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This article summarizes content proceedings of a symposium held at the 2004 Research Society on Alcoholism Scientific Annual Meeting in Vancouver, Canada. The chairs were Friedrich M. Wurst and Raye Litten. The presentations were (1) Introduction, by Raye Litten; (2) Direct Ethanol Metabolites--On the Threshold From Science to Routine Use, by Friedrich M. Wurst; (3) Sialic Acid Index of Plasma Apolipoprotein J (SIJ) as a Viable Marker for Chronic Alcohol Consumption, by Philippe Marmillot; (4) The Emergence of Ethyl Glucuronide (EtG) Testing as a Tool in Monitoring Healthcare Professionals, by Gregory E. Skipper; (5) Application of Biomarkers for Alcohol Use Disorders in Clinical Practice, by Tim Neumann; (6) Utility of Biomarkers in Assessing the Efficacy of Medications for Treating Alcoholism, by Marty Javors; and (7) Discussion, by Raye Litten. [ABSTRACT FROM AUTHOR]

This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers and chairs were William J. McBride and David M. Lovinger. The presentations were (1) Mechanisms of alcohol potentiation of 5-HT3 receptor function, by David M. Lovinger and Tina Machu; (2) Chronic alcohol drinking alters 5-HT3 receptors regulating the mesolimbic dopamine system, by Richard J. Thielen; (3) 5-HT3 receptors in the VTA regulate alcohol drinking and the reinforcing effects of alcohol, by Zachary A. Rodd and James M. Murphy; and (4) Ondansetron as a treatment for 'biological' alcoholism, by John D. Roache and Bankole A. Johnson. [ABSTRACT FROM AUTHOR]

Context: Early-onset alcoholism differs from late-onset alcoholism by its association with greater serotonergic abnormality and antisocial behaviors. Thus, individuals with early-onset alcoholism may be responsive to treatment with a selective serotonergic agent.Objective: To test the hypothesis that drinking outcomes associated with early vs late-onset alcoholism are differentially improved by the selective 5-HT(3) (serotonin) antagonist ondansetron.Design: Double-blind, randomized, placebo-controlled clinical trial.Settings: University of Texas Health Science Center in Houston (April 1995-June 1998) and University of Texas Health Science Center in San Antonio (July 1998-December 1999).Participants: A total of 321 patients with diagnosed alcoholism (mean age, 40.6 years; 70.5% male; 78.6% white) were enrolled, 271 of whom proceeded to randomization.Interventions: After 1 lead-in week of single-blind placebo, patients were randomly assigned to receive 11 weeks of treatment with ondansetron, 1 microg/kg (n = 67), 4 microg/kg (n = 77), or 16 microg/kg (n = 71) twice per day; or identical placebo (n = 56). All patients also participated in weekly standardized group cognitive behavioral therapy.Main Outcome Measures: Self-reported alcohol consumption (drinks per day, drinks per drinking day, percentage of days abstinent, and total days abstinent per study week); and plasma carbohydrate deficient transferrin (CDT) level, an objective and sensitive marker of transient alcohol consumption.Results: Patients with early-onset alcoholism who received ondansetron (1, 4, and 16 microg/kg twice per day) compared with those who were administered placebo, had fewer drinks per day (1.89, 1.56, and 1.87 vs 3.30; P =.03, P =.01, and P =.02, respectively) and drinks per drinking day (4.75, 4.28, and 5.18 vs 6.90; P =.03, P =.004, and P =.03, respectively). Ondansetron, 4 microg/kg twice per day, was superior to placebo in increasing percentage of days abstinent (70.10 vs 50.20; P =.02) and total days abstinent per study week (6.74 vs 5.92; P =.03). Among patients with early-onset alcoholism, there was a significant difference in the mean log CDT ratio between those who received ondansetron (1 and 4 microg/kg twice per day) compared with those who received the placebo (-0.17 and -0.19 vs 0.12; P =.03 and P =.01, respectively).Conclusion: Our results suggest that ondansetron (particularly the 4 microg/kg twice per day dosage) is an effective treatment for patients with early-onset alcoholism, presumably by ameliorating an underlying serotonergic abnormality. JAMA. 2000;284:963-971 [ABSTRACT FROM AUTHOR]

Lack of evidence to guide medication treatments for mild traumatic brain injury (mTBI) in veterans too often results in polypharmacy practices attempting to provide symptomatic relief from multiple postconcussive syndrome symptoms. Therefore, the field needs to find an effective medication that reduces the burden of postconcussive symptoms without complicating the treatment burden of veterans. This clinical trial seeks to determine whether switching veterans to quetiapine monotherapy (intervention) is superior to continuing to receive treatment as usual (TAU, control) polypharmacy for veterans with symptoms of postconcussive syndrome and posttraumatic stress disorder who are receiving rehabilitation treatment for mTBI. This study will test the conceptual mediation model hypothesis that quetiapine monotherapy may enhance recovery from mTBI by (1) increasing engagement in rehabilitation services, and/or (2) reducing the adverse effects of TAU polypharmacy. This study will enroll 146 patients from two Veterans Administration Medical Centers into a 12- week phase III, randomized, pragmatic clinical trial comparing outcomes from treatment with quetiapine monotherapy and TAU. Quetiapine will be cross tapered up to a maximum dose of 200 mg (as tolerated) as other medications are discontinued. The primary outcome measures are postconcussive syndrome symptoms (Neurobehavioral Symptom Inventory), functional disability (World Health Organization Disability Assessment), and quality of life (World Health Organization Quality of Life Assessment). Overall, this study aims to determine whether quetiapine monotherapy is superior to TAU polypharmacy and improves the quality of life for veterans with comorbid postconcussive syndrome and posttraumatic stress disorder symptoms who are receiving rehabilitation treatment for mTBI., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Preclinical research with rodents suggests that the L-type calcium channel blocker isradipine can enhance long-term extinction of conditioned place preference for addictive substances when it is administered in conjunction with extinction training. Although isradipine alone, which is FDA-approved for hypertension, has not shown a direct effect on craving in human drug users, its potential to augment behavioral treatments designed to reduce craving remains unknown. We conducted a triple-blind, randomized placebo-controlled pilot clinical trial of isradipine combined with a novel virtual reality cue exposure therapy (VR-CET) approach with multimodal cues that targeted craving. After 24 hours of abstinence, 78 adults with an ongoing history of daily cigarette use received isradipine (n = 40) or placebo (n = 38) and reported craving levels after each of 10 trials of VR-CET. Consistent with pre-registered hypotheses, the isradipine group had significantly lower mean craving across cue exposure trials at the medication-free 24-hour follow-up (d = -0.42, p = 0.046). There were no serious adverse events; however, side effects such as headache and dizziness occurred more frequently in the isradipine group. The findings of the current study support follow-up clinical trials that specifically test the efficacy of isradipine-augmented VR-CET for reducing smoking relapse rates after an initial quit attempt. clinicaltrials.gov: NCT03083353., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Objective: In posttraumatic stress disorder (PTSD), the assumption of the equipotentiality of traumas ignores potentially unique contexts and consequences of different traumas. Accordingly, Stein et al. (2012) developed a reliable typing scheme in which assessors categorized descriptions of traumatic events into six "types": life threat to self (LTS), life threat to other, aftermath of violence (AV), traumatic loss, moral injury by self (MIS), and moral injury by other (MIO). We extended this research by validating the typing scheme using participant endorsements of type , rather than assesor-based types. We examined the concordance of participant and assesor types, frequency, and validity of participant-based trauma types by examining associations with baseline mental and behavioral health problems., Method: Interviewers enrolled military personnel and veterans ( N = 1,443) in clinical trials of PTSD and helped them select the most currently distressing Criterion-A trauma. Participants and, archivally, assessors typed the distressing aspect(s) of this experience., Results: AV was the most frequently participant-endorsed type, but LTS was the most frequently rated worst part of an event. Although participants endorsed MIS and MIO the least frequently, these were associated with worse mental and behavioral health problems. The agreement between participants and assessors regarding the worst part of the event was poor., Conclusion: Because of discrepancies between participant and assessor typologies, clinical researchers should use participants' ratings, and these should trump assessor judgment. Differences in pretreatment behavioral and mental health problems across some participant-endorsed trauma types partially support the validity of the participant ratings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: The impact of posttraumatic stress disorder (PTSD) is substantial and often results in pervasive functional impairments. Although evidence-based treatments for PTSD are established, there remains room for improvement as many individuals continue to meet diagnostic criteria even after successful treatment completion. Cannabidiol (CBD) has attracted considerable attention based on its potential to treat a myriad of health conditions. CBD may decrease anxiety and facilitate extinction learning processes, two critical targets of trauma-focused psychotherapies. We present the design and methods for a pilot randomized clinical trial to examine the combination of CBD and prolonged exposure for PTSD., Methods: Participants ( n = 24) will be randomized to CBD or placebo for 18 days delivered in combination with ten daily prolonged exposure sessions over two weeks. The study medication will be Epidiolex® (250 mg BID). The PTSD Checklist for DSM-5 will be the primary outcome to assess PTSD severity at baseline, during treatment, and at 1-month follow-up. Blood, saliva, and heart rate will be collected during treatment to assess intervention effects on biological outcomes related to PTSD and the endocannabinoid system., Results: Consistent with the purpose of a pilot, our goals are to evaluate the feasibility of study procedures, safety of the intervention, and the preliminary effect of CBD to inform a larger trial. Descriptive and inferential statistics will be used to address study aims., Conclusion: Findings will inform decision making on combining CBD with behavioral interventions for PTSD to enhance outcomes and mitigate the morbidity of this debilitating condition., Competing Interests: The authors have no conflicts of interest to report., (© 2024 The Authors. Published by Elsevier Inc.)

