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Psychopharmacology Jul 2022The USA has recently entered the third decade of the opioid epidemic. Opioid overdose deaths reached a new record of over 74,000 in a 12-month period ending April 2021.... (Review)
Review
BACKGROUND
The USA has recently entered the third decade of the opioid epidemic. Opioid overdose deaths reached a new record of over 74,000 in a 12-month period ending April 2021. Naloxone is the primary opioid overdose reversal agent, but concern has been raised that naloxone is not efficacious against the pervasive illicit high potency opioids (i.e., fentanyl and fentanyl analogs).
METHODS
This narrative review provides a brief overview of naloxone, including its history and pharmacology, and the evidence regarding naloxone efficacy against fentanyl and fentanyl analogs. We also highlight current advances in overdose treatments and technologies that have been tested in humans.
RESULTS AND CONCLUSIONS
The argument that naloxone is not efficacious against fentanyl and fentanyl analogs rests on case studies, retrospective analyses of community outbreaks, pharmacokinetics, and pharmacodynamics. No well-controlled studies have been conducted to test this argument, and the current literature provides limited evidence to suggest that naloxone is ineffective against fentanyl or fentanyl analog overdose. Rather a central concern for treating fentanyl/fentanyl analog overdose is the rapidity of overdose onset and the narrow window for treatment. It is also difficult to determine if other non-opioid substances are contributing to a drug overdose, for which naloxone is not an effective treatment. Alternative pharmacological approaches that are currently being studied in humans include other opioid receptor antagonists (e.g., nalmefene), respiratory stimulants, and buprenorphine. None of these approaches target polysubstance overdose and only one novel approach (a wearable naloxone delivery device) would address the narrow treatment window.
Topics: Analgesics, Opioid; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Fentanyl; Humans; Illicit Drugs; Naloxone; Narcotic Antagonists; Opiate Overdose; Retrospective Studies
PubMed: 35385972
DOI: 10.1007/s00213-022-06125-5 -
Pharmacology & Therapeutics May 2022Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This... (Review)
Review
Overdose deaths are often viewed as the leading edge of the opioid epidemic which has gripped the United States over the past two decades (Skolnick, 2018a). This emphasis is perhaps unsurprising because opioid overdose is both the number-one cause of death for individuals between 25 and 64 years old (Dezfulian et al., 2021) and a significant contributor to the decline in average lifespan (Dowell et al., 2017). Exacerbated by the COVID 19 pandemic, it was estimated there were 93,400 drug overdose deaths in the United States during the 12 months ending December 2020, with more than 69,000 (that is, >74%) of these fatalities attributed to opioid overdose (Ahmad et al., 2021). However, the focus on mortality statistics (Ahmad et al., 2021; Shover et al., 2020) tends to obscure the broader medical impact of nonfatal opioid overdose. Analyses of multiple databases indicate that for each opioid-induced fatality, there are between 6.4 and 8.4 non-fatal overdoses, exacting a significant burden on both the individual and society. Over the past 7-8 years, there has been an alarming increase in the misuse of synthetic opioids ("synthetics"), primarily fentanyl and related piperidine-based analogs. Within the past 2-3 years, a structurally unrelated class of high potency synthetics, benzimidazoles exemplified by etonitazene and isotonitazene ("iso"), have also appeared in illicit drug markets (Thompson, 2020; Ujvary et al. 2021). In 2020, it was estimated that over 80% of fatal opioid overdoses in the United States now involve synthetics (Ahmad et al., 2021). The unique physicochemical and pharmacological properties of synthetics described in this review are responsible for both the morbidity and mortality associated with their misuse as well as their widespread availability. This dramatic increase in the misuse of synthetics is often referred to as the "3rd wave" (Pardo et al., 2019; Volkow and Blanco, 2020) of the opioid epidemic. Among the consequences resulting from misuse of these potent opioids is the need for higher doses of the competitive antagonist, naloxone, to reverse an overdose. The development of more effective reversal agents such as those described in this review is an essential component of a tripartite strategy (Volkow and Collins, 2017) to reduce the biopsychosocial impact of opioid misuse in the "synthetic era".
Topics: Adult; Analgesics, Opioid; Drug Overdose; Humans; Middle Aged; Naloxone; Opiate Overdose; United States; COVID-19 Drug Treatment
PubMed: 34637841
DOI: 10.1016/j.pharmthera.2021.108019 -
Drug and Alcohol Dependence Jan 2021The United States (U.S.) is experiencing an ongoing opioid crisis. Economic burden estimates that describe the impact of the crisis are needed when considering federal...
