Brain derived neurotrophic factor and treatment outcomes among veterans attending an intensive treatment program for posttraumatic stress disorder.

Brain derived neurotrophic factor (BDNF) may play an important role in the success of treatment for posttraumatic stress disorder (PTSD). Pre- and post-treatment blood samples were analyzed for 40 veterans who completed a 3-week intensive outpatient treatment for PTSD. The treatment included Cognitive Processing Therapy, mindfulness, and yoga as core treatment components. PTSD symptoms were assessed at pre-treatment, post-treatment, and 3-month follow-up. Participants reported large decreases in PTSD symptoms from pre-to post-treatment (d = 1.46, p < 0.001) and pre-treatment to 3-month follow-up (d = 0.91, p < 0.001). Unexpectedly, participants demonstrated a decrease in BDNF from pre-to post-treatment (d = 0.64, p < 0.001). Changes in BDNF from pre-to post-treatment were not significantly associated with PTSD symptom improvement. However, higher levels of post-treatment BDNF were significantly associated with lower PTSD symptoms at 3-month follow-up (n = 27, r = -0.57, p = 0.002) and greater improvements in PTSD symptoms from pre-treatment to 3-month follow-up (n = 27, r = 0.50, p = 0.008). Higher levels of post-treatment BDNF may facilitate the long-term success of intensive PTSD treatment. Further research with larger samples is needed to evaluate the processes by which BDNF may affect consolidation of improvements after completion of PTSD treatment.

What good are positive emotions for treatment? A replication test of whether trait positive emotionality predicts response to exposure therapy for social anxiety disorder.

BACKGROUND: Positive valence emotions serve functions that may facilitate response to exposure therapy - they encourage approach behavior, diminish perceived threat reactivity, and enhance assimilation of new information in memory. Few studies have examined whether positive emotions predict exposure therapy success and extant findings are mixed. METHODS: We conducted a secondary analysis of an exposure therapy trial for social anxiety disorder to test the hypothesis that patients endorsing higher trait positive emotions at baseline would display the greatest treatment response. N = 152 participants enrolled in a randomized controlled trial of d-cycloserine augmentation completed five sessions of group exposure therapy. Pre-treatment positive emotionality was assessed using the NEO Five-Factor Inventory. Social anxiety symptoms were assessed throughout treatment by blinded evaluators using the Liebowitz Social Anxiety Scale. RESULTS: Accounting for baseline symptom severity, multilevel growth curve models revealed that patients with higher pre-treatment positive emotionality displayed faster social anxiety symptom reductions and lower scores at 3-month follow-up. This predictive effect remained significant after controlling for baseline depression and extraversion (without the positive emotionality facet). CONCLUSIONS: These findings add to emerging evidence suggesting that explicitly targeting and enhancing positive emotions during exposure to perceived threat may improve treatment outcomes for anxiety and fear-based disorders. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02066792https://clinicaltrials.gov/ct2/show/NCT02066792.

Using pre-treatment de novo threat conditioning outcomes to predict treatment response to DCS augmentation of exposure-based CBT.

BACKGROUND: Over a decade and a half of research has resulted in inconsistent evidence for the efficacy of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, for augmenting exposure-based cognitive behavioral therapy (CBT) for anxiety- and fear-based disorders. These variable findings have motivated the search for moderators of DCS augmentation efficacy. METHODS: In this secondary analysis of a previous randomized clinical trial, we evaluated the value of de novo threat conditioning outcomes-degree of threat acquisition, extinction, and extinction retention-for predicting treatment response to exposure-based CBT for social anxiety disorder, applied with and without DCS augmentation in a sample of 59 outpatients. RESULTS: We found that average differential skin conductance response (SCR) during extinction and extinction retention significantly moderated the prediction of clinical response to DCS: participants with poorer extinction and extinction retention showed relatively improved treatment response with DCS. No such effects were found for expectancy ratings, consistent with accounts of DCS selectively aiding lower-order but not higher-order extinction learning. CONCLUSIONS: These findings provide support for extinction and extinction retention outcomes from threat conditioning as potential pre-treatment biomarkers for DCS augmentation benefits. Independent of DCS augmentation, the current study did not support threat conditioning outcomes as useful for predicting response to exposure-based CBT.

