adolescent Suicidality", funded by the National Institute of Mental Health (NIMH), will harmonize and analyze data from 11 randomized controlled trials of CP (total individual-level N = 3183, total school-level N = 189). CP is an empirically-supported, child- and family-focused preventive intervention that focuses on reducing externalizing more broadly among youth who exhibit early aggression, which makes it ideally suited to targeting externalizing pathways to suicidality. The project utilizes three measurement and data analysis frameworks that have emerged across multiple independent disciplines: integrative data analysis (IDA), random treatment effects multilevel modeling (RTE-MLM), and propensity score weighting (PSW). If successful, the project will a) provide initial evidence that CP would have gender-specific indirect effects on suicidality through reductions in externalizing for boys and reductions in internalizing for girls and b) identify optimal conditions under which CP is delivered (e.g., groups, individuals, online) across participants on reductions in suicidality and other key intermediate endpoints.

Hien D.A., Fitzpatrick S., Saavedra L.M., Ebrahimi C.T., Norman S.B., Tripp J., Ruglass L.M., Lopez-Castro T., Killeen T.K., Back S.E., Morgan-López A.A.

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.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.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.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.背景/目的: 本研究利用了一个国际创伤后应激障碍和物质使用障碍 (PTSD+SUD) 干预研究人员的专业知识, 以确定对于PTSD+SUD并发患者 针对 SUD, PTSD 或 PTSD+SUD 的干预措施分类方法可能是推进未来系统综述, 元分析和旨在比较各种心理治疗类型效果的比较有效性研究的最佳选择。方法: 使用两步过程来评估分类术语。首先, 我们从 PTSD+SUD 临床试验, 系统和文献综述中检索了文献中预先存在的 PTSD+SUD 干预类别。然后, 我们调查了解了国际创伤和物质使用主题专家对现有干预分类和理想分类命名法的看法。结果: 混合方法分析表明, 过去 20 年 PTSD+SUD 治疗研究的激增带来了许多表征已评估治疗的方法。我们对27名专家的调查结果显示, PTSD+SUD 的干预措施可以按许多似乎彼此高度重叠的方式进行分类。许多专家 (11/27; 41%) 选择了‘创伤聚焦和非创伤聚焦’的类别作为区分治疗类型的最佳方式。尽管几位专家在随后会议中强调了这一点, 但很明显, 任何对治疗进行分类的方法都没有缺陷。结论: 确定了一种可能的分类 (创伤聚焦/非创伤聚焦) 。需要修订用于 PTSD + SUD 治疗分类的语言和命名法, 以适应这一先进领域的需求。.

Simpson T.L., Goldberg S.B., Louden D.K., Blakey S.M., Hawn S.E., Lott A., Browne K.C., Lehavot K., Kaysen D.

Over the past 20 years, numerous treatments addressing comorbid Posttraumatic Stress Disorder (PTSD) and Substance Use Disorder (SUD) have been developed and tested. The current meta-analysis examined the efficacy and acceptability of the two central treatment types- trauma-focused and non-trauma-focused - compared with all comparators and with cognitive-behavioral manualized SUD treatments immediately post-treatment and at longest follow-up. Twenty-eight randomized clinical trials (N = 3247) were included. There were small to large within-group effects for all forms of active treatment (gs = 0.30-1.11). Trauma-focused but not non-trauma-focused treatments outperformed all comparators on PTSD outcomes at post-treatment. Neither trauma-focused nor non-trauma-focused treatment outperformed all comparators on SUD outcomes at post-treatment. Neither trauma- nor non-trauma-focused treatment outperformed manualized SUD treatments on PTSD outcomes at either time point. Manualized SUD treatments outperformed trauma-focused treatments on SUD outcomes at post-treatment and non-trauma-focused treatments on PTSD outcomes at follow-up. Regarding treatment retention, neither trauma-focused nor non-trauma-focused treatments significantly differed from all comparators or from manualized SUD treatments. Between-group results were largely unchanged in trim-and-fill analyses, but were not robust to fail-safe N. Few moderators were detected. Taken together, results suggest that trauma-focused, non-trauma-focused, and manualized SUD interventions are sound options for individuals with comorbid PTSD/SUD.

