Baseline C-reactive protein levels are predictive of treatment response to a neuroimmune modulator in individuals with an alcohol use disorder: a preliminary study.

Background: Inflammation is implicated in alcohol use disorder (AUD). Ibudilast, a neuroimmune modulator, shows promise for the treatment of AUD. Elevated inflammation, indicated by high levels of C-reactive protein (CRP), represents a possible subtype of AUD, which may be associated with treatment response to ibudilast.Objectives: The current study evaluated CRP as a predictor of treatment response to ibudilast; hypothesizing that ibudilast would be more effective at reducing drinking and alcohol cue-reactivity in individuals with higher CRP levels.Methods: This is a secondary analysis of a clinical trial of ibudilast for AUD, which found that ibudilast reduced heavy drinking in individuals with AUD. Fifty-one individuals were randomized to receive ibudilast (n = 24 [16 M/8F]) or placebo (n = 27 [18 M/9F]) for two weeks. Participants provided blood samples at baseline to assess CRP levels, completed daily assessments of alcohol use, and an fMRI alcohol cue-reactivity task at study mid-point. Models tested the effects of medication, CRP levels, and their interaction on drinks per drinking day and alcohol cue-reactivity.Results: There was a significant interaction between medication and CRP (F = 3.80, p = .03), such that the ibudilast high CRP group had fewer drinks per drinking day compared to the ibudilast low CRP group. CRP moderated the effect of medication on brain activation in a cluster extending from the left inferior frontal gyrus to the right-dorsal striatum (Z = 4.55, p < .001). This interaction was driven by attenuated cue-reactivity in the ibudilast high CRP group relative to the ibudilast low CRP and placebo high CRP groups.Conclusions: This study serves as an initial investigation into predictors of clinical response to ibudilast treatment and suggests that a baseline proinflammatory profile may enhance clinical efficacy.

Before and During the First COVID-19 Surge: Work Conditions, Burnout, and Mental Health Among Resident Physicians in a Department of Psychiatry in the USA.

OBJECTIVE: Resident physicians are critical frontline workers during pandemics, and little is known about their health. The study examined occupational and mental health risks among US psychiatry residents before and during the first COVID-19 surge. METHODS: Longitudinal data were collected from a cohort of US psychiatry residents at one academic medical center in October 2019, before the pandemic, and April 2020 after the initiation of a state-level stay-at-home order. Primary outcome measures were psychological work empowerment, defined as one's self-efficacy towards their work role, and occupational burnout. A secondary outcome was mental health. In May and June 2020, resident engagement sessions were conducted to disseminate study findings and consider their implications. RESULTS: Fifty-seven out of 59 eligible residents participated in the study (97%). Half the study sample reported high burnout. From before to during the first COVID-19 surge, psychological work empowerment increased in the total sample (p = 0.03); and mental health worsened among junior residents (p = 0.004), not senior residents (p = 0.12). High emotional exhaustion and depersonalization were associated with worse mental health (p < 0.001). In engagement sessions, themes related to residents' work conditions, COVID-19, and racism emerged as potential explanations for survey findings. CONCLUSIONS: The study is exploratory and novel. During early COVID, psychiatry residents' well-being was impacted by occupational and societal factors. Postpandemic, there is a growing psychiatrist shortage and high demand for mental health services. The findings highlight the potential importance of physician wellness interventions focused on early career psychiatrists who were first responders during COVID.

Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial.

Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro-inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and potential central markers of inflammation in individuals with AUD. This study also explored the predictive relationship of neurometabolite markers with subsequent drinking in the trial. Non-treatment-seeking individuals with an AUD (n = 52) were randomized to receive oral ibudilast (n = 24) or placebo (n = 28) for 2 weeks. Plasma levels of peripheral inflammatory markers were measured at baseline and after 1 and 2 weeks of medication. At study mid-point, proton magnetic resonance spectroscopy was performed to measure potential neurometabolite markers of inflammation: choline-compounds (Cho), myo-inositol (MI) and creatine + phosphocreatine (Cr) in frontal and cingulate cortices from 43 participants (ibudilast: n = 20; placebo: n = 23). The treatment groups were compared on peripheral and central markers. Ibudilast-treated participants had lower Cho in superior frontal white matter and nominally lower MI in pregenual anterior cingulate cortex. Ibudilast-treated participants had nominally lower C-reactive protein levels at visit 2 and nominally lower TNF-α/IL-10 ratios, relative to placebo. C-reactive protein and Cho levels were correlated, controlling for medication. Superior frontal white matter Cho predicted drinking in the following week. Micro-longitudinal ibudilast treatment may induce peripheral and putative central anti-inflammatory responses in patients with AUD. The neurometabolite responses may be associated with reduction in drinking, suggesting an anti-inflammatory component to the therapeutic action of ibudilast.

