Pharmacist-implemented intervention to surmount COVID-19 vaccination hesitancy in adults with substance use disorders.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Substance use disorders (SUDs) increase the risk and severity of infectious diseases, including coronavirus disease 2019 (COVID-19). Adults with a co-occurring SUD and psychiatric disorder were studied to elucidate the association between SUD severity and (1) COVID-19 vaccination status, (2) receptivity to a one-session intervention with a pharmacist advocating the benefits of vaccination, and (3) acceptance of referral for vaccination following the intervention. METHODS: COVID-19 vaccination status was recorded in 460 adults with SUD (324 males and 136 females) upon entry into inpatient treatment. A 2-parameter item response theory (IRT) model quantified SUD severity. Pharmacist-delivered intervention, modeled after the screening, brief intervention, and referral to treatment (SBIRT) protocol, was offered to unvaccinated participants. RESULTS: Higher SUD severity was associated with a lower vaccination rate. Nicotine, opioid, and sedative use disorders were most frequently associated with unvaccinated status. SUD severity was not associated with receptivity to intervention advocating vaccination or subsequent acceptance of a referral for vaccination. The portion of the sample that received the intervention was over 7 times more likely to accept a referral for vaccination when compared to participants who rejected the intervention (20.8% vs 2.8%). CONCLUSION: Pharmacist-administered intervention produced motivation for vaccination in a number of recipients; however, receptivity to the intervention was not related to SUD severity.

Alcohol use disorder conceptualizations and diagnoses reflect their sociopolitical context.

The present paper highlights how alcohol use disorder (AUD) conceptualizations and resulting diagnostic criteria have evolved over time in correspondence with interconnected sociopolitical influences in the United States. We highlight four illustrative examples of how DSM-defined alcoholism, abuse/dependence, and AUD have been influenced by sociopolitical factors. In doing so, we emphasize the importance of recognizing and understanding such sociopolitical factors in the application of AUD diagnoses. Last, we offer a roadmap to direct the process of future efforts toward the improved diagnosis of AUD, with an emphasis on pursuing falsifiability, acknowledging researchers' assumptions about human behavior, and collaborating across subfields. Such efforts that center the numerous mechanisms and functions of behavior, rather than signs or symptoms, have the potential to minimize sociopolitical influences in the development of diagnostic criteria and maximize the treatment utility of diagnoses.

Risk for Suicidal Behavior After Psychiatric Hospitalization Among Sexual and Gender Minority Patients.

Importance: The months following inpatient psychiatric hospitalization are a period of high risk for suicidal behavior. Sexual and gender minority (SGM) individuals have elevated risk for suicidal behavior, but no prior research has examined whether SGM inpatients have disproportionate risk for suicidal behavior following discharge from psychiatric hospitalization. Objectives: To evaluate whether SGM patients have elevated risk for suicidal behavior following discharge from psychiatric hospitalization compared with heterosexual and cisgender patients and to examine whether differences in risk across groups were accounted for by demographic characteristics and clinical factors known to be associated with suicidal behavior. Design, Setting, and Participants: This prospective cohort study was conducted from August 2017 to July 2021 among inpatients aged 18 to 30 years who were voluntarily enrolled during psychiatric hospitalization. The study was conducted at an inpatient psychiatric hospital, with prospective data collected via follow-up visits and electronic health records. Main Outcomes and Measures: Onset and/or recurrence of suicidal behavior following discharge from psychiatric hospitalization, assessed at follow-up visits and through electronic health records. Results: A total of 160 patients were included, with 56 sexual minority (SM) and 15 gender minority (GM) patients. The median (IQR) age of the patients was 23.5 (20.4-27.6) years, 77 (48%) reported male sex assigned at birth, and 114 (71%) identified their race as White. During the follow-up period, 33 suicidal behavior events occurred (among 21% of patients). SM (hazard ratio [HR], 2.02; 95% CI, CI, 1.02-4.00; log-rank P = .04) and GM (HR, 4.27; 95% CI, 1.75-10.40; log-rank P < .001) patients had significantly higher risk for suicidal behavior compared with their heterosexual and cisgender counterparts, respectively, in bivariable analyses. Risk between SM and heterosexual patients was not different after controlling for demographic characteristics and clinical factors associated with suicidal behavior. GM patients exhibited elevated risk during the 100 days following discharge even after controlling for demographic and clinical characteristics (HR, 3.80; 95% CI, 1.18-11.19; P = .03). Conclusions and Relevance: Within this cohort study of psychiatric patients, SGM patients had higher risk for suicidal behavior than non-SGM patients following discharge. While SM patients' risk was accounted for by clinical characteristics, GM patients' risk for suicidal behavior was not accounted for by their acute psychiatric state on admission. Future studies with larger subsamples of GM individuals are needed, and inpatient clinicians must attend to the unique needs of SGM individuals to ensure they receive affirming services.