The intent of this study is to examine treatment impact and efficiency observed when cognitive behavioral treatments for posttraumatic stress disorder (PTSD) are delivered in-person or using telehealth. This study pooled data from 268 veterans enrolled in two PTSD clinical trials. In both trials, treatment was delivered using in-home telehealth ( telehealth arm), in-home in-person ( in-home arm), and in-office care, where patients traveled to the Department of Veterans Affairs for either office-based telehealth or office-based in-person care ( office arm). Average age was 44 ( SD = 12.57); 80.9% were males. The PTSD Checklist for DSM-5 (PCL-5) was used to assess symptom severity. Treatment impact was measured by (a) the proportion of participants who completed at least eight treatment sessions and (b) the proportion with a reliable change of ≥ 10 points on the PCL-5. Treatment efficiency was measured by the number of days required to reach the end point. The proportion of participants who attended at least eight sessions and achieved reliable change on the PCL-5 differed across treatment formats ( p s < .05). Participants in the in-home (75.4%) format were most likely to attend at least eight treatment sessions, followed by those in the telehealth (58.3%) and office (44.0%) formats, the latter of which required patients to travel. Participants in the in-home (68.3%, p < .001) format were also more likely to achieve reliable change, followed by those in the telehealth (50.9%) and office (44.2%) formats. There were no significant differences in the amount of time to complete at least eight sessions. Delivery of therapy in-home results in a significantly greater likelihood of achieving both an adequate dose of therapy and a reliable decrease in PTSD symptoms compared to telehealth and office formats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Military personnel and veterans are at heightened risk for exposure to traumatic events and posttraumatic stress disorder (PTSD), as well as intimate relationship problems associated with PTSD., The purpose of this study was to evaluate the relative efficacy of CBCT and PE in improving intimate relationship functioning in active duty military personnel or veterans and their intimate partners; both conditions were hypothesized to significantly improve PTSD. Method: In this study, 32 military service members or veterans with PTSD and their intimate partners were randomized to receive either Cognitive-Behavioral Conjoint Therapy for PTSD ( n  = 15; CBCT; [Monson, C. M., & Fredman, S. J. (2012). Cognitive-behavioral conjoint therapy for posttraumatic stress disorder: Harnessing the healing power of relationships. Guilford]), a trauma-focused couple therapy, or Prolonged Exposure ( n  = 17; PE; [Foa, E. B., Hembree, E. A., Dancu, C. V., Peterson, A. L., Cigrang, J. A., & Riggs, D. S. (2008). Prolonged exposure treatment for combat-related stress disorders - provider's treatment manual [unpublished]. Department of Psychiatry, University of Pennsylvania]), a front-line evidence-based individual treatment for PTSD., There were significant challenges with recruitment and a significant difference in dropout from treatment for the two therapies (65% for PE; 27% for CBCT). Treatment dropout was differentially related to pre-treatment relationship functioning; those with below average relationship functioning had higher dropout in PE compared with CBCT, whereas those with above average relationship functioning did not show differential dropout. In general, CBCT led to relational improvements, but this was not consistently found in PE. Clinician- and self-reported PTSD symptoms improved with both treatments., This study is the first to test a couple or family therapy against a well-established, front-line recommended treatment for PTSD, with expected superiority of CBCT over PE on relationship outcomes. Lessons learned in trial design, including considerations of equipoise, and the effects of differential dropout on trial analyses are discussed. This trial provides further support for the efficacy of CBCT in the treatment of PTSD and enhancement of intimate relationships.

Cognitive processing therapy (CPT) is an effective treatment for posttraumatic stress disorder (PTSD); however, some patients do not improve to the same extent as others. It is important to understand potential factors that can be modified for better patient outcomes. This clinical trial implemented a three-arm, equipoise-stratified randomization design to allow for the accommodation of patient preference before randomization to one of three CPT treatment modalities: in-home, in-office, or telehealth. This study examined whether satisfaction with the modality, perceived stigma, expectations of therapy, and credibility of the therapist differed between modalities and whether these factors impacted treatment outcomes. We hypothesized that the contributions of these variables would depend upon whether participants opted out of any treatment arms and that these factors would predict treatment outcomes. Participants who endorsed less perceived stigma demonstrated larger reductions in PTSD symptom severity than those with similar levels of perceived stigma in the telehealth and in-office conditions, η 2 = .12-.18. Participants who endorsed lower satisfaction with their treatment modality and were assigned to the in-home condition experienced larger PTSD symptom reductions than those with similar dissatisfaction in the telehealth and in-office conditions, η 2 = .20. The results show the robustness of evidence-based therapies for PTSD given that dissatisfaction did not impede treatment success. In addition, they demonstrate that it is important for clinicians to address stigma before initiating evidence-based therapies for PTSD. Strategies to address these factors are discussed., (© 2023 International Society for Traumatic Stress Studies.)

We assessed the interrater reliability, convergent validity, and discriminant validity of the Self-Injurious Thoughts and Behaviors Interview-Short Form (SITBI-SF) in a sample of 1,944 active duty service members and veterans seeking services for posttraumatic stress disorder (PTSD) and related conditions. The SITBI-SF demonstrated high interrater reliability and good convergent and discriminant validity. The measurement properties of the SITBI-SF were comparable across service members and veterans. Approximately 8% of participants who denied a history of suicidal ideation on the SITBI-SF reported suicidal ideation on a separate self-report questionnaire (i.e., discordant responders). Discordant responders reported significantly higher levels of PTSD symptoms than those who denied suicidal ideation on both response formats. Findings suggest that the SITBI-SF is a reliable and valid interview-based measure of suicide-related thoughts and behaviors for use with military service members and veterans. Suicide risk assessment might be optimized if the SITBI-SF interview is combined with a self-report measure of related constructs.

