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.

Evaluation and Management of Alcohol use Disorder among Older Adults.

PURPOSE OF REVIEW: The prevalence of alcohol use disorder (AUD) among older adults in the United States is rising, but remains underdiagnosed, underreported, and inadequately managed. This review highlights the medical, social, and cultural factors of AUD in older adults and provides guidelines for its screening, evaluation, and management. RECENT FINDINGS: The COVID-19 pandemic has created additional challenges and barriers to care, as older adults may have disproportionate worsening of anxiety, depression, and substance use resulting from increased isolation related to physical distancing and shelter-in-place guidelines. SUMMARY: All older adults should be routinely screened for AUD with standardized screening tools. If a patient's screening results are positive, a clinician should conduct a brief assessment, which may be supplemented by laboratory tests. Most older adults at risk for alcohol misuse do not need specialized SUD treatment, but most can benefit from Screening, Brief Intervention, and Referral to Treatment (SBIRT) to prevent substance misuse before it occurs. Medications for the treatment of AUD in older adults include naltrexone, acamprosate, disulfiram, gabapentin and topiramate. Psychosocial treatments, including mutual help groups, are equally important.

Awareness of Suicide Prevention Programs Among U.S. Military Veterans.

To assess U.S. veterans' awareness and participation in suicide prevention programs offered by the Department of Veterans Affairs (VA). A nationally representative sample of 1002 veterans was surveyed online in 2018. The majority of veterans reported knowing about Vet Centers (72%), the Veterans Crisis Line (65%), and the VA Center for Suicide Prevention (54%). However, only 5% had attended a community event related to veteran suicide and 2% had used VA's Virtual Hope Box. Veterans aware of the Veterans Crisis Line had more medical conditions and were more likely to report VA as their primary healthcare provider. Veterans aware of VA's Center for Suicide Prevention were younger, male, had more medical conditions, and more likely to screen positive for posttraumatic stress disorder, generalized anxiety disorder, and past homelessness. History of suicidal ideation or attempt was not associated with awareness of suicide prevention programs. VA's suicide prevention programs reach a broad segment of the veteran population, including those with and without histories of suicidality. More targeted outreach may be needed for veterans most at-risk for suicide who are unaware of available resources.

Substance Use Disorders in Later Life: A Review and Synthesis of the Literature of an Emerging Public Health Concern.

Substance use disorders (SUDs) among older persons are among the fastest growing health problems in the United States. The number of older persons is projected to exceed 72.1 million persons by 2030, following a trend of general population growth in the mid-1940s to 1960s. The generation, known as "baby boomers," who refashioned drug use during their 20-30s, are increasingly continuing drug habits into later life. This review aims to assess the epidemiology, impact, and treatment of geriatric SUDs. Academic databases including PubMed, PsychInfo, Ovid, and Medline, were queried up to December 2018 for terms of "geriatric," "older," "elderly," "substance abuse," "drug," "drug use," "drug abuse," "drug dependency," "illicit drugs," and "geriatric psychiatry." Articles identified included 17 government documents, 29 studies based upon government documents, 43 studies not related to US government surveys, 19 review articles, 9 commentary pieces, 4 newspaper articles, 2 textbooks, and 1 published abstract. Evaluated studies and documents together suggest that older individuals are using illicit drugs and meeting criteria for SUDs at higher rates than previous geriatric cohorts resulting in substantial negative impacts on medical and psychiatric conditions. These findings represent a novel trend since previous cohorts of older individuals were thought to rarely use illicit substances. Current treatment models are inadequate to address the new wave of older individuals with SUDs. The fields of geriatrics, addiction, and geriatric psychiatry must work together to establish comprehensive care models and treatment modalities for addressing this emerging public health concern.

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).

Addressing Veteran Homelessness to Prevent Veteran Suicides.

The U.S. Department of Veterans Affairs (VA) is shifting its focus from ending veteran homelessness to preventing veteran suicides. With supporting data, this Open Forum argues that VA homelessness services also help address veteran suicides. Analysis of a nationally representative survey of U.S. veterans in 2015 shows that veterans with a history of homelessness attempted suicide in the previous two years at a rate >5.0 times higher compared with veterans without a history of homelessness (6.9% versus 1.2%), and their rates of two-week suicidal ideation were 2.5 times higher (19.8% versus 7.4%). Because the majority of veterans who die by suicide are not engaged in VA care, VA services for the homeless that include outreach efforts to engage new veterans may be reaching some of these veterans. Thus continued federal support for VA homelessness services not only may help address homelessness but also may help prevent suicide of veterans.

