AIMS:We evaluated the safety, efficacy, and patient adherence to oral ANS-6637, a selective, reversible inhibitor of aldehyde dehydrogenase 2 (ALDH2), for treating alcohol use disorder (AUD). METHODS:A 3-arm, double-blind, randomized, proof-of-concept human laboratory study embedded in a 5-week multisite clinical trial tested 200 mg and 600 mg daily doses of ANS-6637 compared to placebo in treatment-seeking adults with AUD. After 1 week of medication, participants completed an alcohol cue reactivity session. Drinking and safety assessments were measured during treatment; other exploratory outcomes were measured 1 week after treatment ended. RESULTS:The study was terminated following enrollment of 43 of 81 planned participants due to clinically significant, reversible increases in liver enzymes in three women. Adverse events consistent with ALDH2 inhibition in the presence of alcohol (heart rate/palpitations, flushing, nausea) were dose dependent. Group differences in cue-elicited craving were not significant; effect sizes (Cohen's d) comparing the 200 mg and 600 mg doses to placebo were .71 and .06, respectively. Secondary endpoints did not differ significantly between groups; Cohen's d ranged from .31 to .57 for the 600 mg dose compared to placebo for continuous drinking outcomes. CONCLUSIONS:Findings of liver toxicity with ANS-6637 led to early termination and reduced power to test hypotheses. Effect size estimates are consistent with the hypothesis that selective ALDH2 inhibition may reduce craving and drinking, however these estimates may be unreliable due to the small sample size. Additional research with non-hepatotoxic selective and reversible ALDH2 inhibitors is needed to evaluate this approach to AUD pharmacotherapy.

Background: Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have therapeutic clinical effects when applied in serial-sessions. The present study sought to preliminarily determine whether serial-sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. Methods: This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2 +/- 9.9 SD) with >= moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10 Hz, 20-total-sessions, two-sessions-per-visit, two-visits-per-week, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre-and post-treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. Results: There were no significant differences in craving between conditions. Participants who received active-rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham-rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Partici-pants who received active-rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period than those receiving sham-rTMS (Active vs. Sham:-0.72; Z=-2.33, p=0.02). Conclusions: This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

A vision-based patient monitoring system (VBPMS), Oxevision, has been introduced in approximately half of National Health Service (NHS) mental health trusts in England. A VBPMS is an assistive tool that supports patient safety by enabling non-contact physiological and physical monitoring. The system aims to help staff deliver safer, higher-quality and more efficient care. This paper summarises the potential health economic impact of using a VBPMS to support clinical practice in two inpatient settings: acute mental health and older adult mental health services. The economic model used a cost calculator approach to evaluate the potential impact of introducing a VBPMS into clinical practice, compared with clinical practice without a VBPMS. The analysis captured the cost differences in night-time observations, one-to-one continuous observations, self-harm incidents, and bedroom falls at night, including those resulting in A&E visits and emergency service callouts. The analysis is based on before and after studies conducted at five mental health NHS trusts, including acute mental health and older adult mental health services. Our findings indicate that the use of a VBPMS results in more efficient night-time observations and reductions in one-to-one observations, self-harm incidents, bedroom falls at night, and A&E visits and emergency service callouts from night-time falls. Substantial staff time in acute mental health and older adult mental health services is spent performing night-time observations, one-to-one observations, and managing incidents. The use of a VBPMS could lead to cost savings and a positive return on investment for NHS mental health trusts. The results do not incorporate all of the potential benefits associated with the use of a VBPMS, such as reductions in medication and length of hospital stay, plus the potential to avoid adverse events which would otherwise have a detrimental impact on a patient’s quality of life.

Understanding the drivers of health and economic cost for the treatment of mental health conditions is critical to meet the accelerating demands for care. We conducted an economic evaluation of real-world healthcare-systems data from 27,540 patients receiving care for a mood or an anxiety disorder within the UK National Healthcare Service. Using Markov models built on discrete health states to compare the cost-effectiveness of different interventions, we show that the principal drivers of healthcare cost relate to waiting times and treatment effectiveness. We find that internet-delivered cognitive behavioral therapy has a ‘dominant’ incremental cost-effectiveness ratio relative to standard care, offering similar clinical effectiveness but with shorter treatment times. In most healthcare systems, the clinical effectiveness of mental healthcare remains unquantified, and long treatment times are common. The potential for these findings to inform mental healthcare policy is substantial, particularly around immediacy of access and the importance of outcomes-focused quality management.