Background: Driving while intoxicated (DWI) is a serious public health problem. However, treatment for DWI arrestees is not readily available. This study examines the effectiveness of a contingency management (CM) procedure using transdermal alcohol concentration (TAC) monitoring to reduce drinking among DWI arrestees., Method: The study participants were 216 DWI arrestees under pretrial and included both Mandated participants undergoing court-ordered TAC monitoring and Non-Mandated participants wearing a study-provided TAC monitor. Participants were randomly assigned to either a CM (Mandated = 35; Non-Mandated = 74) or a Control condition (Mandated = 37; Non-Mandated = 70) and completed the 8-week intervention. CM participants received $50/week for not exceeding a TAC of 0.02 g/dL during the previous week. Payments to Controls were yoked to the CM group., Results: Among Non-Mandated participants, the probability of meeting the contingency was higher and remained stable (about 65%) over time in the CM group, whereas the probability was lower and declined in the Control group, widening the gaps in the probability between the study conditions (16.7%-24.1% greater in the CM group from visit 4 to 8, all p < 0.05). Among Mandated participants, the probability was not significantly different between conditions (p = 0.06-0.95). Furthermore, among Non-Mandated participants, the percentage of heavy drinking days remained low (9.16%-11.37%) in the CM group, whereas it was greater and increased over time (17.43%-26.59%) in the Control group. In Mandated participants, no significant differences in percent heavy drinking days were observed between conditions (p = 0.07-0.10)., Conclusion: We found that contingency effects on alcohol use are more pronounced among frequent and heavy alcohol users, i.e., Non-Mandated DWI arrestees. However, for individuals whose drinking was already suppressed by existing contingencies (i.e., court-mandated TAC monitoring), our CM procedure did not produce additional reductions in drinking., (© 2023 Research Society on Alcohol.)

Adolescence is defined in part by heightened exposure and sensitivity to stressors. In a longitudinal cohort of youth at risk for substance use problems, we examined the age-varying relationship between stress exposure and traits that are central to the dual systems model. The positive associations between stress exposure, impulsivity, sensation seeking varied as function of age. Specifically, the influence of stress exposure on impulsivity strengthened during early adolescence and remained stable into early adulthood, while the influence of stress exposure on sensation seeking strengthened from early- to mid-adolescence and weakened thereafter. These findings suggest that the maturational imbalance between the capacity to regulate impulsive tendencies and sensation seeking may be exaggerated for youth who are exposed to a high number of stressors., (© 2023 Society for Research on Adolescence.)

Importance: Improved, efficient, and acceptable treatments are needed for combat-related posttraumatic stress disorder (PTSD)., Objective: To determine the efficacy of 2 compressed prolonged exposure (PE) therapy outpatient treatments for combat-related PTSD., Design, Setting, and Participants: This randomized clinical trial was conducted among military personnel and veterans at 4 sites in Texas from 2017 to 2019. Assessors were blinded to conditions. Data were analyzed from November 2020 to October 2022., Interventions: The interventions were massed-PE, which included 15 therapy sessions of 90 minutes each over 3 weeks, vs intensive outpatient program PE (IOP-PE), which included 15 full-day therapy sessions over 3 weeks with 8 treatment augmentations. The IOP-PE intervention was hypothesized to be superior to massed-PE., Main Outcomes and Measures: Coprimary outcomes included the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) (CAPS-5) and the PTSD Checklist for DSM-5 (PCL-5) administered at baseline and posttreatment follow-ups. Measures ranged from 0 to 80, with higher scores indicating greater severity. Diagnostic remission and reliable change were secondary outcomes., Results: Among 319 military personnel and veterans screened, 234 were randomized (mean [SD] age, 39.20 [7.72] years; 182 [78%] male participants), with 117 participants randomized to IOP-PE and 117 participants randomized to massed-PE. A total of 61 participants (26%) were African American, 58 participants (25%) were Hispanic, and 102 participants (44%) were White; 151 participants (65%) were married. Linear mixed-effects models found that CAPS-5 scores decreased in both treatment groups at the 1-month follow-up (IOP-PE: mean difference, -13.85 [95% CI, -16.47 to -11.23]; P < .001; massed-PE: mean difference, -14.13 [95% CI, -16.63 to -11.62]; P < .001). CAPS-5 change scores differed from 1- to 6-month follow-ups (mean difference, 4.44 [95% CI, 0.89 to 8.01]; P = .02). PTSD symptoms increased in massed-PE participants during follow-up (mean difference, 3.21 [95% CI, 0.65 to 5.77]; P = .01), whereas IOP-PE participants maintained treatment gains (mean difference, 1.23 [95% CI, -3.72 to 1.27]; P = .33). PCL-5 scores decreased in both groups from baseline to 1-month follow-up (IOP-PE: mean difference, -21.81 [95% CI, -25.57 to -18.04]; P < .001; massed-PE: mean difference, -19.96 [95% CI, -23.56 to -16.35]; P < .001) and were maintained at 6 months (IOP-PE: mean change, -0.21 [95% CI, -3.47 to 3.06]; P = .90; massed-PE: mean change, 3.02 [95% CI, -0.36 to 6.40]; P = .08). Both groups had notable PTSD diagnostic remission at posttreatment (IOP-PE: 48% [95% CI, 36% to 61%] of participants; massed-PE: 62% [95% CI, 51% to 73%] of participants), which was maintained at 6 months (IOP-PE: 53% [95% CI, 40% to 66%] of participants; massed-PE: 52% [95% CI, 38% to 66%] of participants). Most participants demonstrated reliable change on the CAPS-5 (61% [95% CI, 52% to 69%] of participants) and the PCL-5 (74% [95% CI, 66% to 81%] of participants) at the 1-month follow-up., Conclusions and Relevance: These findings suggest that PE can be adapted into compressed treatment formats that effectively reduce PTSD symptoms., Trial Registration: ClinicalTrials.gov Identifier: NCT03529435.

Background: Several therapies and interventions to reduce drinking first target drink-refusal self-efficacy (DRSE) to influence drinking behavior. While higher self-efficacy scores are correlated with better outcomes, it is unclear that increased self-efficacy is the causative step leading to improved outcomes. Instead, this correlation may result from reduced drinking that increased self-efficacy. The current study sought to understand how changes in drinking behavior can influence DRSE., Methods: Data were from 211 driving while intoxicated (DWI) arrestees participating in an 8-week contingency management (CM) study to reduce drinking. Some of participants were mandated by the courts to wear transdermal alcohol monitoring devices (Mandated group) and some were not mandated (Non Mandated group). All wore a transdermal alcohol monitor during the 8-week study and were randomized to CM or a Control condition stratified by the mandate group. Participants completed weekly assessments of DRSE. Group-based trajectory-modeling identified three drinking behavior trajectory groups., Results: While there were no differences in baseline DRSE between the three trajectory groups, participants in the low- and moderate-frequency drinking behavior groups significantly increased DRSE across the study., Conclusion: The present study indicates that being able to maintain abstinence or reduce heavy drinking may increase DRSE., Competing Interests: Competing interest statement The authors do not have any competing interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Prolonged exposure therapy (PE) is an efficacious treatment for active duty service members and veterans with posttraumatic stress disorder (PTSD). However, PE is sometimes associated with high dropout rates, limited tolerability, and temporary symptom exacerbation during treatment. Stellate ganglion blocks (SGBs) are an emerging treatment that has the potential to enhance outcomes for PTSD when combined with trauma-focused psychotherapy. To date, no study of which we are aware has examined the potential additive benefits of SGB injections when administered in conjunction with trauma-focused behavioral treatment for PTSD. Thus, we conducted a nonrandomized clinical trial to evaluate the use of an SGB combined with massed PE therapy for combat-related PTSD. Participants (N = 12) were treated with 10 daily 90-min PE sessions delivered over 2 weeks and received a single SGB injection between Sessions 1 and 2. PE sessions lasted 90 min each. Participants reported a mean posttreatment PTSD symptom reduction of 32 points on the PTSD Checklist for DSM-5 (PCL-5), Hedges' gs = 1.28-2.80. Most participants (90.9%) demonstrated clinically significant change on the PCL-5 (i.e., ≥10 points) by the final treatment session and 50.0% no longer met the diagnostic criteria for PTSD per the Clinician-Administered PTSD Scale for DSM-5 at 1-month follow-up. Adverse events for the combined treatment were consistent with those previously reported for standalone SGB and PE. This combined treatment approach provides promising results for improving the tolerability of trauma-focused therapies, reducing symptom severity, and increasing PTSD remission rates., (© 2022 International Society for Traumatic Stress Studies.)

