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.

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.

Trajectories of alcohol consumption in U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

BACKGROUND AND OBJECTIVES: While alcohol use disorder is prevalent in U.S. veterans, little is known about the nature and determinants of predominant trajectories of alcohol consumption in this population. The objective of the current study was to identify predominant trajectories of alcohol consumption over a 4-year period, and baseline determinants of these trajectories in veterans. METHODS: Data were analyzed from the National Health and Resilience in Veteran Study, which surveyed a nationally representative sample of 3,157 veterans (Wave 1). Assessments (Waves 2 and 3) were conducted every 2 years thereafter. Alcohol consumption was assessed using the Alcohol Use Disorders Identification Test-Consumption, a brief alcohol screen for identifying problematic drinking based on alcohol consumption. Wave 1 sociodemographic, military, health, and psychosocial variables were examined as possible determinants of trajectories of alcohol consumption. RESULTS: Latent growth mixture modeling revealed that a four-class model best fit the data: rare drinkers (65.3%), moderate drinkers (30.2%), excessive drinkers (2.6%), and recovering drinkers (1.9%). Lifetime major depressive disorder (MDD) was linked to an excessive drinking trajectory, while fewer medical conditions and lower social support were linked to a moderate drinking trajectory. Having a secure attachment style and greater social support, and absence of lifetime MDD was linked to recovery from excessive drinking. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Four predominant trajectories of alcohol consumption were identified. Targeting MDD and related interpersonal factors such as attachment style and social support in population-based prevention and treatment initiatives may help prevent, mitigate, and promote recovery from excessive alcohol consumption in veterans. (Am J Addict 2018;XX:1-8).

The burden of alcohol use disorders in US military veterans: results from the National Health and Resilience in Veterans Study.

AIMS: To analyze data from a large, contemporary, nationally representative sample of US veterans to evaluate: (1) the prevalence of life-time alcohol use disorder (AUD) and past-year AUD; (2) common psychiatric comorbidities associated with life-time AUD; and (3) correlates of life-time and past-year probable AUD. DESIGN: Data were analyzed from the National Health and Resilience in Veterans Study (NHRVS), a web-based survey of a random probability sample of a contemporary, nationally representative sample of US military veterans. SETTING: United States. PARTICIPANTS: Nationally representative sample of 3157 US veterans aged 21 years and older. MEASUREMENTS: Life-time alcohol abuse and dependence were assessed according to DSM-IV diagnostic criteria using the Mini International Neuropsychiatric Interview, and combined into a single variable: AUD. Past-year probable AUD was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Correlates of AUD, including psychiatric comorbidities, suicidality and demographic characteristics, were also assessed. FINDINGS: The prevalence of life-time AUD and past-year probable AUD was 42.2% [95% confidence interval (CI) = 40.5-43.9%)] and 14.8% (95% CI = 13.6-16.0%), respectively. Compared with veterans without AUD, those with life-time AUD had substantially elevated rates of life-time and current mood and anxiety disorders [odds ratios (ORs) = 2.6-4.1], drug use disorder (OR = 10.7), life-time suicide attempt (OR = 4.1) and current suicidal ideation (OR = 2.1). Younger age, male sex, lower education, lower annual household income and greater number of life-time traumatic events were associated independently with life-time AUD. Younger age, male sex, unpartnered marital status and a life-time diagnosis of major depressive disorder were associated independently with past-year probable AUD. CONCLUSIONS: More than 40% of US military veterans have a life-time history of alcohol use disorder. Veterans with a life-time history of alcohol use disorder have substantial comorbid psychiatric burden, including elevated rates of suicidal ideation and attempts. Certain socio-demographic (e.g. younger age, male sex, lower education) and clinical (e.g. trauma burden, history of depression) characteristics are associated with increased risk of AUD.

A prospective study of the associations among housing status and costs of services in a homeless population.

