A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder.

Alcohol use disorder (AUD) is a significant contributor to morbidity and mortality in the United States. It contributes to over 140,000 annual deaths, to over 200 related diseases and health conditions globally, and accounts for 5.1% of the global disease burden. Despite its substantial impact, AUD remains undertreated, marked by a scarcity of approved medications. This paper explores the current treatment landscape and novel strategies for both alcohol withdrawal syndrome and AUD. Promising results, including the use of psychedelics alongside psychotherapy, noninvasive neural-circuit-based interventions, phosphodiesterase-4 inhibitors, and GLP-1 receptor agonists, have emerged from recent studies. While these advancements show potential, further research is crucial for a comprehensive understanding of their effectiveness. The clear shortage of approved medications and other treatment modalities underscores the pressing need for ongoing research.

Analysis of nonfatal suicide attempts and demographic characteristics of US military veterans with opioid use disorder: A descriptive VA medical center study.

BACKGROUND AND OBJECTIVES: Suicide and opioid use disorder (OUD) frequently co-occur, and veterans are at a high risk for both conditions. This study aims to determine the characteristics of a cohort of veterans with co-occurring OUD and suicide attempts. METHOD: Three hundred fifty-three (n = 353) veterans registered at a VA medical center with OUD and at least one suicide attempt between January 2010 and December 2021 were analyzed. RESULTS: 9.4% of OUD veterans had lifetime suicide attempts, with 7.1% attempting postdiagnosis. High rates of unemployment (88.1%) and housing instability (73.1%) were observed, along with a 98% prevalence of comorbid psychiatric conditions. DISCUSSION AND CONCLUSIONS: Gaining a deeper understanding of this patient population can help improve strategies for preventing suicide and treating OUD more effectively. SCIENTIFIC SIGNIFIANCE: This study is unique in the current literature for investigating and comparing nonfatal lifetime suicide attempt rates in veterans before and after an OUD diagnosis.

US Medicaid program: An analysis of the spending and utilization patterns for antidepressants from 2017 to 2021.

Background: Major depressive disorder (MDD) is a serious mental health condition that contributes to health complications, financial burden and death. In 2020, about one in five US adults had a lifetime diagnosis of MDD. With Major Depressive Disorder (MDD) being a common mental health concern, it is important to understand treatment patterns within public health systems like Medicaid, as they play a crucial role in providing care to diverse populations. Objective: The study investigated antidepressant usage and market distribution in the Medicaid Program. By doing so, the study aimed to provide insights into how these trends reflect broader changes in mental health treatment practices and policy implications within the Medicaid system during the study period. Methods: Public Medicaid data from 2017 to 2021 were analyzed, focusing on 30 FDA-approved antidepressants. Spending and prescription data were aggregated using Excel and Python. Results: The total US Medicaid expenditure on antidepressants increased from about $1 billion dollars in 2017 to $1.12 billion dollars in 2021, an increase of about 10%. Consistently, SSRIs were the class of antidepressants that Medicaid spent the most on. The highest Medicaid spending on a single antidepressant in 2017 and 2018 was bupropion. During the remaining years of the study (2019, 2020, 2021) Medicaid appropriated most funds toward Vortioxetine. The total number of antidepressant prescriptions increased from 52 million scripts to 59 million scripts (an increase of about 14%). Conclusions: The increase in Medicaid spending on antidepressants during the study period can be explained by an increase in utilization (a 14% increase in antidepressant prescriptions from 2017 to 2021), and a shift toward prescribing newer more costly antidepressants (like SSRIs and others) and away from prescribing older, less costly antidepressants like monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs)."

Sleep-wake disorders in veterans with opioid use disorder: Prevalence and comorbidities.

OBJECTIVE: To determine the prevalence of sleep-wake disorders among veterans with opioid use disorder (OUD) and the demographic characteristics, medical comorbidities, and outpatient medications in this group. METHODS: US veterans seeking care in the VA Connecticut Healthcare System between January 1, 2000, and December 31, 2021 with a diagnosis of OUD (N = 5937) were analyzed retrospectively for sleep-wake disorders (N = 1447). That group was analyzed for demographic characteristics, comorbidities, and medications. RESULTS: Of those with OUD, 24.4% had a diagnosis of any sleep-wake disorder. The most common was obstructive sleep apnea (73.7%). Major depressive disorder (68.6%) and hypertension (67.1%) were the most common comorbid conditions. Commonly prescribed medications included antidepressants (91%) and benzodiazepines (62%). CONCLUSIONS: Veterans with OUD frequently suffer from sleep-wake disorders. Comorbid medical and psychiatric conditions and the detrimental effects of specific medication classes should be considered in this patient population to create more effective prevention and treatment strategies.