Non-pharmacological chronic pain treatments increasingly incorporate values-based approaches as an alternative to opioid therapy. Chronic pain and opioid use may differentially impact value domains such as family or work, and there is little guidance on how to implement values-based treatment to address pain and comorbid opioid use. This study aims to characterize ways in which chronic pain and values interact. Participants (N = 327) 18 or older (M = 46 years) experiencing chronic musculoskeletal pain for > 3 months and actively taking a prescription opioid completed an online, self-report survey assessing the importance of values in six domains (i.e., family, intimate relationships, friendship, work, health, growth). Participants responded to questions about pain interference with and without opioids, and subjective impact of pain within each value domain. There were significant differences between the six value domains in importance ratings. Pain interference also differed among the values with the most reported pain interference occurring in the work and health domains. Pain interference without opioids was significantly greater for work, health, and family than the other values. The subjective impact of pain interference was greatest for family, work, and health as well. Across all value domains, pain interference without opioids was significantly greater than pain interference with the use of opioids. Results highlight that value domains are differentially impacted by chronic pain and opioids are perceived as reducing pain interference across all values. These results provide an initial description from which theory and hypotheses can be developed. Clinical implications and future directions are discussed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The theoretical framework of behavioral economics, a metatheory that integrates operant learning and economic theory, has only recently been applied to posttraumatic stress disorder (PTSD). A behavioral economic theory of PTSD reflects an expansion of prior behavioral conceptualization of PTSD, which described PTSD in terms of respondent and operant conditioning. In the behavioral economic framework of PTSD, negatively reinforced avoidance behavior is overvalued, in part due to deficits in environmental reward, and may be conceptualized as a form of reinforcer pathology (i.e., excessive preference for and valuation of an immediate reinforcer). We investigated cross-sectional relationships between PTSD severity and several constructs rooted in this behavioral economic framework, including future orientation, reward availability, and delay discounting in a sample of 110 military personnel/veterans (87.2% male) who had served combat deployments following September 11, 2001. Total PTSD severity was inversely related to environmental reward availability, β = -.49, ΔR 2 = 0.24, p < .001; hedonic reward availability, β = -.32, ΔR 2 = 0.10, p = .001; and future orientation, β = -.20, ΔR 2 = 0.04, p = .032, but not delay discounting, r = -.05, p = .633. An examination of individual symptom clusters did not suggest that avoidance symptoms were uniquely associated with these behavioral economic constructs. The findings offer support for a behavioral economic model of PTSD in which there is a lack of positive reinforcement as well as a myopic focus on the present., (© 2022 International Society for Traumatic Stress Studies.)

The purpose of this pilot study was to determine if the efficacy of imaginal exposure for symptoms of posttraumatic stress disorder (PTSD) could be improved by adding aerobic exercise. We hypothesized that aerobic exercise would enhance the efficacy of exposure therapy. Active duty service members with clinically significant symptoms of posttraumatic stress (PTSD Checklist-Stressor-Specific Version, [PCL-S], ≥25) were randomized into one of four conditions: exercise only; imaginal exposure only; imaginal exposure plus exercise; no exercise/no exposure therapy (control). Participants ( N = 72) were primarily male, Army, noncommissioned officers ranging in age from 22 to 52. PTSD symptom severity decreased over time ( p < .0001); however, there were no significant differences between the experimental conditions. The prediction that imaginal exposure augmented with aerobic exercise would be superior to either imaginal exposure alone or aerobic exercise alone was not supported, suggesting that engaging in exercise and imaginal exposure simultaneously may not be any better than engaging in either activity alone. A better understanding of individually administered and combined exercise and exposure therapy interventions for PTSD is warranted.

This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment. ClinicalTrials.gov identifier: NCT02655692., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Trauma-focused psychotherapies for combat-related posttraumatic stress disorder (PTSD) in military veterans are efficacious, but there are many barriers to receiving treatment. The objective of this study was to determine if cognitive processing therapy (CPT) for PTSD among active duty military personnel and veterans would result in increased acceptability, fewer dropouts, and better outcomes when delivered In-Home or by Telehealth as compared to In-Office treatment., Methods: The trial used an equipoise-stratified randomization design in which participants (N = 120) could decline none or any 1 arm of the study and were then randomized equally to 1 of the remaining arms. Therapists delivered CPT in 12 sessions lasting 60-min each. Self-reported PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5) served as the primary outcome., Results: Over half of the participants (57%) declined 1 treatment arm. Telehealth was the most acceptable and least often refused delivery format (17%), followed by In-Office (29%), and In-Home (54%); these differences were significant (p = 0.0008). Significant reductions in PTSD symptoms occurred with all treatment formats (p < .0001). Improvement on the PCL-5 was about twice as large in the In-Home (d = 2.1) and Telehealth (d = 2.0) formats than In-Office (d = 1.3); those differences were statistically large and significant (d = 0.8, 0.7 and p = 0.009, 0.014, respectively). There were no significant differences between In-Home and Telehealth outcomes (p = 0.77, d = -.08). Dropout from treatment was numerically lowest when therapy was delivered In-Home (25%) compared to Telehealth (34%) and In-Office (43%), but these differences were not statistically significant., Conclusions: CPT delivered by telehealth is an efficient and effective treatment modality for PTSD, especially considering in-person restrictions resulting from COVID-19., Trial Registration: ClinicalTrials.gov ID NCT02290847 (Registered 13/08/2014; First Posted Date 14/11/2014)., (© 2022. The Author(s).)

Background: The comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT) trial showed that following induction, treatment with the sublingual agonist (buprenorphine-naloxone, BUP-NX) or injected antagonist (extended release naltrexone, XR-NTX) produced similar reductions in opioid relapse in injection users with opioid use disorder (OUD). Because XR-NTX reduces drinking in alcohol use disorder (AUD), we conducted a secondary analysis of the X:BOT sample of patients successfully inducted onto treatment to determine whether XR-NTX (n = 204) was superior to BUP-NX (n = 270) in reducing drinking or heavy drinking in patients with OUD., Methods: Standard drink units consumed were measured using the Timeline Follow-back method. Mixed-models regression was used to examine the monthly frequency of any drinking and heavy drinking over 6 months of treatment. We used a proportional hazard survival analysis to examine the time to first drink., Results: Both treatment groups reduced drinking from baseline to posttreatment (small to medium effect), but no differences between groups were detected. However, only 29% (n = 136) of the sample had AUD and 19% (n = 26/136) of those were abstinent before treatment. Analysis of a subsample enriched for possible drinking included 136 individuals with an AUD diagnosis plus 43 who did not have AUD, but reported at least one day of heavy drinking prior to the study. However, this subsample reported only 32% of days of any drinking with a median of only 13% of days designated as "heavy." Within this subsample, at baseline, the BUP-NX group reported more mean drinks per drinking day than the XR-NTX group (p = 0.03); however, there were no other significant group differences on drinking observed before, during, or at the end of treatment., Conclusions: There was an overall reduction in drinking during treatment of OUD using both agonist and antagonist medications, so that the hypothesis that XR-NTX would be superior to BUP-NX was not supported. The study is limited by low levels of comorbid AUD or heavy drinking observed in X:BOT trial participants seeking treatment for OUD., (© 2021 by the Research Society on Alcoholism.)

The STRONG STAR Consortium (South Texas Research Organizational Network Guiding Studies on Trauma and Resilience) and the Consortium to Alleviate PTSD are interdisciplinary and multi-institutional research consortia focused on the detection, diagnosis, prevention, and treatment of combat-related posttraumatic stress disorder (PTSD) and comorbid conditions in military personnel and veterans. This manuscript outlines the consortia's state-of-the-science collaborative research model and how this can be used as a roadmap for future trauma-related research. STRONG STAR was initially funded for 5 years in 2008 by the U.S. Department of Defense's (DoD) Psychological Health and Traumatic Brain Injury Research Program. Since the initial funding of STRONG STAR, almost 50 additional peer-reviewed STRONG STAR-affiliated projects have been funded through the DoD, the U.S. Department of Veterans Affairs (VA), the National Institutes of Health, and private organizations. In 2013, STRONG STAR investigators partnered with the VA's National Center for PTSD and were selected for joint DoD/VA funding to establish the Consortium to Alleviate PTSD. STRONG STAR and the Consortium to Alleviate PTSD have assembled a critical mass of investigators and institutions with the synergy required to make major scientific and public health advances in the prevention and treatment of combat PTSD and related conditions. This manuscript provides an overview of the establishment of these two research consortia, including their history, vision, mission, goals, and accomplishments. Comprehensive tables provide descriptions of over 70 projects supported by the consortia. Examples are provided of collaborations among over 50 worldwide academic research institutions and over 150 investigators., (Published by Elsevier Inc.)

