Increase In Overdose Deaths Research Articles

Counterfeit Medications and Fentanyl

The steep recent increase in overdose deaths and near-deaths nationwide involving fentanyl signals a new chapter in the epidemic of opioid use. Throughout the United States and Canada, seizures of pill presses, large quantities of active pharmaceutical ingredient in powder form, and counterfeit pills have been reported. Since fall 2013, the highly potent opioid fentanyl and its analogues have contributed to more than 5000 overdose deaths in the United States. In 2014, one-fifth of Ohio’s overdoses were associated with fentanyl; in 2015, two-thirds of New Hampshire’s fatal overdoses and half of Rhode Island’s overdoses were associated with fentanyl. The research letter by Arens et al1 in this issue of JAMA Internal Medicine reports a case series of counterfeit Xanax (alprazolam) tablets containing fentanyl and etizolam detected by poison control and emergency medical professionals in San Francisco, California. The authors should be commended for identifying and warning the public, to prevent further harm occurring as a result of the supply of this counterfeit medication. Language: en

The Opioid Challenge.

The Opioid Challenge.

Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature

Drug overdose is an important, yet an inadequately understood, public health problem. Global attention to unintentional drug overdose has been limited by comparison with the scope of the problem. There has been a substantial increase in drug overdose incidence and prevalence in several countries worldwide over the past decade, contributing to both increased costs and mortality. The aim of this study was to systematically synthesize the peer-reviewed literature to document the global epidemiological profile of unintentional drug overdoses and the prevalence, time trends, mortality rates, and correlates of drug overdoses. We searched different combinations of Medical Subject Headings (MeSH) terms in PubMed for articles published from 1980 until July 2013, and we organized these results in tabular spreadsheets and compared them. We restricted the search to English-language articles that deal with unintentional overdose, focusing on 1 or more of the following key constructs: prevalence, time trends, mortality rates, and correlates. The term "overdose" as a MeSH major topic yielded 1076 publications. In addition, we searched the following combinations of nonmajor MeSH terms: "street drugs" and "overdose" yielded 180, "death" and "overdose" yielded 114, and "poisoning" and "drug users" yielded 17. There was some overlap among the searches. Based on the search and inclusion and exclusion criteria, we selected a total of 169 relevant articles for this article based on a close review of abstracts. We found wide variability in lifetime prevalence of experiencing a nonfatal overdose or witnessing an overdose, and in mortality rates attributable to overdose. Lifetime prevalence of witnessed overdose among drug users (n = 17 samples) ranged from 50% to 96%, with a mean of 73.3%, a median of 70%, and a standard deviation of 14.1%. Lifetime prevalence of drug users personally experiencing a nonfatal overdose (n = 27 samples), ranged from 16.6% to 68.0% with a mean of 45.4%, a median of 47%, and a standard deviation of 14.4%. Population-based crude overdose mortality rates (n = 28 samples) ranged from 0.04 to 46.6 per 100 000 person-years. This range is likely attributable to the diversity in regions, time periods, and samples. Most studies on longitudinal trends of overdose death rates or overdose-related hospitalization rates showed increases in overdose death rates and in overdose-related hospitalization rates across time, which have led to peaks in these rates at the present time. An overall trend of increasing deaths from prescription opioid use and decreasing deaths from illicit drug use in the past several years has been noted across most of the literature. With the increase in prescription opioid overdose deaths, drug overdose is not just an urban problem: rural areas have seen an important increase in overdose deaths. Lastly, cocaine, prescription opioids, and heroin are the drugs most commonly associated with unintentional drug overdoses worldwide and the demographic and psychiatric correlates associated with unintentional drug overdoses are similar globally. There is a need to invest in research to understand the distinct determinants of prescription drug overdose worldwide. Several other countries need to collect in a systematic and continuous fashion such data on sales of prescription opioids and other prescription drugs, nonmedical use of prescription drugs, and hospitalization secondary to overdoses on prescription drugs. The sparse evidence on the environmental determinants of overdose suggests a need for research that will inform the types of environmental interventions we can use to prevent drug overdose. Methodological issues for future studies include enhancing data collection methods on unintentional fatal and nonfatal overdoses, and collecting more detailed information on drug use history, source of drug use (for prescription drugs), and demographic and psychiatric history characteristics of the individual who overdosed.

Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature.

