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Objective: To describe post-traumatic stress disorder (PTSD)-related symptoms and frequent psychiatric comorbidities, treatments received, healthcare resource utilization (HRU), and healthcare costs pre- and post-PTSD diagnosis among adults in the United States., Methods: Adults with PTSD who received a PTSD-related pharmacological treatment (selective serotonin reuptake inhibitor [SSRI], serotonin-norepinephrine reuptake inhibitor [SNRI], atypical antipsychotic [AA]) within 24 months of the first observed PTSD diagnosis (index date) were identified using MarketScan Commercial Database (2015-2020). Study outcomes were assessed during the 6-month pre-diagnosis and 24-month post-diagnosis periods. Subgroup analyses included patients treated or not treated with AAs post-PTSD diagnosis., Results: Of the overall patients ( N  = 26,306; mean age at diagnosis 39.5 years; 73.3% female), 85.9% had PTSD-related symptoms and frequent psychiatric comorbidities during the 6 months pre-diagnosis. Patients treated with AAs post-PTSD diagnosis ( N  = 9,298) tended to have higher rates of PTSD-related symptoms and comorbidities at diagnosis than those not treated with AAs ( N  = 7,011). Following diagnosis, the most commonly observed first-line treatments were SSRI (67.4%), AA (23.4%), and SNRI (22.6%). The rate of PTSD-related symptoms and comorbidities, psychotherapy and pharmacological treatments received, HRU, and healthcare costs increased during the 6 months post-diagnosis relative to the 6 months pre-diagnosis and then declined over time during the 24 months post-diagnosis., Conclusions: The PTSD diagnosis was associated with increased rates of symptoms and frequent psychiatric comorbidities, psychotherapy and pharmacological treatments received, HRU, and healthcare costs, pointing to increased patient monitoring. Within 6 to 12 months after the PTSD diagnosis, these outcomes tended to reduce, perhaps as patients were obtaining targeted and effective care.