COVID-19 Vaccine Hesitancy, Acceptance, and Promotion Among Healthcare Workers: A Mixed-Methods Analysis.

Even with vaccine mandates, COVID-19 vaccine hesitancy remains a concern among healthcare workers, in part due to their role in promoting vaccination among patients and communities. To examine COVID-19 vaccine hesitancy, acceptance, and promotion among healthcare workers, we conducted a mixed-methods analysis of (1) survey responses about COVID-19 vaccination and (2) Twitter messages (i.e., tweets) relevant to COVID-19 vaccination and healthcare. A total of 540 hospital employees completed the survey. Those that completed less than 80% of the survey or did not endorse employment at the hospital were excluded, resulting in a total of 511 valid responses; 93.2% reported receiving at least one dose of a COVID-19 vaccine. Approximately 1/3 of vaccinated individuals indicated they posted about receiving the vaccine on social media. Simultaneously, we analyzed a sample of 3845 tweets; 2299 (60%) were relevant to COVID-19 vaccination and 1863 (81%) were coded as authored by an individual. Of tweets authored by an individual, 6% (n = 106) were authored by a healthcare provider/health sciences student. Among relevant tweets, the most frequent code across all sentiment categories was related to the pharmaceutical industry (n = 529 tweets, 28%; n = 33, 31% of tweets authored by healthcare workers). Triangulation of results found themes including vaccine access, trust, and vaccine safety or negative health impacts. Results suggest that promoting the sharing of COVID-19 vaccine personal narratives on social media, combined with interventions targeting specific reasons for COVID-19 vaccine hesitancy and emphasizing freedom from fear once vaccinated could be effective at reducing COVID-19 vaccine hesitancy among this population.

Comparative Effectiveness of Postdischarge Smoking Cessation Interventions for Hospital Patients: The Helping HAND 4 Randomized Clinical Trial.

Importance: Smoking cessation interventions for hospitalized patients must continue after discharge to improve long-term tobacco abstinence. How health systems can best deliver postdischarge tobacco treatment is uncertain. Objective: To determine if health system-based tobacco cessation treatment after hospital discharge produces more long-term tobacco abstinence than referral to a community-based quitline. Design, Setting, and Participants: This randomized clinical trial was conducted September 2018 to November 2020 in 3 hospitals in Massachusetts, Pennsylvania, and Tennessee. Cigarette smokers admitted to a study hospital who received brief in-hospital tobacco treatment and wanted to quit smoking were recruited for participation and randomized for postdischarge treatment to health system-based Transitional Tobacco Care Management (TTCM) or electronic referral to a community-based quitline (QL). Both multicomponent interventions offered smoking cessation counseling and nicotine replacement therapy (NRT) for up to 3 months. Data were analyzed from February 1, 2021, to April 25, 2022. Interventions: TTCM provided 8 weeks of NRT at discharge and 7 automated calls with a hospital-based counselor call-back option. The QL intervention sent referrals from the hospital electronic health record to the state quitline, which offered 5 counseling calls and an NRT sample. Main Outcomes and Measures: The main outcome was biochemically verified past 7-day tobacco abstinence at 6 months. Self-reported point-prevalence and continuous tobacco abstinence and tobacco treatment utilization were assessed 1, 3, and 6 months after discharge. Results: A total of 1409 participants (mean [SD] age, 51.7 [12.6] years; 784 [55.6%] women; mean [SD] 16.4 [10.6] cigarettes/day) were recruited, including 706 randomized to TTCM and 703 randomized to QL. Participants were comparable at baseline, including 216 Black participants (15.3%), 82 Hispanic participants (5.8%), and 1089 White participants (77.3%). At 1 and 3 months after discharge, more TTCM participants than QL participants used cessation counseling (1 month: 245 participants [34.7%] vs 154 participants [21.9%]; 3 months: 248 participants [35.1%] vs 123 participants [17.5%]; P < .001) and pharmacotherapy (1 month: 455 participants [64.4%] vs 324 participants [46.1%]; 3 months: 367 participants [52.0%] vs 264 participants [37.6%]; P < .001). More TTCM than QL participants reported continuous abstinence for 3 months (RR, 1.30; 95% CI, 1.06-1.58) and point-prevalence abstinence at 1 month (RR, 1.22; 95% CI, 1.08-1.35) and 3 months (RR, 1.23; 95% CI, 1.09-1.37) but not at 6 months (RR, 1.14; 95% CI, 0.99-1.29). The primary outcome, biochemically verified point-prevalence abstinence at 6 months, was not statistically significantly different between groups (19.9% vs 16.9%; RR, 1.18; 95% CI, 0.92-1.50). Conclusions and Relevance: In this randomized clinical trial, biochemically verified tobacco abstinence rates were not significantly different between groups at the 6-month follow-up. However, the health system-based model was superior to the community-based quitline model throughout the 3 months of active treatment. A longer duration of postdischarge treatment may sustain the superiority of the health system-based model. Trial Registration: ClinicalTrials.gov Identifier: NCT03603496.

