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Substance use disorders (SUD) and posttraumatic stress disorder (PTSD) are chronic, debilitating conditions that frequently co-occur. Individuals with co-occurring SUD and PTSD suffer a more complicated course of treatment and less favorable treatment outcomes compared to individuals with either disorder alone. The development of effective psychosocial and pharmacological interventions for co-occurring SUD and PTSD is an active and critically important area of investigation. Several integrated psychosocial treatments for co-occurring SUD and PTSD have demonstrated promising outcomes. While recent studies examining medications to treat co-occurring SUD and PTSD have yielded encouraging findings, there remain substantial gaps in the evidence base regarding the treatment of co-occurring SUD and PTSD. This review will summarize the findings from clinical trials targeting a reduction in SUD and PTSD symptoms simultaneously. These results may improve our knowledge base and subsequently enhance our ability to develop effective interventions for this complex comorbid condition.

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. 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. 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. 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.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) often co-occur and present significant treatment challenges. Cognitive Processing Therapy (CPT) is a widely used, efficacious treatment for PTSD, but the application of CPT among individuals with co-occurring PTSD/AUD has been limited. To address this gap, we developed a novel, 12-session trauma-focused treatment that combines CPT with Relapse Prevention (RP) for AUD (CPT+RP). This paper describes CPT+RP and presents preliminary outcomes from the first six participants enrolled in a larger, ongoing multisite clinical trial of CPT+RP. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD Checklist for DSM-5 (PCL-5). The Timeline Follow-Back (TLFB) assessed frequency (percent days drinking; PDD) and quantity (drinks per drinking day; DDD) of alcohol use, and craving was measured using the Penn Alcohol Craving Scale (PACS). The Client Satisfaction Questionnaire measured acceptability. Pre- to post-treatment reductions were observed in PTSD symptoms (ΔMCAPS-5 = 14.00; ΔMPCL-5 = 20.50), frequency and quantity of alcohol use (ΔMPDD = 38.65; ΔMDDD = 6.24), and craving (ΔPACS = 6.17). Most participants achieved clinically significant improvement in their PTSD symptoms and acceptability was high. Although preliminary, the findings suggest the new CPT+RP intervention is feasible, acceptable, and a promising treatment innovation for co-occurring PTSD and AUD.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) frequently co-occur in youth. Integrated, trauma-focused treatments are recommended, but evidence in youth is limited and the dynamics of symptom change are poorly understood. We investigated within-treatment changes in PTSD and substance use, and their temporal sequencing, in a randomised controlled trial (RCT) comparing integrated treatment with supportive counselling among youth aged 13-25 years. Participants (  = 55) were randomised to an integrated, exposure-based treatment, Concurrent Treatment of PTSD and SUD Using Prolonged Exposure - Adolescent version (COPE-A); or supportive counselling, Person-Centred Therapy (PCT). PTSD and substance use symptoms were assessed at each session. Generalised estimating equations were used to analyse symptom change over time, and Spearman's correlations were used to examine associations between early (sessions 1-5) and later (sessions 5-11) change. COPE-A showed significantly greater reductions in total PTSD symptom severity during treatment (  = -17.00, 95% CI -29.50 to -4.46); with no between-group differences in substance use quantity or frequency. PTSD symptom clusters improved concurrently, but no temporal relationships were observed. Temporal relationships for substance use change were limited, and changes in PTSD symptoms were not associated with concurrent or subsequent changes in substance use. Integrated, trauma-focused treatment reduced PTSD symptoms, reinforcing the safety and tolerability of exposure-based therapy in this youth sample with comorbid PTSD-SUD. PTSD improvement was not associated with either concurrent or subsequent reductions in substance use. Understanding temporal patterns of change may help refine models of PTSD-SUD comorbidity and optimise intervention delivery.

