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BackgroundDespite the focus on overdose deaths co-involving opioids and benzodiazepines, little is known about the epidemiologic characteristics of benzodiazepine-involved overdose deaths in the USA.ObjectiveTo characterize co-involved substances, intentionality, and demographics of benzodiazepine-involved overdose deaths in the USA from 2000 to 2019.DesignCross-sectional study using national mortality records from the National Vital Statistics System.SubjectsUS residents in the 50 states and District of Columbia who died from a benzodiazepine-involved overdose from 2000 to 2019.Main MeasuresDemographic characteristics, intention of overdose, and co-involved substancesKey ResultsA total of 118,208 benzodiazepine-involved overdose deaths occurred between 2000 and 2019 (median age, 43 [IQR, 32–52]; male, 58.6%; White, 93.3%; Black, 4.9%; American Indian and Alaska Native, 0.9%; Asian American and Pacific Islander, 0.9%; Hispanic origin, 6.4%). Opioids were co-involved in 83.5% of the deaths. Nine percent of benzodiazepine-involved overdose deaths did not involve opioids, cocaine, other psychostimulants, barbiturates, or alcohol. Overdose deaths were classified as suicides in 8.5% of cases with benzodiazepine and opioid co-involvement and 36.2% of cases with benzodiazepine but not opioid involvement. Rates of benzodiazepine-involved overdose deaths increased from 0.46 per 100,000 individuals in 2000 to 3.55 per 100,000 individuals in 2017 before decreasing to 2.96 per 100,000 individuals in 2019. Benzodiazepine-involved overdose mortality rates increased from 2000 to 2019 among all racial groups, both sexes, and individuals of Hispanic and non-Hispanic origin. Rates of benzodiazepine-involved overdose deaths decreased among White individuals, but not Black individuals, from 2017 to 2019.ConclusionsInterventions to reduce benzodiazepine-involved overdose mortality should consider the demographics of, co-involved substances in, and presence of suicides among benzodiazepine-involved overdose deaths.

Robert Kleinman and colleagues examine the efficacy and safety of reducing supervised dosing of sublingual buprenorphine-naloxone for opioid use disorder

Hydrocodone and oxycodone are prescribed commonly to treat pain. However, differences in risk of opioid-related adverse outcomes after an initial prescription are unknown. This study aims to determine the risk of opioid-related adverse events, defined as either chronic use or opioid overdose, following a first prescription of hydrocodone or oxycodone to opioid naïve patients. A retrospective analysis of multiple linked public health datasets in the state of Oregon. Adult patients ages 18 and older who a) received an initial prescription for oxycodone or hydrocodone between 2015-2017 and b) had no opioid prescriptions or opioid-related hospitalizations or emergency department visits in the year preceding the prescription were followed through the end of 2018. First-year chronic opioid use was defined as ≥6 opioid prescriptions (including index) and average ≤30 days uncovered between prescriptions. Fatal or non-fatal opioid overdose was indicated from insurance claims, hospital discharge data or vital records. After index prescription, 2.8% (n = 14,458) of individuals developed chronic use and 0.3% (n = 1,480) experienced overdose. After adjustment for patient and index prescription characteristics, patients receiving oxycodone had lower odds of developing chronic use relative to patients receiving hydrocodone (adjusted odds ratio = 0.95, 95% confidence interval (CI) 0.91-1.00) but a higher risk of overdose (adjusted hazard ratio (aHR) = 1.65, 95% CI 1.45-1.87). Oxycodone monotherapy appears to greatly increase the hazard of opioid overdose (aHR 2.18, 95% CI 1.86-2.57) compared with hydrocodone with acetaminophen. Oxycodone combined with acetaminophen also shows a significant increase (aHR 1.26, 95% CI 1.06-1.50), but not to the same extent. Among previously opioid-naïve patients, the risk of developing chronic use was slightly higher with hydrocodone, whereas the risk of overdose was higher after oxycodone, in combination with acetaminophen or monotherapy. With a goal of reducing overdose-related deaths, hydrocodone may be the favorable agent.