State-of-the-art behavioral and pharmacological treatments for alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) and its associated consequences remain significant public health concerns. Given that AUD represents a spectrum of severity, treatment options represent a continuum of care, ranging from single-session brief interventions to more intensive, prolonged, and specialized treatment modalities. OBJECTIVE: This qualitative literature review seeks to describe the best practices for AUD by placing a particular emphasis on identifying those practices which have received the most empirical support. METHOD: This review summarizes psychological and pharmacological intervention options for AUD treatment, with a focus on the relapse prevention phase of recovery. Psychological and pharmacological treatments are summarized in terms of the empirical evidence favoring each approach and the level of AUD severity for which they are most indicated. SCIENTIFIC SIGNIFICANCE: One of the broad assertions from this review is that while AUD is highly prevalent, seeking treatment for AUD is not. There are a myriad of behavioral and pharmacological treatments that have shown compelling evidence of efficacy for the treatment of AUD. In the behavioral treatment literature, cognitive behavioral therapy has received the most consistent support. Opioid antagonism (via naltrexone) has been the most widely studied pharmacotherapy and has produced moderate effect sizes. While none of the treatments reviewed herein represents a so-called silver bullet for AUD, they each have the potential to significantly improve the odds of recovery. Precision medicine, or the identification of best treatment matches for individual patients, looms as an important overarching goal for the field, although specific matches are not yet sufficiently reliable in their empirical evidence to warrant clinical dissemination.

Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial.

BACKGROUND: Genetic variation in the endogenous opioid system has been identified as 1 potential source of individual variability in naltrexone treatment outcomes. The majority of naltrexone pharmacogenetic studies have focused on a particular single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1; rs1799971; commonly known as the Asn40Asp SNP) in Caucasian samples with decidedly mixed results. The goal of this study was to test the pharmacogenetic effects of naltrexone on subjective response to alcohol and self-administration of alcohol in individuals of East Asian descent. We hypothesized that naltrexone, compared with placebo, would potentiate the aversive and sedative effects of alcohol and reduce alcohol self-administration to a greater extent in Asp40 carriers. METHODS: Participants (N = 77; Asn40Asn, n = 29; Asn40Asp, n = 34, and Asp40Asp, n = 14) completed 2 double-blinded and counterbalanced experimental sessions: one after taking naltrexone (50 mg/d) for 5 days and one after taking matched placebo for 5 days. In each experimental session, participants received a priming dose of intravenous alcohol up to the breath alcohol concentration target of 0.06 g/dl which was immediately followed by an alcohol self-administration period (1 hour). RESULTS: There were no pharmacogenetic effects observed for alcohol-induced stimulation, sedation, craving for alcohol, or alcohol self-administration in the laboratory. During the self-administration period, Asp40 carriers consumed fewer drinks and had a longer latency to first drink as compared to Asn40 homozygotes. CONCLUSIONS: These findings in East Asians add to the mixed literature on naltrexone pharmacogenetics from predominantly Caucasian samples and highlight the complexity of these effects and their overall limited replicability. It is plausible that a consistent pharmacogenetic effect in tightly controlled preclinical and experimental medicine models "fades" in more complex and heterogeneous settings and samples.

Trends in Tramadol: Pharmacology, Metabolism, and Misuse.

Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects. The importance of the CYP metabolism has led to the adoption of computer clinical decision support with pharmacogenomics tools guiding tramadol treatment in major medical centers. Tramadol's simultaneous opioid agonist action and serotonin (5-HT) and norepinephrine reuptake inhibitory effects result in a unique side effect profile and important drug interactions that must be considered. Abrupt cessation of tramadol increases the risk for both opioid and serotonin-norepinephrine reuptake inhibitor withdrawal syndromes. This review provides updated important information on the pharmacology, pharmacokinetics, CYP genetic polymorphisms, drug interactions, toxicity, withdrawal, and illicit use of tramadol.