BACKGROUND
The United States (U.S.) is experiencing an ongoing opioid crisis. Economic burden estimates that describe the impact of the crisis are needed when considering federal and state resources devoted to addressing overdoses. In this study, we estimate the societal costs for opioid use disorder and fatal overdose from all opioids in 2017.
METHODS
We estimated costs of fatal overdose from all opioids and opioid use disorder based on the incidence of overdose deaths and the prevalence of past-year opioid use disorder for 2017. Incidence of fatal opioid overdose was obtained from the National Vital Statistics System; prevalence of past-year opioid use disorder was estimated from the National Survey of Drug Use and Health. Costs were estimated for health care, criminal justice and lost productivity. Costs for the reduced quality of life for opioid use disorder and life lost due to fatal opioid overdose were valued using U.S. Department of Health and Human Services guidelines for valuing reductions in morbidity and mortality.
RESULTS
Costs for opioid use disorder and fatal opioid overdose in 2017 were estimated to be $1.02 trillion. The majority of the economic burden is due to reduced quality of life from opioid use disorder and the value of life lost due to fatal opioid overdose.
CONCLUSIONS
These estimates can assist decision makers in understanding the magnitude of opioid use disorder and fatal overdose. Knowing the magnitude and distribution of the economic burden can inform public policy, clinical practice, research, and prevention and response activities.
Topics: Analgesics, Opioid; Cost of Illness; Criminal Law; Delivery of Health Care; Drug Overdose; Humans; Opiate Overdose; Opioid Epidemic; Opioid-Related Disorders; Prevalence; Quality of Life; United States
PubMed: 33121867
DOI: 10.1016/j.drugalcdep.2020.108350 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2023Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States....
INTRODUCTION
Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures.
METHODS
This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary).
RESULTS
Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94).
CONCLUSIONS
In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.
Topics: Adult; Humans; United States; Analgesics, Opioid; Xylazine; Opiate Overdose; Prospective Studies; Coma; Fentanyl; Drug Overdose; Emergency Service, Hospital
PubMed: 37014353
DOI: 10.1080/15563650.2022.2159427 -
JAMA Apr 2022This study assesses trends in drug overdose deaths among US adolescents aged 14 to 18 years from January 2010 to June 2021, by substance type and race and ethnicity,...
This study assesses trends in drug overdose deaths among US adolescents aged 14 to 18 years from January 2010 to June 2021, by substance type and race and ethnicity, using data from the Centers for Disease Control and Prevention WONDER database.
Topics: Adolescent; Analgesics, Opioid; Drug Overdose; Humans; United States
PubMed: 35412573
DOI: 10.1001/jama.2022.2847 -
Drug and Alcohol Dependence Jan 2022Alcohol-involved overdose deaths are increasing and often occur with other substances but have been minimally studied compared to other causes of overdose.
BACKGROUND
Alcohol-involved overdose deaths are increasing and often occur with other substances but have been minimally studied compared to other causes of overdose.
METHODS
We used national Veterans Health Administration (VHA) records linked to National Death Index data from 2012 to 2018 to examine trends in alcohol-related overdose mortality. Patient characteristics and treatment receipt were compared across categories of alcohol overdose deaths (alcohol-only, alcohol+opioids which may include additional substances, and alcohol+other substances without opioids).
RESULTS
From 2012-2018, 2421 Veterans died from an alcohol-involved overdose (alcohol-only: 868, alcohol+opioids: 1269, alcohol+other substances: 284). The alcohol-involved overdose rate increased 57% during this period. Compared to those who died of an alcohol-only overdose, Veterans who died from alcohol+opioids and alcohol+other substances were more likely Black or Hispanic, and to have an opioid use disorder, but less likely to live in rural areas or to be diagnosed with alcohol use disorder (AUD). Only 32.5% of those who died from alcohol-involved overdose received treatment in a substance use disorder clinic in the year preceding death, compared to 65.1% seen in mental health and 85.7% in primary care. Only 9.5% of Veterans who died from alcohol overdose received medication treatment for AUD and 24.8% received psychotherapy for AUD in the year preceding death.
CONCLUSIONS
Alcohol overdose is increasing primarily related to overdoses involving opioids and other substances. Most patients did not receive any effective medication or psychotherapy treatments for AUD, suggesting further need to identify those at risk and to target treatment for this vulnerable group in healthcare settings.