Longitudinal Outcomes of the top 20 Utilizers of VA Connecticut's Psychiatric Emergency Services Between 2010 and 2020.

Frequent utilizers of emergency services represent a clinically important cohort with potentially unmet health care needs despite demanding a high volume of costly services. However, not much is known about their longitudinal course. This study identified the top 20 utilizers of VA Connecticut's psychiatric emergency services and conducted a chart review of their longitudinal outcomes during an 11-year period between 2010 and 2020, including their visit diagnoses, medical and psychiatric comorbidities, and types and frequency of other medical services and supports received. At the index visit, 19 of the 20 patients had substance use disorder and 14 patients had at least one non-substance psychiatric diagnosis. Despite all patients receiving primary care and other services, such as residential treatments, outpatient therapy, and social work consults, 11 of the 12 patients remaining alive and residing in the state continued to utilize psychiatric emergency services in 2020, revealing a pattern of persistent use.

Opioid use disorder: current trends and potential treatments.

Opioid use disorder (OUD) is a major public health threat, contributing to morbidity and mortality from addiction, overdose, and related medical conditions. Despite our increasing knowledge about the pathophysiology and existing medical treatments of OUD, it has remained a relapsing and remitting disorder for decades, with rising deaths from overdoses, rather than declining. The COVID-19 pandemic has accelerated the increase in overall substance use and interrupted access to treatment. If increased naloxone access, more buprenorphine prescribers, greater access to treatment, enhanced reimbursement, less stigma and various harm reduction strategies were effective for OUD, overdose deaths would not be at an all-time high. Different prevention and treatment approaches are needed to reverse the concerning trend in OUD. This article will review the recent trends and limitations on existing medications for OUD and briefly review novel approaches to treatment that have the potential to be more durable and effective than existing medications. The focus will be on promising interventional treatments, psychedelics, neuroimmune, neutraceutical, and electromagnetic therapies. At different phases of investigation and FDA approval, these novel approaches have the potential to not just reduce overdoses and deaths, but attenuate OUD, as well as address existing comorbid disorders.

A Review of Immunotherapeutic Approaches for Substance Use Disorders: Current Status and Future Prospects.

Substance use disorders (SUDs) have been a major public health challenge for decades and continue to cause significant morbidity and mortality worldwide. Due to limitations in pharmacologic treatment options, there remains a significant need for the development of novel immunotherapeutic approaches. In this review, we discuss the therapeutic potential of vaccines for SUDs. Although early preclinical animal studies were optimistic and successful, few vaccines have reached human clinical trials. Only nicotine and cocaine vaccines have successfully advanced to Phase 3 clinical trials and neither are currently available as a treatment option. Various innovative approaches in vaccine design have been made to overcome limitations and improve immunogenicity, including the use of nanoparticles, synthetic haptens, and more immunogenic adjuvants. While success has thus far been elusive, with substantial scientific advancements in vaccine technology, immunotherapy remains a promising and viable option for the treatment of SUDs.

Moral Injury in the Context of Substance Use Disorders: a Narrative Review.

The rate of annual drug overdose deaths in the USA recently topped 100,000 (CDC/National Center for Health Statistics 2021), an illustration of the critical need to prevent and treat substance use disorders (SUDs). As a complex, chronic medical condition, substance use treatment requires psychological, emotional, and spiritual interventions along with medical care. The recently developed concept of moral injury has been increasingly studied and applied to military service members who experience conflict between the expectations or survival needs of combat and their moral values. This review explores whether moral injury, along with the related emotional, psychological, and spiritual symptoms, can also develop in the context of SUDs. This review identified 5 manuscripts related to moral injury arising in a substance use context. These studies were small in sample size and qualitative in nature but did indicate the presence of moral injury within the context of substance use. Further studies are needed to better understand and treat moral injury related to SUDs. A conceptualization of how moral injury may arise in the context of substance use is presented here. It is suggested that the activation of the primitive dopaminergic reward system causes a potential conflict between the experienced need for the addictive substance and a person's moral code or values. The moral injury resulting from this collision may impact treatment and recovery.

