Illicit Opioid Intoxication: Diagnosis and Treatment

Opioid intoxications and overdose are associated with high rates of morbidity and mortality. Opioid overdose may occur in the setting of intravenous or intranasal heroin use, illicit use of diverted opioid medications, intentional or accidental misuse of prescription pain medications, or iatrogenic overdose. In this review, we focused on the epidemiology of illict opioid use in the United States and on the mechanism of action of opioid drugs. We also described the signs and symptoms, and diagnoses of intoxication and overdose. Lastly, we updated the reader about the most recent recommendations for treatment and prevention of opioid intoxications and overdose.

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Pharmacologic and Clinical Considerations of Nalmefene, a Long Duration Opioid Antagonist, in Opioid Overdose

Psychiatry International ◽

10.3390/psychiatryint2040028 ◽

2021 ◽

Vol 2 (4) ◽

pp. 365-378

Author(s):

Amber N. Edinoff ◽

Catherine A. Nix ◽

Tanner D. Reed ◽

Elizabeth M. Bozner ◽

Mark R. Alvarez ◽

...

Keyword(s):

Respiratory Depression ◽

The United States ◽

Opioid Use Disorder ◽

Opioid Antagonist ◽

Opioid Overdose ◽

Opioid Use ◽

Physical Damage ◽

Onset Of Action ◽

Duration Of Action ◽

Opioid Intoxication

Opioid use disorder is a well-established and growing problem in the United States. It is responsible for both psychosocial and physical damage to the affected individuals with a significant mortality rate. Given both the medical and non-medical consequences of this epidemic, it is important to understand the current treatments and approaches to opioid use disorder and acute opioid overdose. Naloxone is a competitive mu-opioid receptor antagonist that is used for the reversal of opioid intoxication. When given intravenously, naloxone has an onset of action of approximately 2 min with a duration of action of 60–90 min. Related to its empirical dosing and short duration of action, frequent monitoring of the patient is required so that the effects of opioid toxicity, namely respiratory depression, do not return to wreak havoc. Nalmefene is a pure opioid antagonist structurally similar to naltrexone that can serve as an alternative antidote for reversing respiratory depression associated with acute opioid overdose. Nalmefene is also known as 6-methylene naltrexone. Its main features of interest are its prolonged duration of action that surpasses most opioids and its ability to serve as an antidote for acute opioid overdose. This can be pivotal in reducing healthcare costs, increasing patient satisfaction, and redistributing the time that healthcare staff spend monitoring opioid overdose patients given naloxone.

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The Concurrent Initiation of Medications Is Associated with Discontinuation of Buprenorphine Treatment for Opioid Use Disorder

10.1101/2020.01.15.20017715 ◽

2020 ◽

Author(s):

Pengyue Zhang ◽

Chien-Wei Chiang ◽

Sara Quinney ◽

Macarius Donneyong ◽

Bo Lu ◽

...

Keyword(s):

Large Scale ◽

The United States ◽

Opioid Use Disorder ◽

Retention Rates ◽

P Value ◽

Opioid Use ◽

Pain Medications ◽

Real World Evidence ◽

Opioid Medications ◽

Buprenorphine Treatment

ABSTRACTIntroductionRetention in buprenorphine treatment for opioid use disorder (OUD) yields better opioid abstinence and reduces all-cause mortality for patients with OUD. Despite significant efforts have been made to expand the availability and use of buprenorphine in the United States, its retention rates remain on a low level. The current study examines discontinuation of buprenorphine with respect to concurrent initiation of other medications using real-world evidence.MethodsCase-crossover study was conducted to examine discontinuation of buprenorphine using a large-scale longitudinal health dataset including 148,306 commercially-insured individuals initiated on medications for opioid use disorder (MOUD). Odds ratios and Bonferroni adjusted p-values were calculated for medications and therapeutic classes of medications.ResultsClonidine was associated with increased discontinuation risk of buprenorphine both using the buprenorphine dataset alone (OR = 1.583 and adjusted p-value = 1.22 × 10−6) and using naltrexone as a comparison drug (OR = 2.706 and adjusted p-value = 4.11 × 10−5). Opioid medications (oxycodone, morphine and fentanyl) and methocarbamol were associated with increased discontinuation risk of buprenorphine using the buprenorphine dataset alone (adjusted p-value < 0.05), but not significant using naltrexone as a comparison drug. 6 drug therapeutic classes were associated with increased discontinuation risk of buprenorphine both using the buprenorphine dataset alone and using naltrexone as a comparison drug (adjusted p-value < 0.05).ConclusionConcurrent initiation of medications is associated with increased discontinuation risk of buprenorphine. Opioid medications are prescribed among patients on MOUD and associated with increased discontinuation risk of buprenorphine. Analgesics is associated with increased discontinuation risk of buprenorphine for patients without previous exposure of pain medications.