Saavedra L.M., Morgan-López A.A., Hien D.A., López-Castro T., Ruglass L.M., Back S.E., Fitzpatrick S., Norman S.B., Killeen T.K., Ebrahimi C.T., Hamblen J.

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.

Koob G.F., Powell P., White A.

Najavits L.M., Clark H.W., DiClemente C.C., Potenza M.N., Shaffer H.J., Sorensen J.L., Tull M.T., Zweben A., Zweben J.E.

Posttraumatic stress disorder (PTSD) commonly co-occurs with substance use disorder (SUD) and is challenging to treat. We review all behavioral therapy models with at least one randomized controlled trial in a current PTSD/SUD population. We identify factors in selecting a model for clinical use, emphasizing a public health framework that balances the need for evidence with the need for feasibility in frontline settings. Seven published models and 6 unpublished models are reviewed. Public health considerations for choosing a model include the following: whether it has been studied across a broad range of SUDs and in complex SUD patients; whether it can be conducted in group modality; its appeal to patients and providers; its cost; workforce requirements; and its ability to reduce substance use in addition to PTSD. There are two broad types of models: those that originated in the PTSD field versus the SUD field. Overall, the latter are stronger on public health factors and more feasible in SUD settings. Published models in this category include Relapse Prevention, BRENDA, and Seeking Safety. PTSD/SUD research is at an early stage and there is a need for methodology that quantifies “level of burden” (patients’ socioeconomic disadvantages) across trials.

Petrakis I., Ralevski E., Arias A.J., DeNegre D., Newcomb J., Gianoli M., McCarthy E., Meshberg‐Cohen S., Yoon G.

Background and objectives There are high rates of comorbid alcohol use disorder (AUD) among those who have posttraumatic stress disorder (PTSD). Ideally, treatment for comorbidity should address both disorders simultaneously. Zonisamide, an anticonvulsant, may be effective in decreasing alcohol use and may attenuate symptoms of PTSD. Treatment strategies can include medication in combination with a proven evidence-based psychotherapy designed to treat PTSD, such as cognitive processing therapy (CPT). Methods This 12-week pilot study was designed to test feasibility, acceptability, and preliminary efficacy of zonisamide (400 mg) as an adjunct to CPT for veterans with PTSD and comorbid AUD. Veterans (n = 24) with PTSD and current alcohol dependence were randomized in a 3:1 ratio to receive zonisamide or placebo in a double-blind fashion. All subjects received CPT enhanced to include sessions addressing drinking behavior. Results Subjects overall reported a significant decrease in drinking outcomes, craving, and symptoms of PTSD. Zonisamide was well-tolerated and easily administered with CPT, which was also well-tolerated. Exploratory analysis of comparison of groups suggests there was no advantage of zonisamide vs placebo in drinking or PTSD outcomes. There was a numeric but nonsignificant higher rate of abstinence with zonisamide (50%) vs placebo (33%). Conclusion and scientific significance The interpretation of the results is limited by the pilot nature of this study. The combination of psychosocial treatment with medication management mimics real-world treatment. In order to isolate the individual contributions of medication vs psychotherapy a much larger study would need to be conducted. (Am J Addict 2020;29:515-524).

Kehle-Forbes S.M., Chen S., Polusny M.A., Lynch K.G., Koffel E., Ingram E., Foa E.B., Van Horn D.H., Drapkin M.L., Yusko D.A., Oslin D.W.