Opioid use disorder (OUD) and posttraumatic stress disorder (PTSD) frequently co-occur. However, there are no psychotherapy treatments intentionally designed for this comorbidity, nor designed to be augmented with medications for OUD. In this open-label pilot trial, we tested Helping Opioid Use Disorder and PTSD with Exposure (HOPE), a novel integrated, trauma-focused treatment for individuals (N = 6) with OUD/PTSD who were stabilized on medications for OUD. HOPE was delivered weekly for 10–12 sessions, and one follow-up visit was conducted ~1-month post-treatment. Primary outcomes included urine drug screens, the Timeline Followback, Desire for Drugs Questionnaire, Clinician-Administered PTSD Scale-5 (CAPS-5), and PTSD Checklist-5 (PCL-5). Boot-strapped linear mixed effect models and generalized estimating equations showed that PTSD symptoms (CAPS-5: B = −7.16, SE = 1.24, p < 0.01; PCL-5: B = −2.04, SE = 0.26, p < 0.01), desire for opioids (B = −0.56, SE = 0.15, p < 0.01), depression symptoms (B = −0.43, SE = 0.09, p < 0.01), and anxiety symptoms (B = −0.50, SE = 0.08, p < 0.01) decreased significantly over time. Client satisfaction increased throughout the study (B = 0.18, SE = 0.08, p = 0.02), and 83.3% of participants completed the therapy and follow-up visit. There were no significant changes in opioid or other substance use from baseline to follow-up. Although preliminary, results show high acceptability and feasibility of the HOPE therapy and demonstrate significant improvements in PTSD and associated symptoms with an integrated, trauma-focused treatment.

IntroductionEmerging research indicates that integrated treatment of co-occurring post-traumatic stress disorder (PTSD) and substance use disorder can be effective among adolescents and young people. However, various barriers exist to young people accessing evidence-based treatments. Telehealth offers an opportunity to address these barriers and provide a scalable and accessible alternative to inperson treatment. This paper describes the study protocol for a randomised controlled trial (RCT) examining the efficacy, safety and cost-effectiveness of an integrated trauma-focused cognitive-behavioural treatment for traumatic stress and substance use among adolescents and young adults (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure – Adolescent and Young Adult version (COPE-A)) when delivered in person compared with via telehealth.Methods and analysisA two-arm, parallel group, single-blind, non-inferiority RCT with follow-up at 4 months and 12 months post study entry will be conducted in Sydney, Australia. Participants (170 adolescents and young adults aged 12–25 years) will be allocated to receive COPE-A either in person or via telehealth (allocation ratio 1:1) using minimisation. Project psychologists will administer treatment via both modes of delivery over a maximum of 16 sessions of 60–90 min. The primary outcome will be between-group differences in change in the severity of PTSD symptoms from baseline to 4-month follow-up, as measured by the Clinician-Administered PTSD Scale for Children and Adolescents for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.Ethics and disseminationThis study has been approved by the Sydney Children’s Hospitals Network Human Research Ethics Committee (2024/ETH01050). Research findings will be published in peer-reviewed journals and presented at scientific conferences.Trial registration numberACTRN12624000776505.Protocol versionV.2.3, 20 March 2025.

Background Most patients with Posttraumatic Stress Disorder (PTSD) suffer residual symptoms following first-line treatment. Oxidative stress has been implicated in the pathophysiology of PTSD. N-acetylcysteine (NAC) is a precursor of the brain’s primary antioxidant, glutathione, and may diminish oxidative cellular damage. An 8-week pilot study of NAC in veterans with PTSD found that symptoms were significantly reduced in the NAC group compared to placebo. This study aims to confirm these findings with a larger sample in a double-blind, placebo-controlled trial to further explore the efficacy of NAC as an adjunctive therapy in treatment-resistant PTSD. Methods A multicentre, randomised, double-blind, placebo-controlled trial for adult patients who still meet criteria for PTSD following first-line treatment. The intervention comprises either NAC as a fixed dose regime of 2.7 g/day (900 mg three times daily) administered orally for 12 weeks, or placebo. Standard care for PTSD will continue in addition, including other pharmacotherapies. Detailed clinical data will be collected at randomisation and weeks 4, 8, 12, 16, and 64 post-randomisation, with self-report measures completed weekly from baseline to 16 weeks and at 64 weeks post-randomisation. Blood-based biomarkers will be collected at baseline and 12 weeks to assess the mechanism of effect. The primary outcome measure will be change in Clinician-Administered PTSD Scale for DSM-5 at 12 weeks compared with baseline. Secondary outcomes will be change in quality of life, depression, anxiety, substance use and craving, and somatic symptoms. With 126 completed participants (63 per arm), the study is powered at 80% to detect a true difference in the primary outcome measure using a two-tailed analysis with alpha = 0.05, beta = 0.2. Discussion This is the first multicentre, double blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. NAC has an established safety profile, is readily available and easy to administer, and has a favourable tolerability profile, therefore making it an attractive adjunctive therapy. Inclusion of blood analyses to assess potential target engagement biomarkers of oxidative stress and neuroinflammation may help gauge the biological mechanisms of effect of NAC. Trial registration ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004 .