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Assessing the Relationships Between COVID-19 Stay-at-Home Orders and Opioid Overdoses in the State of Pennsylvania

Journal of Drug Issues ◽

10.1177/00220426211006362 ◽

2021 ◽

pp. 002204262110063

Author(s):

Brian King ◽

Ruchi Patel ◽

Andrea Rishworth

Keyword(s):

Age Groups ◽

The United States ◽

Opioid Use Disorder ◽

Opioid Overdose ◽

Policy Recommendations ◽

Opioid Use ◽

Fentanyl Analogs ◽

Measure Change ◽

Using Data ◽

At Home

COVID-19 is compounding opioid use disorder throughout the United States. While recent commentaries provide useful policy recommendations, few studies examine the intersection of COVID-19 policy responses and patterns of opioid overdose. We examine opioid overdoses prior to and following the Pennsylvania stay-at-home order implemented on April 1, 2020. Using data from the Pennsylvania Overdose Information Network, we measure change in monthly incidents of opioid-related overdose pre- versus post-April 1, and the significance of change by gender, age, race, drug class, and naloxone doses administered. Findings demonstrate statistically significant increases in overdose incidents among both men and women, White and Black groups, and several age groups, most notably the 30–39 and 40–49 ranges, following April 1. Significant increases were observed for overdoses involving heroin, fentanyl, fentanyl analogs or other synthetic opioids, pharmaceutical opioids, and carfentanil. The study emphasizes the need for opioid use to be addressed alongside efforts to mitigate and manage COVID-19 infection.

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Preparing pharmacists to increase naloxone dispensing within community pharmacies under the Pennsylvania standing order

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxaa387 ◽

2020 ◽

Author(s):

Heather M Santa ◽

Samira G Amirova ◽

Daniel J Ventricelli ◽

George E Downs ◽

Alexandra A Nowalk ◽

...

Keyword(s):

Community Pharmacists ◽

The United States ◽

Health Concern ◽

Community Pharmacies ◽

Opioid Overdose ◽

Patient Counseling ◽

Opioid Use ◽

Overdose Prevention ◽

Standing Order ◽

Overdose Deaths

Abstract Purpose Opioid misuse and overdose deaths remain a public health concern in the United States. Pennsylvania has one of the highest rates of opioid overdose deaths in the country, with Philadelphia County’s being 3 times higher than the national average. Despite several multimodal interventions, including use of SBIRT (screening, brief intervention, and referral to treatment) methods and naloxone distribution, the rate of overdose deaths remains high. Methods To gain insights on strategies for improving access to naloxone and naloxone distribution by pharmacists in Philadelphia County, a study was conducted in 11 community pharmacies (chain and independent) in Philadelphia. Twenty-four pharmacists were recruited and completed SBIRT and naloxone trainings. Each pharmacy elected to have at least 1 pharmacy champion who received additional training on and helped develop pharmacy site–specific naloxone dispensing protocols. Results Pre-post survey results showed a reduction in stigmatizing attitudes regarding naloxone dispensing and an increase in pharmacists’ understanding of the standing order and appropriate naloxone use. There was an increase in pharmacists’ self-reported confidence in their ability to appropriately identify, discuss, and dispense naloxone to patients. All pharmacies increased their average monthly dispensing rate following protocol implementation. Conclusion Pharmacists who received both trainings were more likely to change naloxone dispensing practices, leading to an overall increase in naloxone dispensing by community pharmacists. The study addressed overall gaps in pharmacists’ knowledge, reduced stigma, and prepared pharmacists to address opioid use and overdose prevention with their patients. The described pharmacist-led patient counseling and intervention service for overdose prevention may be explored as a model for other community pharmacies to adopt to improve naloxone dispensing and similar interventions to reduce overdose deaths.