Drug overdose is an important, yet an inadequately understood, public health problem. Global attention to unintentional drug overdose has been limited by comparison with the scope of the problem. There has been a substantial increase in drug overdose incidence and prevalence in several countries worldwide over the past decade, contributing to both increased costs and mortality. The aim of this study was to systematically synthesize the peer-reviewed literature to document the global epidemiological profile of unintentional drug overdoses and the prevalence, time trends, mortality rates, and correlates of drug overdoses. We searched different combinations of Medical Subject Headings (MeSH) terms in PubMed for articles published from 1980 until July 2013, and we organized these results in tabular spreadsheets and compared them. We restricted the search to English-language articles that deal with unintentional overdose, focusing on 1 or more of the following key constructs: prevalence, time trends, mortality rates, and correlates. The term "overdose" as a MeSH major topic yielded 1076 publications. In addition, we searched the following combinations of nonmajor MeSH terms: "street drugs" and "overdose" yielded 180, "death" and "overdose" yielded 114, and "poisoning" and "drug users" yielded 17. There was some overlap among the searches. Based on the search and inclusion and exclusion criteria, we selected a total of 169 relevant articles for this article based on a close review of abstracts. We found wide variability in lifetime prevalence of experiencing a nonfatal overdose or witnessing an overdose, and in mortality rates attributable to overdose. Lifetime prevalence of witnessed overdose among drug users (n = 17 samples) ranged from 50% to 96%, with a mean of 73.3%, a median of 70%, and a standard deviation of 14.1%. Lifetime prevalence of drug users personally experiencing a nonfatal overdose (n = 27 samples), ranged from 16.6% to 68.0% with a mean of 45.4%, a median of 47%, and a standard deviation of 14.4%. Population-based crude overdose mortality rates (n = 28 samples) ranged from 0.04 to 46.6 per 100 000 person-years. This range is likely attributable to the diversity in regions, time periods, and samples. Most studies on longitudinal trends of overdose death rates or overdose-related hospitalization rates showed increases in overdose death rates and in overdose-related hospitalization rates across time, which have led to peaks in these rates at the present time. An overall trend of increasing deaths from prescription opioid use and decreasing deaths from illicit drug use in the past several years has been noted across most of the literature. With the increase in prescription opioid overdose deaths, drug overdose is not just an urban problem: rural areas have seen an important increase in overdose deaths. Lastly, cocaine, prescription opioids, and heroin are the drugs most commonly associated with unintentional drug overdoses worldwide and the demographic and psychiatric correlates associated with unintentional drug overdoses are similar globally. There is a need to invest in research to understand the distinct determinants of prescription drug overdose worldwide. Several other countries need to collect in a systematic and continuous fashion such data on sales of prescription opioids and other prescription drugs, nonmedical use of prescription drugs, and hospitalization secondary to overdoses on prescription drugs. The sparse evidence on the environmental determinants of overdose suggests a need for research that will inform the types of environmental interventions we can use to prevent drug overdose. Methodological issues for future studies include enhancing data collection methods on unintentional fatal and nonfatal overdoses, and collecting more detailed information on drug use history, source of drug use (for prescription drugs), and demographic and psychiatric history characteristics of the individual who overdosed.

Abuse-deterrent opioid formulations: part of a public health strategy to reverse the opioid epidemic.

