Project description:BackgroundThe psychological treatment of comorbid post-traumatic stress disorder (PTSD) and substance use disorder (SUD) is clinically challenging, and outcomes are often poor.ObjectiveThis paper describes a systematic review and meta-analysis which sought to establish the current efficacy for a number of established psychological approaches for adults and adolescents, in comparison to interventions for SUD alone, or other active approaches, following a pre-registered protocol.MethodThis review followed PRISMA and Cochrane Collaboration guidelines. Data extraction and risk of bias judgements using Cochrane criteria were undertaken by all authors. Primary outcomes were PTSD severity and substance use post-treatment. The quality of findings was assessed using GRADE. Following a comprehensive search, conducted to 13 September 2021, 27 studies were included.ResultsWe found a relatively high level of dropout across studies. In our main comparisons, we found no benefits for present-focused treatment approaches aimed at improving coping skills beyond those for SUD-only interventions. We found modest benefits for trauma-focused intervention plus SUD intervention post-treatment for PTSD (standardized mean difference (SMD) = -0.36, 95% confidence interval (CI) -0.64, -0.08), and at 6-13 months for PTSD (SMD = -0.48, 95% CI -0.81, -0.15) and alcohol use (SMD = -0.23, 95% CI -0.44, -0.02). There were no benefits for cognitive restructuring interventions as a group, but we found a modest effect for integrated cognitive behavioural therapy (ICBT) for PTSD post-treatment (SMD = -0.33, 95% CI -0.62, -0.04). There was evidence of some benefit for trauma-focused intervention over present-focused intervention for PTSD from a single study and for reduction in dropout for incentivized attendance for trauma-focused intervention from another single study. Most findings were of very low quality.ConclusionThere is evidence that trauma-focused therapy and ICBT can improve PTSD for some individuals, but many patients do not fully engage with treatment and average treatment effects are modest.HighlightsFor PTSD, evidence was strongest for trauma-focused CBT-based approaches, but effects were modest.There was little evidence of any added benefit on substance use, beyond that of standard addiction treatments, for any included intervention.Dropout from treatment was high.
Project description:Problem statementSeeking Safety (SS) is a widely implemented cognitive-behavioral therapy for comorbid post-traumatic stress disorder (PTSD) and substance use disorder (SUD). It is a present-focused coping skills model that is highly flexible, with varied methods of delivery, to maximize acceptability and client access. The purpose of this meta-analysis is to examine the effect of SS on comorbid PTSD and SUD across randomized control trials (RCTs). In addition, ours is the first meta-analysis to examine the dose-response of SS by comparing delivery of all 25 SS topics versus fewer.Methods and designArticles published before January 2, 2023 (CINAHL n = 16, PsycINFO n = 31, MEDLINE n = 27, Cochrane n = 38, and Scopus n = 618) were searched. Seven studies were included for meta-analysis and dose-response analysis.ResultsBased on effect sizes (ES), meta-analysis revealed that SS has a medium group, time (p = .04), and time by group effect on substance use per the Addiction Severity Index at 3 months and a small effect on Clinician-Administered PTSD Scale scores by group, a large effect by time, and a medium time by group (p = .002) effect at 6 months. Based on the pooled ES examining various measures across multiple timepoints, SS had small to medium effects on substance use by time, group, or time by group and medium to large effects on PTSD symptoms by time, group, or time by group (except for the group effect at 3-month follow-up). Significant effects were found for substance use by time at 3 and 6 months and for PTSD postintervention, at 6 months and 9 months by group, time, and time by group while only by time at 3 months. Meta-regression revealed that partial dose versions of SS generally function as well as the full dose version of SS when observing long-term effects (greater than 3 months).DiscussionFindings suggest SS has merit in treating PTSD symptoms and SUD. Based on the summarized effect sizes, SS appears more effective in reducing PTSD than substance use, which converges with the larger treatment outcome literature that consistently finds this. We explore reasons that treatment of SUD is more challenging than treating PTSD and offer suggestions for practitioners. We emphasize the need for future studies to utilize common measures and provide full details of treatment delivery for optimal comparison across studies.