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Differences in Opioid Overdose Mortality Rates Among Middle-Aged Adults by Race/Ethnicity and Sex, 1999-2018

Public Health Reports ◽

10.1177/0033354920968806 ◽

2020 ◽

pp. 003335492096880

Author(s):

Rachel A. Hoopsick ◽

Gregory G. Homish ◽

Kenneth E. Leonard

Keyword(s):

The United States ◽

Mortality Rates ◽

Opioid Overdose ◽

Research Database ◽

Opioid Use ◽

Middle Aged ◽

Synthetic Opioids ◽

Race Ethnicity ◽

Middle Aged Adults ◽

Overdose Mortality

Objectives The types of opioids abused in the United States have changed from prescription opioids to heroin to fentanyl. However, the types of opioids abused may differ by demographic factors, especially among middle-aged adults. We examined national trends in opioid overdose mortality rates among middle-aged adults by race/ethnicity and sex. Methods Using 1999-2018 data from the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research database, we examined overdose mortality rates per 100 000 population in 2018 among adults aged 45-64 that involved natural and semisynthetic opioids, heroin, synthetic opioids (excluding methadone), and methadone. We tested for significant differences in mortality rates by race/ethnicity and sex. We plotted drug-specific trends by race/ethnicity and sex from 1999 to 2018. Results In 2018, non-Hispanic White adults had the highest rates per 100 000 population of natural and semisynthetic overdose mortality (men: 8.7; women: 7.9; P < .001), and non-Hispanic Black adults had the highest rates of heroin (men: 17.7; women: 5.4; P < .001) and synthetic opioid (men: 36.0; women: 11.2; P < .001) overdose mortality. Men had significantly higher overdose mortality rates than women did for deaths involving natural and semisynthetic opioids, heroin, and synthetic opioids, but not methadone. From 1999 to 2018, mortality rates increased sharply for heroin and synthetic opioids, increased modestly for natural and semisynthetic opioids, and decreased for methadone. The greatest increases were among non-Hispanic Black men for heroin overdose (3.3 in 1999 to 17.7 in 2018) and synthetic opioid overdose (0.1 in 1999 to 36.0 in 2018). Conclusions Policy making should consider unique subgroup risks and alternative trajectories of opioid use other than people being prescribed opioids, developing opioid use disorder, subsequently moving to heroin, and then to fentanyl.

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Discrepancies in Written Versus Calculated Durations in Opioid Prescriptions: Pre-Post Study (Preprint)

10.2196/preprints.16199 ◽

2019 ◽

Author(s):

Benjamin H Slovis ◽

John Kairys ◽

Bracken Babula ◽

Melanie Girondo ◽

Cara Martino ◽

...

Keyword(s):

The United States ◽

Opioid Use ◽

Duration Of Treatment ◽

Record System ◽

Opioid Prescription ◽

Increased Risk ◽

The Us ◽

Control And Prevention ◽

Opioid Medications

BACKGROUND The United States is in the midst of an opioid epidemic. Long-term use of opioid medications is associated with an increased risk of dependence. The US Centers for Disease Control and Prevention makes specific recommendations regarding opioid prescribing, including that prescription quantities should not exceed the intended duration of treatment. OBJECTIVE The purpose of this study was to determine if opioid prescription quantities written at our institution exceed intended duration of treatment and whether enhancements to our electronic health record system improved any discrepancies. METHODS We examined the opioid prescriptions written at our institution for a 22-month period. We examined the duration of treatment documented in the prescription itself and calculated a duration based on the quantity of tablets and doses per day. We determined whether requiring documentation of the prescription duration affected these outcomes. RESULTS We reviewed 72,314 opioid prescriptions, of which 16.96% had a calculated duration that was greater than what was documented in the prescription. Making the duration a required field significantly reduced this discrepancy (17.95% vs 16.21%, <i>P</i><.001) but did not eliminate it. CONCLUSIONS Health information technology vendors should develop tools that, by default, accurately represent prescription durations and/or modify doses and quantities dispensed based on provider-entered durations. This would potentially reduce unintended prolonged opioid use and reduce the potential for long-term dependence.