Rapid increases in the supplyofopioid analgesicshave largely driven the nearly unremitting increase in overdose deaths in the United States, which have grown bymore than 150%over thepast decade, from16 849 in 1999 to41 502 in 2012.1,2 Since the 1990s, opioid analgesic sales have increased more than 4-fold,with risingandwidely variable regional prescribing patterns. Increased market supply makes opioids more available for misuse and diversion to people engaging in recreational use and topeoplewith addiction. In both cases,misuseanddiversion increase, elevatingpopulationoverdose risk. In fact, geographic areas with higher opioid prescribing rates experience higher overdose rates.2 In addition, patient-level data demonstrate that the intensity of opioid exposure, includinghigherprescribeddosesand longerdurationof therapy, elevates overdose risk.3,4 Given this opioid-overdose epidemic, the clinical literature isunderstandably repletewithefforts that target individuals most at risk, including strategies such as routine screening for risk of addiction, patient agreements, andurine toxicologymonitoring.Unfortunately, these approaches havenot yet demonstratedwidespread effectiveness in reversing the epidemic.5 Public health approaches to reduce opioid-related overdosesarealsoneeded,sincemostoverdosesdonotoccuramong patients who are receiving daily prescribed opioids or among those receiving thehighestdosesdespite the fact thatdoseand daily use confer elevated risk at an individual level.2 In this issueofJAMAInternalMedicine,Larochelleandcolleagues6highlight the critical importance of one public health lever: market supply of opioids. The authors studied 2 nearly simultaneously implementedpharmaceuticalmarket changes among commercial health plan beneficiaries: substitution of abuse-deterrent long-actingoxycodonehydrochloride (which reducespotential tamperingof its time-releasemechanism) for the non–abuse-deterrent formulation and the removal of the weak opioid propoxyphene. Following thesemarket changes, the rate of nonfatal emergency department visits and inpatient visits for opioid analgesic overdoses decreased. The pharmaceutical market changes were also associated with a decrease in overall milligrams of morphineequivalent doses (MEDs) dispensed, resulting in adecrease of dispensed opioid dose per covered beneficiary from a high of 163 mg MED in late 2010 to 139 mg MED in early 2012. These market changes in the opioid supply may have reduced the numbers of overdoses for several reasons. With fewer opioids prescribed, beneficiaries with prescriptions consumed less, lowering individual risk, particularly from long-acting oxycodone,which is amore commonlyprescribedopioid than propoxypheneandassociatedwithhigheroverdose risk.3 Less opioidprescribing also likely led to fewer opioids available for diversion (to both beneficiaries andnonbeneficiaries), lowering population risk. Finally, making long-acting oxycodone availableonly inanabuse-deterrent formulationmayhaveprevented divertedmedications from being used parenterally or intranasally—both riskier than oral use. Regardless, making long-actingopioidsexclusivelyavailable inabuse-deterrent formulations, particularly for new medications as they are released to the market, is a structural lever that may minimize adverse public health consequences of long-acting opioids. Abuse-deterrent formulations composeonlypart of apublic health strategy to reduce overdose andmisuse. These formulationswill not prevent people receivinghighdoses of opioids fromoverdosing. It remainspossible tooverdoseby taking oralmedications, evenwhenusing themas directed, particularlywhen incombinationwithotherprescribedor illicitdrugs. Abuse-deterrentmedicationsalsodonotprevent the initial exposure to opioids. Most opioid use carries some risk, and intensity of the exposure via dose and length of treatment increases subsequent risk of misuse and overdose. Related article page 978 Effect of Abuse-Deterrent Oxycodone Introduction and PropoxypheneWithdrawal Original Investigation Research

A collaborative opioid prescribing (CoOP) model linking opioid treatment programs with office-based buprenorphine providers

Background Despite abundant research demonstrating good efficacy, pharmacotherapies for substance use disorders are underutilized. Buprenorphine holds promise to significantly increase the availability of medication-assisted therapy for opioid use disorder; yet despite dramatic increases in overdose deaths driven largely by prescription opioid use, only about half of DATA-waivered physicians prescribe buprenorphine.

Prescription drug overdose: between patients and their doctors

Prescription drug overdose: between patients and their doctors

The Development of the Washington State Emergency Department Opioid Prescribing Guidelines

The Centers for Disease Control and Prevention (CDC) has classified prescription drug abuse as an epidemic due to the recent dramatic increase in prescription drug overdose deaths. In addition to an increase in overdose deaths involving opioid analgesics, there has also been an increase in substance abuse treatment admissions and an increase in emergency department (ED) visits for nonmedical use of opioid analgesics [1]. According to the Drug Abuse Warning Network, the estimated number of ED visits for nonmedical use of opioid analgesics more than doubled from 2004 to 2008 (from 144,600 to 305,900 visits) [2]. Although quantifying the amount of opioids prescribed from an ED in comparison to other specialties has been a challenge, data from the 2003–2004 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey suggest that the ED accounts for 39 % of opioid administration or medical record prescription mentions compared with 30.5 % for primary care offices [3]; however, this source does not likely account for the small total amount prescribed from the ED. Analyses of the Vector One National database suggest that ED physicians are among the top five outpatient specialties prescribing opioids to patients 39 years old and younger along with primary care physicians, dentists, and pediatricians [4]. Among individuals who abused prescription opioids upon entering methadone treatment, 13 % reported obtaining their opioids from EDs; [5] Washington State Department of Health (WSDOH) had been concerned regarding data suggesting higher rates of drug overdose deaths and a higher percentage of nonmedical use of prescription pain medication in Washington State compared to the rest of the nation [6]. In 2010, opioid analgesic prescribing per capita in Washington State was significantly higher than the national average—ranking ninth in the nation. In addition, Washington State ranked 14th in the nation in drug overdose deaths in 2008 [1].