Project description:The increasing comorbidity of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) associated with traumatic brain injury (TBI) is a serious medical, economic, and social issue. However, the molecular toxicology and pathophysiological mechanisms of comorbid AUD and PTSD are not well understood and the identification of the comorbidity state markers is significantly challenging. This review summarizes the main characteristics of comorbidity between AUD and PTSD (AUD/PTSD) and highlights the significance of a comprehensive understanding of the molecular toxicology and pathophysiological mechanisms of AUD/PTSD, particularly following TBI, with a focus on the role of metabolomics, inflammation, neuroendocrine, signal transduction pathways, and genetic regulation. Instead of a separate disease state, a comprehensive examination of comorbid AUD and PTSD is emphasized by considering additive and synergistic interactions between the two diseases. Finally, we propose several hypotheses of molecular mechanisms for AUD/PTSD and discuss potential future research directions that may provide new insights and translational application opportunities.
Project description:Highlights • Interventions versus controls had a small positive effect on PTSD and none on SUD.• One of the two studies reporting emotion regulation found a small positive effect.• Attrition and effects were similar for the subset with high substance use severity.• The review support recommendations to assess ACE history during addiction treatment.• The transdiagnostic role of emotion regulation in PTSD/SUD/ACEs needs more research. Background Adverse childhood experiences (ACEs) have long-term effects on adult health, including unresolved trauma and substance use disorder (SUD). There are hypotheses of a mediating role of emotion regulation. This systematic literature review and narrative synthesis assessed the effectiveness of psychological interventions on emotion regulation, PTSD and SUD symptoms. Methods Searches were conducted using the Cochrane Handbook for Systematic Reviews methodology. Eligible studies were randomised controlled trials (RCTs) and quasi-experimental psychological interventions published between 2009 and 2019. Study characteristics, results and methodological quality were systematically analysed. Results Thirteen studies, including nine RCTs, were selected. Integrated SUD and PTSD treatments consisted of Seeking Safety, exposure-based treatment, Trauma Recovery and Empowerment Model, and integrated cognitive behavioural therapy. Two studies reported emotion regulation. Five studies found a small to medium positive effect size of psychological interventions on PTSD outcomes. Two studies had a small positive effect size on SUD outcomes and two a small negative effect size. Attrition was high across most studies. Characteristics likely to affect the applicability of the review were described. Conclusion The review found some evidence of a small inconsistent positive effect of psychological interventions on PTSD outcomes, and no evidence of effect on SUD outcomes. The range of theoretical models was narrow. Overall quality was low with high clinical heterogeneity and missing key information, particularly on emotion regulation, an important transdiagnostic feature. Further research is required to establish interventions that can treat these multiple conditions with a focus on effectiveness, acceptability, and implementation in real life clinical practice.
Project description:Post-traumatic stress disorder (PTSD) symptoms are highly prevalent among individuals with substance use disorders (SUD), presenting a difficult-to-treat, complex comorbidity. Prognostic factors for treatment outcomes may characterize heterogeneity of the treated population and/or implicate mechanisms of action that are salient for improving treatments. High frequency heart rate variability (HF-HRV) is a suggested biomarker for emotion regulation-the ability to generate appropriate emotional responses via the influence of the parasympathetic nervous system on the heart. This initial study investigated the utility of baseline resting HF-HRV for predicting PTSD symptoms and substance use outcomes following treatment of 37 SUD participants with comorbid PTSD symptoms. Participants completed either standard cognitive- behavioral therapy (CBT) for SUD or a novel treatment of integrated post-traumatic stress and substance use that combined CBT for SUD with cognitive processing therapy for PTSD. Analyses demonstrated that higher HF-HRV predicted greater reduction in PTSD symptoms following both types of treatment. This suggests prognostic value of HF-HRV as a predictor of PTSD treatment outcomes; those with poorer autonomic emotional regulation may not respond as well to psychotherapy in general. This hypothesis-generating analysis identifies a putative biomarker that might have utility in treatment prediction.
Project description:DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3' un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway.