ABSTRACT Objective Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55–64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective. Methods A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to explore the uncertainty around the parameters. Results The novel tissue valve was potentially associated with higher quality-adjusted life years (QALYs) of 0.01 per person. Potential cost savings were greatest for those aged 55–64 (£408) versus those aged 65+(£53). DSA indicated the results to be most dependent on relative differences in general mortality, procedure costs, and reoperation rates. PSA estimated around 75% of the iterations to be cost-effective at £20,000 per QALY for those aged 55–64, and 57% for those aged 65+. Conclusions The exploratory analysis suggests that the novel tissue valve could be a cost-effective intervention for people over the age of 55 with AS who are suitable for SAVR in the UK.

ABSTRACT Introduction/Purpose Behaviorally based in-person multidisciplinary programs for weight loss have been studied for decades; however, delivery, scalability, and accessibility remain a challenge. We report pilot findings from a new asynchronous protocol-based telehealth weight loss program. Methods This 12-wk single-arm pilot study included adults (18–65 yr old) with body mass index (BMI) of 25–40 kg·m−2. The Home Weight Loss (HWL) program consisted of weekly app- and e-mail-delivered lesson modules covering traditional diet, exercise, and behavioral topics for weight loss. Daily weight and activity level were monitored automatically via a wireless scale and an activity tracker, and participants logged their caloric intake into the system. Monitoring data were reviewed weekly by clinicians who provided brief video-recorded feedback for participants to view at their convenience. Weight and height were measured in person at baseline and postintervention. Postintervention participants completed a satisfaction survey. Results Thirty participants (70% female; 80% White; mean age = 41 yr, standard deviation (SD) = 13.7 yr; mean BMI = 32.4 kg·m−2, SD = 4.3 kg·m−2) were enrolled, and 27 provided posttreatment data. Percent weight loss was 4.12% (SD = 4.22%). Overall, 93% of participants reported being satisfied with their overall experience in the program, and 59% cited individualized feedback as a benefit of the program. Conclusions The HWL program produced modest weight loss and demonstrated feasibility and participant acceptability. This model appears to be generally scalable for broader use and can be used to extend weight loss services for those not residing near medical centers and those in need of asynchronous and virtual feedback.

Objective: The aim of this study was to determine the efficacy of doxazosin, an α1-adrenergic antagonist, for the treatment of co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD).Methods: This 12-week, double-blind, randomized controlled trial of doxazosin (16 mg/d) was conducted between June 2016 and December 2019 at the Ralph H. Johnson VA Medical Center in Charleston, South Carolina. Participants were military veterans (N = 141) who met DSM-5 criteria for current PTSD and AUD and were randomly assigned to receive doxazosin (n = 70) or placebo (n = 71). Primary outcome measures were the Clinician Administered PTSD Scale (CAPS-5), the PTSD Checklist for DSM-5 (PCL-5), and the Timeline Follow-Back (TLFB).Results: Findings from the intent-to-treat analyses revealed that participants in both groups demonstrated statistically significant reductions in CAPS-5 and PCL-5 scores (P < .0001), but, contrary to hypotheses, no significant differences were observed between groups. Percent drinking days and percent heavy drinking days also decreased significantly during treatment, but there were no differences between groups (P < .0001). Abstinence during treatment was significantly higher in the doxazosin versus the placebo group (22% vs 7%, P = .017); however, participants in the doxazosin group consumed a greater number of drinks on drinking days (6.15 vs 4.56, P = .0096). A total of 74.5% of the sample completed the treatment phase, and there were no group differences in retention or adverse events.Conclusions: Doxazosin was safe and tolerable but was not more effective than placebo in reducing PTSD or AUD severity in this dually diagnosed sample. Clinical considerations such as heterogeneity of PTSD and AUD presentation and potential moderators are discussed in the context of future research directions.Trial Registration: ClinicalTrials.gov Identifier: NCT02500602.