Protocol for a multi-site randomized controlled trial of a stepped-care intervention for emergency department patients with panic-related anxiety.

BACKGROUND: Approximately 40% of Emergency Department (ED) patients with chest pain meet diagnostic criteria for panic-related anxiety, but only 1-2% are correctly diagnosed and appropriately managed in the ED. A stepped-care model, which focuses on providing evidence-based interventions in a resource-efficient manner, is the state-of-the art for treating panic disorder patients in medical settings such as primary care. Stepped-care has yet to be tested in the ED setting, which is the first point of contact with the healthcare system for most patients with panic symptoms. METHODS: This multi-site randomized controlled trial (RCT) aims to evaluate the clinical, patient-centred, and economic effectiveness of a stepped-care intervention in a sample of 212 patients with panic-related anxiety presenting to the ED of Singapore's largest public healthcare group. Participants will be randomly assigned to either: 1) an enhanced care arm consisting of a stepped-care intervention for panic-related anxiety; or 2) a control arm consisting of screening for panic attacks and panic disorder. Screening will be followed by baseline assessments and blocked randomization in a 1:1 ratio. Masked follow-up assessments will be conducted at 1, 3, 6, and 12 months. Clinical outcomes will be panic symptom severity and rates of panic disorder. Patient-centred outcomes will be health-related quality of life, daily functioning, psychiatric comorbidity, and health services utilization. Economic effectiveness outcomes will be the incremental cost-effectiveness ratio of the stepped-care intervention relative to screening alone. DISCUSSION: This trial will examine the impact of early intervention for patients with panic-related anxiety in the ED setting. The results will be used to propose a clinically-meaningful and cost-effective model of care for ED patients with panic-related anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT03632356. Retrospectively registered 15 August 2018.

Abnormal intestinal milieu in posttraumatic stress disorder is not impacted by treatment that improves symptoms.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder, resulting from exposure to traumatic events. Current recommended first-line interventions for the treatment of PTSD include evidence-based psychotherapies, such as cognitive processing therapy (CPT). Psychotherapies are effective for reducing PTSD symptoms, but approximately two-thirds of veterans continue to meet diagnostic criteria for PTSD after treatment, suggesting there is an incomplete understanding of what factors sustain PTSD. The intestine can influence the brain and this study evaluated intestinal readouts in subjects with PTSD. Serum samples from controls without PTSD (n = 40) from the Duke INTRuST Program were compared with serum samples from veterans with PTSD (n = 40) recruited from the Road Home Program at Rush University Medical Center. Assessments included microbial metabolites, intestinal barrier, and intestinal epithelial cell function. In addition, intestinal readouts were assessed in subjects with PTSD before and after a 3-wk CPT-based intensive treatment program (ITP) to understand if treatment impacts the intestine. Compared with controls, veterans with PTSD had a proinflammatory intestinal environment including lower levels of microbiota-derived metabolites, such as acetic, lactic, and succinic acid, intestinal barrier dysfunction [lipopolysaccharide (LPS) and LPS-binding protein], an increase in HMGB1, and a concurrent increase in the number of intestinal epithelial cell-derived extracellular vesicles. The ITP improved PTSD symptoms but no changes in intestinal outcomes were noted. This study confirms the intestine is abnormal in subjects with PTSD and suggests that effective treatment of PTSD does not alter intestinal readouts. Targeting beneficial changes in the intestine may be an approach to enhance existing PTSD treatments.NEW & NOTEWORTHY This study confirms an abnormal intestinal environment is present in subjects with PTSD. This study adds to what is already known by examining the intestinal barrier and evaluating the relationship between intestinal readouts and PTSD symptoms and is the first to report the impact of PTSD treatment (which improves symptoms) on intestinal readouts. This study suggests that targeting the intestine as an adjunct approach could improve the treatment of PTSD.