Recent clinical practice guidelines recommend the delivery of evidence-based psychotherapies for both substance use disorder (SUD) and posttraumatic stress disorder (PTSD) within the same treatment episode for patients with SUD/PTSD comorbidity. This randomized clinical trial evaluated the comparative effectiveness of integrating versus phasing evidence-based psychotherapies for SUD and PTSD among veterans with co-occurring SUD/ PTSD.183 veterans with DSM-IV PTSD and SUD at two VA Medical Centers were randomized to one of two psychotherapies during which Motivational Enhancement Therapy [MET] for SUD and Prolonged Exposure [PE] for PTSD were either phased or integrated throughout treatment. Primary outcomes as evaluated by blinded assessors were percent days with drug use or heavy drinking and PTSD symptomology. We hypothesized integrated MET/PE (n = 95) would yield better SUD and PTSD-related outcomes at posttreatment than phased MET/PE (n = 88).In intent-to-treat analyses (n=183), both treatment groups achieved clinically (d=0.46 - 1.06) and statistically significant reductions in SUD (p < 0.01) and PTSD (p < 0.01) symptomology; the time by treatment interactions were not significant. Post-hoc analyses could not confirm statistical non-inferiority; between-group effect sizes suggest a lack of clinically-meaningful differences between the two treatment approaches (d=0.08 - 0.27).Our hypothesis that integrated MET/PE would result in better outcomes than phased MET/PE across a range of PTSD and SUD measures was not supported; both strategies for combining two single-disorder treatments for co-occurring SUD/PTSD yielded significant symptom reduction.

Higgins J.P., Savović J., Page M.J., Elbers R.G., Sterne J.A.

Norman S.B., Trim R., Haller M., Davis B.C., Myers U.S., Colvonen P.J., Blanes E., Lyons R., Siegel E.Y., Angkaw A.C., Norman G.J., Mayes T.

Importance Co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common and associated with psychiatric and functional problems. Understanding whether exposure therapy is tolerable and efficacious for treating PTSD and AUD is critical to ensure that best practice treatments are available. Objective To compare the efficacy of integrated (ie, targeting both PTSD and alcohol use) prolonged exposure (I-PE) therapy with present-centered integrated coping skills (I-CS) therapy, a more commonly available treatment, in reducing PTSD symptoms and alcohol use. Design, Setting, and Participants This prospective randomized clinical trial with masked assessments considered 186 veterans seeking Veterans Affairs mental health services. A total of 119 veterans with PTSD and AUD were randomized. Data were collected from February 1, 2013, to May 31, 2017, before treatment, after treatment, and at 3- and 6-month follow-ups. Intention-to-treat analyses were performed. Interventions Veterans underwent I-PE (Concurrent Treatment of PTSD and Substance Use Disorder Using Prolonged Exposure) or I-CS (Seeking Safety) therapy. Main Outcomes and Measures A priori planned outcomes were PTSD symptoms (Clinician Administered PTSD Scale forDSM-5) and percentage of heavy drinking days (Timeline Follow-Back) before treatment, after treatment, and at 3- and 6-month follow-ups. Results A total of 119 veterans (mean [SD] age, 41.6 [12.6] years; 107 [89.9%] male) were randomized. Linear mixture models found that PTSD symptoms decreased in both conditions, with a significantly greater decrease for I-PE treatment compared with I-CS treatment (treatment × time interaction, −2.83;F3,233.1 = 4.92; Cohend = 0.41;P = .002). The percentage of heavy drinking days improved in both conditions but was not statistically different between I-PE and I-CS treatment (treatment × time interaction, 1.8%;F3,209.9 = 0.18; Cohend = 0.04;P = .91). Conclusions and Relevance The I-PE arm had a greater reduction in PTSD symptoms than the I-CS arm and comparable drinking decreases. The study provides evidence that exposure therapy is more efficacious in treating PTSD than a more commonly available integrated treatment without exposure for comorbid PTSD and AUD. Trial Registration ClinicalTrials.gov identifier:NCT01601067

Hamblen J.L., Norman S.B., Sonis J.H., Phelps A.J., Bisson J.I., Nunes V.D., Megnin-Viggars O., Forbes D., Riggs D.S., Schnurr P.P.