Background: Effective pharmacologic treatments for comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are lacking. Kappa (κ) opioid receptor antagonists may address this unmet need. Buprenorphine is a κ-opioid antagonist and a partial agonist of mu (μ) opioid receptors. Whereas naltrexone blocks all μ-mediated effects combining it with buprenorphine yields a pharmacologic net effect of opioid receptor antagonism. Because no κ-opioid receptor antagonist it available for clinical use, we tested this combination in a proof-of-concept study., Methods: Consenting participants were enrolled in a Phase II, multisite, double-blind, randomized, placebo-controlled trial evaluating the effectiveness of sublingual (SL) buprenorphine combined with extended-release (XR) injectable naltrexone for the treatment of comorbid AUD and PTSD. Eligible participants (n = 75) were randomized (1:1:1) to receive either buprenorphine 2 mg/day plus naltrexone-XR (n = 35), buprenorphine 8 mg/day plus naltrexone-XR (n = 6) or SL plus injectable placebo (n = 34) for 12 weeks. The buprenorphine 8 mg/day plus naltrexone-XR arm was dropped early in the trial due to the negative impact of COVID-19 on enrollment. A binary primary outcome of response at week 8 was defined as a decrease from baseline of ≥10 points on the past week Clinician-Administered PTSD Scale (CAPS-5) and a reduction of ≥1 of past month alcohol risk level, as defined by the World Health Organization (WHO) and measured by the Timeline Follow-Back., Results: Based on the results of a futility analysis, enrollment was stopped prior to reaching the initial goal of 90 participants. At the week eight primary timepoint, there were no statistically significant differences between buprenorphine plus naltrexone-XR and placebo group for the primary composite outcome (OR = 0.63; p-value = 0.52), or the subcomponents of the PTSD outcome (OR = 0.76; p-value = 0.69) and AUD outcome (OR = 0.17; p-value = 0.08). The placebo arm had a significantly higher proportion of participants with ≥1 WHO risk level reduction than the buprenorphine plus naltrexone-XR arm (OR = 0.18, p value = 0.02)., Conclusions: This is the first study to evaluate the potential of κ-opioid receptor antagonism for the treatment of comorbid AUD and PTSD. The combination of buprenorphine and naltrexone-XR showed no significant improvement over placebo for the composite, PTSD, or alcohol measures., (© 2023 The Authors. Alcohol: Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Complementary integrative medicine, such as mindfulness-based interventions, (MBI) have demonstrated efficacy in the treatment of depression, anxiety, substance use disorders (SUDs), and pain. Mindfulness-based relapse prevention (MBRP) is an aftercare intervention targeting SUD relapse that integrates cognitive-behavioral relapse prevention and mindfulness meditation practices, raising awareness of substance use triggers and reactive behavioral patterns. This study evaluated the efficacy of MBRP in reducing relapse in veterans following completion of an SUD treatment program., Methods: This study was a two-site, randomized controlled trial comparing MBRP to 12-step facilitation (TSF) aftercare in military veterans following completion of intensive treatment for SUDs. The 8 weeks of 90-minute, group-based MBRP or TSF sessions were followed by 3-, 6- and 10-month follow-up periods with assessments of alcohol/substance use and secondary outcomes of depression, anxiety, and mindfulness., Results: Forty-seven percent of veterans attended ≥75 % of sessions. Veterans in both the MBRP and TSF aftercare groups maintained reductions in alcohol and illicit substance use during the aftercare treatment. Nineteen participants (11 %; 19/174) reported returning to alcohol use during the study treatment period and the study found no difference between study groups [MBRP: 9 % vs. TSF 13 %; p = 0.42]. Thirteen participants (7.5 %; 13/174) reported a return to illicit substance use during study treatment [MBRP: 5.4 % vs. TSF 10.3 % p = 0.34]. The number of days of drinking and illicit substance use was not different between groups (alcohol, p = 0.53; illicit substance use, p = 0.28)., Conclusion: Although retention in treatment limits interpretation of the findings, both MBRP and TSF were effective in maintenance of treatment gains following an intensive treatment program for veterans with SUDs. Future studies should focus on strategies to improve treatment participation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest. Sarah Bowen is the developer of manualized therapy and author of “Mindfulness Based Relapse Prevention: A clinician's guide.”, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In this secondary analysis of the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study we used antidepressant response trajectories to assess the association of treatment and multiple clinical/demographic factors with the probability of response., Methods: Using data from VAST-D, a multi-site, randomized, single-blind trial with parallel-assignment to one of three treatment interventions in 1522 Veterans whose major depressive disorder was unresponsive to at least one antidepressant trial, we evaluated response patterns using group-based trajectory modeling (GBTM). A weighted multinomial logistic regression analysis with backward elimination and additional exploratory analyses were performed to evaluate the association of multiple clinical/demographic factors with the probability of inclusion into specific trajectories. Additional exploratory analyses were used to identify factors associated with trajectory group membership that could have been missed in the primary analysis., Results: GBTM showed the best fit for depression symptom change was comprised of six trajectories, with some trajectories demonstrating minimal improvement and others showing a high probability of remission. High baseline depression and anxiety severity scores decreased, and early improvement increased, the likelihood of inclusion into the most responsive trajectory in both the GBTM and exploratory analyses., Conclusion: While multiple factors influence responsiveness, the probability of inclusion into a specific depression symptom trajectory is most strongly influenced by three factors: baseline depression, baseline anxiety, and the presence of early improvement., (© 2023 The Authors. Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC on behalf of American Psychiatric Association.)

Stimulant use disorders are emerging as a serious global threat to health. Although research, clinical, and policy efforts have largely concentrated on opioid use disorders over the past decade, exponential rises in prevalence and overdose deaths attributable to stimulant use disorders warrant renewed attention. To date, no approved medications are available to treat stimulant use disorders; however, behavioral interventions have been effective and should be proactively promoted. Similarly, complementary and integrative therapies and harm reduction services have emerging evidence for effectiveness in treating these conditions. Research, practice, and policy interventions should address stigma for medications for stimulant use disorders when available, vaccine hesitancy if vaccines are approved and safe, environmental surveillance to reduce population exposure to toxic effects of methamphetamines, and educational interventions for health providers to increase competency to reduce the long-term effects on various body systems. [ Journal of Psychosocial Nursing and Mental Health Services, 61 (3), 13-18.].