Increasing Mindfulness Skills of Veterans With PTSD Through Daily Mindfulness Training Incorporated Into an Intensive Treatment Program.

OBJECTIVES: Mindfulness training is frequently included as part of an integrative care approach to treating PTSD in veterans. However, the utility and acceptability of daily group mindfulness training in an intensive treatment program (ITP) for PTSD have not been explored. The study objectives were to determine: (a) whether mindfulness skills significantly increased from pre- to post-treatment and (b) if daily group mindfulness training was acceptable to veterans. METHODS: Veterans (N = 170 outpatients, age M = 40.7 (SD 9.3), 67.6% male) in this prospective study were consecutively enrolled in a 3-week ITP that included daily mindfulness group sessions. Mindfulness skills were assessed using the Five Facet of Mindfulness Questionnaire (FFMQ) at intake and post-treatment. Acceptability was assessed using an anonymous post-treatment program satisfaction survey. RESULTS: Paired t tests demonstrated significant increases in overall mindfulness skills from pre- to post-treatment (t(169) = - 6.33, p < 0.001, d = 0.49). Small to medium effect sizes were observed across subscales: describing, (t(169) = - 5.91, p < 0.001, d = 0.38); acting with awareness, (t(169) = - 3.70, p < 0.001, d = 0.29); nonjudging, (t(169) = - 7.54, p < 0.001, d = 0.58); and nonreactivity, (t(169) = - 4.84, p < 0.001, d = 0.41). Most veterans (n = 125, 74.4%) found daily mindfulness training moderately to very helpful. CONCLUSIONS: Veterans' mindfulness skills significantly increased over the course of a 3-week ITP, and mindfulness training was found acceptable. Mindfulness training can be delivered daily as part of an ITP for veterans with PTSD, and mindfulness skills can meaningfully increase over the course of 3 weeks. A significant limitation is the lack of control condition.

Sleep quality and outcome of exposure therapy in adults with social anxiety disorder.

INTRODUCTION: Poor sleep is prevalent among individuals with social anxiety disorder (SAD) and may negatively affect exposure therapy outcomes. Poor sleep may impair memory and learning, and thus compromise fear extinction learning thought to take place in exposure therapy. We examined poor sleep as a predictor of exposure therapy outcomes for SAD and the moderating role of d-cycloserine (DCS) on this relationship. METHODS: Participants were 152 individuals with a primary diagnosis of SAD. As part of a randomized clinical trial evaluating the efficacy of DCS for enhancing the effects of exposure therapy, they completed self-report baseline measure of sleep quality, and self-report sleep diaries assessing sleep duration (total sleep time [TST]) and sleep quality the nights before and after treatment sessions. RESULTS: Poorer baseline sleep quality was significantly associated with slower improvement over time and worse symptom outcomes at the end of treatment and follow-up after controlling for baseline symptoms of depression and social anxiety. Greater TST the night before treatment predicted lower SAD symptoms at the next session, after controlling for symptoms at the previous session. There was no relation between prior or subsequent night sleep quality on symptoms at the next session. No associations were moderated by DCS. CONCLUSIONS: We replicated and extended findings indicating that poor sleep quality is associated with poorer exposure therapy outcomes for SAD. Assessing for sleep difficulties before treatment initiation and incorporating sleep interventions into treatment may enhance exposure therapy outcomes for SAD.

Impact of intensive treatment programs for posttraumatic stress disorder on suicidal ideation in veterans and service members.