Motivational Interviewing Strategies for Addressing COVID-19 Vaccine Hesitancy.

Severe acute respiratory syndrome coronavirus 2, or coronavirus disease 2019 (COVID-19), vaccine hesitancy, defined as a behavioral phenomenon whereby individuals neither fully accept nor fully reject the COVID-19 vaccine, presents a major health threat in the midst of the current pandemic. Traditional approaches for addressing vaccine hesitancy in health care lack empirical support and, in some instances, have actually increased vaccine hesitancy. Thus, there is an urgent need for approaches that effectively address COVID-19 vaccine hesitancy, especially in health care settings. The current article highlights the need for and importance of motivational interviewing (MI), which emphasizes collaborative communication between physicians and patients, in addressing vaccine hesitancy. We describe a 3-step process for addressing COVID-19 vaccine hesitancy that includes using a guiding style, using the MI toolbox, and responding mindfully and skillfully to the individual's degree of hesitancy. The discussion concludes with a consideration of possible challenges in implementing these steps when addressing and resolving COVID-19 vaccine hesitancy.

Characteristics and treatment preferences of individuals with opioid use disorder seeking to transition from buprenorphine to extended-release naltrexone in a residential setting.

BACKGROUND AND OBJECTIVES: Treatment for individuals receiving medication for opioid use disorder (MOUD) should follow an informed patient-centered approach. To better support patient autonomy in the decision-making process, clinicians should be aware of patient preferences and be prepared to educate and assist patients in transitioning from one MOUD to another, when clinically indicated. This posthoc analysis describes the characteristics of clinical trial participants (NCT02696434) with a history of opioid use disorder (OUD) seeking to transition from buprenorphine (BUP) to extended-release naltrexone (XR-NTX). METHODS: The posthoc analysis included adults with OUD currently receiving BUP (≤8 mg/day) and seeking transition to XR-NTX (N = 101) in a residential setting. Baseline participant characteristics and OUD treatment history were reviewed. All patients completed a screening questionnaire that asked about their reasons for seeking transition to XR-NTX and for choosing BUP. RESULTS: The most common reasons for initiating a transition to XR-NTX were "Seeking to be opioid-free" (63.4%) and "Tired of daily pill taking" (25.7%). Positive predictors of transition included a more extensive BUP treatment history and a history of prescription opioid abuse. Most participants stated they were not aware of XR-NTX as a treatment option when initiating BUP (78.2%). DISCUSSIONS AND CONCLUSIONS: Patients' reasons for seeking XR-NTX transition, more extensive BUP treatment history, and a history of prescription opioid abuse, may positively predict outcomes. SCIENTIFIC SIGNIFICANCE: These findings may assist clinicians in optimizing outcomes of the BUP to XR-NTX transition and supporting patients to make better informed MOUD decisions.