Emerging Drugs of Abuse: What Was New Yesterday Is NEW Today

We are pleased to present this special focus issue of the Journal of Medical Toxicology on emerging drugs of abuse. Since early humans first experienced euphoria with psychotropic plants more than 6,000 years ago, creative individuals have explored new ways of achieving drug-induced euphoria without getting in trouble with the law or dying. This issue is appropriately timed because the availability of new drugs has accelerated at a mind-boggling pace over the last decade. Ivory Wave? Meow Meow? Spice? These are not terms of affection for one’s significant other, but instead street names for emerging drugs of abuse readers should have heard by now and will learn more about in this issue. The drugs of abuse described in this issue are nontraditional, emerging, and web-based—so for simplicity, we will refer to them collectively as NEW drugs. It is now estimated that 100 persons die of drug overdose daily in the USA, a threefold increase in overdose deaths in less than 20 years [1]. Although misuse and diversion of prescribed opioids have clearly been linked to this increase, a significant proportion of increasing deaths can also be attributed to NEW drugs as illustrated in two sobering case reports included in this issue: Murray and colleagues from North Carolina report a death from bath salts; Warrick and coauthors describe a death from a methylone–butylone product in Michigan [2, 3]. Twenty years ago, the USA made up 60% of the world’s recreational drug market, but now this problem is a global one. Although we are no longer surprised, the internet has contributed significantly to the global explosion of emerging drugs. The potential impact of the internet on this problem was news when first reported by Paul Wax 10 years ago in his prescient paper cleverly titled “Just a click away: recreational drug web sites on the internet” [4]. Toxicologists have an underappreciated expertise and unique perspective on emerging drug problems, so we are fortunate this issue includes two excellent reviews from experts on the cutting edge of these trends. Prosser and Nelson provide a focused, high-level review of bath salts, an epidemic described in vivid detail on the front page of every major US newspaper in the last year; Rosenbaum and coauthors provide a broader examination of NEW drugs with their review of synthetic cathinones, kratom, salvia, methoxetamine, and piperazines in their smartly titled paper, “Here today, gone tomorrow…and back again?” [5, 6]. Partisan websites on the internet, instant text messaging on smartphones, and other new technology have allowed easier connections between users and imaginative chemists staying ahead of legislative efforts to limit the availability of these drugs [7, 8]. As Barbara Carerno of the DEA commented: “It’s hard to keep up with everything…there are a lot of gifted chemists out there.” Understanding the effects of these NEW drugs is complicated because clinicians primarily interface with users only when a complication results in an emergency department visit—the majority of NEW drug users never end up in a health care facility. Getting a handle on this rapidly evolving problem demands better understanding of unexpected complications, such as seizures from synthetic cannabinoids described by Schneir in this issue, and gaining insights from users who never seek medical care [9]. Useful knowledge can be gained from innovative approaches. In this issue of the Journal of Medical Toxicology (JMT), Edward Boyer continues to push the conventional limits of clinical toxicology scholarship with preliminary findings from his iHeal project—clearly his work is grounded in the technological age of the twenty-first century where iPods, iPhones, and iEverything are ubiquitous [10]. Boyer and his team developed iHeal to gain insights into drug craving using modern technology. We eagerly await subsequent findings from their ambitious project. Up until recently, the best way to learn about NEW drug trends was to read nonmedical reports and surf the net. This issue of JMT provides a valuable contribution to the growing body of peer-reviewed literature on this topic. The articles here should inform toxicologists, front line clinicians, policy makers, and the community about the dangers of NEW drugs and empower us to act collaboratively. So pay attention, learn NEW lingo, think outside conventional boxes, and contribute your observations to this journal in the same way the authors represented in this issue have done. Please also tune in to the new Journal of Medical Toxicology podcast where editorial board members Howard Greller and Dan Rusyniak discuss articles from this issue in more detail. The JMT podcast is available at the ACMT website (http://www.acmt.net/ACMTPodcasts.html) and the iTunes Store.

Emergency Department Visits Among Recipients of Chronic Opioid Therapy

There has been an increase in overdose deaths and emergency department visits (EDVs) involving use of prescription opioids, but the association between opioid prescribing and adverse outcomes is unclear. Data were obtained from administrative claim records from Arkansas Medicaid and HealthCore commercially insured enrollees, 18 years and older, who used prescription opioids for at least 90 continuous days within a 6-month period between 2000 and 2005 and had no cancer diagnoses. Regression analysis was used to examine risk factors for EDVs and alcohol- or drug-related encounters (ADEs) in the 12 months following 90 days or more of prescribed opioids. Headache, back pain, and preexisting substance use disorders were significantly associated with EDVs and ADEs. Mental health disorders were associated with EDVs in HealthCore enrollees and with ADEs in both samples. Opioid dose per day was not consistently associated with EDVs but doubled the risk of ADEs at morphine-equivalent doses over 120 mg/d. Use of short-acting Drug Enforcement Agency Schedule II opioids was associated with EDVs compared with use of non-Schedule II opioids alone (relative risk range, 1.09-1.74). Use of Schedule II long-acting opioids was strongly associated with ADEs (relative risk range, 1.64-4.00). Use of Schedule II opioids, headache, back pain, and substance use disorders are associated with EDVs and ADEs among adults prescribed opioids for 90 days or more. It may be possible to increase the safety of chronic opioid therapy by minimizing the prescription of Schedule II opioids in these higher-risk recipients.