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Epigenome-Wide Study of Brain DNA Methylation Among Opioid Users and Controls

10.1101/2020.11.10.377069 ◽

2020 ◽

Author(s):

Chang Shu ◽

David W. Sosnowski ◽

Ran Tao ◽

Amy Deep-Soboslay ◽

Joel E. Kleinman ◽

...

Keyword(s):

Dna Methylation ◽

Multiple Testing ◽

The United States ◽

Opioid Abuse ◽

Current Evidence ◽

Opioid Use ◽

Multiple Testing Correction ◽

Potential Biomarker ◽

Opioid Intoxication ◽

Opioid Users

AbstractOpioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. To clarify the association between opioid abuse and DNA methylation, we conducted an epigenome-wide analysis (EWAS) of DNA methylation in brains of individuals who died from opioid intoxication and controls. Tissue samples were extracted from the dorsolateral prefrontal cortex of 160 deceased individuals (Mage = 35.15, SD = 9.42 years; 62% male; 78% White). The samples included 73 individuals who died of opioid intoxication, 59 group-matched psychiatric controls, and 28 group-matched normal controls. EWAS was implemented using the Illumina Infinium MethylationEPIC BeadChip; analyses adjusted for sociodemographic characteristics, negative control and ancestry principal components, cellular composition, and surrogate variables. Epigenetic age was calculated using the Horvath and Levine clocks, and gene ontology (GO) analyses were performed. No CpG sites were epigenome-wide significant after multiple testing correction, but 13 sites reached nominal significance (p < 1.0 x 10-5). There was a significant association between opioid use and Levine phenotypic age (b = 2.24, se = 1.11, p = .045). Opioid users were approximately two years phenotypically older compared to controls. GO analyses revealed enriched pathways related to cell function and neuron differentiation, but no terms survived multiple testing correction. Results inform our understanding of the neurobiology of opioid use, and future research with larger samples across stages of opioid use will elucidate the complex genomics of opioid abuse.

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If We Build It, Will They Come? Perspectives on Pharmacy-Based Naloxone Among Family and Friends of People who use Opioids: A Mixed Methods Study

10.21203/rs.3.rs-1167901/v1 ◽

2021 ◽

Author(s):

Susannah Slocum ◽

Jenny E. Ozga ◽

Alexander Y. Walley ◽

Robin A. Pollini ◽

Rebecca Joyce

Keyword(s):

Mixed Methods ◽

Drug Use ◽

Support Groups ◽

Perceived Risk ◽

The United States ◽

Opioid Antagonist ◽

Prescription Opioid ◽

Opioid Overdose ◽

Opioid Use ◽

The Impact

Abstract Background: Expanding access to the opioid antagonist naloxone to reduce overdose mortality is a public health priority in the United States. Naloxone standing orders (NSOs) have been established in many states to increase naloxone dispensing at pharmacies, but increased pharmacy access does not ensure optimal uptake among those likely to witness an overdose. In a prior statewide purchase trial, we documented high levels of naloxone access at Massachusetts pharmacies under a statewide NSO. In this study, we characterize barriers to pharmacy-based naloxone uptake among potential opioid overdose “bystanders” (friends or family of people who use opioids) that may be amenable to intervention.Methods: Eligible bystanders were Massachusetts residents >18 years of age, did not use illicit opioids in the past 30 days, and knew someone who currently uses illicit opioids. We used a sequential mixed methods approach, in which a series of semi-structured qualitative interviews (N=22) were conducted to inform the development of a subsequent quantitative survey (N=260). Results: Most survey participants (77%) reported ever obtaining naloxone but few (21%) attempted to purchase it at a pharmacy. Qualitative participants revealed that barriers to utilizing the NSO included low perceived risk of overdose, which was rooted in misconceptions regarding the risks of prescription opioid misuse, denial about their loved one’s drug use, and drug use stereotypes; inaccurate beliefs about the impact of naloxone on riskier opioid use; and concerns regarding anticipated stigma and confidentiality. Many participants had engaged in mutual support groups, which served as a source of free naloxone for half (50%) of those who had ever obtained naloxone.Conclusions: Despite high levels of pharmacy naloxone access in Massachusetts, few bystanders in our study had attempted to obtain naloxone under the NSO. Low perceived risk of overdose, misinformation, stigma and confidentiality were important barriers to pharmacy naloxone uptake, all of which are amenable to intervention. Support groups provided a setting for addressing stigma and misinformation and provided a discreet and comfortable setting for naloxone access. Where these groups do not exist and for bystanders who do not participate in such groups, pharmacies are well-positioned to fill gaps in naloxone availability.