Increased burden of cardiovascular risk among youth suicide attempters.

BACKGROUND: Suicide and cardiovascular disease rank among the leading causes of disability and premature mortality worldwide. Young adult suicide attempters are at increased risk of mortality from cardiovascular disease even compared to those with major depressive disorder suggesting an increased burden of cardiovascular risk factors. We compared the cardiovascular risk burden between youth attempters and other high-risk individuals. METHODS: Participants were from the Collaborative Psychiatric Epidemiology Surveys (CPES), a U.S. population-based study, aged 18-30 years [suicide attempt (SA): n = 303; suicidal ideation (SI): n = 451; controls: n = 3671]; and psychiatric inpatients admitted for a SA (n = 38) or SI (n = 40) and healthy controls (n = 37) aged 15-30 years. We computed a cardiovascular risk score and high- and low-risk latent classes based on risk factors of high blood pressure, obesity, and smoking. RESULTS: Suicide attempters showed an increased cardiovascular risk score (CPES: B = 0.43, 95% confidence interval (CI) 0.31-0.54, p < 0.001; inpatient sample: B = 1.61, 95% CI 0.53-2.68, p = 0.004) compared to controls. They were also more likely to be classified in the high cardiovascular risk group (CPES: odds ratio (OR) 3.36, 95% CI 1.67-6.78, p = 0.001; inpatient sample: OR 9.89, 95% CI 1.38-85.39, p = 0.03) compared to those with SI (CPES: OR 1.15, 95% CI 0.55-2.39, p = 0.71; inpatient sample: OR 1.91, 95% CI 0.25-15.00, p = 0.53). CONCLUSIONS: Youth attempters show an increased burden for cardiovascular risk compared to other high-risk individuals in inpatient and population-based samples. Clinicians should pay particular attention to cardiovascular risk factors among suicide attempters in order to reduce their risk for cardiovascular events.

Understanding engagement behaviors and rapport building in tobacco cessation telephone counseling: An analysis of audio-recorded counseling calls.

INTRODUCTION: Though telephone counseling is a modality commonly used to promote health behavior change, including tobacco cessation, specific counselor and participant behaviors that indicate engagement and therapeutic alliance remain poorly characterized in the literature. We sought to explore smokers' and counselors' engagement and rapport-building behaviors in telephone counseling for smoking cessation and patterns of these behaviors by smokers' psychiatric symptoms. METHODS: The study team transcribed, audio-recorded tobacco cessation counseling calls for the presence of engagement and rapport-building behaviors among recently hospitalized participants enrolled in a smoking cessation randomized controlled trial (RCT). The study used baseline data from the RCT to explore frequencies of counselors' and smokers' behaviors among smokers who had reported more (vs. fewer) symptoms of depression (PHQ8 ≥ 10) or anxiety (GAD7 ≥ 10) at study entry. RESULTS: Participants (n = 37) were mostly female (23/37), White (26/37), with a median age of 58. At study entry while hospitalized, moderate-to-severe symptoms of depression (18/37) and anxiety (22/37) were common. Participant-led engagement behaviors included referencing past quit attempts, asking questions, elaborating response to yes/no questions, expressing commitment to behavior change, and assigning importance to nonautomated calls. Counselor-led behaviors included building off prior interaction, empathy, normalizing challenges, reframing and summarizing, validating achievements, and expressing shared experience. Both participants and counselors engaged via general discussion and humor. Participant-led engagement behaviors appeared more often in call transcripts among patients with higher baseline depression and anxiety symptoms compared to those with lower symptom scores. CONCLUSIONS: This study classified participant-led, counselor-led, and shared engagement behaviors during tobacco cessation counseling calls. Increased engagement via telephone counseling may be important for individuals with psychiatric symptoms identified at the start of treatment.

Opioid use as a proximal risk factor for suicidal behavior in young adults.

