High-Dose Buprenorphine Initiation: A Scoping Review.

OBJECTIVE: The aim of the study is to review and synthesize the literature on high-dose buprenorphine initiation (>12-mg total dose on day of initiation). METHODS: A scoping review of literature about high-dose buprenorphine initiation was conducted. MEDLINE, Embase, PsycINFO, and Cochrane Central were searched. Randomized controlled trials, prospective and retrospective cohort studies, and case studies/reports published in English before February 13, 2023, were included. RESULTS: Fifteen studies reporting outcomes from 580 high-dose buprenorphine initiations were included. Eight studies were in inpatient settings, 3 in emergency departments, 3 in outpatient settings, and 1 in a first-responder setting. Four studies reported high-dose initiations among individuals exposed to fentanyl. There were no reported events of fatal or nonfatal overdose or respiratory depression, although adverse event reporting was inconsistent in published reports. The most reported side effects with high-dose buprenorphine initiation were nausea or vomiting (n = 17) and precipitated withdrawal (n = 7). The most serious reported adverse event was hypotension requiring oral hydration (n = 2). Most studies reported improvements in subjective or objective withdrawal symptoms. The duration of follow-up ranged from none to 8 months. CONCLUSIONS: High-dose buprenorphine initiation has not been associated with reported cases of overdose or respiratory depression. However, the current literature about high-dose buprenorphine is limited by inconsistent side effect reporting, limited power to detect rare safety events such as respiratory depression, limited follow-up data, and few comparison studies between high-dose and regular initiation protocols. Further prospective data are needed to evaluate the safety and effectiveness of this initiation strategy.

Rethinking Substance Use as Social History: Charting a Way Forward.

Physicians have traditionally asked about substance use within the Social History section of the consultation note. Drawing on social science theory and using the authors' own experiences as generalists and addiction scholars, we consider the possible unintended harms associated with this approach. The inclusion of the substance use history within the Social History reproduces the discourse of substance use disorders as "life-style choices" rather than medical conditions, and reinforces stigma among healthcare workers through the attribution of personal responsibility for complications associated with problematic substance use. The ongoing placement of the substance use history within the Social History may lead to a failure to diagnose and make appropriate management plans for clients with substance use disorders. These missed opportunities may include inadequate withdrawal management leading to discharge before medically advised, insufficient use of evidence-based pharmacotherapy and psychotherapy, polypharmacy, medical complications, and repeated admissions to hospital. We argue instead that the Substance Use History should be a stand-alone section within the consultation note. This new section would reduce the invisibility of substance use disorders within our medical systems and model that these chronic medical conditions are amenable to prevention, treatment and harm reduction through the application of evidence-based practices.

Characteristics, treatment patterns and retention with extended-release subcutaneous buprenorphine for opioid use disorder: A population-based cohort study in Ontario, Canada.

BACKGROUND: Uptake and retention for opioid agonist treatment (OAT) remains low. Novel extended-release formulations may improve OAT accessibility by reducing the frequency of healthcare visits. Our aim was to examine uptake, characteristics, treatment patterns and retention of individuals initiating extended-release subcutaneous buprenorphine (BUP-ER), a monthly injectable OAT. METHODS: We conducted a population-based cohort study among adults aged 18+ initiated on BUP-ER between February 3, 2020 and March 31, 2022 in Ontario, Canada. Using administrative health data, we defined continuous BUP-ER use based on repeat injections within a 56-day period and used Kaplan-Meier curves to estimate time on treatment. Among new BUP-ER recipients, we described individual and prescriber characteristics, healthcare utilization and treatment patterns. RESULTS: 2366 individuals initiated BUP-ER. The median time to BUP-ER discontinuation was 183 days (interquartile range: 66-428 days) and 52.0% of individuals were co-prescribed buprenorphine/naloxone at least once throughout the period of BUP-ER receipt. Among individuals who initiated on a dose of 300mg BUP-ER and had three or more injections, 18.8% continued to receive only 300mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100mg (N=341 of 1194) had a subsequent dose increase to 300mg. CONCLUSIONS: On average, people initiating BUP-ER discontinue within the first 6 months of treatment. While BUP-ER is likely providing an important OAT option, the high occurrence of discontinuation, supplementation with buprenorphine/naloxone, and frequent dose increases suggest inadequacy of current dosing recommendations among a proportion of individuals.

Assessing the impact of the slow-release oral morphine drug shortages in Ontario, Canada: A population-based time series analysis.

BACKGROUND: Slow-release oral morphine (SROM) is used to manage pain, and as opioid agonist treatment (OAT). Between 2017 and 2021 in Canada, several drug shortages occurred for Kadian© (SROM-24). The purpose of this study was to evaluate the impact of these shortages on people's ability to remain on this medication. METHODS: We conducted a retrospective population-based time series analysis of SROM-24 dispensed between January 1, 2014, and December 31, 2021, in Ontario, Canada. Using interventional autoregressive integrated moving average models (ARIMA) models, we evaluated the association between SROM-24 drug shortages and treatment discontinuation. Analyses were also stratified by the SROM-24 indication (pain or OAT). RESULTS: We identified 22,479 SROM-24 recipients, of which one-third (33.9%) were aged 65 or above and just over half (51.9%) were female. In our primary analysis of monthly SROM-24 discontinuation, we observed a significant sustained monthly increase following the shortages in November 2019 (+0.29%/month; 95% CI: 0.16%, 0.43%; p < .001) with significant sudden, temporary changes following the shortages in March 2020 (+2.00%; 95% CI: 0.95%, 3.05%; p < .001), July 2021 (+3.53%; 95% CI: 2.20%, 4.86%; p < .001), and August 2021 (+4.98%; 95% CI: 3.49%, 6.47%; p < .001). Similar results were observed in our stratified analyses, with sustained high rates of discontinuation among people accessing SROM-24 as OAT. CONCLUSIONS: The SROM-24 shortages resulted in significant treatment disruptions across all recipients. These findings have important implications for those with few treatment alternatives, including people using SROM-24 as OAT who are at risk of adverse outcomes following treatment disruptions.