COVID-19 Vaccine Administration and Hesitation Among Psychiatric Emergency Services Patients.

Psychiatric Emergency Services (PES) at Connecticut Department of Veterans Affairs (VACT) began offering the COVID-19 vaccine to eligible veterans in February 2021. From February 10 to March 17, 2021 there were 110 encounters where a veteran was offered the vaccine (96 unique veterans). Of those 96 veterans, 39 (40.6%) were interested in receiving the vaccine. Of those, 23 (60.0%) veterans received the first dose of the Pfizer-BioNTech vaccine and among those, 21 (91.3%) eventually received the second dose. Sixteen veterans were interested but unable to receive the vaccine due to PES-related obstacles. Common themes regarding vaccine hesitancy among this population include vaccine mistrust and concerns about side effects. Offering the vaccine to PES patients allowed VACT to reach a vulnerable subset of veterans who may be at higher risk of contracting the virus and experience worse disease outcomes.

Learning About and Destigmatizing Substance Use Disorders: a Video-Based Educational Module Using Simulated Patients.

OBJECTIVE: The authors developed and tested video clips depicting three paradigmatic substance use disorder (SUD) clinical scenarios, each portrayed by a different simulated patient interacting with the same clinician. METHODS: The authors embedded 21 short video clips (with a cumulative duration of 27 min) into a 2-h session on SUDs. The didactic was delivered online through synchronous videoconferencing with Zoom. The primary outcome compared learners' scores on the Attitudes and Confidence in the Treatment of Patients with Substance Use Disorders (ACT-SUDS) before and after participating in the didactic. RESULTS: Fifty-eight second-year medical students participated and completed the survey prior to the didactic; 42 (72%) of them completed the survey immediately after. Compared to baseline, ACT-SUDS increased after the didactic: from 3.7 ± 0.5 to 4.0 ± 0.4 (mean difference = 0.4 [95% confidence interval = 0.2-0.5], paired-t = 5.75, p < 0.001), as did each of its four subscales: confidence, enjoyment, SUD as a medical disorder, and attitudes toward Alcoholics Anonymous (AA; t ≥ 3.0, p ≤ 0.005). CONCLUSIONS: The video-based educational module proved easy to implement in the virtual classroom and led to measurable changes in perceptions and attitudes toward SUDs. The module is available to view or freely download and is amenable for adaptation by end-use instructors.

Looking beyond the opioid receptor: A desperate need for new treatments for opioid use disorder.

The mainstay of treatment for opioid use disorder (OUD) is opioid agonist therapy (OAT), which modulates opioid receptors to reduce substance craving and use. OAT maintains dependence on opioids but helps reduce overdose and negative sequelae of substance abuse. Despite increasing availability of OAT, its effectiveness is limited by difficulty in initiating and maintaining patients on treatment. With the worsening opioid epidemic in the United States and rising overdose deaths, a more durable and effective treatment for OUD is necessary. This paper reviews novel treatments being investigated for OUD, including neuromodulatory interventions, psychedelic drugs, and other novel approaches. Neuromodulatory interventions can stimulate the addiction neural circuitry involving the dorsolateral prefrontal cortex and deeper mesolimbic structures to curb craving and reduce use, and multiple clinical trials for interventional treatment for OUD are currently conducted. Similarly, psychedelic agents are being investigated for efficacy in OUD specifically. There is a resurgence of interest in psychedelic agents' therapeutic potential, with evidence of improving mood symptoms and decreased substance use even after just one dose. Exact mechanism of their anti-addictive effect is not fully elucidated, but psychedelic agents do not maintain opioid dependence and some may even be helpful in abating symptoms of withdrawal. Other potential approaches for OUD include targeting different parts of the dopamine-dependent addiction pathway, identifying susceptible genes and modulating gene products, as well as utilizing vaccines as immunotherapy to blunt the addictive effects of substances. Much more clinical data are needed to support efficacy and safety of these therapies in OUD, but these proposed novel treatments look beyond the opioid receptor to offer hope for a more durably effective OUD treatment.

Patient Volume and Dispositions in a VA Psychiatric Emergency Room During COVID-19.