INTRODUCTION: There is a concomitant rise in suicide rates with the prevalence of opioids involved in overdose deaths, especially among adolescents and young adults. However, there are limited studies on whether opioid use prospectively predicts suicidal behavior in youth. METHODS: Our sample included 183 psychiatric patients (18-30 years) admitted for a suicide attempt (SA), have current suicidal ideation (SI), and psychiatric controls without ideation or attempt (PC). Suicidal behavior was assessed using the Columbia Suicide Severity Rating Scale. We also recruited a healthy control group (HC; n = 40). Patients and controls were followed over a year. ANOVA, regression, and cox regression were used. RESULTS: Suicide attempt (ß = 0.87, CI [0.1-1.6], p = 0.02) and SI [(ß = 0.75, CI [0.03-1.5], p = 0.04) were significantly more likely than HCs to have used opioids in the past year at baseline. Opioid use was associated with increased anxiety symptoms (ß = 0.75, CI [0.001-1.5], p = 0.05), PTSD symptoms (ß = 3.90, CI [1.1-6.7], p = 0.01), and aggression (ß = 0.02, CI [0.01-0.04], p = 0.02). Opioid use in the month prior to hospitalization predicted SA at 6 months (OR = 1.87, CI [1.06-3.31], p = 0.032). CONCLUSIONS: Opioid use is a proximal predictor for SA. These findings may help clinicians better identify patients at risk for suicidal behavior, allowing for more personalized treatment approaches.

Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone.

BACKGROUND: Pharmacologic treatment is recommended for many individuals with opioid use disorder (OUD). For patients who select opioid antagonist treatment, effective management of opioid withdrawal symptoms during transition to antagonist treatment requires consideration of the patient experience. OBJECTIVES: To compare patterns of opioid withdrawal between those withdrawing from untreated opioid use and those withdrawing from buprenorphine. METHODS: We performed a post hoc, cross-study comparison of the temporal pattern of opioid withdrawal during 1-week induction onto extended-release naltrexone by similar protocols enrolling two participant populations: participants with OUD entering a study with untreated opioid use (N = 378, NCT02537574) or on stable buprenorphine (BUP) treatment (N = 101, NCT02696434). RESULTS: The temporal pattern of withdrawal from induction day 1 through day 7 differed between the two participant populations for Clinical Opiate Withdrawal Score (COWS) and Subjective Opiate Withdrawal Score (SOWS): participants with untreated OUD prior to study entry were more likely to experience an earlier relative peak in opioid withdrawal followed by a gradual decline, whereas participants on stable BUP treatment prior to study entry were more likely to experience a relatively later, though still mild, peak opioid withdrawal. The peak COWS was reached at a mean (standard deviation) of 1.9 (1.5) days for participants with untreated OUD and 5.0 (1.5) days for participants on stable BUP. Daily peak cravings were generally higher for participants with untreated OUD than participants on stable BUP. CONCLUSION: Awareness of population-specific variations in the patient experience of opioid withdrawal may help clinicians anticipate the expected course of withdrawal.

Racial inequity in medication treatment for opioid use disorder: Exploring potential facilitators and barriers to use.

BACKGROUND: Despite evidence that individuals with opioid use disorder (OUD) have a lower risk of mortality when using evidence-based medications for OUD (MOUD), only 20 % of people with OUD receive MOUD. Black patients are significantly less likely than White patients to initiate MOUD. We measured the association between various facilitators and barriers to initiation, including criminal justice, human services, and health care factors, and variation in initiation of MOUD by race. METHODS: We used data from a comprehensive, linked data set of health care, human services, and criminal justice programs from Allegheny County in Western Pennsylvania to measure disparities in MOUD initiation by race in the first 180 days after an OUD diagnosis, as well as mediation by potential facilitators and barriers to treatment, among Medicaid enrollees. This is a cross-sectional analysis. RESULTS: Among 6374 Medicaid enrollees who met study criteria, Black enrollees were 18.2 percentage points less likely than White enrollees to start MOUD after controlling for gender, age, and Medicaid eligibility (95 % CI: -21.5 % - -14.8 %). Each day in the emergency department or county jail was associated with a decrease in the likelihood of initiation, as was the presence of a non-OUD substance use disorder diagnosis or participation in intensive non-MOUD treatment. Mediators accounted for approximately one-fifth of the variation in initiation related to race. CONCLUSIONS: Acute care facilities and settings in which people with OUD are incarcerated may have an opportunity to increase the use of MOUD overall and close the racial gap in initiation.

Correction to: Comparative effectiveness of post-discharge strategies for hospitalized smokers: Study protocol for the Helping HAND 4 randomized controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

Comparative effectiveness of post-discharge strategies for hospitalized smokers: Study protocol for the Helping HAND 4 randomized controlled trial.