Objective: Among veterans with posttraumatic stress disorder (PTSD), supported employment that utilizes the individual placement and support (IPS) model has resulted in consistently better employment and functional outcomes than usual vocational rehabilitation services. This study aimed to compare these two approaches in terms of health services use and associated costs., Methods: A secondary analysis of a multisite randomized controlled trial of 541 unemployed veterans with PTSD used archival data from electronic medical records to assess the use and costs of health services of IPS and usual care (i.e., a transitional work [TW] program) over 18 months. Comparisons were also made to an 18-month postintervention period., Results: The two study groups did not differ in number of inpatient days or in utilization or cost of high-intensity services. Annual per-person costs of health services were approximately 20% higher for IPS than for TW participants (mean difference=$4,910 per person per year, p<0.05) during the intervention period, largely driven by higher utilization and costs for vocational services in the IPS group (p<0.001). These costs declined postintervention to nonsignificant differences. The mean annual per-person vocational service cost was $6,388 for IPS and $2,549 for TW (mean difference=$3,839, p<0.001) during the intervention period., Conclusions: In keeping with IPS’s intensive case management approach, veterans receiving IPS used more vocational services and had correspondingly higher costs than veterans receiving TW. The two groups did not differ in use or cost of other types of health services. Future research should examine whether higher short-term costs associated with IPS relative to usual care result in long-term cost savings or higher quality of life for persons with PTSD.

Objectives: This study evaluates the effects of treatment with mindfulness-based stress reduction (MBSR) compared to the active control, present-centered group therapy (PCGT), on morning plasma cortisol, interleukin-6 (IL-6), and C-reactive protein (CRP) in veterans diagnosed with post-traumatic stress disorder (PTSD)., Methods: In a post hoc exploratory analysis, we pooled biomarkers and clinical outcomes of mindfulness, PTSD, and depression from two randomized controlled trials comparing MBSR ( n = 104) to PCGT ( n = 106) in U.S. military veterans diagnosed with PTSD. Linear mixed-effects modeling was used to evaluate associations between changes in biomarkers and clinical outcomes from baseline to 9-week primary endpoint and 16-week follow-up endpoint., Results: Cortisol levels were inversely related to self-reported PTSD symptoms at baseline ( p = 0.02). Cortisol increased from baseline to 9-week endpoint for both groups, but significantly less so in the MBSR group compared to PCGT group (mean difference 1.69 ± 0.8 SE; p = 0.035). Changes in IL-6 and CRP did not differ between groups at either baseline or week 9. From baseline to week 9, increased mindfulness was significantly associated with increased cortisol ( p = 0.02) and decreased PTSD and depression severity ( p < 0.01). Increased IL-6 and CRP were significantly associated with decreased PTSD severity ( p < 0.05), but not depression. Pooled analysis corroborated earlier findings that MBSR is significantly better than PCGT in improving clinical outcomes. Increased mindfulness was strongly associated with improved symptoms., Conclusions: Increased mindfulness is associated with a recalibration of cortisol levels which may be indicative of therapeutic response, especially in patients with lower baseline cortisol. Furthermore, mindfulness-based practices improve symptoms of PTSD and depression in a significant correlation with self-reported levels of mindfulness., Clinical Trial Registration Clinicaltrialsgov: NCT01532999 and NCT01548742., Competing Interests: Conflict of Interest The authors declare no competing interests.

