Association of Posttraumatic Stress Disorder and Race on Readmissions After Stroke.

BACKGROUND: There is limited research on outcomes of patients with posttraumatic stress disorder (PTSD) who also develop stroke, particularly regarding racial disparities. Our goal was to determine whether PTSD is associated with the risk of hospital readmission after stroke and whether racial disparities existed. METHODS: The analytical sample consisted of all veterans receiving care in the Veterans Health Administration who were identified as having a new stroke requiring inpatient admission based on the International Classification of Diseases codes. PTSD and comorbidities were identified using the International Classification of Diseases codes and given the date of first occurrence. The retrospective cohort data were obtained from the Veterans Affairs Corporate Data Warehouse. The main outcome was any readmission to Veterans Health Administration with a stroke diagnosis. The hypothesis that PTSD is associated with readmission after stroke was tested using Cox regression adjusted for patient characteristics including age, sex, race, PTSD, smoking status, alcohol use, and comorbidities treated as time-varying covariates. RESULTS: Our final cohort consisted of 93 651 patients with inpatient stroke diagnosis and no prior Veterans Health Administration codes for stroke starting from 1999 with follow-up through August 6, 2022. Of these patients, 12 916 (13.8%) had comorbid PTSD. Of the final cohort, 16 896 patients (18.0%) with stroke were readmitted. Our fully adjusted model for readmission found an interaction between African American veterans and PTSD with a hazard ratio of 1.09 ([95% CI, 1.00-1.20] P=0.047). In stratified models, PTSD has a significant hazard ratio of 1.10 ([95% CI, 1.02-1.18] P=0.01) for African American but not White veterans (1.05 [95% CI, 0.99-1.11]; P=0.10). CONCLUSIONS: Among African American veterans who experienced stroke, preexisting PTSD was associated with increased risk of readmission, which was not significant among White veterans. This study highlights the need to focus on high-risk groups to reduce readmissions after stroke.

A phase 3, randomized, placebo-controlled, trial to evaluate the efficacy and safety of bedtime sublingual cyclobenzaprine (TNX-102 SL) in military-related posttraumatic stress disorder.

Sleep disturbances in posttraumatic stress disorder (PTSD) are a potential target for improving PTSD severity with pharmacotherapy. TNX-102 SL is a bedtime sublingual formulation of cyclobenzaprine with potent binding and antagonist activity at 5-HT2A, α1-adrenergic, H1 histaminergic, and M1 muscarinic receptors, which play roles in the pharmacological management of sleep disturbances. This Phase 3 trial evaluated the efficacy and safety of TNX-102 SL in patients with military-related PTSD. Early and sustained improvements in sleep were associated with TNX-102 SL treatment by PROMIS Sleep Disturbance scale and Clinician Administered PTSD Scale (CAPS-5) "sleep disturbance" item, establishing a sleep quality benefit. Primary analysis comparing change from baseline in CAPS-5 total severity between TNX-102 SL and placebo at week 12 was not significant; however, week 4 was associated with an improvement. Secondary analyses showed TNX-102 SL treatment was associated with benefits on the Clinician Global Impression of Improvement at week 4 and the Patient Global Impression of Change at week 12. Time since trauma exposure was a discriminator of CAPS-5 treatment response in the subgroup ≤ 9 years since the index event. This study provides preliminary evidence that TNX-102 SL is well-tolerated and may promote recovery from PTSD by addressing sleep-related symptoms.

Patient journey of civilian adults diagnosed with posttraumatic stress disorder-A chart review study.

OBJECTIVE: To assess the journey of individuals from experiencing a traumatic event through onset of symptoms, diagnosis, and treatment of posttraumatic stress disorder (PTSD). METHODS: Patient- and psychiatrist-level data was collected (02/2022-05/2022) from psychiatrists who treated ≥1 civilian adult diagnosed with PTSD. Eligible charts covered civilian adults diagnosed with PTSD (2016-2020), receiving ≥1 PTSD-related treatment (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], atypical antipsychotics [AAs]), and having ≥1 medical visit in the last 12 months. Collected information included clinical and treatment characteristics surrounding the PTSD diagnosis. RESULTS: A total of 273 psychiatrists contributed data on 687 patients with PTSD (average age 36.1; 60.4% female). On average, the traumatic event and symptom onset occurred 8.7 years and 6.5 years prior to PTSD diagnosis, respectively. In the 6 months before diagnosis, 88.9% of patients had received a PTSD-related treatment. At time of diagnosis, 87.8% of patients had intrusion symptoms and 78.9% had alterations in cognition/mood; 41.2% had depressive disorder and 38.7% had anxiety. Diagnosis prompted treatment changes for 79.3% of patients, receiving treatment within 1.9 months on average, often with a first-line SSRI as either monotherapy (52.8%) or combination (24.9%). At the end of the 24-month study period, 34.4% of patients achieved psychiatrist-recorded remission. A total of 23.0% of psychiatrists expressed dissatisfaction with approved PTSD treatments, with 88.3% at least somewhat likely to prescribe AAs despite lack of FDA approval. CONCLUSION: PTSD presents heterogeneously, with an extensive journey from trauma to diagnosis with low remission rates and limited treatment options.