Alcohol use disorder (AUD) and depressive disorders are among the most prevalent psychiatric disorders and co-occur more often than expected by chance. The aim of this review is to characterize the prevalence, course, and treatment of co-occurring AUD and depressive disorders. Studies have indicated that the co-occurrence of AUD and depressive disorders is associated with greater severity and worse prognosis for both disorders. Both pharmacologic and behavioral treatments have demonstrated efficacy for this population. However, treatment response is somewhat modest, particularly for drinking outcomes, highlighting the importance of further research on the etiology and treatment of co-occurring AUD and depressive disorders. Key future directions include studies to understand the heterogeneity of both AUD and depressive disorders, research on novel treatment approaches to enhance outcomes, and better understanding of sex and gender differences.

Exposure to stress is associated with poor outcomes in people with chronic pain. Dispositional variables, such as pain catastrophizing and distress intolerance, may impact reactivity to stressors. Importantly, these variables can be modified with treatment. The aim of this study was to investigate whether pain catastrophizing and distress intolerance were associated with tolerance of a pain stressor or a psychosocial stressor, and heightened negative affect following these stressors. A sample of 50 adults with chronic pain completed self-report measures and pain and psychosocial stress inductions. Results indicated that pain catastrophizing was associated with heightened anxiety during pain induction. Distress intolerance was associated with negative affect following a psychosocial stressor, and with poorer tolerance of the psychosocial stressor. Pain catastrophizing and distress intolerance are related factors, however, they exhibit distinct associations with amplification of pain and psychosocial stress reactivity. These variables may be important treatment targets in people with chronic pain.

Bipolar disorder and alcohol use disorder represent a significant comorbid population, which is significantly worse than either diagnosis alone in presentation, duration, co-morbidity, cost, suicide rate, and poor response to treatment. They share some common characteristics in relation to genetic background, neuroimaging findings, and some biochemical findings. They can be treated with separate care, or ideally some form of integrated care. There are a number of pharmacotherapy trials, and psychotherapy trials that can aid program development. Post-treatment prognosis can be influenced by a number of factors including early abstinence, baseline low anxiety, engagement with an aftercare program and female gender. The future development of novel therapies relies upon increased psychiatric and medical awareness of the co-morbidity, and further research into novel therapies for the comorbid group.

Rates of opioid use disorder (OUD) have increased among women over the past 2 decades. Medication treatment for opioid use disorder (MOUD) is effective but underused. Gender-specific treatments for women have been associated with improved substance use outcomes. However, these treatments have not specifically targeted women's engagement in MOUD, and the impact of existing gender-specific treatments is restricted by in-person delivery. The aim of this study was to develop a digital intervention to feasibly deliver gender-specific care that addresses the individualized needs of women with OUD to increase engagement in MOUD. A mixed methods, user-centered design approach was used to inform the development of a digital intervention. In phase 1, qualitative interviews were conducted with women with lived experience of OUD (n=20) and providers who treat women with OUD (n=8). Interviews were recorded, transcribed, and coded for themes. In addition, a larger sample of treatment providers (n=55) completed an online survey to further inform the content of the digital intervention. Phase 2 consisted of designing, beta-testing (n=5), and refining the intervention. The age of women with lived experience ranged from 21 to 59 (mean 38.5, SD 9.4) years; 63% (5/8) of providers interviewed were female participants. The qualitative interview data from women with lived experience and providers were grouped into 6 thematic categories: 3 treatment-related (1) barriers to treatment, (2) facilitators to successful recovery, and (3) important issues to address in treatment, and 3 technology-related (4) positives of using technology as part of treatment, (5) suggested technology features, and (6) barriers to using technology. Across the treatment-related categories, several themes touched on women-specific factors including family responsibilities, abusive partners, stigma, and motivation for treatment (eg, pregnancy). The technology-related categories provided information for designing the features of the intervention, as well as revealing barriers to technology use, which could be helpful in developing implementation strategies. Provider survey participants were primarily female participants (40/55, 73%), with a mean age of 42.5 (SD 12.5) years. Survey data provided additional information on barriers to treatment and suggested technology features. Based on these data and preliminary work, the Healthy Women intervention was created. Minor edits to content and visual design were made in the beta-testing phase. The final version includes a web-based component with 6 topic modules and a mobile component. Topics in the web-based component are presented through infographics, text, videos, and interactive questions. The mobile component includes daily motivational messages, skills practice activities (2/wk), weekly check-ins, and resources (always available). Important themes and suggested features from women with lived experience and providers were incorporated into a digital intervention for women with OUD. Data on feasibility, satisfaction, and engagement with the Healthy Women intervention are currently being collected in phase 3, a pilot randomized controlled trial.