Clinical practice guidelines (CPGs) are used to support clinicians and patients in diagnostic and treatment decision-making. Along with patients' preferences and values, and clinicians' experience and judgment, practice guidelines are a critical component to ensure patients are getting the best care based on the most updated research findings. Most CPGs are based on systematic reviews of the treatment literature. Although most reviews are now restricted to randomized controlled trials, others may consider nonrandomized effectiveness trials. Despite a reliance on similar procedures and data, methodological decisions and the interpretation of the evidence by the guideline development panel can result in different recommendations. In this article, we will describe key methodological points for 5 recently released CPGs on the treatment of posttraumatic stress disorder in adults and highlight some of the differences in both the process and the subsequent recommendations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Ackerman B., Schmid I., Rudolph K.E., Seamans M.J., Susukida R., Mojtabai R., Stuart E.A.

Randomized trials are considered the gold standard for assessing the causal effects of a drug or intervention in a study population, and their results are often utilized in the formulation of health policy. However, there is growing concern that results from trials do not necessarily generalize well to their respective target populations, in which policies are enacted, due to substantial demographic differences between study and target populations. In trials related to substance use disorders (SUDs), especially, strict exclusion criteria make it challenging to obtain study samples that are fully "representative" of the populations that policymakers may wish to generalize their results to. In this paper, we provide an overview of post-trial statistical methods for assessing and improving upon the generalizability of a randomized trial to a well-defined target population. We then illustrate the different methods using a randomized trial related to methamphetamine dependence and a target population of substance abuse treatment seekers, and provide software to implement the methods in R using the "generalize" package. We discuss several practical considerations for researchers who wish to utilize these tools, such as the importance of acquiring population-level data to represent the target population of interest, and the challenges of data harmonization.

Back S.E., Killeen T., Badour C.L., Flanagan J.C., Allan N.P., Ana E.S., Lozano B., Korte K.J., Foa E.B., Brady K.T.

A substantial amount of individuals with substance use disorders (SUD) also meet criteria for posttraumatic stress disorder (PTSD). Prolonged Exposure (PE) is an effective, evidence-based treatment for PTSD, but there is limited data on its use among individuals with current alcohol or drug use disorders. This study evaluated the efficacy of an integrated treatment that incorporates PE (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure or COPE) among veterans.Military veterans (N = 81, 90.1% male) with current SUD and PTSD were randomized to 12 sessions of COPE or Relapse Prevention (RP). Primary outcomes included the Clinician Administered PTSD Scale (CAPS), PTSD Checklist-Military version (PCL-M), and the Timeline Follow-back (TLFB).On average, participants attended 8 out of 12 sessions and there were no group differences in retention. Intent-to-treat analyses revealed that COPE, in comparison to RP, resulted in significantly greater reductions in CAPS (d = 1.4, p < .001) and PCL-M scores (d = 1.3, p = .01), as well as higher rates of PTSD diagnostic remission (OR = 5.3, p < .01). Both groups evidenced significant and comparable reductions in SUD severity during treatment. At 6-months follow-up, participants in COPE evidenced significantly fewer drinks per drinking day than participants in RP (p = .05).This study is the first to report on the use of an integrated, exposure-based treatment for co-occurring SUD and PTSD in a veteran sample. The findings demonstrate that integrated, exposure-based treatments are feasible and effective for military veterans with SUD and PTSD. Implications for clinical practice are discussed.

Schäfer I., Lotzin A., Hiller P., Sehner S., Driessen M., Hillemacher T., Schäfer M., Scherbaum N., Schneider B., Grundmann J.

Forman-Hoffman V., Cook Middleton J., Feltner C., Gaynes B.N., Palmieri Weber R., Bann C., Viswanathan M., Lohr K.N., Baker C., Green J.