Factors Affecting Antidepressant Response Trajectories: A Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes Trial Report.

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.

Neural correlates of PTSD in women with childhood sexual abuse with and without PTSD and response to paroxetine treatment: A placebo-controlled, double-blind trial.

Objective: Childhood sexual abuse is the leading cause of posttraumatic stress disorder (PTSD) in women, and is a prominent cause of morbidity and loss of function for which limited treatments are available. Understanding the neurobiology of treatment response is important for developing new treatments. The purpose of this study was to assess neural correlates of personalized traumatic memories in women with childhood sexual abuse with and without PTSD, and to assess response to treatment. Methods: Women with childhood sexual abuse with (N = 28) and without (N = 17) PTSD underwent brain imaging with High-Resolution Positron Emission Tomography scanning with radiolabeled water for brain blood flow measurements during exposure to personalized traumatic scripts and memory encoding tasks. Women with PTSD were randomized to paroxetine or placebo followed by three months of double-blind treatment and repeat imaging with the same protocol. Results: Women with PTSD showed decreases in areas involved in the Default Mode Network (DMN), a network of brain areas usually active when the brain is at rest, hippocampus and visual processing areas with exposure to traumatic scripts at baseline while women without PTSD showed increased activation in superior frontal gyrus and other areas (p < 0.005). Treatment of women with PTSD with paroxetine resulted in increased anterior cingulate activation and brain areas involved in the DMN and visual processing with scripts compared to placebo (p < 0.005). Conclusion: PTSD related to childhood sexual abuse in women is associated with alterations in brain areas involved in memory and the stress response and treatment with paroxetine results in modulation of these areas.

Patient journey before and after a formal post-traumatic stress disorder diagnosis in adults in the United States - a retrospective claims study.

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.

Effect of next-step antidepressant treatment on suicidal ideation: findings from the VAST-D trial.

BACKGROUND: Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a 'next-step'. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted. METHOD: The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored. RESULTS: Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to 'next-step' treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI. CONCLUSION: SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

Comorbid alcohol use disorder and posttraumatic stress disorder: A proof-of-concept randomized placebo-controlled trial of buprenorphine and naltrexone combination treatment.

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.

Efficacy of mindfulness-based relapse prevention in a sample of veterans in a substance use disorder aftercare program: A randomized controlled trial.

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.

Are We Witnessing a New Wave of Substance Use Disorders?: A Spotlight on Stimulant Use Disorders.

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.].

Identifying individuals with undiagnosed post-traumatic stress disorder in a large United States civilian population - a machine learning approach.

BACKGROUND: The proportion of patients with post-traumatic stress disorder (PTSD) that remain undiagnosed may be substantial. Without an accurate diagnosis, these patients may lack PTSD-targeted treatments and experience adverse health outcomes. This study used a machine learning approach to identify and describe civilian patients likely to have undiagnosed PTSD in the US commercial population. METHODS: The IBM® MarketScan® Commercial Subset (10/01/2015-12/31/2018) was used. A random forest machine learning model was developed and trained to differentiate between patients with and without PTSD using non-trauma-based features. The model was applied to patients for whom PTSD status could not be confirmed to identify individuals likely and unlikely to have undiagnosed PTSD. Patient characteristics, symptoms and complications potentially related to PTSD, treatments received, healthcare costs, and healthcare resource utilization were described separately for patients with PTSD (Actual Positive PTSD cohort), patients likely to have PTSD (Likely PTSD cohort), and patients without PTSD (Without PTSD cohort). RESULTS: A total of 44,342 patients were classified in the Actual Positive PTSD cohort, 5683 in the Likely PTSD cohort, and 2,074,471 in the Without PTSD cohort. While several symptoms/comorbidities were similar between the Actual Positive and Likely PTSD cohorts, others, including depression and anxiety disorders, suicidal thoughts/actions, and substance use, were more common in the Likely PTSD cohort, suggesting that certain symptoms may be exacerbated among those without a formal diagnosis. Mean per-patient-per-6-month healthcare costs were similar between the Actual Positive and Likely PTSD cohorts ($11,156 and $11,723) and were higher than those of the Without PTSD cohort ($3616); however, cost drivers differed between cohorts, with the Likely PTSD cohort experiencing more inpatient admissions and less outpatient visits than the Actual Positive PTSD cohort. CONCLUSIONS: These findings suggest that the lack of a PTSD diagnosis and targeted management of PTSD may result in a greater burden among undiagnosed patients and highlights the need for increased awareness of PTSD in clinical practice and among the civilian population.