Background Individuals with opioid use disorder (OUD) are frequently hospitalized for injection-related medical complications, yet they often receive inadequate treatment for the OUD itself. We previously conducted a qualitative study to adapt an existing remotely delivered intensive outpatient program (IOP) specifically for hospitalized patients with OUD. We then conducted a pilot feasibility and acceptability study to assess the program. Methods The 4-week IOP consisted of asynchronous video content and in-person peer support. The primary outcomes were the feasibility of recruitment, acceptability of the treatment as assessed by the completion of videos, and engagement with the peer recovery coach. Secondary outcomes included OUD treatment retention. Results Of the 12 participants, the mean age was 40.9 years, 58.3% were female, and 58.3% had an injection-related serious infection. Results demonstrated potentially acceptable recruitment feasibility (70.6%, 95% CI [48.9–92.3]), but the median percentage of video completion was only 2% (range: 0–16%) and the median percentage of engagement with recovery coach was 31.8% (range: 16.7–66.7%). All participants received medications for OUD (MOUD) during the hospital stay (methadone 83%, buprenorphine 17%), and 33.3% remained retained in MOUD treatment at 28 days. Conclusions Hospitalized patients with OUD desired additional support through an IOP along with MOUD. While recruitment feasibility was acceptable, the overall program was not. Future research should explore IOP content that is more personalized and engaging while also including peer support.

Although hospitalizations for injection drug use-associated infective endocarditis (IDU-IE) have increased during the opioid crisis, utilization of and mortality associated with receipt of medication for opioid use disorder (MOUD) after discharge from the hospital among patients with IDU-IE are unknown. To assess the proportion of patients receiving MOUD after hospitalization for IDU-IE and the association of MOUD receipt with mortality. This retrospective cohort study used a population registry with person-level medical claims, prescription monitoring program, mortality, and substance use treatment data from Massachusetts between January 1, 2011, and December 31, 2015; IDU-IE-related discharges between July 1, 2011, and June, 30, 2015, were analyzed. All Massachusetts residents aged 18 to 64 years with a first hospitalization for IDU-IE were included; IDU-IE was defined as any hospitalization with a diagnosis of endocarditis and at least 1 claim in the prior 6 months for OUD, drug use, or hepatitis C and with 2-month survival after hospital discharge. Data were analyzed from November 11, 2018, to June 23, 2020. Receipt of MOUD, defined as any treatment with methadone, buprenorphine, or naltrexone, within 3 months after hospital discharge excluding discharge month for IDU-IE. The main outcome was all-cause mortality. The proportion of patients who received MOUD in the 3 months after hospital discharge was calculated. Multivariable Cox proportional hazard regression models were used to examine the association of MOUD receipt with mortality, adjusting for sex, age, medical and psychiatric comorbidities, and homelessness. In the secondary analysis, receipt of MOUD was considered as a monthly time-varying exposure. Of 679 individuals with IDU-IE, 413 (60.8%) were male, the mean (SD) age was 39.2 (12.1) years, 298 (43.9%) were aged 18 to 34 years, 419 (72.3) had mental illness, and 209 (30.8) experienced homelessness. A total of 134 individuals (19.7%) received MOUD in the 3 months before hospitalization and 165 (24.3%) in the 3 months after hospital discharge. Of those who received MOUD after discharge, 112 (67.9%) received buprenorphine. The crude mortality rate was 9.2 deaths per 100 person-years. MOUD receipt within 3 months after discharge was not associated with reduced mortality (adjusted hazard ratio, 1.29; 95% CI, 0.61-2.72); however, MOUD receipt was associated with reduced mortality in the month that MOUD was received (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.89). In this cohort study, receipt of MOUD was associated with reduced mortality after hospitalization for injection drug use-associated endocarditis only in the month it was received. Efforts to improve MOUD initiation and retention after IDU-IE hospitalization may be beneficial.