Topics: Alcoholism; Analgesics, Opioid; Drug Overdose; Humans; Opioid-Related Disorders; Veterans
PubMed: 34894477
DOI: 10.1016/j.drugalcdep.2021.109196 -
Journal of Health Organization and... Nov 2019The purpose of this paper is to present a detailed case study of the evaluation strategies of a complex, multi-faceted response to a public health emergency:...
PURPOSE
The purpose of this paper is to present a detailed case study of the evaluation strategies of a complex, multi-faceted response to a public health emergency: drug-related overdose deaths. It sets out the challenges of evaluating such a complex response and how they were overcome. It provides a pragmatic example of the rationale and issues faced to address the what, the why and particularly the how of the evaluation.
DESIGN/METHODOLOGY/APPROACH
The case study overviews British Columbia's Provincial Response to the Overdose Public Health Emergency, and the aims and scope of its evaluation. It then outlines the conceptual approach taken to the evaluation, setting out key methodological challenges in evaluating large-scale, multi-level, multisectoral change.
FINDINGS
The evaluation is developmental and summative, utilization focused and system informed. Defining the scope of the evaluation required a strong level of engagement with government leads, grantees and other evaluation stakeholders. Mixed method evaluation will be used to capture the complex pattern of relationships that have informed the overdose response. Working alongside people with drug use experience to both plan and inform the evaluation is critical to its success.
ORIGINALITY/VALUE
This case study builds on a growing literature on evaluating large-scale and complex service transformation, providing a practical example of this.
Topics: British Columbia; Drug Overdose; Humans; Opioid-Related Disorders; Public Health
PubMed: 32364344
DOI: 10.1108/JHOM-05-2019-0139 -
Annals of Medicine Dec 2022Alongside the emergence of COVID-19 in the United States, several reports highlighted increasing rates of opioid overdose from preliminary data. Yet, little is known...
INTRODUCTION
Alongside the emergence of COVID-19 in the United States, several reports highlighted increasing rates of opioid overdose from preliminary data. Yet, little is known about how state-level opioid overdose death trends and decedent characteristics have evolved using official death records.
METHODS
We requested vital statistics data from 2018-2020 from all 50 states and the District of Columbia, receiving data from 14 states. Accounting for COVID-19, we excluded states without data past March 2020, leaving 11 states for analysis. We defined state-specific analysis periods from March 13 until the latest reliable date in each state's data, then conducted retrospective year-over-year analyses comparing opioid-related overdose death rates, the presence of specific opioids and other psychoactive substances, and decedents' sex, race, and age from 2020 to 2019 and 2019 to 2018 within each state's analysis period. We assessed whether significant changes in 2020 vs. 2019 in opioid overdose deaths were new or continuing trends using joinpoint regression.
RESULTS
We found significant increases in opioid-related overdose death rates in Alaska (55.3%), Colorado (80.2%), Indiana (40.1%), Nevada (50.0%), North Carolina (30.5%), Rhode Island (29.6%), and Virginia (66.4%) - all continuing previous trends. Increases in synthetic opioid-involved overdose deaths were new in Alaska (136.5%), Indiana (27.6%), and Virginia (16.5%), whilst continuing in Colorado (44.4%), Connecticut (3.6%), Nevada (75.0%), and North Carolina (14.6%). We found new increases in male decedents in Indiana (12.0%), and continuing increases in Colorado (15.2%). We also found continuing increases in Black non-Hispanic decedents in Massachusetts (43.9%) and Virginia (33.7%).
CONCLUSION
This research analyzes vital statistics data from 11 states, highlighting new trends in opioid overdose deaths and decedent characteristics across 10 of these states. These findings can inform state-specific public health interventions and highlight the need for timely and comprehensive fatal opioid overdose data, especially amidst concurrent crises such as COVID-19. Key messages:Our results highlight shifts in opioid overdose trends during the COVID-19 pandemic that cannot otherwise be extracted from aggregated or provisional opioid overdose death data such as those published by the Centres for Disease Control and Prevention.Fentanyl and other synthetic opioids continue to drive increases in fatal overdoses, making it difficult to separate these trends from any possible COVID-19-related factors.Black non-Hispanic people are making up an increasing proportion of opioid overdose deaths in some states.State-specific limitations and variations in data-reporting for vital statistics make it challenging to acquire and analyse up-to-date data on opioid-related overdose deaths. More timely and comprehensive data are needed to generate broader insights on the nature of the intersecting opioid and COVID-19 crises.