Comparing Service Use and Costs of Individual Placement and Support With Usual Vocational Services for Veterans With PTSD.

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.

The Economic Burden of Posttraumatic Stress Disorder in the United States From a Societal Perspective.

Objective: To estimate the economic burden of posttraumatic stress disorder (PTSD) in the United States civilian and military populations from a societal perspective.Methods: A prevalence-based and human capital approach was used to estimate the total excess costs of PTSD in 2018 from insurance claims data, academic literature, and governmental publications. Excess direct health care costs (pharmacy, medical), direct non-health care costs (research and training, substance use, psychotherapy, homelessness, disability), and indirect costs (unemployment, productivity loss, caregiving, premature mortality) associated with PTSD were compared between adults with PTSD and adults without PTSD, or the general population if information was not available for adults without PTSD.Results: The total excess economic burden of PTSD in the US was estimated at $232.2 billion for 2018 ($19,630 per individual with PTSD). Total excess costs were $189.5 billion (81.6%) in the civilian population and $42.7 billion (18.4%) in the military population, corresponding to $18,640 and $25,684 per individual with PTSD in the civilian and military populations, respectively. In the civilian population, the excess burden was driven by direct health care ($66.0 billion) and unemployment ($42.7 billion) costs. In the military population, the excess burden was driven by disability ($17.8 billion) and direct health care ($10.1 billion) costs.Conclusions: The economic burden of PTSD goes beyond direct health care costs and has been found to rival costs for other costly mental health conditions. Increased awareness of PTSD, development of more effective therapies, and expansion of evidence-based interventions may be warranted to reduce the large clinical and economic burden of PTSD.

Childhood adversity and adulthood major depressive disorder.

OBJECTIVE: Examine how specific types of childhood adversity are associated with clinical features and treatment in adults with Major Depressive Disorder (MDD). METHOD: This is a secondary analysis of the 35-site VA Augmentation and Switching Treatments for Improving Depression Outcomes study. A 10-item Adverse Childhood Events (ACE) survey was administered at baseline. RESULTS: 83% experienced at least one of the 10 ACEs and 20.7% experienced 6 or more. Participants with childhood adversities were more likely to be younger, female, unemployed, single or divorced, and to have had more severe depression and anxiety, more lifetime episodes, a younger age of first diagnosed MDD, more comorbid PTSD, worse quality of life, and more suicidal ideation than those no or fewer adversities. Neither the overall number nor any of the specific types of adversities were associated with lower remission rates after administration of standard "next-step" treatment strategies, while histories of different specific types were associated with lower depression severity, better quality of life, and less suicidal ideation post-treatment. CONCLUSIONS: Attention to different forms of childhood adversity and to diverse clinical outcomes beyond remission and relapse are important considerations when treating individuals with MDD with histories of childhood maltreatment. CLINICALTRIALS: gov identifier: NCT01421342.

Feasibility and Acceptability of a Mindfulness-Based Relapse Prevention Intervention for Opioid Use Disorders.

In 2021, drug overdose deaths exceeded 100,000 for the first time in U.S. history, mostly attributable to opioid overdoses. Medications for opioid use disorders are considered the gold standard for treatment; however, treatment initiation and adherence remain a challenge. Mindfulness-based interventions show efficacy for substance use disorders, and peer support has been shown to improve treatment outcomes. The purpose of the current study was to examine the feasibility and acceptability of the Minds and Mentors Program. Enrollment, randomization, and retention rates were 36%, 49%, and 57%, respectively. Client satisfaction scores ranged from 84.4% to 100%. Approximately 64% of participants attended 10 of 12 treatment sessions, representing treatment adherence. Qualitative analysis revealed four main domains: Permission to Be Honest and Open, Applicability for Everyday Life, Hope Restored, and Changing the Way I Think. [Journal of Psychosocial Nursing and Mental Health Services, 60(3), 11-14.].

Transition from Military Service: Mental Health and Well-being Among Service Members and Veterans with Service-connected Disabilities.