Hruska B., Piccirillo M.L., Lenferink L.I., Pacella-LaBarbara M.L., Contractor A.A., Price M., Greene T.

Norman S.B., Luciano M.T., Panza K.E., Davis B.C., Lyons M., Martis B., Matthews S.C., Angkaw A.C., Haller M., Lacefield K., Brody A.L., Schnurr P.P., Batki S.L., Simpson T.L., Anthenelli R.M.

Zhao J., Guo Y., Tan Y., Zhang Y., Liu S., Liu Y., Li J., Ruan J., Liu L., Ren Z.

Swannell M., Bradlow R., Pham D., Gabriel J., Manahan Y., Arunogiri S.

Romano N., Luba R.

Alcohol use disorder (AUD) commonly co-occurs with other psychiatric disorders. AUD most frequently co-occurs with other substance use disorders, attention deficit hyperactivity disorder, major depressive disorder, and anxiety disorders, among others. The co-occurrence of AUD with psychiatric disorders significantly amplifies the risks associated with both conditions. Overlapping symptoms of both AUD and other psychiatric conditions exist and may precipitate or perpetuate the other. It is important to assess for and consider the directionality of comorbid conditions to inform diagnostic considerations and subsequent treatments. Although the pathophysiology of AUD with other psychiatric conditions is not well understood, theories exist to describe the underlying mechanisms of comorbidity, including the common liability pathway and the gateway hypothesis, each considering the interplay and directionality of genetic, environmental, epigenetic, and psychosocial factors. The dynamic interplay between the co-occurring disorders underscores the complexity of diagnosis and treatment. Importantly, the treatment of AUD comorbid with other psychiatric disorders should be integrated and simultaneous. Treatment approaches include both pharmacologic and psychotherapeutic interventions, which offer improved benefits when combined.

Thomas J., Carrano J., Schacht R.L., Fishman M., Wenzel K.

Blakey S.M., Alsobrooks A.K., Morgan-López A.A., Kruskamp N., Simpson T.L., Daughters S.B., DuBois C.M., Huang J.S., Evans J., Serrano B.N., Calhoun P.S., Beckham J.C., Elbogen E.B.

Nearly 2 million U.S. veterans live with co-occurring alcohol use disorder and posttraumatic stress disorder (AUD/PTSD). Extant AUD/PTSD treatments emphasize symptom reduction, sometimes overlooking psychosocial functioning improvements, and have dropout rates as high as 50 %. Additionally, current approaches to measuring psychosocial functioning are limited to self-report. This study protocol describes a 1:1 parallel, two-arm, pilot randomized controlled trial comparing Behavioral Activation (BA) psychotherapy to Relapse Prevention (RP) psychotherapy for veterans with AUD/PTSD.

Patton S.C., Watkins L.E., Killeen T.K., Hien D.A.

We review prevalence, etiology, impact on treatment, and best practices for treatment of posttraumatic stress disorder (PTSD) in a substance use disorder (SUD) treatment setting. Recommendations are given related to screening, assessment, and symptom monitoring. PTSD and SUDs are highly comorbid. This comorbidity is associated with higher acuity, more difficulty completing treatment, and worse prognosis. Integrated treatment is recommended, and trauma-focused psychotherapies combined with pharmacotherapy show particular promise. PTSD is highly prevalent in substance using samples, negatively impacting treatment course and worsening prognosis. This comorbidity has been explained by a variety of models, with self-medication having garnered the most support. Trauma-focused psychotherapies combined with pharmacotherapy demonstrate the most efficacy and are recommended when treating co-occurring SUDs and PTSD. Specifically, prolonged exposure (PE), concurrent treatment of PTSD and SUDs using PE (COPE), and cognitive processing therapy (CPT) have been seen as promising trauma-focused treatments. Investigations into ways to best augment therapy are also underway, both through treatment format and neuromodulation. Several recommendations are given.

O’Neil M.E., Cameron D., Krushnic D., Baker Robinson W., Hannon S., Clauss K., Cheney T., Cook L., Niederhausen M., Pugh M.J.