Background and aims Treating patients in psychiatric intensive care units (PICUs) is costly for the English National Health Service (NHS), requiring significant staff time. Oxevision, a non-contact system, providing vision-based patient monitoring and management (VBPMM) has been introduced in some NHS mental health trusts which aims to help clinicians to deliver safer and more efficient care. The objective of this early economic evaluation was to explore the impact of introducing VBPMM with standard care, versus standard care alone on health and economic outcomes in PICUs across England.Methods The model uses a cost calculator approach to evaluate the potential benefits of introducing VBPMM, capturing differences in observation hours and critical events such as assaults. Effectiveness data were primarily based on a 24-month observational before and after study undertaken in an NHS mental health trust using VBPMM. Outcomes reported in this study are incremental costs and reduction in clinical events presented as per occupied bed days, per patient, per average ward, and for the English NHS overall. Scenario analysis was conducted to test the uncertainty of results using statistical significance of key inputs.Results and conclusions The analysis indicates that introducing VBPMM may be cost saving compared with standard care alone. The biggest driver of estimated cost savings was from the potential reduction in one to one observation hours, which may have significant impact in PICUs. Limitations of the analysis include the single center data underpinning the analysis and assumptions made about transferability of clinical data to different sized wards. Scenario analysis was conducted, and the results were robust to statistically significant changes in input parameters. This study suggests that introducing VBPMM on PICUs has the potential to reduce costs and improve efficiency of resource allocation, but results should be confirmed with additional clinical study evidence.

WW is a validated behavioral weight management program that encourages healthy habits. WW developed a method of personalizing the SmartPoints® budget depending on dietary and lifestyle preferences, and participants were placed into one of three plans as a pilot evaluation of this new program. In this 6-month, single-arm pilot study, participants attended weekly workshops and used an app to monitor eating and physical activity. Baseline and 6-month assessments included weight, waist circumference, blood pressure, energy intake, cravings, happiness, health-related quality of life, hunger, and fullness. Of 145 adults assessed at baseline, 126 (87%) provided follow-up data. Pre-post changes showed significant reductions in body weight (7.39% ± 5.93%), calories consumed (24.79% ± 32.35%) and significant improvements in cravings, happiness, all SF-36 scales and hunger but not in fullness. Greater % weight loss was related to greater improvements in happiness (r = .38, p < .001), general health perceptions (r = .29, p = .001), and health change (r = .31, p = .001), and greater reduction in role limitations due to personal or emotional problems (r = .24, p = .01). Greater % reduction in caloric intake was associated with greater reductions in cravings (r = .23, p = .01), as well as with greater improvements in happiness (r = .23, p = .01), physical functioning (r = .23, p = .01), and general health perceptions (r = .23, p = .01). Participants in this modified program achieved significant weight loss, regardless of dietary plan, as well as improvements in a variety of other physical and psychological constructs. Those who achieved greater reductions in weight also reported greater improvements in cravings, happiness and some quality of life measures.

Background Obesity is associated with heart failure with preserved ejection fraction (HFpEF). Weight loss can improve exercise capacity in HFpEF. However, previously reported methods of weight loss are impractical for widespread clinical implementation. We tested the hypothesis that an intensive lifestyle modification program would lead to relevant weight loss and improvement in functional status in patients with HFpEF and obesity. Methods and Results Patients with ejection fraction >45%, at least 1 objective criteria for HFpEF, and body mass index ≥30 kg/m2 were offered enrollment in an established 15‐week weight management program that included weekly visits for counseling, weight checks, and provision of meal replacements. At baseline, 15 weeks, and 26 weeks, Minnesota Living With Heart Failure score, 6‐minute walk distance, echocardiography, and laboratory variables were assessed. A total of 41 patients completed the study (mean body mass index, 40.8 kg/m2), 74% of whom lost >5% of their baseline body weight following the 15‐week program. At 15 weeks, mean 6‐minute walk distance increased from 223 to 281 m (P=0.001) and then decreased to 267 m at 26 weeks. Minnesota Living With Heart Failure score improved from 59.9 to 37.3 at 15 weeks (P<0.001) and 37.06 at 26 weeks. Changes in weight correlated with change in Minnesota Living With Heart Failure score (r=0.452; P=0.000) and 6‐minute walk distance (r=−0.388; P<0.001). Conclusions In a diverse population of patients with obesity and HFpEF, clinically relevant weight loss can be achieved with a pragmatic 15‐week program. This is associated with significant improvements in quality of life and exercise capacity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02911337.