OBJECTIVE: The complex needs of homeless populations result in use of a wide range of services and high costs for housing programs and psychiatric and general medical care. Allocation of resources often is not congruent with assessed needs. A series of cost-congruence hypotheses was developed to test assumptions that needs are associated with resources provided for appropriate services in homeless populations. METHODS: Individuals (N=255) who were homeless were followed for two years and were categorized by housing status over time (consistently housed, housed late, lost housing, or consistently homeless). Detailed information about the individuals was obtained at baseline, and follow-up data were collected one and two years later. Extensive data about the costs of services provided by type (medical, psychiatric, substance abuse, and homeless maintenance and amelioration) were derived from 23 agencies, and service use information was collected from the agencies and by self-report. Multiple regression models were used to test the hypotheses. RESULTS: Medical, psychiatric, and homeless maintenance costs varied by housing status. Serious mental illness predicted costs for psychiatric services, as expected, but also costs for substance abuse services and acute behavioral health care and total costs. Alcohol use disorders predicted substance abuse service costs. CONCLUSIONS: This study followed a homeless cohort prospectively and provided estimates of costs of service use derived from a large number of agencies. This research increases the understanding of patterns of service use in a homeless population and informs the provision of services appropriate to the complex needs of this difficult-to-serve population.

Deriving costs of service use among an urban homeless population.

The purpose of this study was to describe a novel approach to calculating service use costs across multiple domains of service for homeless populations. A randomly-selected sample of homeless persons was interviewed in St. Louis, MO and followed for 2 years. Service- and cost-related data were collected from homeless individuals and from the agencies serving them. Detailed interviews of study participants and of agency personnel in specific domains of service (medical, psychiatric, substance abuse, homeless maintenance, and homeless amelioration services) were conducted using a standardized approach. Service utilization data were obtained from agency records. Standardized service-related costs were derived and aggregated across multiple domains from agency-reported data. Housing status was not found to be significantly associated with costs. Although labor intensive, this approach to cost estimation allows costs to be accurately compared across domains. These methods could potentially be applied to other populations.

Availability and attitudes toward correctional psychiatry training: results of a national survey of training directors.

An online survey was developed and administered to estimate how often psychiatry residents train at correctional facilities and to explore the residency directors' attitudes towards this training. The survey contained two factual and eight opinion questions assessing their experiences with and attitudes toward resident training in correctional facilities, and allowed for free responses. Ninety-five people participated out of 492 for a response rate of 20%. Thirty percent of responders make a correctional rotation mandatory and another 25% offer it as an elective. Approximately one-third (36%) of responders have worked at a correctional facility themselves. Opinions towards correctional psychiatry were mostly positive with the exception of various logistical difficulties being mentioned in free responses. These provisional findings should generate interest in this area as providing more resident rotations at correctional facilities may increase access to care of this patient population and provide residents valuable training opportunities.

Can we address the shortage of psychiatrists in the correctional setting with exposure during residency training?

Psychiatry residents at the University of Texas Southwestern Medical Center were surveyed to investigate their attitudes towards inmates, towards various aspects of correctional psychiatry and whether rotating at the local jail is associated with these attitudes. The overall opinion towards correctional psychiatry was fairly neutral though significantly more negative than towards inpatient psychiatry. While citing a high need for psychiatrists at correctional facilities, residents reported they are not likely to work there when they complete residency. No statistical differences were found between those residents who had rotated at the local jail and those who had not. Given the severe shortage of mental health providers in correctional facilities it is important to expose residents to this and understand ways to promote correctional psychiatry as a career.

Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets.

Ketogenic diets (KDs) are used for treatment of refractory epilepsy and metabolic disorders. The classic saturated fatty acid-enriched (SAT) KD has a fat:carbohydrate plus protein ratio of 4:1, in which the predominant fats are saturated. We hypothesized that a polyunsaturated fat-enriched (POLY) KD would induce a similar degree of ketosis with less detrimental effects on carbohydrate and lipid metabolism. Twenty healthy adults were randomized to two different weight-maintaining KDs for 5 d. Diets were 70% fat, 15% carbohydrate, and 15% protein. The fat contents were 60 or 15% saturated, 15 or 60% polyunsaturated, and 25% monounsaturated for SAT and POLY, respectively. Changes in serum beta-hydroxybutyrate, insulin sensitivity (S(I)), and lipid profiles were measured. Mean circulating beta-hydroxybutyrate levels increased 8.4 mg/dl in the POLY group (P = 0.0004), compared with 3.1 mg/dl in the SAT group (P = 0.07). S(I) increased significantly in the POLY group (P = 0.02), whereas total and low-density lipoprotein cholesterol increased significantly in the SAT group (both P = 0.002). These data demonstrate that a short-term POLY KD induces a greater level of ketosis and improves S(I), without adversely affecting total and low-density lipoprotein cholesterol, compared with a traditional SAT KD. Thus, a POLY KD may be superior to a classical SAT KD for chronic administration.