Petrakis I.L., Nolen T., Vandergrift N., Hirsch S., Krystal J.H., De Vivo M., Sabados J., Pisani E., Newcomb J., Kosten T.R.

AbstractBackground and ObjectivesNoradrenergic dysregulation is important in the pathophysiology of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD); pharmacotherapies targeting adrenergic function have potential as treatment for comorbidity. Dexmedetomidine (sublingual film formulation—BXCL501; IGALMI) is a highly potent, selective ⍺2‐adrenergic receptor agonist and may be superior to other pharmacotherapeutic approaches. A within subjects, phase 1b safety laboratory study was conducted to evaluate adverse effects of BXCL501 when combined with alcohol; BXCL501's potential efficacy was also explored.MethodsHeavy drinker participants with a diagnosis of or who were at risk for PTSD participated in three separate test days which included pretreatment with BXCL501 (40 µg, 80 µg or placebo) administered in a randomized, double‐blind fashion, followed by three testing conditions: alcohol cue reactivity, trauma‐induced reactivity, and IV ethanol administration. Safety outcomes included blood pressure (BP) and sedation. Exploratory outcomes included alcohol craving, trauma‐induced anxiety and craving and subjective effects of alcohol.ResultsTen of twelve randomized participants competed the entire study. BXCL501 (80 µg) was associated with expected mild changes in BP and sedation; administration with alcohol did not affect those parameters. There were no clinically significant adverse effects. BXCL501 attenuated trauma‐induced anxiety and attenuated subjective effects of alcohol.Discussions and ConclusionsBXCL501 is safe for use in humans who may drink alcohol while undergoing treatment. BXCL501 may be explored as a potential treatment for PTSD and AUD.Scientific SignificanceThis is the first study to provide scientific support for BXCL501's potential to treat PTSD and comorbid AUD.

Ebrahimi C.T., Gette J.A., Saraiya T.C., Hien D.A.

This chapter aims to provide an overview of co-occurring posttraumatic stress disorder and substance use disorder (PTSD-SUD). We review the prevalence of PTSD-SUD; history of treatment approaches; overview of current treatment modalities for PTSD-alone, SUD-alone, and co-occurring PTSD-SUD treatment; and clinical considerations. A primary focus of this chapter is to provide a summary and critical analysis of sequential and integrated treatments for PTSD-SUD. In particular, sequential treatments covered in this chapter include Relapse Prevention, Contingency Management, Prolonged Exposure, and Cognitive Processing Therapy. Integrated treatments discussed include Seeking Safety, Concurrent Treatment of PTSD and SUD Using Prolonged Exposure, Integrated Cognitive Behavioral Therapies, and pharmacological SUD interventions in combination with behavioral PTSD therapies. Further, this chapter provides clinical guidelines for treatment selection, managing complex trauma, and considerations for common clinical difficulties such as low motivation, attendance, and treatment nonadherence. The chapter concludes with a clinical vignette to illustrate a PTSD-SUD case utilizing an integrated approach.

Hong S., Kim H., Walton B., Kaboi M.

Individuals with co-occurring psychiatric and substance use disorders (COD) face challenges, including accessing treatment, accurate diagnoses, and effective treatment for both disorders. This study aimed to develop a COD prediction model by examining the intersectionality of COD with race/ethnicity, age, gender identity, pandemic year, and behavioral health needs and strengths. Individuals aged 18 or older who participated in publicly funded behavioral health services (N = 22,629) were selected. Participants completed at least two Adult Needs and Strengths Assessments during 2019 and 2020, respectively. A chi-squared automatic interaction detection (CHAID) decision tree analysis was conducted to identify patterns that increased the likelihood of having COD. Among the decision tree analysis predictors, Involvement in Recovery emerged as the most critical factor influencing COD, with a predictor importance value (PIV) of 0.46. Other factors like Legal Involvement (PIV = 0.12), Decision-Making (PIV = 0.12), Parental/Caregiver Role (PIV = 0.11), Other Self-Harm (PIV = 0.10), and Criminal Behavior (PIV = 0.09) had progressively lower PIVs. Age, gender, race/ethnicity, and pandemic year did not show statistically significant associations with COD. The CHAID decision tree analysis provided insights into the dynamics of COD. It revealed that legal involvement played a crucial role in treatment engagement. Individuals with legal challenges were less likely to be involved in treatment. Individuals with COD displayed more complex behavioral health needs that significantly impaired their functioning compared to individuals with psychiatric disorders to inform the development of targeted interventions.