Topics: Analgesics, Opioid; COVID-19; Drug Overdose; Humans; Male; Opiate Overdose; Pandemics; Retrospective Studies; United States
PubMed: 35467475
DOI: 10.1080/07853890.2022.2067350 -
Substance Abuse 2022Opioid overdose is a preventable injury leading to high morbidity and premature mortality in communities across the United States. Overdoses take place where people use...
BACKGROUND
Opioid overdose is a preventable injury leading to high morbidity and premature mortality in communities across the United States. Overdoses take place where people use drugs, including commercial and public locations like community pharmacies, and necessitate swift detection and response to avoid harm and, even more seriously, death. The presence of emergency and safety protocols improves occupational health and safety for all in the workplace. The aim of this study was to assess the prevalence of experience with on-site pharmacy overdose and to explore pharmacist and site characteristics associated with having a known protocol for responding to on-site overdose emergencies.
UNLABELLED
: An anonymous, online survey about naloxone provision and opioid safety was delivered by email, through professional pharmacy associations and continuing education attendance lists, to 3,100 pharmacists in Massachusetts and Rhode Island between October 2017 and January 2018. Survey items gauged socio-demographics, practice site characteristics, safer opioid dispensing and naloxone provision. Summary statistics and bivariate analyses were conducted to describe characteristics associated with items pertaining to on-site overdose policy awareness.
UNLABELLED
: Of the 357 respondents (11.5% response rate), 154 (5.0%) answered the questions of interest: 17.5% reported having at least one suspected overdose on-site at their practice location, while 42.9% reported that they were knowledgeable about and could locate at their practice location an on-site overdose protocol detailing how to respond to an overdose. Pharmacists who were knowledgeable about protocols were also more likely to offer naloxone to patients ( = 0.02) and did not practice at a chain pharmacy ( = 0.01).
UNLABELLED
: Community pharmacies that stock and distribute naloxone are key parts of community efforts to address the opioid crisis. Pharmacies and other healthcare settings should develop and implement on-site overdose response protocols and cultivate a norm of naloxone provision to patients.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Pharmacies; Pharmacists; Pharmacy; United States
PubMed: 32186478
DOI: 10.1080/08897077.2020.1736236 -
Drug and Alcohol Dependence Mar 2022Patients with medically-treated opioid overdose are at high risk for subsequent adverse outcomes, including repeat overdose. Understanding factors associated with repeat...
BACKGROUND
Patients with medically-treated opioid overdose are at high risk for subsequent adverse outcomes, including repeat overdose. Understanding factors associated with repeat overdose can aid in optimizing post-overdose interventions.
METHODS
We conducted a longitudinal, retrospective cohort study using NJ Medicaid data from 2014 to 2019. Medicaid beneficiaries aged 12-64 with an index opioid overdose from 2015 to 2018 were followed for one year for subsequent overdose. Exposures included patient demographics; co-occurring medical, mental health, and substance use disorders; service and medication use in the 180 days preceding the index overdose; and MOUD following index overdose.
RESULTS
Of 4898 individuals meeting inclusion criteria, 19.6% had repeat opioid overdoses within one year. Index overdoses involving heroin/synthetic opioids were associated with higher repeat overdose risk than those involving prescription/other opioids only (HR = 1.44, 95% CI = 1.22-1.71). Risk was higher for males and those with baseline opioid use disorder diagnosis or ED visits. Only 21.7% received MOUD at any point in the year following overdose. MOUD was associated with a large decrease in repeat overdose risk among those with index overdose involving heroin/synthetic opioids (HR = 0.30, 95% CI = 0.20-0.46). Among those receiving MOUD at any point in follow-up, 10.5% (112/1065) experienced repeat overdose versus 22.1% (848/3833) for those without MOUD.
CONCLUSIONS
Repeat overdose was common among individuals with medically-treated opioid overdose. Risk factors for repeat overdose varied by type of opioid involved in index overdose, with differential implications for intervention. MOUD following index opioid overdose involving heroin/synthetic opioids was associated with reduced repeat overdose risk.
Topics: Adolescent; Adult; Analgesics, Opioid; Child; Drug Overdose; Humans; Male; Medicaid; Middle Aged; Opiate Overdose; Opioid-Related Disorders; Retrospective Studies; Survivors; United States; Young Adult
PubMed: 35038609
DOI: 10.1016/j.drugalcdep.2022.109269