Alcohol Withdrawal and Lithium Toxicity: A Novel Psychiatric Mannequin-Based Simulation Case for Medical Students.

Introduction: High-fidelity mannequin-based simulation is frequently used to compliment medical student education during clinical clerkships. However, psychiatric educators have not broadly adopted this modality, focusing rather on standardized patient actors. We developed and delivered a simulation case involving a patient with alcohol withdrawal and lithium toxicity followed by a debriefing session to medical students at the end of their psychiatric clerkship. Methods: The case involves a 40-year-old male truck driver with a history of bipolar disorder who presents to the emergency room after a truck accident. The patient is in alcohol withdrawal, which responds to benzodiazepines. A workup reveals that the patient also has lithium toxicity related to the co-ingestion of lithium and naproxen for pain. Participants learn to evaluate and treat alcohol withdrawal, consider medical comorbidities and legal consequences, and complete a brief intervention for substance use. This case requires a simulation mannequin. Results: To date, 150 second-, third-, and fourth-year medical students have participated in this case and 76 have been surveyed. Participants have provided a postsession rating of 4.49 on a 5-point Likert scale (1 = strongly disagree and 5 = strongly agree) on a question about enjoyment, and 3.93 on a question about confidence with evaluation and treatment of patients in alcohol withdrawal. Discussion: Psychiatric education currently underutilizes mannequin-based simulation compared to other medical disciplines. Mannequin simulation is feasible and effective in psychiatric education, especially in cases involving medical complexity, as shown in this novel case involving a patient with alcohol withdrawal and lithium toxicity.

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.

Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence.

The wars in Iraq and Afghanistan are associated with high rates of post-traumatic stress disorder (PTSD) and comorbid alcohol use disorders. The pharmacotherapy of these comorbid conditions has received relatively little study. The current study compared the serotonin uptake inhibitor, paroxetine, to the norepinephrine uptake inhibitor, desipramine. It also evaluated the adjunctive efficacy of the Food and Drug Administration (FDA)-approved alcoholism pharmacotherapy, naltrexone, relative to placebo. Four groups of predominately male veterans (n=88) meeting current diagnostic criteria for both alcohol dependence (AD) and PTSD were randomly assigned under double-blind conditions to one of four groups: paroxetine+naltrexone; paroxetine+placebo; desipramine+naltrexone; desipramine+placebo. Main outcome measures included standardized scales that assessed symptoms of PTSD and alcohol consumption. Paroxetine did not show statistical superiority to desipramine for the treatment of PTSD symptoms. However, desipramine was superior to paroxetine with respect to study retention and alcohol use outcomes. Naltrexone reduced alcohol craving relative to placebo, but it conferred no advantage on drinking use outcomes. Although the serotonin uptake inhibitors are the only FDA-approved medications for the treatment of PTSD, the current study suggests that norepinephrine uptake inhibitors may present clinical advantages when treating male veterans with PTSD and AD. However, naltrexone did not show evidence of efficacy in this population. This study was registered with ClinicalTrials.gov, registration number NCT00338962 and URL: http://clinicaltrials.gov/ct2/show/NCT00338962?term=desipramine+AND+alcohol+dependence+AND+depression&recr=Closed&rank=1.

Characterization of the interactive effects of glycine and D-cycloserine in men: further evidence for enhanced NMDA receptor function associated with human alcohol dependence.

Reduced responses to N-methyl-D-aspartate (NMDA) glutamate receptor antagonists in alcohol-dependent animals and humans provided evidence that chronic alcohol consumption increased NMDA receptor function. To further probe alterations in NMDA glutamate receptor function associated with human alcohol dependence, this study examined the interactive effects of agents acting at the glycine(B) coagonist site of the NMDA receptor. In doing so, it tested the hypothesis that raising brain glycine concentrations would accentuate the antagonist-like effects of the glycine(B) partial agonist, D-cycloserine (DCS). Twenty-two alcohol-dependent men and 22 healthy individuals completed 4 test days, during which glycine 0.3 g/kg or saline were administered intravenously and DCS 1000 mg or placebo were administered orally. The study was conducted under double-blind conditions with randomized test day assignment. In this study, DCS produced alcohol-like effects in healthy subjects that were deemed similar to a single standard alcohol drink. The alcohol-like effects of DCS were blunted in alcohol-dependent patients, providing additional evidence of increased NMDA receptor function in this group. Although glycine administration reduced DCS plasma levels, glycine accentuated DCS effects previously associated with the NMDA receptor antagonists, ketamine and ethanol. Thus, this study provided evidence that raising glycine levels accentuated the NMDA receptor antagonist-like effects of DCS and that alcohol-dependent patients showed tolerance to these DCS effects.