To compare the outcomes of Seeking Safety (SS) and cognitive processing therapy (CPT) in veterans with PTSD in a specialty clinic of an urban VA medical center. Retrospective chart review of electronic medical records was conducted for 420 veterans with PTSD who received treatment with either CPT (n = 227) or SS (n = 193) in group setting. 1) treatment completion rate, 2) self-reported PTSD symptom severity measured by PTSD checklist (PCL), and 3) additional mental health services received within 12 months after treatment. Data were analyzed for the 160 who had both a pre and post PCL documented in their charts. The final analysis sample included n = 94 for CPT and n = 66 for SS veterans with a mean age of 49.71[SD = 14] years, 24 women [15%]; mean baseline PCL score was 68.41 [9]. Significantly more veterans completed SS treatment (SS, 59 [89%] than CPT, 47 [50%] (p = <.001). However, PCL score decreases were significantly greater for patients who completed CPT treatment than those in SS (treatment x time interaction, 9.60 vs.4.98, respectively; difference, 4.62; t 84  = 2.16; p = .02). The patients who received SS used significantly more mental health services of the PTSD clinical team than patients who completed CPT treatment (p = .01). The results of this study demonstrate the need for alternative approaches where dually diagnosed patients would not be delayed in their receipt of trauma-focused care - i.e., where treatment is initiated concurrently rather than sequentially to substance abuse treatment.

Alcohol-impaired driving is a common and costly public health problem associated with alcohol misuse. This investigation aims to understand the role of social support and drinking motives in motivating alcohol-impaired drivers to reduce alcohol use. One hundred nineteen participants with a history of driving-while-intoxicated arrest were recruited from either a correctional treatment facility ( n = 59) or the community ( n = 60) and asked about their motivation to change alcohol use. Motivation to change was tested in relationships with two types of social support (i.e. Abstinence-Specific Social Support and General Social Support ) and drinking motives ( Coping, Enhancement , and Social Motives ). The results showed: (1) only Abstinence-Specific Social Support was positively associated with motivation to change; (2) Coping and Social Motives had a negative association with motivation to change; (3) the impact of Abstinence-Specific Social Support on motivation to change was greater among those with a stronger Enhancement Motives . In other words, those who drink primarily for pleasure showed a greater increase in motivation to change when more Abstinence-Specific Social Support is available, compared to those with lower Enhancement Motives . The findings of this investigation contribute to our knowledge of the roles of communication in the rehabilitation of alcohol-impaired drivers.

This study was a secondary data analysis of clinical trial data collected from 268 active duty U.S. military service members seeking cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) at Fort Hood, Texas, related to combat operations following September 11, 2001. Our primary aim was to evaluate changes in PTSD symptom severity and alcohol misuse as a function of baseline hazardous drinking and treatment format (i.e., group or individual). At baseline and posttreatment, PTSD was assessed using the PTSD Symptom Scale-Interview Version and PTSD Checklist for DSM-5. Hazardous drinking was categorically defined as an Alcohol Use Disorder Identification Test total score of 8 or higher. Employing intent-to-treat, mixed-effects regression analysis, all groups reported reduced PTSD symptom severity, Hedges' gs = -0.33 to -1.01, except, unexpectedly, nonhazardous drinkers who were randomized to group CPT, Hedges' g = -0.12. Hazardous drinkers who were randomized to individual therapy had larger reductions in PTSD symptoms than nonhazardous drinkers who were randomized to group CPT, Hedges' g = -0.25. Hazardous drinkers also reported significant reductions in alcohol misuse, regardless of treatment format, Hedges' gs = -0.78 to -0.86. This study builds upon an emerging literature suggesting that individuals with PTSD and co-occurring alcohol use disorder can engage successfully in CPT, which appears to be an appropriate treatment for these individuals whether it is delivered individually or in a group format. However, as a portion of participants remained classified as hazardous drinkers at posttreatment, some individuals may benefit from integrated treatment., (© 2020 International Society for Traumatic Stress Studies.)

Veterans with posttraumatic stress disorder (PTSD) report more aggression than civilians with PTSD. Because emotion regulation difficulties mediated the relationship between PTSD symptoms and impulsive aggression in veterans, we developed an intervention to increase emotion regulation skills. This pilot study tested the feasibility and acceptability of a three-session treatment, Manage Emotions to Reduce Aggression (MERA), and examined its effectiveness at reducing aggression and emotion dysregulation. Male combat veterans with PTSD and impulsive aggression completed assessments before and 4 weeks after MERA. Overt Aggression Scale measured frequency of aggression; Difficulties in Emotion Regulation Scale assessed emotion dysregulation. Most veterans (95%) who completed MERA and the posttreatment assessment (n = 20) reported MERA was helpful. Veterans in the intent-to-treat sample demonstrated a significant decrease in their frequency of aggression (Cohen's d = -0.55) and emotion dysregulation (Cohen's d = -0.55). MERA may be an innovative treatment that helps veterans reduce aggression.

Background: Selective serotonergic reuptake inhibitors (SSRIs) are first-line pharmacologic treatments for patients with posttraumatic stress disorder (PTSD), but must be given over extended period of time before the onset of action. The use of SSRIs in PTSD patients with mild traumatic brain injury (mTBI) is problematic since SSRIs could exacerbate post-concussion syndrome (PCS) symptoms. VA/DOD guidelines identify trauma-focused psychotherapy as the best evidence-based treatment for PTSD, but overall effectiveness is limited by reduced levels of patient engagement and retention. A previous study from this research group suggested that quetiapine monotherapy, but not risperidone or valproate, could increase engagement in trauma-focused psychotherapy., Methods: We report the study protocol of a pilot study funded under the South-Central Mental Illness Research, Education, and Clinical Center pilot study program from the U.S. Department of Veterans Affairs. This randomized, open-label study was designed to evaluate the feasibility of completing a randomized trial of quetiapine vs. treatment as usual to promote patient engagement in PTSD patients with a history of mTBI., Discussion: We expect that the success of this ongoing study should provide us with the preliminary data necessary to design a full-scale randomized trial. Positive efficacy results in a full- scale trial should inform new VA guidelines for clinical practice by showing that quetiapine-related improvements in patient engagement and retention may be the most effective approach to assure that VA resources achieve the best possible outcome for veterans., Trial Registration: NCT04280965 .

Cognitive-behavioral conjoint therapy for posttraumatic stress disorder (CBCT for PTSD; Monson & Fredman, 2012) is efficacious in improving PTSD symptoms and relationship adjustment among couples with PTSD. However, there is a need for more efficient delivery formats to maximize engagement and retention and to achieve faster outcomes in multiple domains. This nonrandomized trial was designed to pilot an abbreviated, intensive, multi-couple group version of CBCT for PTSD (AIM-CBCT for PTSD) delivered over a single weekend for 24 couples that included an active-duty service member or veteran with PTSD who had deployed in support of combat operations following September 11, 2001. All couples completed treatment. Assessments conducted by clinical evaluators 1 and 3 months after the intervention revealed significant reductions in clinician-rated PTSD symptoms (ds = -0.77 and -0.98, respectively) and in patients' self-reported symptoms of PTSD (ds = -0.73 and -1.17, respectively), depression (ds = -0.60 and -0.75, respectively), anxiety (ds = -0.63 and -0.73, respectively), and anger (ds = -0.45 and -0.60, respectively), relative to baseline. By 3-month follow-up, partners reported significant reductions in patients' PTSD symptoms (d = -0.56), as well as significant improvements in their own depressive symptoms (d = -0.47), anxiety (d = -0.60), and relationship satisfaction (d = 0.53), relative to baseline. Delivering CBCT for PTSD through an abbreviated, intensive multi-couple group format may be an efficient strategy for improving patient, partner, and relational well-being in military and veteran couples with PTSD., (Copyright © 2020. Published by Elsevier Ltd.)