Intensive treatment programs (ITPs) are treating veterans with posttraumatic stress disorder (PTSD) and suicidal ideation (SI). The reduction of SI is a target to the abatement of suicide risk. This study examined whether ITPs utilizing PTSD treatments reduce SI and whether SI reduction is associated with PTSD symptom improvement. Veterans (N = 684) enrolled in a 2-week Prolonged Exposure (PE)-ITP or a 3-week Cognitive Processing Therapy (CPT)-ITP. Study data were drawn from self-report measures [PTSD Checklist for DSM-5 (PCL-5); item 9 of the Patient Health Questionnaire-9 (PHQ-9)] administered at intake and throughout treatment. The ITPs produced large treatment effects for PTSD. SI scores also decreased over time. Lower PTSD symptom severity was associated with less severe SI in both the PE-ITP and CPT-ITP. In conclusion, both PE- and CPT-ITPs effectively treat PTSD and reduce SI among veterans in as little as 2 weeks of intensive PTSD treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Maintenance of treatment gains up to 12-months following a three-week cognitive processing therapy-based intensive PTSD treatment programme for veterans.

BACKGROUND: Intensive treatment programmes (ITPs) have shown promise for reducing PTSD and depression symptoms. It is still unknown whether treatment gains are maintained following completion. OBJECTIVE: This study examined whether veterans were able to maintain treatment gains for up to 12 months after an ITP for PTSD and whether reductions in negative posttrauma cognitions predicted treatment gain maintenance. METHODS: 209 veterans (62.7% male, mean age = 40.86 years) completed a 3-week, CPT-based ITP for PTSD. Participants' PTSD (PCL-5) and depression (PHQ-9) symptoms were assessed at pre-treatment, post-treatment, and at 3-, 6-, and 12-month follow-up timepoints. RESULTS: Despite small symptom increases from post-treatment to 3-month follow-up, significant and clinically meaningful reductions in PTSD and depression symptoms were reported from intake to 12 months follow-up (averaging >18 points on the PCL-5 and >6 points on the PHQ-9; d = 1.28, and d = 1.18, respectively). Greater reductions in negative posttrauma cognitions during treatment were associated with lower PTSD (p <.001) and depression (p =.005) severity at follow-up. Most veterans who completed the aftercare survey followed treatment recommendations and reported seeing a mental health provider at 3-, 6-, and 12-months post-treatment. Aftercare treatment did not significantly predict whether veterans maintained treatment gains at follow-up. CONCLUSIONS: Overall maintenance of treatment gains long-term suggests veterans may be able to apply skills acquired during the ITP following treatment. These findings further support the feasibility and effectiveness of intensive, trauma-focused, evidence-based therapy delivery.

Antecedentes: Los programas de tratamiento intensivos (ITPs por sus siglas en inglés) han mostrado ser promisorios para reducir el TEPT y los síntomas depresivos. Se desconoce aún si las ganancias del tratamiento se mantienen después de la finalización. Este estudio examinó si los veteranos fueron capaces de mantener las ganancias del tratamiento después de 12 meses de un ITP para TEPT y si las reducciones de las cogniciones negativas postrauma predijeron la mantención de las ganancias del tratamiento.Método: 209 veteranos (62,7% varones, edad media=40,86 años) completaron una ITP de 3 semana basado en CPT. Los síntomas de TEPT (PCL-5) y depresión (PHQ-9) de los participantes se evaluaron pre-tratamiento,post tratamiento y a los 3,6 y 12 meses de seguimiento.Resultados: A pesar de un pequeño aumento de los síntomas a los tres meses de seguimiento después de terminado el tratamiento, se reportaron reducciones clínicamente significativas e importantes en el TEPT y síntomas depresivos desde el inicio hasta los 12 meses de seguimiento (un promedio ˃18 puntos en el PCL-5 y ˃6 puntos en el PHQ-9; d=1.28, y d=1.18, respectivamente. Las mayores reducciones en las cogniciones negativas postrauma durante el tratamiento se asociaron con una menor severidad del TEPT (p˂ .001) y depresión (p=.005) en el seguimiento. La mayoría de los veteranos que completaron la encuesta de cuidados posteriores siguieron las recomendaciones del tratamiento e informaron haber visto a algún profesional de salud mental a los 3, 6 y 12 meses post-tratamiento. Los cuidados posteriores al tratamiento no predijeron significativamente si los veteranos mantenían las ganancias del tratamiento en el seguimiento.Conclusiones: el mantenimiento general de las ganancias del tratamiento a largo plazo sugiere que los veteranos pueden aplicar las habilidades adquiridas durante la PTI después del tratamiento.Estos hallazgos respaldan aún más la viabilidad y efectividad de la administración en forma intensiva de una terapia basada en la evidencia y centrada en el trauma.