A Pilot Study of the Safety and Initial Efficacy of Ivermectin for the Treatment of Alcohol Use Disorder.

BACKGROUND: Ivermectin (IVM) is an antiparasitic agent that has been shown to reduce alcohol intake in mice, suggesting IVM as a potential treatment for alcohol use disorder (AUD). However, the safety profile of IVM administered in combination with an intoxicating dose of alcohol has not been characterized in humans. METHODS: This pilot project sought to provide the first clinical evidence that IVM could be repositioned as an AUD pharmacotherapy by examining (i) the safety of combining IVM (30 mg oral , once a day [QD]) with an intoxicating dose of intravenous alcohol (0.08 g/dl) and (ii) the effects of IVM on alcohol cue-induced craving and subjective response to alcohol. Eleven individuals with AUD participated in a randomized, placebo-controlled, crossover study in which they received the study medication, participated in a cue exposure paradigm followed by intravenous alcohol administration, and remained in an inpatient unit overnight for observation. RESULTS: IVM treatment, versus placebo, did not increase the number or severity of adverse effects during alcohol administration or throughout the visit. However, IVM did not reduce cue-induced craving nor did it significantly affect subjective response to alcohol. CONCLUSIONS: These results suggest that IVM (30 mg oral, QD) is safe in combination with an intoxicating dose of alcohol, but do not provide evidence that this dose of IVM is effective in reducing alcohol craving or its reinforcing effects. Given the preclinical data suggesting IVM is effective in reducing alcohol consumption in mice, additional studies testing larger samples and alternate dosing regimens are warranted to further characterize the potential efficacy of IVM as an AUD treatment.

A narrative review: The effects of opioids on sleep disordered breathing in chronic pain patients and methadone maintained patients.

BACKGROUND AND OBJECTIVES: Opioids increase the risk for sleep disordered breathing (SDB), but there are few studies examining the prevalence and risk factors for SDB, specifically central sleep apnea (CSA), and obstructive sleep apnea (OSA) in chronic pain patients on opioids as well as methadone maintained patients (MMPs). METHODS: A literature review was conducted in which SDB was confirmed by polysomnography (PSG) in chronic pain patients on opioids as well as patients with a diagnosis of an opioid use disorder or opioid dependence on methadone maintenance treatment (MMT). RESULTS: About 22 reports were included. Six were with MMPs, and 16 were with chronic pain patients on opioids. Among MMPs, the prevalence of SDB ranged from 42.3% to 70%; 0-60% had CSA and 10-35.2% had OSA. In chronic pain patients on opioids, the prevalence of SDB ranged from 71% to 100%; 17-80% had CSA and 20-39% had OSA. In MMPs, studies found a positive association between BMI, weight gain, duration of MMT, non-Caucasian race and the number of obstructive apneas, as well as blood methadone concentrations and the number of central apneas. In chronic pain patients on opioids, older age, higher BMI, male gender, and higher opioid doses predicted more obstructive apneas; older age, lower BMI, male gender, higher pain levels, higher benzodiazepine doses, and higher opioid doses predicted more central apneas. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: CSA and OSA are common in MMPs and chronic pain patients on opioids. Among chronic pain patients, higher opioid doses appear to be a risk factor for CSA, and to a lesser extent OSA. Therefore, it is important for providers to screen these patient populations for SDB. (Am J Addict 2016;25:452-465).

Varenicline, naltrexone, and their combination for heavy-drinking smokers: preliminary neuroimaging findings.

RATIONALE: Heavy drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available. OBJECTIVE: The present study used a double-blind, randomized, 2 × 2 medication design, testing varenicline alone (VAR; 1 mg twice daily), naltrexone alone (NTX; 25 mg once daily), varenicline plus naltrexone, and placebo for effects on neural activation to cigarette cues in a sample (n = 40) of heavy drinking daily smokers (≥10 cigarettes/day). METHODS: All participants were tested after a 10-12-day titration period designed to reach steady state on the target medication. Participants underwent functional neuroimaging (fMRI) for examination of brain responses to visual smoking-related (vs. neutral) cues. RESULTS: Region of interest (ROI) analyses of brain responses to Cigarette vs. Neutral Cues indicated that the combination of VAR + NTX was associated with reduced activation of the bilateral anterior cingulate cortex as compared to placebo and to NTX alone. Exploratory whole-brain analyses also indicated significant differences in brain activation during cigarette cues in the active medications versus placebo condition. All medications suppressed left nucleus accumbens activation relative to placebo, suggesting the possibility that both medications, either alone or in combination, reduce neural signals associated with appetitive behavior. CONCLUSIONS: Although preliminary, these neuroimaging findings indicate that clinical studies of the combination of VAR + NTX for heavy drinkers trying to quit smoking may be warranted.