Cigarette smoking remains a leading cause of preventable death in the United States, contributing to over 480,000 deaths each year. Although significant strides have been made in the development of effective smoking cessation treatments, most established interventions are associated with high relapse rates. One avenue for increasing the effectiveness of smoking cessation interventions is to design focused, efficient, and rigorous experiments testing engagement of well-defined mechanistic targets. Toward this aim, the current protocol will apply a pharmacologic augmentation strategy informed by basic research in animal models of addiction. Our goal is to evaluate the enhancing effect of isradipine, an FDA-approved calcium channel blocker, on the extinction of craving-a key mechanism of drug relapse after periods of abstinence. To activate craving robustly in human participants, we will use multimodal smoking cues including novel 360° video environments developed for this project and delivered through consumer virtual reality headsets. Adult smokers will take either isradipine or placebo and complete the cue exposure protocol in a double-blind randomized control trial. In order to test the hypothesis that isradipine will enhance retention of craving extinction, participants will repeat cue exposure 24 h later without the administration of isradipine or placebo. The study will be implemented in a primary care setting where adult smokers receive healthcare, and smoking behavior will be tracked throughout the trial with ecological momentary assessment., Competing Interests: Declaration of Competing Interest A. Perrone, C. Gebhardt, J. Roache, and C. Young report no conflict of interests with their funding. S. Papini receives support from the National Institutes of Health and the Donald D. Harrington Foundation. H. Morikawa receives support from the National Institutes of Health. M. Otto receives support from the National Institutes of Health and compensation as a speaker and Chair of the Scientific Advisory Board for Big Health. J. Smits receives support from the National Institutes of Health, compensation for his work as a consultant to Big Health, as editor for Elsevier and the American Psychological Association, and royalties from various book publishers. The authors declared that these funding organizations had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cognitive behavioral therapy for insomnia (CBTi) is well established as the first-line treatment for the management of chronic insomnia. Identifying predictors of response to CBTi should enable the field to efficiently utilize resources to treat those who are likely to respond and to personalize treatment approaches to optimize outcomes for those who are less likely to respond to traditional CBTi. Although a range of studies have been conducted, no clear pattern of predictors of response to CBTi has emerged. The purpose of this study was to examine the impact and relative importance of a comprehensive group of pretreatment predictors of insomnia outcomes in 99 active-duty service members who received in-person CBTi in a randomized clinical trial. Results indicated that higher levels of baseline insomnia severity and total sleep time predicted greater improvements on the Insomnia Severity Index (ISI) following treatment. Higher depression symptoms and a history of head injury predicted a worse response to treatment (i.e., smaller improvements on the ISI). Clinically meaningful improvements, as measured by the reliable change index (RCI), were found in 59% of the sample. Over and above baseline insomnia severity, only depressive symptoms predicted this outcome. Future studies should examine if modifications to CBTi based on these predictors of response can improve outcomes., (Copyright © 2020. Published by Elsevier Ltd.)

Study Objectives: The aim of this study was to obtain preliminary data on the efficacy, credibility, and acceptability of Exposure, relaxation, and rescripting therapy for military service members and veterans (ERRT-M) in active duty military personnel with trauma-related nightmares., Methods: Forty participants were randomized to either 5 sessions of ERRT-M or 5 weeks of minimal contact control (MCC) followed by ERRT-M. Assessments were completed at baseline, posttreatment/postcontrol, and 1-month follow-up., Results: Differences between ERRT-M and control were generally medium in size for nightmare frequency (Cohen d = -0.53), nights with nightmares (d = -0.38), nightmare severity (d = -0.60), fear of sleep (d = -0.44), and symptoms of insomnia (d = -0.52), and depression (d = -0.51). In the 38 participants who received ERRT-M, there were statistically significant, medium-sized decreases in nightmare frequency (d = -0.52), nights with nightmares (d = -0.50), nightmare severity (d = -0.55), fear of sleep (d = -0.48), and symptoms of insomnia (d = -0.59), posttraumatic stress disorder (PTSD) (d = -0.58) and depression (d = -0.59) from baseline to 1-month follow-up. Participants generally endorsed medium to high ratings of treatment credibility and expectancy. The treatment dropout rate (17.5%) was comparable to rates observed for similar treatments in civilians., Conclusions: ERRT-M produced medium effect-size reductions in nightmares and several secondary outcomes including PTSD, depression, and insomnia. Participants considered ERRT-M to be credible. An adequately powered randomized clinical trial is needed to confirm findings and to compare ERRT-M to an active treatment control., Clinical Trial Registration: Registry: ClinicalTrials.gov; Title: A Pilot Randomized Controlled Trial of Treatment for Trauma-Related Nightmares In Active Duty Military Personnel; Identifier: NCT02506595; URL: https://clinicaltrials.gov/ct2/show/NCT02506595., (© 2020 American Academy of Sleep Medicine.)

(i) To describe an integrated model of psychiatric care for the treatment of posttraumatic stress disorder (PTSD) in veterans with mild traumatic brain injury (mTBI). (ii) To evaluate access to and engagement in psychiatric care among veterans with comorbid PTSD and mTBI after implementation of an Integrated Care (IC) model compared to the previous Usual Care (UC). 100 randomly selected charts, 50 from each of UC and IC were reviewed in this non-concurrent case- control study. Polytrauma Network Site (PNS), an outpatient rehabilitation clinic, for veterans who suffered from brain and other traumatic injuries at an urban VA Polytrauma Rehabilitation Center. Veterans receiving treatment for mTBI symptoms by the rehabilitation team were referred for medication management for PTSD to UC and IC. Co-located access to psychiatric care for medication management as part of the interdisciplinary team with the goal of expediting rehabilitation and functional recovery. Number of consults for psychiatric care for medication management scheduled and completed within 30 days, and number of veterans offered, initiating, and completing evidence-based psychotherapies for PTSD in UC compared to IC. After implementation of IC there were significant improvements in timely completion of consults and patient engagement with a psychiatrist. There also were improvements in number of referrals, initiation, and completion of evidence-based psychotherapies for the treatment of PTSD. IC within the PNS shows promise as an effective care model for increasing access and engagement in care for veterans with comorbid PTSD/mTBI. Future research is needed to examine the utility of this model in other sites.

Background: Several studies have objectively quantified drinking through the use of Alcohol Monitoring System's (AMS) transdermal alcohol concentration (TAC) device known as SCRAM CAM. Criteria that AMS uses to detect drinking are known to be conservative and only reliably detect heavy drinking equivalent to 5 or more standard drinks. Our group has developed Research Rules used to process TAC data in a manner that will detect low-level and moderate drinking even though it is below the AMS criteria for detection., Methods: Sixteen male and 14 female paid research volunteers wore TAC monitors for 28 days in their natural environments and responded daily to text message prompts to self-report the previous day's drinking. Current analyses describe the Research Rules that we developed and how use of those rules impacts the detection of self-reported drinking treated as the standard in sensitivity/specificity analysis., Results: We observed 606 occurrences of positive TAC events over a total of 867 days and processed the TAC data to retain 345 as possible drinking events, even though AMS criteria confirmed drinking for only 163 of these events. The kinds of TAC events removed or retained by our rules are illustrated as cases of low and moderate drinking days that were detected by our rules but not by the conservative AMS criteria. AMS-confirmed TAC events have a high specificity (99.8%) to detect primarily heavy drinking, but have a poor sensitivity to detect lower-level drinking and a poor specificity as an indicator of alcohol abstinence. In contrast, our Research Rules detected 100% of TAC events detected by AMS but also detected 31% of the lower-level drinking events not detected by AMS, with 91% specificity., Conclusions: Reliance upon the AMS criteria for alcohol detection affords a high specificity for detection of heavy drinking but is a poor indicator of abstinence rates. In contrast, use of our Research Rules provides more sensitive means to quantify either any drinking or low-moderate levels of drinking while still maintaining good specificity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: We evaluated patterns and predictors of change from three efficacy trials of trauma-focused cognitive-behavioral treatments (TF-CBT) among service members (N = 702; mean age = 32.88; 89.4% male; 79.8% non-Hispanic/Latino). Rates of clinically significant change were also compared with other trials., Method: The trials were conducted in the same setting with identical measures. The primary outcome was symptom severity scores on the PTSD Symptom Scale-Interview Version (PSS-I; Foa, Riggs, Dancu, & Rothbaum, 1993)., Results: Symptom change was best explained by baseline scores and individual slopes. TF-CBT was not associated with better slope change relative to Present-Centered Therapy, a comparison arm in 2 trials. Lower baseline scores (β = .33, p < .01) and higher ratings of treatment credibility (β = -.22, p < .01) and expectancy for change (β = -.16, p < .01) were associated with greater symptom change. Older service members also responded less well to treatment (β = .09, p < .05). Based on the Jacobson and Truax (1991) metric for clinically significant change, 31% of trial participants either recovered or improved., Conclusions: Clinicians should individually tailor treatment for service members with high baseline symptoms, older patients, and those with low levels of credibility and expectancy for change. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Few studies have investigated the patterns of posttraumatic stress disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study, we aimed to understand the patterns of PTSD symptom change in both PE and present-centered therapy (PCT)., Methods: Participants were active duty military personnel (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE; 10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10 sessions over 2 weeks). Using latent profile analysis, we determined the optimal number of PTSD symptom change classes over time and analyzed whether baseline and follow-up variables were associated with class membership., Results: Five classes, namely rapid responder (7-17%), steep linear responder (14-22%), gradual responder (30-34%), non-responder (27-33%), and symptom exacerbation (7-13%) classes, characterized each treatment. No baseline clinical characteristics predicted class membership for S-PE and M-PE; in PCT, more negative baseline trauma cognitions predicted membership in the non-responder v. gradual responder class. Class membership was robustly associated with PTSD, trauma cognitions, and depression up to 6 months after treatment for both S-PE and M-PE but not for PCT., Conclusions: Distinct profiles of treatment response emerged that were similar across interventions. By and large, no baseline variables predicted responder class. Responder status was a strong predictor of future symptom severity for PE, whereas response to PCT was not as strongly associated with future symptoms.