A Case Report of Cognitive Processing Therapy Delivered over a Single Week.

Although evidence-based treatments for posttraumatic stress disorder (PTSD), such as Cognitive Processing Therapy (CPT), have been developed and widely disseminated, the rate of veterans engaging in and completing these therapies is low. Alternative methods of delivery may be needed to help overcome key barriers to treatment. Delivering evidence-based therapies intensively may address practical barriers to treatment attendance as well as problems with avoidance. This report details the case of a combat veteran who received 10 sessions of Cognitive Processing Therapy delivered twice per day over a single, five-day work week (CPT-5). Post-treatment, the veteran reported large and clinically meaningful decreases in PTSD and depression symptom severity as well as in guilt cognitions, which is a purported mechanism of successful treatment. These effects persisted six weeks after treatment ended. Despite the intensive nature of the treatment, the veteran found CPT-5 tolerable and could cite many benefits to completing therapy in one work week. In conclusion, CPT-5 holds promise as a way to efficiently deliver an evidence-based therapy that is both clinically effective and acceptable to patients, although more rigorous clinical trials are needed to test this treatment delivery format.

Dose Timing of D-Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder: A Randomized Clinical Trial.

Importance: Findings suggest that the efficacy of D-cycloserine (DCS) for enhancing exposure therapy may be strongest when administered after sessions marked by low fear at the conclusion of exposure practice. These findings have prompted investigation of DCS dosing tailored to results of exposure sessions. Objective: To compare tailored postsession DCS administration with presession DCS administration, postsession DCS administration, and placebo augmentation of exposure therapy for social anxiety disorder. Design, Setting, and Participants: This double-blind randomized clinical trial involved adults with social anxiety disorder enrolled at 3 US university centers. Symptom severity was assessed at baseline, weekly during treatment, and at 1-week and 3-month follow-up. Data analysis was performed from September 2019 to March 2020. Interventions: Participants completed a 5-session treatment and received pills commensurate with their condition assignment at sessions 2 through 5, which emphasized exposure practice. Main Outcomes and Measures: Symptom severity was evaluated by the Liebowitz Social Anxiety Scale and Social Phobic Disorders-Severity Form as administered by independent evaluators. Results: A total of 152 participants were enrolled (mean [SD] age, 29.24 [10.16] years; 84 men [55.26%]). Compared with placebo, presession and postsession conditions showed greater symptom improvement (b = -0.25; 95% CI, -0.37 to -0.13; P < .001; d = 1.07; and b = -0.20; 95% CI, -0.32 to -0.07; P = .002; d = 0.85) and lower symptom severity (b = -0.51; 95% CI, -0.81 to -0.21; P < .001; d = 0.76; and b = -0.49; 95% CI, -0.80 to -0.18; P = .002; d = 0.72) at 3-month follow-up. No differences were found between presession and postsession conditions. The tailored condition showed no advantage over placebo. Compared with the tailored condition, presession and postsession conditions evidenced greater decreases (b = -0.22; 95% CI, -0.34 to -0.10; P < .001; d = 0.94; and b = -0.17, 95% CI, -0.29 to -0.04; P = .008; d = 0.72) and lower symptom severity (b = -0.44, 95% CI, -0.73 to -0.14; P = .004; d = 0.64; and b = -0.41, 95% CI, -0.72 to -0.11; P = .008; d = 0.61) at 3-month follow-up. Conclusions and Relevance: Administration of DCS enhanced exposure therapy for social anxiety disorder when given before or after the exposure session. However, the study failed to achieve the aim to develop a tailored clinical application. Trial Registration: ClinicalTrials.gov Identifier: NCT02066792.