Increased levels of interleukin-6, -8 and -10 are associated with fatal outcome following severe traumatic brain injury.

BACKGROUND: Despite the involvement of cytokine production in neurotrauma, there is still controversy regarding cytokines levels and clinical outcome following severe traumatic brain injury (TBI). OBJECTIVE: The present study was designed to investigate whether cytokine levels (of IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α) are associated with primary outcome (death or survival) after severe TBI. METHODS: This prospective study enrolled 24 male patients, victims of severe TBI. Venous blood samples were taken in the Intensive Care Unit (ICU) (study entry), 24 and 48 hours later. Plasma cytokine levels were assayed by flow cytometry. RESULTS: Severe TBI was associated with a 42% mortality rate. TBI patients had a significant increase in the levels of all cytokines measured, except for IL-1ß, compared to controls. Statistically significant increases in the IL-10, -8 and -6 levels were observed in the non-survivors TBI patients compared to the survivors sub-group measured in the first sample (study entry) and in the subsequent sample (24 hours later). There were no significant differences in IL-1ß, TNF-α and IL-12p70 levels between survivors and non-survivors in any time sampled. CONCLUSIONS: The findings indicate that increased IL-10, -8 and -6 levels may constitute an early predictor of unfavourable outcome in severe TBI patients.

A practice quit model to test early efficacy of medications for alcohol use disorder in a randomized clinical trial.

RATIONALE: Screening novel medications for alcohol use disorder (AUD) requires models that are both efficient and ecologically-valid. Ideally, such models would be associated with the outcomes of a given medication in clinical trials. OBJECTIVES: To test a novel human laboratory model in which individuals with intrinsic motivation to change their drinking engage in a "practice quit" attempt consisting of 6 days of complete abstinence from alcohol. METHOD: Individuals with current AUD completed a randomized, double-blind, placebo-controlled study of naltrexone (50 mg), varenicline (2 mg bid), or matched placebo. Participants were titrated onto the study medication for 1 week prior to starting the 6-day practice quit attempt. During the practice quit attempt, participants completed daily interviews with research staff. All participants completed an alcohol cue-exposure paradigm before starting the study medication and after 2 weeks of study medication. RESULTS: There were no significant medication effect on drinks per drinking day (F(2,49) = 0.66, p = 0.52) or percent days abstinent (F(2,49) = 0.14, p = 0.87) during the 6-day practice quit period. There were no medication effects on alcohol cue-reactivity (F(2,44) = 0.80, p = 0.46). Notably, participants sharply reduced their drinking during the entire 13-day medication treatment period, as compared to reducing only during the 6-day practice quit period. During the total medication period, higher levels of motivation to change was associated with higher percent days abstinent (F(1,49) = 8.12, p < 0.01). CONCLUSIONS: This study reports mostly null findings, which challenges us to decompose its nuanced design to consider model refinements. Possible changes to the model include considering the requirement for intrinsic motivation for change, including a longer practice quit period, encompassing the medication administration timeframe in the practice quit period, increasing the required sample size for signal detection, and examining a post COVID-19 pandemic cohort.

Subjective response to alcohol among alcohol-dependent individuals: effects of the µ-opioid receptor (OPRM1) gene and alcoholism severity.