Back to table of contents previous chapternext chapter No AccessChapter 20.Neurobiology and Treatment of Sedative-, Hypnotic-, and Anxiolytic-Related DisordersEdited by:https://doi.org/10.1176/appi.books.9781615373970.kb20AboutSectionsView chapterExcerptView Full Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View chapterSectionsTreatment Applications | Epidemiology | Neurobiology and Pharmacology | Adverse Effects | Additional Risks With Concurrent Opioid Use | Evaluation and Management Considerations | Conclusion | ReferencesExcerptThroughout history, numerous compounds have been utilized to restore tranquility and promote sleep. These therapeutic agents have gone by various names, including tranquilizers, sedatives, hypnotics, and anxiolytics. Consumption of alcohol and opium alkaloids derived from the poppy plant for their sedative-hypnotic properties predates written history. In the late nineteenth and early twentieth centuries, other compounds such as chloral hydrate, paraldehyde, and the bromide salts were also utilized in medicine for their sedative properties, although they have never been approved by the U.S. Food and Drug Administration (FDA). In modern times, compounds with these intended effects have been characterized as sedative-hypnotic agents. Although alcohol and opium possess sedative-hypnotic properties, they are considered separately in this textbook because of their unique pharmacology and abuse liability. Sedative-hypnotic agents are commonly categorized according to their chemical structure as barbiturates, benzodiazepines, and nonbenzodiazepine hypnotics (colloquially referred to as "Z-drugs" because their generic names typically start with the letter "z"). Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byNone The American Psychiatric Association Publishing Textbook of Substance Use Disorder Treatment Information©American Psychiatric Association Publishing History Published online 2 February 2021 Published in print 15 January 2021

Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are two prevalent psychiatric conditions in the U.S. The co-occurrence of AUD and PTSD is also common, and associated with a more severe clinical presentation and worse treatment outcomes across the biopsychosocial spectrum (e.g., social and vocational functioning, physical health) as compared to either disorder alone. Despite the high co-occurrence and negative outcomes, research on effective medications for AUD/PTSD is sparse and there is little empirical evidence to guide treatment decisions. The study described in this paper addresses this knowledge gap by testing the efficacy of N-acetylcysteine (NAC) in reducing alcohol use and PTSD symptoms. Animal studies and prior clinical research suggest a role for NAC in the treatment of substance use disorders and PTSD via glutamate modulation. NAC is a cysteine pro-drug that stimulates the cystine-glutamate exchanger, normalizes glial glutamate transporters, and restores glutamatergic tone on presynaptic receptors in reward regions of the brain. Moreover, NAC is available over-the-counter, has a long-established safety record, and does not require titration to achieve the target dose. This paper describes the rationale, study design, and methodology of a 12-week, randomized, double-blind, placebo-controlled trial of NAC (2400 mg/day) among adults with co-occurring AUD and PTSD. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) are utilized to investigate the neural circuitry and neurochemistry underlying comorbid AUD/PTSD and identify predictors of treatment outcome. This study is designed to determine the efficacy of NAC in the treatment of co-occurring AUD/PTSD and provide new information regarding mechanisms of action implicated in co-occurring AUD/PTSD.