Background: Evidence-based treatments for posttraumatic stress disorder (PTSD) are associated with reduction in suicidal ideation (SI), yet the mechanisms underlying this reduction are unclear. The current study investigated improvements in PTSD, depression, and social support as potential mediators of the change in SI over time., Method: Participants (N = 200) were active duty military personnel with PTSD randomized to prolonged exposure therapy (PE) or present-centered therapy (PCT). Using parallel mediation and serial mediation models, we examined the relative influence of the mediators on suicidal ideation over time., Results: Consistent with our hypotheses, lagged mediation analyses revealed that depression was the strongest mediator of improvements in SI over time in PE and PCT. Reductions in PTSD were associated with subsequent reductions in depression, which was associated with reductions in SI. Treatment condition did not moderate this relationship, and social support was not a significant mediator., Conclusions: In active duty military personnel, reduction in depression was the strongest mediator of reduction in suicidal ideation in PE and PCT for PTSD. These results were not altered by treatment condition., Trial Registration: Clinicaltrials. gov identifier: NCT01049516. http://www.clinicaltrials.gov/show/NCT01049516., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The efficacy of prolonged exposure (PE) on suicide ideation (SI) as a secondary outcome among individuals with posttraumatic stress disorder (PTSD) is unclear. The purpose of this study was to compare the efficacy of PE in two formats (spaced, S-PE, 10 sessions over 8 weeks, and massed, M-PE, 10 sessions over 2 weeks) to Present Centered Therapy (PCT) and minimal contact control (MCC) on SI exacerbation among patients without suicide intent or plans. Active duty military personnel (n = 335) were randomized to: (1) S-PE vs. PCT and (2) M-PE vs. MCC. All participants completed the Beck Scale for Suicide Ideation and the Beck Depression Inventory (Suicide item) at baseline, posttreatment, and follow-ups. S-PE and PCT had significant and comparable reductions in SI during treatment. M-PE had significantly steeper reductions in SI during treatment compared to MCC. Specifically, more participants in M-PE compared to MCC had reliable improvement versus reliable exacerbation. Reduction in PTSD symptoms was significantly associated with reduction of SI. PE was associated with significant reductions in SI over time that were comparable to PCT and superior to MCC. These findings suggest that both trauma- and non-trauma-focused treatments are associated with reductions in SI, and that trauma-focused treatments improve SI relative to waitlist., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Posttraumatic stress disorder (PTSD) is a debilitating disorder with limited medication treatment options. Recent reports have described the dearth of research on new drug development as a crisis in the pharmacotherapy of PTSD. There are only two PTSD medications approved by the U.S. Food and Drug Administration, and both are serotonergic antidepressants. Therefore, there is a tremendous need to identify more effective and more rapidly acting pharmacotherapies for PTSD that work through novel neural mechanisms. Pilot evidence and case reports provided preliminary evidence supporting the safety and utility of investigating the therapeutic effects of ketamine in PTSD. However, the efficacy of this drug for PTSD has not yet been tested in active duty military or veteran populations. Here, we report the design and methods of a study funded under the Consortium to Alleviate PTSD. The study is a multisite, placebo-controlled, double-blind, randomized clinical trial to examine the dose-related efficacy of ketamine, as compared to placebo, in producing a rapid and sustained reduction in PTSD symptomatology in veterans and active duty military populations with antidepressant-resistant PTSD. Approximately 198 eligible participants who meet criteria for PTSD will be randomized to the study drug (i.e., ketamine 0.5 mg/kg, ketamine 0.2 mg/kg, or placebo). The study drug will be administered intravenously twice per week for 4 weeks, followed by a 4-week follow-up period. This ongoing study is the only trial of therapeutic effects of ketamine for PTSD and the first placebo-controlled trial to determine the dose-related effects of repeated ketamine on PTSD., (Published by Elsevier Inc.)

To evaluate the outcomes of the antiarousal medications valproate, risperidone, and quetiapine on completion of treatment of cognitive processing therapy (CPT) for PTSD. A case series of fifty treatment-seeking adult (≥18 years) veterans with mild traumatic brain injury and combat-related PTSD who had unsuccessful trials of 2 or more first-line agents and previously declined treatment with trauma-focused therapy, seen at the psychiatric outpatient services of the local Polytrauma Rehabilitation Center from January 1, 2014, through December 31, 2017. Patients were prescribed valproate (n = 8), risperidone (n = 17), or quetiapine (n = 25) and were referred for individual weekly treatment with CPT. Outcome measurements of interest were measures of engagement and completion rate of CPT, PTSD Checklist total score (range, 0-80; higher scores indicate greater PTSD severity) and arousal subscale score (range, 0-24; higher scores indicate greater arousal severity), and clinical observations of sleep variables. Of the 50 patients included in the study, 48 (96%) were men; mean (SD) age was 36 (8) years. Eighteen (86%) patients initially receiving quetiapine and none taking valproate or risperidone became adequately engaged in and completed CPT. Among patients who completed CPT, the mean decrease in the PTSD Checklist score was 25 [95% CI, 30 to 20] and 9 (50%) patients no longer met criteria for PTSD. These preliminary findings support quetiapine as an adjunctive medication to facilitate CPT. A pragmatic trial is needed to evaluate the efficacy, safety, and feasibility of quetiapine to improve engagement in and completion rate of CPT.