Abstract: Substance use treatment inequities among rural populations are well documented and the COVID-19 pandemic has exacerbated these inequalities, forcing healthcare providers to be creative in the delivery of treatment. Systematic reviews on the use of telehealth to treat patients with substance use disorder indicate that it is a promising alternative to in-person services. This article examines the evidence supporting the use of telehealth in treating patients with opioid use disorder and explores other promising options that can help overcome pandemic-related barriers to treatment., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This article describes the design and baseline sample of a single-site trial comparing Individual Placement and Support (IPS) supported employment delivered within a Veterans Health Administration (VHA) primary care Patient Aligned Care Team (PACT) to treatment-as-usual vocational rehabilitation (TAU-VR) that includes transitional work., Methods: Unemployed U.S. military veterans receiving care in a VHA PACT who were seeking competitive work, otherwise eligible for vocational rehabilitation, and diagnosed with a mental health condition other than a psychotic or bipolar I disorder were prospectively randomized to receive either IPS or TAU-VR. Employment outcomes and measures of quality of life, self-esteem, and community reintegration are being collected for 12 months., Results: The participant sample (n = 119) is comprised of 17.6% female, 73.1% African-Americans, and 1.7% Hispanic. Average age is 38.2 (SD ± 8.41) years; 80.7% served in the military since 2001; 78% are receiving or applying for U.S. Department of Veterans Affairs (VA) service-connected disability; 26.9% have not held a competitive job in the past 3 years; and the average length of pre-randomization unemployment is 1.4 (SD ± 2.3) years., Conclusions: Unique design features include evaluating the efficacy of evidenced-based IPS within the primary care setting, having broad diagnostic eligibility, and defining the primary outcome criterion as "steady employment", i.e. holding a competitive job for ≥26 weeks of the 12-month follow-up period. The findings illustrate the characteristics of a primary care veteran sample in need of employment services., Trial Registration: www.clinicaltrials.gov Identifier: NCT02400736.

Objective: In this secondary analysis of data from the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, the authors sought to determine the effectiveness of early improvement (or lack thereof) for predicting remission from depression with antidepressant therapy., Methods: This study used data from the VAST-D study, a multisite, randomized, single-blind trial with parallel assignment to one of three medication interventions for 1,522 veterans whose major depressive disorder was unresponsive to at least one course of antidepressant treatment meeting minimal standards for dosage and duration. The authors calculated the positive predictive value (PPV) and negative predictive value (NPV) of early improvement on remission, response, or greater than minimal improvement from depression for various degrees of improvement (10%-50%) on the Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C) at 1, 2, 4, and 6 weeks., Results: The end of week 2 of treatment was identified as the best time to evaluate early improvement. The presence of a ≥20% drop from the baseline QIDS-C score by the end of week 2 resulted in a PPV for remission of 38% and an NPV of 93% by week 12. Extending the observational window to week 6 minimally improved NPV (97%). This association did not differ across treatment groups., Conclusions: A lack of early improvement at the end of week 2 of antidepressant therapy can be used to inform clinical decisions on the likelihood of nonremission of depression during the subsequent 10 weeks, even when dosage optimization is incomplete., (© 2019 American Psychiatric Association.)

Objective: This article describes the methodology and the baseline characteristics of veterans with posttraumatic stress disorder (PTSD) enrolled in a multisite trial comparing supported employment individual placement and support (IPS) to a stepwise vocational transitional work program (TWP)., Method: The Veterans Affairs Cooperative Studies Program randomized 541 veterans with PTSD across 12 Veterans Affairs Medical Centers to either IPS or TWP. Demographic and clinical characteristics were evaluated at baseline., Results: Participants averaged 42 (SD ± 11) years of age and had PTSD for 13 (SD ± 11) years. The group was comprised of 18% female, 42% African Americans, and 16% Latino participants. Approximately 60% of participants served in the military since 2001, 89% were receiving or applying for service-connected disability, 60% had PTSD from nonsexual combat-related trauma, and 17% had PTSD from military sexual trauma. One third had not held a competitive job in the past 3 years; the average length of unemployment was 2.8 (SD ± 4) years. Unique study features included the focus on veterans with PTSD, a comparison of a promising practice with a usual-care practice, and the outcome criterion of achieving steady competitive employment. Conclusions and Implication for Practice: This study is the first large-scale randomized trial of IPS in a PTSD population. These baseline findings illustrate the characteristics of the study sample, which are representative of a veteran population in need of vocational rehabilitation services and can be used to help guide the implementation of tailored veteran-centered programs. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