Absence of significant interactive effects of high-dose D-cycloserine and ethanol in healthy human subjects: preliminary insights into ethanol actions at the glycine B site of NMDA glutamate receptors.

BACKGROUND: Ethanol reduces N-methyl-d-aspartate (NMDA) glutamate receptor function via multiple cellular targets. It is not yet clear whether direct ethanol antagonism of the glycine(B) co-agonist site of NMDA receptors is relevant to this effect. The purpose of this study was to evaluate whether ethanol effects at the glycine(B) co-agonist site was clinically relevant by evaluating some aspects of the psychopharmacologic interactions between the glycine(B) partial agonist, D-cycloserine (DCS), and ethanol in healthy human subjects. METHODS: All subjects completed 4 test days under double-blind conditions in which DCS or placebo was administered orally prior to ethanol or an ethanol-tainted placebo drink. Two groups of healthy subjects were studied. A first group of subjects (n = 25) were pretreated orally with DCS 500 mg or placebo 4 hours prior to ethanol (0.8 g/kg, p.o. or placebo) administration. A second group of subjects (n = 20) were pretreated with DCS 1000 mg or placebo prior to ethanol administration. Outcomes included subjective and cognitive responses to the experimental interventions. RESULTS: Predictable ethanol responses were observed in both groups of subjects, although the response to ethanol and the breath alcohol levels, but not plasma alcohol levels, were slightly but significantly lower in the group that received the higher DCS dose. DCS produced mild sedative effects that were greater for the lower than the higher dose. It also produced a mild impairment of verbal fluency without impairing attention. No statistically significant interactions between ethanol and DCS emerged in analyses. However, the combination of ethanol and DCS produced significantly greater impairment than both ethanol or DCS administered alone on a test of verbal fluency and aspects of memory function. IMPLICATIONS: DCS and ethanol both produced sedative and cognitive effects, consistent with their ability to reduce NMDA receptor function. However, the absence of interactive effects observed in this study raises questions about the clinical significance of the glycine(B) site as a target for ethanol in the brain at levels of ethanol intoxication associated with social drinking. However, it should be noted that this conclusion is limited to the dependent measures evaluated and the doses of ethanol and DCS studied.

Altered NMDA glutamate receptor antagonist response in individuals with a family vulnerability to alcoholism.

OBJECTIVE: A family history of alcoholism is a risk factor for the development of ethanol dependence. Ethanol is an antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, and alterations in NMDA receptor function are thought to be involved in ethanol abuse and dependence. The purpose of this study was to determine in healthy individuals with no ethanol dependence whether response to the NMDA receptor antagonist ketamine would differentiate those with a family history of ethanol dependence from those without such a family history. METHOD: Healthy subjects between the ages of 21 and 30 received 40-minute intravenous infusions of saline, low-dose ketamine (0.1 mg/kg), and high-dose ketamine (0.5 mg/kg) on three separate test days in a randomized order under double-blind conditions. The healthy individuals with at least one first-degree relative and another first- or second-degree relative with ethanol dependence (N=16) were compared with those who had no family history of ethanol dependence in any first- or second-degree relative (N=29). Outcome measures included the Brief Psychiatric Rating Scale, Clinician-Administered Dissociative States Scale, verbal fluency, Hopkins Verbal Learning Test, a biphasic alcohol effects scale, visual analog scales of mood states, and ketamine levels. RESULTS: During ketamine infusion, individuals with a family history of ethanol dependence showed an attenuated response in terms of perceptual alterations and dysphoric mood relative to those without such a family history. CONCLUSIONS: These data suggest that alterations in NMDA receptor function may contribute to subjective response to ethanol and therefore also to the risk of developing alcoholism.