Background: Obesity is associated with incident heart failure (HF), particularly HF with preserved ejection fraction (HFpEF). Weight loss is difficult to achieve in patients with limited physical capacity and the benefits remain uncertain in established HF. Methods: Patients with EF > 50% and at least 1 objective criteria for HFpEF (BNP 200 pg/ml, elevated resting or exercise wedge pressure (15 or 25 mmHg) or pulmonary edema on CXR) and BMI 30 kg/m2 were enrolled in a 15-week weight management program that entailed weekly counseling, weight checks, and meal replacement (twice daily weeks 1-8, once daily weeks 9-12). Primary endpoints were change from baseline to 15-weeks for weight, Minnesota Living With HF (MLWHF) score and 6 minute walk (6MW). Paired t-test was used to test for differences from baseline to the 15 week clinical endpoint, and one-way ANOVA was used to evaluate if these differences persisted at 26 week follow up. Results: 65 patients signed consent, 41 completed the 15-week program and 37 had 26-week follow up. Mean age was 67±9 years, BMI 41±6 kg/m 2 , 65% were female, and 43% black. Mean weight decreased by 8.1±6.6 kg at the 15-week endpoint (p<0.001) and persisted at 26-week follow up (p<0.001). 74% of patients lost more than 5% of their baseline body weight at week 15. Blacks lost a mean of 6±6% body weight compared to 9±4% in Caucasians (p<0.05). At 15 weeks, mean 6MW distance increased from 221±111 m to 286±99 m (p<0.001) and then fell to 275±144 m at 26 weeks (p=0.043). MLWHF score improved from 60±24 to 38±27 (p<0.001) and 38±26 (p<0.001) at 15 and 26 weeks, respectively. BNP did not change (109 to 114 pg/ml). E/e’ decreased significantly from 13.9±6.8 to 11.9±5.6 at 26 weeks follow up (p<0.01). BNP levels decreased by 39±103 pg/ml in blacks vs. an increase of 17±53 mg/dl in Caucasians (p<0.05) at 15-week follow up. Conclusions: Clinically relevant weight loss is possible in patients with established HFpEF and when it occurs, this is associated with significant improvements in quality of life and exercise capacity. There may be racial differences in the biochemical response to weight management in this population.

Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both ‘Intention to Treat’ (ITT) and ‘As Per Protocol’ (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.

Currently there are few evidence based treatments for Cannabis Use Disorder (CUD), and those that are available have limited efficacy [1]. Cannabis craving is a commonly described behavioral construct in CUD [2], and may have clinical relevance. An expanding evidence base suggests that repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) decreases craving across a variety of different substance use disorders and may have treatment efficacy [3].

Objective Research suggests that individuals seeking weight loss treatment do so for a variety of reasons. Limited work has explored relations of reasons for weight loss to patient characteristics or to weight loss outcomes. The current study examined these relations. Methods The sample consisted of 588 patients in a 15-week fee-for-service weight loss programme. Prior to the intervention, patients completed questionnaires including items on reasons for weight loss, demographic characteristics, and a variety of weight-based characteristics. Patients' weight change outcomes were expressed as percent weight loss and also categorized into one of three previously described weight loss trajectories. Results The results of chi-squared and t-test analyses suggested that endorsement of health concerns, mobility concerns, or another person's recommendation was associated with higher body mass index (BMI) and older age. These reasons were more likely to be endorsed by White patients than Black patients and by male patients than female patients. Endorsement of doctor recommendation was more likely to be seen among Black patients than White patients. There was no significant relation of any weight loss reason with weight loss outcome. Conclusions While certain reasons for weight loss were more often cited by certain patient groups, no specific reason predicted a better or worse outcome.

Background: Despite advances in behavioral and pharmacotherapy interventions, substance use disorders (SUDs) are frequently refractory to treatment. Glutamatergic dysregulation has received increasing attention as one common neuropathology across multiple substances of abuse. Ketamine is a potent N-methyl-D-aspartate (NMDA) glutamatergic receptor antagonist which has been found to be effective in the treatment of severe depression. Here we review the literature on the efficacy of ketamine in the treatment of SUDs. Methods: A systematic review of the PubMed, Scopus, and ClinicalTrials.gov databases was undertaken to identify completed and ongoing human studies of the effectiveness of ketamine in the treatment of SUDs between January 1997 and January 2018. Results and conclusion: Seven completed studies were identified. Two studies focused on alcohol use disorder, two focused on cocaine use disorder, and three focused on opioid use disorder. Both cocaine studies found improvements in craving, motivation, and decreased cocaine use rates, although studies were limited by small sample sizes, a homogeneous population and short follow-up. Studies of alcohol and opioid use disorders found improvement in abstinence rates in the ketamine group, with significant between-group effects noted for up to two years following a single infusion, although these were not placebo-controlled trials. These results suggest that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment. We conclude with an overview of the six ongoing studies of ketamine in the treatment of alcohol, cocaine, cannabis, and opioid use disorders and discuss future directions in this emerging area of research.