Roepke S., Schellong J., Bergemann N., Frommberger U., Schmidt U.

Neben traumafokussierter Psychotherapie ist besonders bei Patientinnen und Patienten mit schwerer posttraumatischer Belastungsstörung (PTBS) eine pharmakologische Behandlung oft unumgänglich. Sofern nicht die komorbiden Störungen handlungsleitend bei der Pharmakotherapie sind, kann zur PTBS-Behandlung auf die in Deutschland zugelassenen Präparate Sertralin und Paroxetin und weitere off-label verschreibungsfähige Substanzen zurückgegriffen werden. Besonders Venlafaxin konnte in Studien gute Wirksamkeit zeigen. Für Risperidon wurde eine allerdings geringe Wirksamkeit bei der Augmentation nachgewiesen. Insgesamt ist bei allen Substanzen mit nur kleinen bis mittleren Effektstärken zu rechnen. Eine wichtige Rolle spielt die Psychopharmakotherapie bei den bei der PTBS hochprävalenten Schlafstörungen. Eine Behandlung traumabezogener Albträume kann mit Doxazosin oder Clonidin versucht werden. Für die Psychopharmakotherapie PTBS-assoziierter Ein- und Durchschlafstörungen liegen hingegen nur wenige empirische Daten vor; eine Orientierung kann die pharmakologische Behandlung der Insomnie geben.

Back S.E., Jarnecke A.M., Norman S.B., Zaur A.J., Hien D.A.

AbstractPosttraumatic 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.

López-Castro T., Sohler N., Riback L., Bravo G., Ohlendorf E., Ghiroli M., Fox A.D.

Abstract Background Syringe services programs (SSPs) are critical healthcare access points for people with opioid use disorder (OUD) who face treatment utilization barriers. Co-locating care for common psychiatric comorbidities, like posttraumatic stress disorder (PTSD), at SSPs may reduce harms and enhance the health of individuals with OUD. To guide the development of onsite psychiatric care at SSPs, we collected quantitative survey data on the prevalence of PTSD, drug use patterns, treatment experiences associated with a probable PTSD diagnosis, and attitudes regarding onsite PTSD care in a convenience sample of registered SSP clients in New York City. Methods Study participants were administered the PTSD Checklist for the DSM-5 (PCL-5) and asked about sociodemographic characteristics, current drug use, OUD and PTSD treatment histories, and desire for future SSP services using a structured interview. Probable PTSD diagnosis was defined as a PCL-5 score ≥ 31. Results Of the 139 participants surveyed, 138 experienced at least one potentially traumatic event and were included in the present analysis. The sample was primarily male (n = 108, 78.3%), of Hispanic or Latinx ethnicity (n = 76, 55.1%), and middle-aged (M = 45.0 years, SD = 10.6). The mean PCL-5 score was 35.2 (SD = 21.0) and 79 participants (57.2%) had a probable PTSD diagnosis. We documented frequent SSP utilization, significant unmet PTSD treatment need, and high interest in onsite PTSD treatment. Conclusions Study findings point to the ubiquity of PTSD in people with OUD who visit SSPs, large gaps in PTSD care, and the potential for harm reduction settings like SSPs to reach people underserved by the healthcare system who have co-occurring OUD and PTSD.