We present an evidence-based review of post-trauma interventions used to prevent posttraumatic stress disorder (PTSD). Literature search of PubMed from 1988 to March 2016 using keywords "Early Intervention AND Prevention of PTSD" yielded 142 articles, of which 52 intervention studies and 6 meta-analyses were included in our review. Trauma-focused cognitive behavioral therapy and modified prolonged exposure delivered within weeks of a potentially traumatic event for people showing signs of distress have the most evidence in the treatment of acute stress and early PTSD symptoms, and the prevention of PTSD. Even though several pharmacological agents have been tried, only hydrocortisone prior to high-risk surgery, severe traumatic injury, or during acute sepsis has adequate evidence for effectiveness in the reduction of acute stress symptoms and prevention of PTSD. There is an urgent need to determine the best targets for interventions after trauma to accelerate recovery and prevent PTSD.

Background: Homeless patients face unique challenges in obtaining primary care responsive to their needs and context. Patient experience questionnaires could permit assessment of patient-centered medical homes for this population, but standard instruments may not reflect homeless patients' priorities and concerns., Objectives: This report describes (a) the content and psychometric properties of a new primary care questionnaire for homeless patients; and (b) the methods utilized in its development., Methods: Starting with quality-related constructs from the Institute of Medicine, we identified relevant themes by interviewing homeless patients and experts in their care. A multidisciplinary team drafted a preliminary set of 78 items. This was administered to homeless-experienced clients (n=563) across 3 VA facilities and 1 non-VA Health Care for the Homeless Program. Using Item Response Theory, we examined Test Information Function (TIF) curves to eliminate less informative items and devise plausibly distinct subscales., Results: The resulting 33-item instrument (Primary Care Quality-Homeless) has 4 subscales: Patient-Clinician Relationship (15 items), Cooperation among Clinicians (3 items), Access/Coordination (11 items), and Homeless-specific Needs (4 items). Evidence for divergent and convergent validity is provided. TIF graphs showed adequate informational value to permit inferences about groups for 3 subscales (Relationship, Cooperation, and Access/Coordination). The 3-item Cooperation subscale had lower informational value (TIF<5) but had good internal consistency (α=0.75) and patients frequently reported problems in this aspect of care., Conclusions: Systematic application of qualitative and quantitative methods supported the development of a brief patient-reported questionnaire focused on the primary care of homeless patients and offers guidance for future population-specific instrument development.

Objective: Preclinical and clinical studies demonstrate a hyperactivity of the norepinephrine system in patients with posttraumatic stress disorder (PTSD). a(2) adrenergic agonists have been shown to ameliorate symptoms of PTSD, likely because of their ability to dampen noradrenergic tone. This study tests the ability of the a(2) adrenergic agonist, guanfacine, to reduce the symptoms of PTSD., Experimental Design: Patients with chronic PTSD were randomized (1:1) to an 8-week double-blind, placebo-controlled treatment of guanfacine followed by a 2 month open label extension phase. Patients were maintained on their stable doses of allowed antidepressants during the trial. Efficacy was measured by the following assessment scales: Clinician Administered PTSD Scale (CAPS), Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement (CGI-I), and Davidson Trauma Scale (DTS, self-report)., Principal Observations: There were no significant differences in the drug versus placebo responses for the clinician-administered or patient self-report outcome measures in this small sample of predominantly male combat veterans with PTSD. However, the medication was well tolerated., Conclusion: Similar to previous findings, this small pilot study failed to show differences in the response to guanfacine versus placebo in a small sample of predominantly male combat veterans with PTSD.