Double-blind randomized controlled study of the efficacy, safety and tolerability of eszopiclone vs placebo for the treatment of patients with post-traumatic stress disorder and insomnia.

BACKGROUND: Sleep disturbance is a core feature of post-traumatic stress disorder (PTSD). Given the relationship between sleep disturbance and PTSD, there has been a relative paucity of studies examining the potential therapeutic impact of using pharmacotherapy to target sleep disturbance in patients with PTSD. Eszopiclone (ESZ) is a non-benzodiazepine y-aminobutyric acid-A receptor agonist indicated for the treatment of sleep and may affect sleep in patients with PTSD. AIM: To evaluate the efficacy of ESZ vs placebo (PBO) for patients with PTSD and insomnia. METHODS: The study was a 12-wk, double blind, randomized controlled trial with 3 mg of ESZ (n = 13) or PBO (n = 12). RESULTS: Patients in both arms experienced significant improvement in PTSD symptoms as assessed by the Clinician-Administered PTSD Scale for DSM-IV (CAPS): ESZ (t11 = -3.12, P = 0.005) and PBO (t11 = -3.5, P = 0.002) and by self-report with the Short PTSD Rating Interview (ESZ t11 = -3.38, P = 0.003 and PBO t11 = -4.48, P = 0.0005). There were no significant differences between treatments on the CAPS (t22 = -0.13, P = 0.70) or the Short PTSD Rating Interview (t22 = -0.58, P = 0.56). Similarly, both treated groups improved on sleep measures as assessed by the Pittsburgh Sleep Quality Index with PTSD Addendum (PSQI) and on total sleep time (TST) and sleep latency assessed by actigraphy with no significant differences between groups (PSQI t22 = -0.24, P = 0.81; total sleep time t10 = 0.13, P = 0.90 and sleep latency t10 = 0.68, P = 0.50). There was a significant correlation between improvement in sleep and overall improvement in PTSD as measured by change scores on the PSQI and CAPS, r(8) = 0.79, P = 0.01 for ESZ treated subjects, but not for those treated with PBO r(9) = 0.16, P = 0.69. Adverse events of ESZ were consistent with the known profile of the medication including dysgeusia (30%, mild), sedation (20%, mild) and headache (20%, moderate to severe). CONCLUSION: Results do not support the hypothesis of a specific positive effect of ESZ compared to PBO for measures of PTSD and associated sleep disturbance.

The Postencounter Form System: Viewpoint on Efficient Data Collection Within Electronic Health Records.

Electronic health records (EHRs) offer opportunities for research and improvements in patient care. However, challenges exist in using data from EHRs due to the volume of information existing within clinical notes, which can be labor intensive and costly to transform into usable data with existing strategies. This case report details the collaborative development and implementation of the postencounter form (PEF) system into the EHR at the Road Home Program at Rush University Medical Center in Chicago, IL to address these concerns with limited burden to clinical workflows. The PEF system proved to be an effective tool with over 98% of all clinical encounters including a completed PEF within 5 months of implementation. In addition, the system has generated over 325,188 unique, readily-accessible data points in under 4 years of use. The PEF system has since been deployed to other settings demonstrating that the system may have broader clinical utility.

Improving outcomes for a 3-week intensive treatment program for posttraumatic stress disorder in survivors of military sexual trauma.