BACKGROUND: Subjective response to alcohol has been examined as a marker of alcoholism risk. The A118G single-nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1) gene has been previously associated with subjective response to alcohol in heavy drinkers. This study seeks to extend the literature by examining the effect of OPRM1 genotype on responses to alcohol in a sample of alcohol-dependent individuals. A secondary aim of this study is to examine alcoholism severity as a predictor of subjective responses to alcohol. METHODS: Nontreatment seeking problem drinkers (n = 295) were assessed in the laboratory for clinical dimensions of alcohol dependence. Following prospective genotyping, 43 alcohol-dependent individuals across the 2 genotype conditions (AA, n = 23 and AG/GG, n = 20) were randomized to 2 intravenous infusion sessions: 1 of alcohol (target breath alcohol concentration = 0.06 g/dl) and 1 of saline. Measures of subjective responses to alcohol were administered in both infusion sessions. RESULTS: Alcohol-dependent G-allele carriers reported greater alcohol-induced stimulation, vigor, and positive mood, as compared to A-allele homozygotes. There was no genotype effect on alcohol-induced sedation or craving. There was a statistical trend-level severity × alcohol interaction such that individuals at higher levels of severity reported greater alcohol-induced tension reduction. CONCLUSIONS: These results support the hypothesis that OPRM1 genotype moderates the hedonic effects of alcohol, but not the sedative and unpleasant effects of alcohol, in a sample of alcohol-dependent patients. Results are discussed in light of a clinical neuroscience framework to alcoholism.

Alcohol Use Among Treatment-Seeking Individuals With Opioid Use Disorder.

OBJECTIVE: Individuals in the United States with opioid use disorder (OUD) have high rates of co-occurring alcohol use disorder. However, there is limited research on co-use patterns among opioid and alcohol use. The present study examined the relationship between alcohol and opioid use in treatment-seeking individuals with an OUD. METHOD: The study used baseline assessment data from a multisite, comparative effectiveness trial. Participants with an OUD who had used nonprescribed opioids in the last 30 days (n = 567) reported on their alcohol and opioid use during the past 30 days using the Timeline Followback. Two mixed-effects logistic regression models were used to assess the effect of alcohol use and binge alcohol use (≥4 drinks/day for women and ≥5 drinks/day for men) on opioid use. RESULTS: The likelihood of same-day opioid use was significantly lower on days in which participants drank any alcohol (p < .001) as well as on days in which participants reported binge drinking (p = .01), controlling for age, gender, ethnicity, and years of education. CONCLUSIONS: These findings suggest that alcohol or binge alcohol use is associated with significantly lower odds of opioid use on a given day, which was not related to gender or age. The prevalence of opioid use remained high on both alcohol use and non-alcohol use days. In line with a substitution model of alcohol and opioid co-use, alcohol may be used to treat symptoms of opioid withdrawal and possibly play a secondary and substitutive role in individuals with OUD substance use patterns.

Ibudilast moderates the effect of mood on alcohol craving during stress exposure.

Neuroinflammation is implicated in the development and maintenance of alcohol use disorder (AUD) and neuroimmune therapeutics show promise in treating AUD. Proinflammatory signaling contributes to progressive elevations in the dysfunction of mood and alcohol craving. The current study sought to examine potential biobehavioral mechanisms of neuroimmune modulation in AUD under experimental conditions. In a community sample of individuals with AUD who completed a placebo-controlled crossover trial of ibudilast, we tested the effect of ibudilast on the relationship between mood states and alcohol craving. Multilevel modeling analyses tested the hypothesis that ibudilast would moderate the effect of positive and negative mood states on alcohol craving during stress and cue exposures. Results revealed that after stress-induction, participants' feelings of depression and happiness were more strongly predictive of their craving for alcohol while taking ibudilast as compared with placebo (ps < .03). These results suggest that with neuroimmune modulation, positive and negative mood states may have a stronger influence on one's desire to drink, such that craving may be more mood dependent. No moderating effect of ibudilast on mood states and craving were observed after alcohol cue exposure. Given the potential of anti-inflammatory treatments to reduce depressive symptomatology, this strengthened relationship between mood and craving under ibudilast might reduce the likelihood of stress-related craving and subsequent drinking over time. Moreover, ibudilast may enhance the benefits of happiness, such that maintaining positive mood in the face of acute stress may attenuate craving. Future trials directly testing the clinical implications of these mechanistic findings are warranted. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder.

Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very heterogeneous disorder, it is unlikely that one single medication will be effective for all individuals with an AUD. As such, there is a need to develop new, more effective, and diverse pharmacological treatment options for AUD with the hopes of increasing utilization and improving care. In this qualitative literature review, we discuss the efficacy, mechanism of action, and tolerability of approved, repurposed, and novel pharmacotherapies for the treatment of AUD with a clinical perspective. Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Overall, many repurposed and novel agents discussed in this review demonstrate clinical effectiveness and promise for the future of AUD treatment. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD.

Elevated plasma prolactin in abstinent methamphetamine-dependent subjects.