The COVID-19 pandemic led to a decline in emergency department visits in the United States. Less is known about how COVID-19 has impacted psychiatric emergency services (PES). This report compares visits to the Connecticut Department of Veterans Affairs psychiatric emergency room from March-August 2020 to the same period from three prior years (2017, 2018, 2019) to evaluate the impact of COVID-19 on patient volume and dispositions. Compared to prior years, there was a decline in visits in March-August 2020, particularly in April. This coincided with the peak of COVID-19 in the state. Rates of hospitalizations remained consistent, while rates of referrals to residential programs decreased. The decline in visits likely indicates that many veterans postponed necessary mental health and substance use treatment. This delay could have significant clinical ramifications for veterans and may lead to an eventual surge in demand for emergency mental health care.

Brief Report: Rates of Fentanyl Use Among Psychiatric Emergency Room Patients.

BACKGROUND AND OBJECTIVES: Opioid overdose-related deaths increased from approximately 18 000 deaths in 2007 to 46 802 deaths in 2018. Fentanyl is primarily responsible for the increase in opioid overdose deaths from 2011 through 2017. The primary aim of this study is to determine the rates of fentanyl in the urine drug screens of all patients who presented to the psychiatric emergency room at VA Connecticut, over 7 months in 2018. METHODS: Data were collected for all patient presentations between June 2018 and December 2018. There were 746 total patient presentations, with 497 being unique. Collected data included basic demographic information, psychiatric diagnosis, and urine drug screen for various illicit substances, including fentanyl. RESULTS: Over 15% of patients screened positive for fentanyl. Patients who tested positive for fentanyl were further classified based on positive urine drug screening results for other opioids, cocaine, or both. Twenty percent of patients who screened positive for fentanyl and cocaine tested negative for other opioids. This category suggests that some veterans might be consuming fentanyl with cocaine. DISCUSSION AND CONCLUSIONS: Fentanyl was found at a high rate, even in the absence of other opioids, which suggests that some veterans might be consuming fentanyl with cocaine. Consequently, harm reduction strategies should be broadened to include all patients at risk of fentanyl overdose, including patients who use substances (eg, cocaine) that are potentially adulterated with fentanyl. SCIENTIFIC SIGNIFICANCE: This study is the first one of its kind that looked at rates of fentanyl use in all presentations to a psychiatric emergency room. While it is well-known that fentanyl is highly prevalent, these findings extend the current state of knowledge by replication in a psychiatric emergency population. (Am J Addict 2021;30:92-95).

Brief Training on Medication-Assisted Treatment Improves Community Mental Health Clinicians' Confidence and Readiness to Address Substance Use Disorders.

Despite the availability and effectiveness of medication-assisted treatment (MAT) for substance use disorders (SUDs), utilization of these medications remains suboptimal, especially in public sector settings. A key limitation is clinicians' reluctance to include MAT in their routine practice due, in part, to low confidence about managing SUDs and limited awareness of the disease model of addiction. This study evaluates the impact of a 1-day MAT training for community mental health clinicians using a 30-item pre- and post-training questionnaire. Of the 109 clinicians who attended the training, 107 completed the pre- and post-training questionnaires. Factor analysis of the questionnaire identified two domains: readiness to address SUDs among patients (factor 1) and understanding SUDs as diseases (factor 2). Post training, there was a significant change in both factor 1 (p = .00001) and factor 2 (p = .00003), indicating that a brief MAT training can increase clinicians' confidence and readiness to address SUDs and improve their understanding of the disease model of addiction.

Buprenorphine initiation to treat opioid use disorder in emergency rooms.

Emergency rooms across the United States regularly treat patients with opioid use disorder and patients experiencing opioid overdose. Four to six million people in the US are estimated to have opioid use disorder. Over half of overdose related deaths in 2016 resulted from the use of opioids. The majority of deaths involved the use of fentanyl. There is an opioid epidemic plaguing the nation and with emergency rooms at the forefront of the proverbial battlefield; they can potentially play a key role in addressing the problem. Currently, there are three FDA approved, evidence-based medications for the treatment of opioid use disorder. These are buprenorphine, methadone and extendedrelease naltrexone. Buprenorphine induction in emergency room settings has shown great promise. Research suggests that it is an effective, safe and cost-effective treatment to initiate in emergency rooms. In order to successfully treat opioid use disorder and overdose in emergency rooms, they must have waivered providers and they must be equipped with the necessary resources. The VA Connecticut has been able to overcome some of the challenges to initiating buprenorphine in the emergency room setting and has established a feasible model for treating opioid overdose and managing opioid use disorder.