NMDA receptor antagonism and the ethanol intoxication signal: from alcoholism risk to pharmacotherapy.

This paper reviews clinical evidence suggesting that antagonism of the N-methyl-D-aspartate subtype of glutamate receptors by ethanol may convey an important component of the ethanol intoxication signal, that is, subjective and objective responses associated with the consumption of a large amount of ethanol. It will then review recent evidence that two phenotypes associated with increased risk for heavy alcohol consumption, recovering ethanol-dependent patients, and healthy individuals with a family history of alcohol dependence, exhibit reduced sensitivity to the dysphoric consequences of administration of the NMDA receptor antagonist, ketamine. Each of these groups displays reduced sensitivity to a potentially important response that might normally trigger the cessation of ethanol consumption. These data raise the possibility that alterations in NMDA receptor function that reduce the response to the NMDA antagonist component of ethanol may increase the risk for heavy drinking. This hypothesis is consistent with growing evidence that NMDA receptor antagonists may play a role in the treatment of alcoholism by suppressing alcohol withdrawal, reducing the development or expression of alcohol tolerance, or preventing or reversing the sensitiziation to ethanol effects.

Altered NMDA glutamate receptor antagonist response in recovering ethanol-dependent patients.

Ethanol is an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. Ethanol dependence upregulates NMDA receptors and contributes to crosstolerance with selective NMDA receptor antagonists in animals. This study evaluated whether recovering ethanol-dependent patients show evidence of a reduced level of response to the effects of the NMDA receptor antagonist, ketamine. In this double-blind study, 34 recently detoxified alcohol-dependent patients and 26 healthy comparison subjects completed 3 test days involving a 40-min infusion of saline, ketamine 0.1 mg/kg, or ketamine 0.5 mg/kg in a randomized order. Recovering ethanol-dependent patients showed reduced perceptual alterations, dysphoric mood, and impairments in executive cognitive functions during ketamine infusion relative to the healthy comparison group. No attenuation of ketamine-induced amnestic effects, euphoria, or activation was observed. The alterations in NMDA receptor function observed in recovering ethanol-dependent patients may have important implications for ethanol tolerance, ethanol dependence, and the treatment of alcoholism.

N-methyl-D-aspartate glutamate receptors and alcoholism: reward, dependence, treatment, and vulnerability.

This review takes a translational neuroscience perspective on the role of glutamate systems in human ethanol abuse and dependence. Ethanol is a simple molecule with profound effects on many chemical systems in the brain. Glutamate is the primary excitatory neurotransmitter in the brain. Glutamatergic systems are targets for the actions of ethanol via its antagonism of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor and other mechanisms. The modulation of glutamatergic function by ethanol contributes to both euphoric and dysphoric consequences of ethanol intoxication. Adaptations within glutamatergic systems appear to contribute to ethanol tolerance and dependence and to both acute and protracted features of ethanol withdrawal. Perhaps because of the important glutamatergic mediation of the behavioral effects of ethanol, glutamatergic systems appear to contribute to the vulnerability to alcoholism, and novel glutamatergic agents may play a role in the treatment of ethanol abuse and dependence.

The effect of tryptophan depletion on alcohol self-administration in non-treatment-seeking alcoholic individuals.

BACKGROUND: Alcohol self-administration in the laboratory has been used to evaluate pharmacological treatments and neurobiological mechanisms that underlie alcohol use in alcohol-dependent individuals. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the amount of alcohol consumed in a self-administration paradigm in non-treatment-seeking individuals with alcohol use disorders. METHODS: Individuals with alcohol dependence (n = 8) and alcohol abuse (n = 4) who were not seeking treatment were recruited by advertisement and participated in two test days, 1 week apart. Each test session was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. The test session began with a cue exposure session where subjects were exposed to their favorite alcoholic beverage and asked to rate their craving for alcohol. After this, subjects were administered a priming drink designed to raise blood alcohol levels to 0.02 g%. Subjects then had the opportunity to drink up to eight additional drinks, each designed to raise blood alcohol levels by 0.02 g%, or to receive $3 for each drink not consumed over a 2-hr period. RESULTS: There were no significant differences in alcohol consumed or subjective intoxication with active tryptophan depletion compared with placebo. Self-reported craving correlated with the amount of alcohol consumed in the session. CONCLUSIONS: These data question the dependence of alcohol self-administration on the ongoing synthesis of serotonin.