Project description:Post-traumatic stress disorder (PTSD) is common among people with substance use disorders, and the comorbidity is associated with negative outcomes. We report on a randomized controlled trial comparing the effect of integrated cognitive-behavioral therapy (ICBT) plus standard care, individual addiction counseling plus standard care and standard care alone on substance use and PTSD symptoms.Three-group, multi-site randomized controlled trial.Seven addiction treatment programs in Vermont and New Hampshire, USA.Recruitment took place between December 2010 and January 2013. In this single-blind study, 221 participants were randomized to one of three conditions: ICBT plus standard care (SC) (n = 73), individual addiction counseling (IAC) plus SC (n = 75) or SC only (n = 73). One hundred and seventy-two patients were assessed at 6-month follow-up (58 ICBT; 61 IAC; 53 SC). Intervention and comparators: ICBT is a manual-guided therapy focused on PTSD and substance use symptom reduction with three main components: patient education, mindful relaxation and flexible thinking. IAC is a manual-guided therapy focused exclusively on substance use and recovery with modules organized in a stage-based approach: treatment initiation, early abstinence, maintaining abstinence and recovery. SC are intensive out-patient program services that include 9-12 hours of face-to-face contact per week over 2-4 days of group and individual therapies plus medication management.Primary outcomes were PTSD severity and substance use severity at 6 months. Secondary outcomes were therapy retention.PTSD symptoms reduced in all conditions with no difference between them. In analyses of covariance, ICBT produced more favorable outcomes on toxicology than IAC or SC [comparison with IAC, parameter estimate: 1.10; confidence interval (CI)?= 0.17-2.04; comparison with SC, parameter estimate: 1.13; CI = 0.18-2.08] and had a greater reduction in reported drug use than SC (parameter estimate: -9.92; CI =?-18.14 to -1.70). ICBT patients had better therapy continuation versus IAC (P<0.001). There were no unexpected or study-related adverse events.Integrated cognitive behavioral therapy may improve drug-related outcomes in post-traumatic stress disorder sufferers with substance use disorder more than drug-focused counseling, but probably not by reducing post-traumatic stress disorder symptoms to a greater extent.
Project description:BACKGROUND:Post-traumatic stress disorder (PTSD) is a severe and disabling condition that may lead to functional impairment and reduced productivity. Psychological interventions have been shown to be effective in its management. The objective of this study was to assess the cost-effectiveness of a range of interventions for adults with PTSD. METHODS:A decision-analytic model was constructed to compare costs and quality-adjusted life-years (QALYs) of 10 interventions and no treatment for adults with PTSD, from the perspective of the National Health Service and personal social services in England. Effectiveness data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion. RESULTS:Eye movement desensitisation and reprocessing (EMDR) appeared to be the most cost-effective intervention for adults with PTSD (with a probability of 0.34 amongst the 11 evaluated options at a cost-effectiveness threshold of £20,000/QALY), followed by combined somatic/cognitive therapies, self-help with support, psychoeducation, selective serotonin reuptake inhibitors (SSRIs), trauma-focused cognitive behavioural therapy (TF-CBT), self-help without support, non-TF-CBT and combined TF-CBT/SSRIs. Counselling appeared to be less cost-effective than no treatment. TF-CBT had the largest evidence base. CONCLUSIONS:A number of interventions appear to be cost-effective for the management of PTSD in adults. EMDR appears to be the most cost-effective amongst them. TF-CBT has the largest evidence base. There remains a need for well-conducted studies that examine the long-term clinical and cost-effectiveness of a range of treatments for adults with PTSD.
Project description:Individuals with both post-traumatic stress disorder and major depressive disorder (PTSD+MDD) often show greater social and occupational impairment and poorer treatment response than individuals with PTSD alone. Increasing evidence reveals that the amygdala, a brain region implicated in the pathophysiology of both of these conditions, is a complex of structurally and functionally heterogeneous nuclei. Quantifying the functional connectivity of two key amygdala subregions, the basolateral (BLA) and centromedial (CMA), in PTSD+MDD and PTSD-alone could advance our understanding of the neurocircuitry of these conditions. 18 patients with PTSD+MDD, 28 with PTSD-alone, and 50 trauma exposed healthy controls (TEHC), all from a cohort who survived the same large earthquake in China, underwent resting-state functional magnetic resonance imaging. Bilateral BLA and CMA functional connectivity (FC) maps were created using a seed-based approach for each participant. The analysis of covariance of FC was used to determine between-group differences. A significant interaction between amygdala subregion and diagnostic group suggested that differences in connectivity patterns between the two seeds were mediated by diagnosis. Post-hoc analyses revealed that PTSD+MDD patients showed weaker connectivity between right BLA and (a) left anterior cingulate cortex/supplementary motor area, and (b) bilateral putamen/pallidum, compared with PTSD-alone patients. Higher CMA connectivities left ACC/SMA were also observed in PTSD+MDD compared with PTSD-alone. An inverse relationship between the connectivity of right BLA with right putamen/pallidum and MDD symptoms was found in PTSD+MDD. These findings indicate a relationship between the neural pathophysiology of PTSD+MDD compared with PTSD-alone and TEHC and may inform future clinical interventions.