Background/Objectives: The co-occurrence of posttraumatic stress disorder (PTSD) and cannabis use disorder (CUD) symptoms is common following sexual assault, particularly among emerging adult women. CUD is associated with more severe PTSD symptoms and other mental health comorbidities including depression, suicidality, and emotion dysregulation. Addressing these issues concurrently soon after sexual assault could help decrease the risk for downstream negative health outcomes. Integrated trauma-focused interventions for PTSD and co-occurring substance use disorders have been shown to decrease PTSD severity and substance use. Yet, existing protocols are lengthy and have rarely been applied following recent trauma exposure or specifically to address CUD symptoms. Methods: This case series describes the application of Written Exposure Therapy (WET) for PTSD adapted to integrate cognitive-behavioral skills training for substance use among women following recent sexual assault. The adapted integrated intervention, Skills Training and Exposure for PTSD and Substance Misuse (STEPS), was delivered to three emerging adult women (age range = 19–25) who experienced recent sexual assault (weeks since assault range = 1–12 weeks). Results: This case series describes the novel intervention and examines clinical outcomes post-treatment and at the 1-month follow-up. Past-week PTSD symptoms (based on a clinical interview) and past-month cannabis use decreased among all participations after receiving STEPS. Conclusions: Preliminary findings from the case series provide new knowledge and insights regarding the application of STEPS following recent sexual assault among individuals with co-occurring PTSD and CUD. Therapeutic strategies for addressing PTSD and CUD concurrently and implications for future clinical research are discussed.

Experts in PTSD+SUD clinical trials were surveyed to identify principles for treatment classification of PTSD+SUD behavioural therapies. Results indicated some consensus around 'trauma-focused' vs 'non-trauma-focused' as one designation but further agreement is needed. 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.

IntroductionPost-traumatic stress disorder (PTSD) and substance use disorder frequently co-occur and tend to have their onset during adolescence. Although research has highlighted the importance of treating these disorders in an integrated fashion, there is a dearth of empirically validated integrated treatment options for adolescents with this comorbidity. This paper describes the study protocol for a randomised controlled trial (RCT) examining the efficacy of an integrated trauma-focused cognitive–behavioural treatment for traumatic stress and substance use among adolescents (Concurrent Treatment of PTSD and Substance Use Using Prolonged Exposure - Adolescent (COPE-A)), relative to a supportive counselling control condition (Person-Centred Therapy (PCT)).Methods and analysisA two-arm, parallel, single-blind RCT with blinded follow-up at 4 and 12 months poststudy entry will be conducted in Sydney, Australia. Participants (n~100 adolescents aged 12–18 years) and their caregivers (caregiver participation is optional) will be allocated to undergo either COPE-A or PCT (allocation ratio 1:1) using minimisation. Both therapies will be delivered individually by project psychologists over a maximum of 16 sessions of 60–90 min duration and will include provision of up to four 30 min optional caregiver sessions. The primary outcome will be between-group differences in change in the severity of PTSD symptoms from baseline to 4-month follow-up, as measured by the Clinician-Administered PTSD Scale for Children and Adolescents for DSM-5.Ethics and disseminationEthical approval has been obtained from the human research ethics committees of the Sydney Children’s Hospital Network (HREC/17/SCHN/306) and the University of Sydney (HREC 2018/863). Findings will be published in peer-reviewed journals and presented at scientific conferences.Trial registration numberACTRN12618000785202; Pre-reults.Protocol versionVersion 1, 31 July 2017.