BACKGROUND: Tobacco smoking remains the leading preventable cause of death in the US. A hospital admission provides smokers with a unique opportunity to stop smoking because it requires temporary tobacco abstinence while illness may enhance motivation to quit. Hospital interventions must continue post-discharge to increase tobacco abstinence long-term, but how best to accomplish this remains unclear. Building on two previous randomized controlled trials, each of which tested smoking cessation interventions that began in hospital and continued after discharge, this trial compares two interventions that provide sustained smoking cessation treatment after hospital discharge with the goal of improving long-term smoking cessation rates among hospitalized smokers. METHODS/DESIGN: Helping HAND 4 is a three-site randomized controlled trial that compares the effectiveness of two active interventions for producing validated past 7-day tobacco abstinence 6 months after hospital discharge. Smokers who are admitted to three hospitals receive a standard in-hospital smoking intervention, and those who plan to quit smoking after discharge are recruited and randomly assigned to two interventions that begin at discharge, Personalized Tobacco Care Management (PTCM) or Quitline eReferral. Each lasts 3 months. At discharge, PTCM provides 8 weeks of free nicotine replacement (NRT; a participant's choice of patch, gum, lozenge, or a combination) and then proactive smoking cessation support using an automated communication platform and live contact with a tobacco treatment specialist who is based in the health care system. In the eReferral condition, a direct referral is made from the hospital electronic health record to a community-based resource, the state's telephone quitline. The quitline provides up to 8 weeks of free NRT and offers behavioral support via a series of phone calls from a trained coach. Outcomes are assessed at 1, 3, and 6 months after discharge. The study hypothesis is that PTCM will produce higher quit rates than eReferral. DISCUSSION: Helping HAND 4 is a pragmatic trial that aims to evaluate interventions in real-world conditions. This project will give hospital systems critical evidence-based tools for meeting National Hospital Quality Measures for tobacco treatment and maximizing their ability to improve cessation rates and overall health for the millions of smokers hospitalized annually in the US. TRIAL REGISTRATION: Prospectively registered prior to start of enrollment at Clinicaltrials.gov, NCT03603496 (July 27, 2018). https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S00084MJ&selectaction=Edit&uid=U00002G7&ts=2&cx=ff0oxn.

Transition of Patients with Opioid Use Disorder from Buprenorphine to Extended-Release Naltrexone: A Randomized Clinical Trial Assessing Two Transition Regimens.

BACKGROUND AND OBJECTIVE: When patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended-release naltrexone (XR-NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR-NTX is evaluated in this study. METHODS: In a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (1:1) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO-N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR-NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR-NTX. RESULTS: There was no statistical difference between groups for participants receiving a first dose of XR-NTX: 68.6% (NTX/BUP) vs 76.0% (PBO-N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1-7) was similar for NTX/BUP and PBO-N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR-NTX induction and post-XR-NTX observation period (days 8-11) were mild and similar between groups (mean peak COWS score: NTX/BUP, 5.1 vs PBO-N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Low ascending doses of oral NTX did not increase induction rates onto XR-NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well-tolerated approach for patients seeking transition from BUP to XR-NTX. (Am J Addict 2020;00:00-00).

A brief motivational intervention for enhancing medication adherence for adolescents with bipolar disorder: A pilot randomized trial.

BACKGROUND: Youth with bipolar disorder (BP) exhibit poor medication adherence, contributing to affective recurrence. Brief Motivational Interventions (BMIs) improve adherence among adolescents with chronic conditions. METHODS: In an open pilot series, we developed a 3-session BMI for BP adolescents targeting medication adherence and conducted a pilot randomized trial comparing Standard Care (SC) versus SC+BMI. Participants include 43 adolescents with BP prescribed psychotropic medications. We assessed medication adherence objectively via bluetooth-enabled electronic pillbox (MedTracker). A blinded evaluator assessed mood symptoms at intake, 3- and 6-months. RESULTS: The BMI was well-received. Average objective medication adherence increased with time in SC+BMI, but decreased in SC-Alone (p < 0.0001). Adolescents' baseline self-rated expectation of improvement with treatment moderated the effect of treatment on improvement in adherence over time (p = 0.003). Across groups, poor adherence predicted increased likelihood of depression and hypo/mania symptoms in the subsequent two weeks; medication adherence mediated the effect of the BMI on the likelihood of depressive symptoms (p = 0.007). LIMITATIONS: Electronic pillbox use (across groups) may enhance adherence, resulting in overestimates compared with naturalistic conditions. This pilot randomized trial may have been underpowered to detect some group differences. CONCLUSIONS: A BMI offers promise as a disseminable adjunctive intervention for improving medication adherence for adolescents with BP. Future studies with larger samples can establish efficacy. NCT03203720.