Transitioning from military service is stressful for veterans with service-connected disabilities seeking civilian employment. This descriptive study examined self-assessed mental health, well-being, and substance use of men and women shortly before or after transition from US military service, compared to norms from community and military samples. As part of a prospective study evaluating an innovative employment program, researchers interviewed 229 current and former service members with service-connected disabilities transitioning from U.S. military service. Compared to published norms, respondents reported significantly poorer outcomes on 5 of 6 standardized measures, indicating less life satisfaction, poorer mental health, more symptoms of depression and posttraumatic stress disorder, and greater financial distress. In the previous year, 42% were prescribed opioid medications, over twice the annual opioid prescription rate of 19% in the general US population. Systematic strategies are needed to ensure access for transitioning veterans with serious behavioral health issues to appropriate evidence-based practices.

Biomarker Response to Mindfulness Intervention in Veterans Diagnosed with Post-traumatic Stress Disorder.

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.

Evaluation of an Employment Intervention for Veterans Transitioning From the Military: A Randomized Controlled Trial.

ABSTRACT: Military personnel face numerous challenges transitioning from military jobs to meaningful civilian employment. The Independence Project compared an innovative employment program (National Career Coach Program) with standard employment services (Local Community Resources) in a randomized controlled trial. Study participants were transitioning veterans with self-reported service-connected disabilities seeking permanent employment. The primary outcomes were paid employment and disability ratings over 1 year. Secondary outcomes included health and well-being. At 1-year follow-up, National Career Coach Program participants were significantly more likely to work, had significantly greater earnings, and reported significantly greater improvements in physical and mental health compared with participants assigned to Local Community Resources. Both groups increased in disability ratings over 12 months, with no difference between groups. Multifaceted supports delivered by the National Career Coach Program increased employment, earnings, mental health, and physical health over 1 year. These significant differences appeared even though control group participants achieved considerable employment success.

A Randomized Controlled Trial Evaluating the Effectiveness of Supported Employment Integrated in Primary Care.

OBJECTIVES: Mental health issues can cause serious problems in occupational functioning, including higher rates of unemployment. Individual placement and support (IPS) is an evidence-based supported employment intervention that is typically integrated within a mental health setting; however, many primary care patients view referral to a mental health clinic as stigmatizing. Thus, this study examined whether delivery of IPS in a primary care setting provides an effective treatment option and avoids unnecessary delays in obtaining competitive employment. METHODS: U.S. military veterans (N=119) who had a diagnosis in a broad range of nonpsychotic psychiatric disorders and who were receiving care from Veterans Health Administration (VHA) patient-aligned care teams were prospectively randomly assigned to IPS (N=58) or standard VHA non-IPS vocational rehabilitation (VR) (N=61). The primary outcome was achievement of steady worker status, defined as holding a competitive job for ≥6 months of the 12-month follow-up. RESULTS: As hypothesized, a significantly greater proportion of IPS participants achieved steady worker status (45%), compared with VR participants (25%) (p=0.02; odds ratio=2.49, 95% confidence interval=1.14-5.43). On average, the IPS participants worked significantly more weeks (p=0.003) and earned significantly more income (p=0.033) from competitive jobs, compared with VR participants. CONCLUSIONS: The results provide supporting evidence for offering IPS within primary care with the aim of restoring meaningful and sustained competitive employment for veterans living with a mental disorder. Such modifications could improve veterans' vocational outcomes, moving a significantly greater number of disabled veterans back to full and productive lives in the community.

Cost-Effectiveness of Individual Placement and Support Compared to Transitional Work Program for Veterans with Post-traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) leads to significant disability, unemployment, and substantial healthcare costs. The cost-effectiveness of vocational rehabilitation (VR) interventions is important to consider when determining which services to offer. This study assesses the cost-effectiveness and return on investment of Individual Placement and Support (IPS) compared to transitional work (TW) programs. Employment outcomes from a multisite randomized trial comparing IPS to TW in military veterans with PTSD (n = 541) were linked to Veterans Health Administration (VHA) archival medical record databases to examine the comparative cost-effectiveness and return on investment. Effectiveness was defined as hours worked and income earned in competitive jobs. Costs for VR, mental health, and medical care and income earned from competitive sources were annualized and adjusted to 2019 US dollars. The annualized mean cost per person of outpatient (including vocational services) were $3970 higher for IPS compared to TW ($23,245 vs. $19,276, respectively; P = 0.004). When TW income was included in costs, mean grand total costs per person per year were similar between groups ($29,828 IPS vs. $26,772 TW; P = 0.17). The incremental cost-effectiveness analysis showed that while IPS is more costly, it is also more effective. The return on investment (excluding TW income) was 32.9% for IPS ($9762 mean income/$29,691 mean total costs) and 29.6% for TW ($7326 mean income/$24,781 mean total costs). IPS significantly improves employment outcomes for individuals with PTSD with negligible increase in healthcare costs and yields very good return on investment compared to non-IPS VR services.