Emergency Department Visits Involving Nonmedical Use of Selected Prescription Drugs in the United States, 2004–2008

EDITOR'S ABSTRACTThis report, adapted from the lead article in the June 10, 2010, issue of Morbidity and Mortality Weekly Reports, describes the alarming increase in overdose deaths involving prescription drugs. Oxycodone, hydrocodone, and methadone were the drugs most highly implicated. Data were derived from the federal Drug Abuse Warning Network (Dawn). Other drugs commonly used in managing pain patients, including benzodiazepines and muscle relaxants, also were implicated.

Fatal poisoning in Nordic drug addicts in 2002

The present study from 2002 includes medicolegally examined fatal poisonings among drug addicts in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. A common definition “drug addict” is applied by the participating countries. The number of deaths, age, sex, place of death, main intoxicant and other drugs present in the blood are recorded in order to obtain national data, as well as comparable Nordic data and data comparable to earlier studies from 1997 and 1991. The Icelandic results are commented on separately due to the low number of cases. The most fatal overdoses are seen in Norway, in both the death rate (number per 100,000 inhabitants = 8.44) and in absolute number ( n = 232). The comparable figures for the other four countries are Denmark 5.43 ( n = 175), Iceland 3.6 ( n = 6), Finland 2.93 ( n = 94) and Sweden 2.56 ( n = 136). In earlier studies from 1991 and 1997, the highest death rate is seen in Denmark, with Norway as number two. Denmark is the only country where the death rate decreases from 1997 to 2002. A relatively large increase in deaths in the younger age groups (<30 years) is noted from 1997 to 2002, except in Denmark, where only a small increase in overdose deaths in very young people (15–19 years) is observed. Females account for 12–20% of the overdoses (three out of six deaths in Iceland). Relatively fewer deaths are recorded in the capital areas in 2002 than in 1997 and 1991, suggesting more geographically widespread drug use in the Nordic countries. Heroin/morphine is the single most frequently encountered main intoxicant, varying from 10% of the cases in Finland to 72% of the cases in Norway. Finland differs from the other countries in that a high percentage of the fatal overdoses in Finland are not caused by an illicit drug; buprenorphine overdoses are seen, and relatively few deaths resulting from heroin are seen. Methadone is the main intoxicant in 41% of the Danish overdose cases, 15% of the Norwegian cases, 4% of the Swedish cases and none of the Finnish overdose cases, an observation probably linked to different national prescription rules for methadone. The analytical screening reveals extended polydrug use. Frequently seen substances, in addition to the main intoxicant are amphetamine, tetrahydrocannabinol (THC), benzodiazepines and ethanol.

Trends in drug overdose deaths in England and Wales 1993-98: methadone does not kill more people than heroin.

To test the hypothesis that methadone is responsible for a greater increase in overdose deaths than heroin, and causes proportionally more overdose deaths than heroin at weekends. Multivariate analysis of 3961 death certificates mentioning heroin, morphine and/or methadone held on the Office for National Statistics drug-related poisoning mortality database from 1993 to 1998 in England and Wales. Percentage increase in deaths by year by drug, odds ratio (OR) of dying at the weekend from methadone-related overdose compared to dying from heroin/morphine overdose. From 1993 to 1998, annual opiate overdose deaths increased from 378 to 909. There was a 24.7% (95% confidence interval (CI) 22-28%) yearly increase in heroin deaths compared to 9.4% (95% CI 6-13%) for methadone only. This difference was significant (P < 0.001 by test of interaction) after adjustment for sex, age group, polydrug use, area of residence and underlying cause of death. The largest number of deaths occurred on Saturday (673). The OR of death from methadone overdose on Saturday and Sunday was 1.48 (95% CI 1.29-1.71) for methadone-only deaths compared to dying from heroin/morphine at the weekend after adjustment for other covariates, but the OR was not significant (1.09, 95% CI 0.95-1.25) if the weekend was defined as Friday and Saturday. There was no evidence that the threefold increase in deaths over time was due to methadone. There was equivocal support only for the hypothesis that there was an excess of deaths from methadone at weekends. Increased interventions to prevent overdose among injectors in England and Wales are long overdue.