Methadone-involved overdose deaths in the United States before and during the COVID-19 pandemic.

BACKGROUND: Few studies have characterized methadone-involved overdose deaths in the US since 2014 despite changing patterns of opioid use, the onset of the COVID-19 pandemic, and changes to take-home dose guidance in opioid treatment programs (OTPs) in March 2020. METHODS: Data on monthly overdose deaths in the US from January 1, 2007 to March 31, 2021 were obtained through CDC WONDER. Interrupted time series models were used to assess for changes in series levels starting in April 2020. Analyses were stratified by involvement of synthetic opioids in overdose deaths. RESULTS: An increase in methadone-involved overdoses of 105.4 deaths per month (95 % CI: 73.8-137.0) occurred starting in April 2020 compared with prior trends (p < 0.001). Trends in methadone-involved overdose deaths showed a step increase starting in April 2020 both with (54.2 deaths per month; 95 % CI: 39.4-68.9) and without (51.7 deaths per month; 95 % CI: 23.4-78.0) synthetic opioid involvement (p < 0.001 for both). Among overdose deaths without synthetic opioids, the increase in methadone-involved overdose deaths accounted for 26.5 % of the increase between the 12-month periods before and after March 2020. The relative percentage increase in methadone-involved overdose deaths, both with and without synthetic opioid co-involvement, was highest among Hispanic and non-Hispanic Black individuals. CONCLUSIONS: Methadone-involved overdose deaths, both with and without other synthetic opioid co-involvement, increased during the 12-month period after March 2020, compared with prior trends. These results provide a cautionary addition to previous findings of no or limited methadone-related harms after the US regulatory changes during the COVID-19 pandemic.

Suicide, Homicide, and Other Violent Deaths Among People Experiencing Homelessness in the United States: A Cross-sectional Study.

OBJECTIVES: Limited information exists about violent deaths among people experiencing homelessness (PEH) across the United States. Using data from a national reporting system, we describe characteristics of suicides, homicides, and other deaths classified as violent among PEH in the United States. METHODS: We obtained data on demographic characteristics, mechanisms of injury, and circumstances surrounding violent deaths from January 1, 2016, through December 31, 2018, in 31 states from the National Violent Death Reporting System. RESULTS: Of 122 113 violent deaths in 31 states during 2016-2018, 1757 (1.4%) occurred among PEH and 3952 (3.2%) occurred among people for whom homelessness status was unknown or missing. Of all violent deaths among PEH, 878 were suicides (1.1% of all suicides), 458 were homicides (1.6% of all homicides), 352 were of undetermined intent (2.8% of all deaths of undetermined intent), and 59 were the result of legal interventions (3.8% of all deaths due to legal interventions). Hanging/suffocation/strangulation was the most common mechanism of suicide among PEH (44.4%), followed by deaths due to firearms (21.6%). Firearms were the most common mechanism of homicide deaths among PEH (48.0%). Black PEH were more likely to die by homicide than by suicide, and White PEH were more likely to die by suicide than by homicide. Among the 843 suicide victims for whom additional information was known, 345 (40.9%) had a history of suicidal thoughts or plans, 245 (29.1%) had disclosed intent to die by suicide, and 183 (21.7%) were receiving treatment for a mental health condition. CONCLUSIONS: Efforts to reduce mortality and improve health outcomes among PEH should consider the high rates of violent deaths in this population.

Taking an Evidence-Based Approach to Involuntary Psychiatric Hospitalization.

The field of psychiatry has placed a growing emphasis on research-based diagnostic and treatment practices related to mental illness. Involuntary hospitalization is a controversial and potentially lifesaving intervention in psychiatric care; yet, to what degree is this practice evidence based? This Open Forum examines the ethical and logistical limitations to traditional research, such as randomized controlled trials and observational studies, surrounding involuntary psychiatric hospitalization. Given recent efforts across the United States to expand the use of involuntary hospitalization, the authors call for systematic data collection to monitor, study, and guide the use of this intervention.

Benzodiazepine-Involved Overdose Deaths in the USA: 2000-2019.

BACKGROUND: Despite 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. OBJECTIVE: To characterize co-involved substances, intentionality, and demographics of benzodiazepine-involved overdose deaths in the USA from 2000 to 2019. DESIGN: Cross-sectional study using national mortality records from the National Vital Statistics System. SUBJECTS: US residents in the 50 states and District of Columbia who died from a benzodiazepine-involved overdose from 2000 to 2019. MAIN MEASURES: Demographic characteristics, intention of overdose, and co-involved substances KEY RESULTS: A 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. CONCLUSIONS: Interventions to reduce benzodiazepine-involved overdose mortality should consider the demographics of, co-involved substances in, and presence of suicides among benzodiazepine-involved overdose deaths.