Posttraumatic stress disorder (PTSD) and alcohol use disorder are frequently comorbid and present significant treatment challenges. Unfortunately, since the September 11, 2001, terrorist attacks in the United States, the rates of PTSD and hazardous drinking among active duty service members have increased significantly. Previous research on PTSD has typically excluded participants with current substance abuse. However, there is some research examining independent treatments for PTSD and substance abuse provided consecutively, concurrently, or as enhancements to other treatment. The current study examined the association between current hazardous drinking and PTSD treatment among 108 active duty service members with PTSD in a randomized controlled trial of group cognitive processing therapy and group present-centered therapy. Total scores above 8 on the Alcohol Use Disorders Identification Test defined hazardous alcohol use. At baseline, 25.0% of the sample was categorized as hazardous drinkers, and the hazardous and nonhazardous drinking groups did not differ in PTSD symptom severity, F(1, 106) = 0.08, p = .777, d = 0.06. Over the course of treatment, the two groups also did not differ significantly in PTSD symptom severity change on the PTSD Checklist, F(1, 106) = 1.20, p = .280, d = 0.33. Treatment for PTSD did not exacerbate hazardous drinking, and the hazardous drinking group showed significant reductions in drinking following PTSD treatment. Limitations and implications for treatment considerations are discussed., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Background : Caffeine use is highly prevalent among active duty military personnel and can be beneficial to performance in the short term. However, regular caffeine use has been found to contribute to sleep disturbances, which are elevated among the significant number of military personnel with posttraumatic stress disorder (PTSD). The current study is the first to examine caffeine use and its relationship with sleep disturbances in military personnel seeking treatment for PTSD. Participants : Active duty military personnel ( N = 366) who had returned from deployments to Afghanistan or Iraq and were seeking treatment for PTSD. Methods : Pearson correlations were used to examine the relationships between caffeine use, sleep disturbances, and PTSD symptom clusters. Results : The majority of the sample (89%) reported some caffeine use, with coffee being the largest contributor to total caffeine intake. Contrary to hypotheses, higher caffeine use was associated with lower insomnia symptom severity; follow-up analysis indicated that this was due to elevated insomnia symptom severity in those reporting no caffeine use. Caffeine use was not associated with any other measures of sleep disturbance or with PTSD symptoms. Conclusions : Caffeine use was not associated with greater reported sleep disturbances in this sample, possibly because those with elevated insomnia symptom severity abstained from any caffeine, or because insomnia symptoms were elevated in this sample.

Objectives: The Alcohol Use Disorders Identification Test (AUDIT) is used to assess the level of alcohol use/misuse and to inform the intensity of intervention delivered within screening, brief intervention, and referral to treatment (SBIRT) programs. Policy initiatives are recommending delivery of SBIRT within health care settings to reduce alcohol misuse and prevent alcohol-impaired driving. Recent reports are considering extending delivery of SBIRT to criminal justice settings. One consideration in implementing SBIRT delivery is the question of resource utilization; the amount of effort required in delivering the 4 different intensities of intervention in SBIRT: Alcohol education, simple advice, brief counseling and continued monitoring, and brief counseling and referral to specialist (from least to most intense in terms of delivery time, the skill level of the provider, and personnel resources)., Methods: In order to inform expectations about intervention intensity, this article describes the AUDIT scores from 982 adults recently arrested for alcohol-impaired driving. The distribution of scores is extrapolated to state rates for individuals arrested for alcohol-impaired driving by intervention level., Results: Though alcohol education was the most common intervention category, about one quarter of the sample scored in a range corresponding with the more intensive interventions using the brief counseling, continued monitoring for ongoing alcohol use, and/or referral to specialist for diagnostic evaluation and treatment., Conclusions: This article provides local distribution of AUDIT scores and state estimates for the number of individuals scoring in each level of risk (AUDIT risk zone) and corresponding intervention type. Routine criminal justice practice is well positioned to deliver alcohol screening, education, simple advice, and continued alcohol monitoring, making delivery of SBIRT feasible for the majority of alcohol-impaired drivers. Challenges to implementing the full range of SBIRT services include resource demands of brief counseling, identifying the appropriate providers within a criminal justice context, and availability of community providers for referral to diagnostic and specialty care. Solutions may vary by state due to differences in population density and incidence rates of alcohol-impaired driving.

Background: Social support has been linked to many therapeutic benefits (e.g., treatment retention, reduced posttreatment relapse) for individuals with alcohol use disorder. However, the positive impacts of social support have not been well understood in the context of alcohol-impaired driving. This article examines the role of social support in motivating those with histories of driving while intoxicated (DWI) arrest to reduce alcohol use by testing 3 major models of social support: the Main-Effects model, the Buffering model, and the Optimal Matching model., Methods: One hundred and nineteen participants with histories of DWI arrest were recruited from a correctional treatment facility (n = 59) and the local community (n = 60). Participants completed interviews to assess alcohol consumption, psychiatric/physical conditions, and psychosocial factors associated with drinking behavior (e.g., social support, alcohol-related problems, and motivation to change). Hierarchical regression analyses were conducted to test the 3 models. Additionally, the relative magnitude of the effects of general and recovery-specific social support was compared based on the approach of statistical inference of confidence intervals., Results: Overall social support was positively associated with some motivation to change (i.e., importance of change, confidence in change) among alcohol-impaired drivers, supporting the Main-Effects model. However, the impact of overall social support on motivation to change was not moderated by alcohol-related problems of individuals arrested for DWI, which did not confirm the Buffering model. Last, recovery-specific social support, rather than general social support, contributed to increasing motivation to reduce alcohol use, which supported the Optimal Matching model., Conclusions: These findings highlight the benefits of social support (i.e., increased motivation to change alcohol use) for alcohol-impaired drivers. Regardless of the severity of alcohol-related problems of alcohol-impaired drivers, social support had direct positive impacts on motivation to change. In particular, the results underscore that social support can be more effective when it is matched to the recovery effort of individuals, which is consistent with the Optimal Matching model., (© 2018 by the Research Society on Alcoholism.)

Background: In soldiers with posttraumatic stress disorder (PTSD), symptom provocation was found to induce increased connectivity within the salience network, as measured by functional magnetic resonance imaging ( f MRI) and global brain connectivity with global signal regression (GBCr). However, it is unknown whether these GBCr disturbances would normalize following effective PTSD treatment., Methods: 69 US Army soldiers with (n = 42) and without PTSD (n = 27) completed f MRI at rest and during symptom provocation using subject-specific script imagery. Then, participants with PTSD received 6 weeks (12 sessions) of group cognitive processing therapy (CPT) or present-centered therapy (PCT). At week 8, all participants repeated the f MRI scans. The primary analysis used a region-of-interest approach to determine the effect of treatment on salience GBCr. A secondary analysis was conducted to explore the pattern of GBCr alterations posttreatment in PTSD participants compared to controls., Results: Over the treatment period, PCT significantly reduced salience GBCr ( p = .02). Compared to controls, salience GBCr was high pretreatment (PCT, p = .01; CPT, p = .03) and normalized post-PCT ( p = .53), but not post-CPT ( p = .006). Whole-brain secondary analysis found high GBCr within the central executive network in PTSD participants compared to controls. Post hoc exploratory analyses showed significant increases in executive GBCr following CPT treatment ( p = .01)., Conclusion: The results support previous models relating CPT to central executive network and enhanced cognitive control while unraveling a previously unknown neurobiological mechanism of PCT treatment, demonstrating treatment-specific reduction in salience connectivity during trauma recollection., Competing Interests: Conflicts of Interest CGA has served as a consultant and/or on advisory boards for FSV7, Genentech and Janssen, and editor of Chronic Stress for Sage Publications, Inc.; he has filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). JHK is a consultant for AbbVie, Inc., Amgen, Astellas Pharma Global Development, Inc., AstraZeneca Pharmaceuticals, Biomedisyn Corporation, Bristol-Myers Squibb, Eli Lilly and Company, Euthymics Bioscience, Inc., Neurovance, Inc., FORUM Pharmaceuticals, Janssen Research & Development, Lundbeck Research USA, Novartis Pharma AG, Otsuka America Pharmaceutical, Inc., Sage Therapeutics, Inc., Sunovion Pharmaceuticals, Inc., and Takeda Industries; is on the Scientific Advisory Board for Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Inc., Naurex, Inc., and Pfizer; is a stockholder in Biohaven Pharmaceuticals; holds stock options in Mnemosyne Pharmaceuticals, Inc.; holds patents for Dopamine and Noradrenergic Reuptake Inhibitors in Treatment of Schizophrenia, US Patent No. 5,447,948 (issued September 5, 1995), and Glutamate Modulating Agents in the Treatment of Mental Disorders, U.S. Patent No. 8,778,979 (issued July 15, 2014); and filed a patent for Intranasal Administration of Ketamine to Treat Depression. U.S. Application No. 14/197,767 (filed on March 5, 2014); US application or Patent Cooperation Treaty international application No. 14/306,382 (filed on June 17, 2014). Filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). All other co-authors declare no conflict of interest.