BACKGROUND: The experience of Military Sexual Trauma (MST) in the form of sexual assault and sexual harassment is common during service in the U.S. Armed Forces and often leads to adverse health outcomes including posttraumatic stress disorder (PTSD). Improving treatment of MST-related PTSD across settings is important to optimize treatment for survivors. The delivery of Cognitive Processing Therapy (CPT) in an intensive treatment program (ITP) shows promise for rapid reduction of PTSD symptoms for veterans and service members (veterans). However, a recent outcome study suggested that this modality is significantly less effective in reducing symptoms of PTSD for survivors of MST compared to veterans recovering from combat trauma. METHODS: -The current study examines the utility of modifications made to a CPT-based ITP designed to treat PTSD secondary to MST in a mixedgender sample (N = 285). Treatment modifications included the introduction of skills-based groups in emotion regulation and interpersonal domains. Individual skills-consultation sessions were also offered to participants on an as-needed basis. Further, training was provided to both clinical and non-clinical staff to increase understanding of the unique experiences and needs of MST survivors. RESULTS: Program changes proved beneficial, resulting in PTSD treatment outcomes that were comparable for survivors of MST and combat traumas. LIMITATIONS: Further research is needed to determine which of these specific program changes were most impactful in improving symptom outcomes. CONCLUSIONS: Our findings suggest that short-term, intensive PTSD treatment for MST survivors may be improved by integrating present-focused, skills-based therapies and staff sensitivity training.

Examining Insomnia During Intensive Treatment for Veterans with Posttraumatic Stress Disorder: Does it Improve and Does it Predict Treatment Outcomes?

Previous research has demonstrated that sleep disturbances show little improvement with evidence-based psychotherapy for posttraumatic stress disorder (PTSD); however, sleep improvements are associated with PTSD treatment outcomes. The goal of the current study was to evaluate changes in self-reported insomnia symptoms and the association between insomnia symptoms and treatment outcome during a 3-week intensive treatment program (ITP) for veterans with PTSD that integrated cognitive processing therapy (CPT), mindfulness, yoga, and other ancillary services. As part of standard clinical procedures, veterans (N = 165) completed self-report assessments of insomnia symptoms at pre- and posttreatment as well as self-report assessments of PTSD and depression symptoms approximately every other day during treatment. Most veterans reported at least moderate difficulties with insomnia at both pretreatment (83.0%-95.1%) and posttreatment (69.1-71.3%). Statistically significant reductions in self-reported insomnia severity occurred from pretreatment to posttreatment; however, the effect size was small, d = 0.33. Longitudinal mixed-effects models showed a significant interactive effect of Changes in Insomnia × Time in predicting PTSD and depression symptoms, indicating that patients with more improvements in insomnia had more positive treatment outcomes. These findings suggest that many veterans continued to struggle with sleep disruption after a 3-week ITP, and successful efforts to improve sleep could lead to better PTSD treatment outcomes. Further research is needed to establish how adjunctive sleep interventions can be used to maximize both sleep and PTSD outcomes.

Feasibility of a 3-week intensive treatment program for service members and veterans with PTSD.

OBJECTIVE: The purpose of the present study was to detail the patient flow and establish the feasibility of a brief 3-week intensive treatment program (ITP) for veterans with posttraumatic stress disorder (PTSD). METHOD: The present study examined data from 648 veterans referred to a non-Veterans Affairs ITP for PTSD from January 2016 to February 2018 to determine the flow of patients into and through the ITP and evaluate individuals' satisfaction with treatment. RESULTS: On average, 25.9 individuals contacted the ITP each month expressing interest in the program. A large proportion of individuals who completed an intake evaluation were accepted (72.2%) into the ITP. Of those accepted, 70.6% ultimately attended the ITP, and the vast majority of veterans who attended the ITP completed treatment (91.6%). Logistic regression results suggested that among veterans who were accepted to the program, those who were legally separated or divorced had significantly greater odds of attending the program compared to single veterans. Veterans were highly satisfied with the 3-week ITP and rated cognitive processing therapy components as the most helpful part of the program. CONCLUSIONS: The present study demonstrates that ITP formats for PTSD are of interest and acceptable to veterans, and this format allows individuals to receive high doses of evidence-based treatments in a short amount of time. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Changes in Dosing and Dose Timing of D-Cycloserine Explain Its Apparent Declining Efficacy for Augmenting Exposure Therapy for Anxiety-related Disorders: An Individual Participant-data Meta-analysis.

The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/).