BACKGROUND: Methamphetamine (MA) use disorders are pervasive global social problems that produce large medical and public health burdens. Abnormalities in pituitary hormonal regulation have been observed in preclinical models of substance abuse and in human substance abusers. They have, however, not been studied before in MA-dependent human subjects. OBJECTIVES: To determine if MA-dependent research volunteers differ from healthy control subjects in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, or prolactin, or in pituitary dopamine D(2) receptor availability during early abstinence from MA. METHODS: MA-dependent subjects (N = 31), who were not seeking treatment, resided on an inpatient ward for up to 5 weeks. Abstinence was confirmed by daily urine drug screening. Venous blood was sampled for plasma hormone levels, and positron emission tomography with [(18)F]fallypride was performed to determine dopamine D(2) receptor availability during the first week of abstinence. Venous blood was sampled again for hormone levels during the fourth week of abstinence. Matched healthy volunteers (N = 23) participated as a comparison group. RESULTS: MA-dependent and healthy comparison subjects did not differ in plasma ACTH or cortisol levels, but had an elevated plasma prolactin at both the first week and fourth week of abstinence. There was no group difference in pituitary dopamine D(2) receptor availability. CONCLUSION: MA-dependent individuals have abnormalities in prolactin regulation, which is not likely due to alterations in pituitary dopamine D(2) receptor availability. SCIENTIFIC SIGNIFICANCE: MA dependence is associated with elevated prolactin levels, which may contribute to medical comorbidity in afflicted individuals.

Psychological Distress Among Women Healthcare Workers: A Health System's Experience Developing Emotional Support Services During the COVID-19 Pandemic.

Ensuring the mental health and well-being of the healthcare workforce globally, especially women healthcare workers (HCWs), is an ongoing challenge that has been accentuated by the novel coronavirus (COVID-19) pandemic. Already at high risk of experiencing symptoms of stress, burnout, and depression, women HCWs are now also facing the psychosocial impacts of the COVID-19 pandemic. Although different types of mental health interventions have been introduced to support HCW well-being, the current needs of women HCWs have not been emphasized and replicable processes for developing and implementing specific emotional support services for women HCWs have not yet been well-described in the literature. Therefore, in this perspective, we discuss the approach our institution (University of California, Los Angeles) took for developing emotional support services for women HCWs that incorporate aspects of disaster behavioral health models and address various barriers to support and treatment. In addition, we describe and illustrate the process that we utilized to develop individual-level and institutional-level emotional support services. Finally, based on our institution's experience, we share recommendations for developing emotional support services for women HCWs during the COVID-19 pandemic and other future crises.

Combined varenicline and naltrexone attenuates alcohol cue-elicited activation in heavy drinking smokers.

BACKGROUND: There is a strong bidirectional relationship between the use of alcohol and cigarettes which results in various challenges for treating those who co-use both substances. While varenicline and naltrexone each have FDA-approval for nicotine and alcohol use disorder, respectively, there is evidence that their clinical benefit may extend across the two disorders. Critically, the effect of combined varenicline and naltrexone on neural reactivity to alcohol cues among heavy drinking smokers has not yet been studied. Probing the effect of the combination therapy on alcohol cue-reactivity may give insight to the mechanisms underlying its efficacy. METHODS: Forty-seven heavy drinking smokers enrolled in two medication studies were randomized to receive varenicline alone (n = 11), varenicline plus naltrexone (n = 11), or placebo (n = 25). Participants completed an fMRI alcohol cue-reactivity task and rated their in-scanner alcohol craving. Whole-brain analyses examined the effect of medication on alcohol cue-elicited neural response. RESULTS: Varenicline plus naltrexone attenuated alcohol cue-elicited activation in mesolimbic regions relative to varenicline alone and to placebo (Z > 2.3, p < 0.05). The combination varenicline and naltrexone group also endorsed lower in-scanner alcohol craving relative to varenicline alone group (p = 0.04). CONCLUSIONS: These findings provide evidence for the benefit of combined therapy of varenicline and naltrexone over varenicline alone for the attenuation of alcohol cue-elicited neural activation. This study provides a preliminary proof-of-mechanism for this combination pharmacotherapy and suggests that naltrexone may be driving the reductions in cue-elicited alcohol craving in the brain. Further clinical studies using the combined therapy to treat heavy drinking smokers are warranted.