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1045Patterns, predictors and outcomes of opioid use in Australia: evidence for an epidemic?

International Journal of Epidemiology ◽

10.1093/ije/dyab168.309 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Jenni Ilomaki ◽

Samanta Lalic ◽

Natasa Gisev ◽

Suzanne Nielsen

Keyword(s):

Data Analysis ◽

Motor Vehicle ◽

The United States ◽

Prescription Opioid ◽

High Dose ◽

Opioid Use ◽

Head Of School ◽

Pain Medications ◽

Strong Opioids

Abstract Focus and outcomes for participants This symposium will focus on evidence from pharmacoepidemiological research on prevalence and incidence of prescription opioid prevalence, opioid utilisation patterns and related harms in Australia. The symposium will also discuss interventions to reduce opioid-related harm. The speakers will discuss how opioid use and prescribing culture has evolved over the last two decades and provide insight from recent research using big data analysis on prescription opioid use and related outcomes. Rationale for the symposium, including for its inclusion in the Congress In 2016, there were 679 overdose deaths involving opioid pain medications in Australia, with the majority of these deaths unintentional. There is growing concern that harm from opioid pain medications in Australia may mimic the situation in the United States and Canada, where the problem has been labelled an epidemic. Recent Monash led research using Australia’s Pharmaceutical Benefits Scheme data for 2013 to 2018 found that approximately 3 million Australians adults use opioids each year and approximately 1.9 million adults start taking opioids. Of this population of adults that start using opioids, 2.6% become long-term users for over a year. Long-term use and the use of strong opioids are associated with a range of adverse health outcomes. High-dose opioid use has also been associated with falls, fractures, hospitalisations and motor vehicle injuries. The rationale of this symposium is to draw on the expertise of the presenters and share innovative epidemiological and data analysis methods to understand opioid use in the Australian context. The creation of such a forum at the World Congress will allow for enhanced knowledge sharing on both a national and international platform and assist in planning strategies to better anticipate and manage potential harms when opioid pain medications are initiated. Presentation program The Symposium consists of four presentations: Names of presenters Names of facilitator or chair Professor Danny Liew, Deputy Head of School, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia Ms. Michelle Steeper, Research Officer, Centre for Medicine Use and Safety, Monash University, Melbourne, Australia

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Opioid Overdose Education, Prevention, and Management (DRAFT)

10.1093/med/9780190265366.003.0013 ◽

2018 ◽

Cited By ~ 1

Author(s):

Bernd Wollschlaeger

Keyword(s):

The United States ◽

Opioid Use Disorder ◽

Opioid Overdose ◽

Opioid Use ◽

Death Rates ◽

Overdose Prevention ◽

Overdose Death ◽

Good Samaritan ◽

Opioid Deaths ◽

Good Samaritan Laws

In reviewing the elements of opioid overdose education, prevention, and management, this chapter focuses particularly on practical interventions that are available and deserve advocacy; e.g., provision of naloxone to those with opioid use disorder and to possible first responders. It moves from a discussion of the epidemiology of opioid deaths to the more individual topic of patient risk for overdose. Prophylactic interventions in the form of education of the patient’s family and friends, and agreements for treatment with informed consent are described. There follows a discussion of management of the opioid poisoning itself, including use/distribution of naloxone injection. Two figures are included: drug overdose death rates in the United States (2014); a map describing the current states with naloxone or “good Samaritan” laws impacting opioid overdose management. A text box with resources includes directions for initiation of community overdose prevention and intervention schemes.

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