Signaling networks in inflammatory pathways and risk for suicidal behavior.

BACKGROUND: Suicide is a leading cause of death in the young adult population, with few biological markers identified thus far to be associated with suicidality. Cytokines (including IL-6 and TNFα) may contribute to increased risk for depression and suicidality. Few studies have examined the associations of cytokine mRNA expression with depression and suicidal ideation and behavior. This study examines these associations and whether cytokine signaling networks differentiate suicide attempters (SA), suicide ideators (SI), and healthy controls (HC). METHODS: Cytokine pathway marker (CPM; e.g. cytokines and proteins in cytokine signaling pathways) mRNA gene expression in whole blood was examined in suicide attempters (n = 38), suicide ideators (n = 38), and healthy controls (n = 36). Between-group differences in CPM gene expression were examined. We also examined association of the mRNA of these genes with the severity of depression and suicidal ideation. Novel Gaussian Graphical Model (GGM) techniques were utilized to examine between-network partial correlation differences in cytokine signaling networks relevant to IL-6 and TNFα signaling pathways. RESULTS: The severity of depression symptoms was positively associated with TNFα mRNA levels and negatively associated with IL-10 mRNA levels, but CPM expression was not associated with suicidal ideation severity. There were no between-group differences in CPM markers among healthy controls, SI and SA groups after correcting for multiple comparisons. In network analyses, we found suggestive results of between-group network differences between SI and control groups in gene pairs with IL-6R and STAT3 as common nodes. DISCUSSION: In a cohort of suicide attempters and ideators, TNFα and IL-10 mRNA levels appear to be associated with depressive symptomology, consistent with elevation of pro-inflammatory cytokine production and reduction of anti-inflammatory cytokine production. Additionally, cytokine signaling networks may differentiate suicide ideators from healthy controls based on between-network differences, with differences possibly related to relationships of IL6R or STAT3 with other components of cytokine signaling networks.

Depressive and Anxiety Symptoms Predict Obsessive and Compulsive Cravings among Depressed Alcoholics.

Objectives: Alcohol craving is often associated with mood symptoms and predicts alcohol use in individuals with alcohol dependence. However, little is known about the impact of mood symptoms on alcohol craving in comorbid mood disorders and alcohol dependence. This study examines the predictive value of depressive and anxiety symptoms for obsessive and compulsive aspects of alcohol craving in adults with comorbid Major Depressive Disorder (MDD) and Alcohol Dependence. Methods: Fifty-five adults (47% female; mean age of 39.35 (SD=8.80)) with DSM-IV diagnoses of comorbid MDD and alcohol dependence were prospectively assessed over a six-month period. They completed the Hamilton Rating Scales for Depression and Anxiety, the Alcohol Timeline Followback, the Obsessive Compulsive Drinking Scale (OCDS), the Alcohol Dependence Scale (ADS), and the Addiction Severity Index (ASI). The linear mixed model analyses for repeated measures was used to test weather depressive and anxiety symptoms predict OCDS subscale scores. Results: Depressive and anxiety symptoms were strongly associated with obsessive and compulsive subscales of the OCDS. Baseline ASI-alcohol scores were associated with both the obsessive and compulsive and with the obsessive subscale scores in the predictive model including depressive symptoms, and that including anxiety symptoms respectively. Conclusions: Results suggest that depressive and anxiety symptoms predict obsessive and compulsive aspects of alcohol craving in adults with comorbid MDD and alcohol dependence. Assessing the severity of depressive and anxiety symptoms and alcohol use in this population may identify those more likely to experience intense alcohol craving states and at increased risk of relapse.