Effect of d-cycloserine on fear extinction training in adults with social anxiety disorder.

Preclinical and clinical data have shown that D-cycloserine (DCS), a partial agonist at the N-methyl-d-aspartate receptor complex, augments the retention of fear extinction in animals and the therapeutic learning from exposure therapy in humans. However, studies with non-clinical human samples in de novo fear conditioning paradigms have demonstrated minimal to no benefit of DCS. The aim of this study was to evaluate the effects of DCS on the retention of extinction learning following de novo fear conditioning in a clinical sample. Eighty-one patients with social anxiety disorder were recruited and underwent a previously validated de novo fear conditioning and extinction paradigm over the course of three days. Of those, only 43 (53%) provided analyzable data. During conditioning on Day 1, participants viewed images of differently colored lamps, two of which were followed by with electric shock (CS+) and a third which was not (CS-). On Day 2, participants were randomly assigned to receive either 50 mg DCS or placebo, administered in a double-blind manner 1 hour prior to extinction training with a single CS+ in a distinct context. Day 3 consisted of tests of extinction recall and renewal. The primary outcome was skin conductance response to conditioned stimuli, and shock expectancy ratings were examined as a secondary outcome. Results showed greater skin conductance and expectancy ratings in response to the CS+ compared to CS- at the end of conditioning. As expected, this difference was no longer present at the end of extinction training, but returned at early recall and renewal phases on Day 3, showing evidence of return of fear. In contrast to hypotheses, DCS had no moderating influence on skin conductance response or expectancy of shock during recall or renewal phases. We did not find evidence of an effect of DCS on the retention of extinction learning in humans in this fear conditioning and extinction paradigm.

A placebo-controlled pilot study of a wearable morning bright light treatment for probable PTSD.

BACKGROUND: Evidence-based treatments for post-traumatic stress disorder (PTSD) have poor uptake and remission rates, suggesting that alternative treatments are needed. Morning bright light may be an effective treatment for PTSD given its established effects on mood and sleep, however, there are no published trials. METHODS: We conducted a placebo-controlled pilot trial of a wearable light device, the Re-timer®, for individuals with probable PTSD. Individuals were randomly assigned to the active Re-timer® (n = 9) or a placebo Re-timer® dimmed with neutral density filters (n = 6). Participants self-administered the treatment at home 1 hr each morning over 4 weeks. PTSD and depression symptoms were assessed at pre- and post-treatment. RESULTS: The Re-timer® was well tolerated and the perceived benefit was high, though treatment adherence was only moderate. Those in the active group were more likely to achieve a minimal clinically important change in PTSD and depression symptoms and had larger symptom reductions than those in the placebo group CONCLUSIONS: A wearable morning light treatment was acceptable and feasible for patients with probable PTSD. This study provides initial proof-of-concept that light treatment can improve PTSD. A larger trial is warranted to establish treatment efficacy. NCT#: 03513848.

"I knew it was wrong the moment I got the order": A narrative thematic analysis of moral injury in combat veterans.

OBJECTIVE: Moral injury is a nascent construct intended to capture reactions to events that violate deeply held beliefs and moral values. Although a model of moral injury has been proposed, many of the theoretical propositions of this model have yet to be systematically studied. METHOD: We conducted semistructured interviews with eight veterans who reported experiencing morally injurious events during war zone deployments. RESULTS: Using narrative thematic analysis, five main themes and associated subthemes emerged from the data. The main themes capture the timing of the event, contextual factors that affected the decision-making process during the morally injurious event, reactions to the moral injurious event, search for purpose and meaning, and opening up. CONCLUSION: The findings from the present study supported an existing model of moral injury, while extending it in several important ways. Preliminary clinical recommendations and directions for future research are discussed based on the study findings. These include directly exploring the context surrounding the morally injurious event, examining the veterans' moral appraisals, and helping them assume appropriate responsibility for their actions to reduce excessive self-blame. (PsycINFO Database Record (c) 2019 APA, all rights reserved).