Abuse Of Prescription Opioid Analgesics Research Articles

Considering sex-specific adverse drug reactions should be a priority in pharmacovigilance and pharmacoepidemiological studies

Considering sex-specific adverse drug reactions should be a priority in pharmacovigilance and pharmacoepidemiological studies

Opioids with abuse-deterrent properties: A regulatory and technological overview.

Three concurrent public health problems coexist in the United States: endemic nonmedical use/misuse of opioid analgesics, epidemic overdose fatalities involving opioid analgesics, and endemic chronic pain in adults. These intertwined issues comprise an opioid crisis that has spurred the development of formulations of opioids with abuse-deterrent properties and label claims (OADP). To reduce abuse and misuse of prescription opioids, the federal Food and Drug Administration (FDA) has issued a formal Guidance to drug developers that delineates four categories of testing to generate data sufficient for a description of a product's abuse-deterrent properties, along with associated claims, in its Full Prescribing Information (FPI). This article reviews the epidemiology of the crisis as background for the development of OADP, summarizes the FDA Guidance for Industry regarding abuse-deterrent technologies, and provides an overview of some technologies that are currently employed or are under study for incorporation into OADP. Such technologies include physical and chemical barriers to abuse, combined formulations of opioid agonists and antagonists, inclusion of aversive agents, use of delivery systems that deter abuse, development of new molecular entities and prodrugs, and formulation of products that include some combination of these approaches. Opioids employing these novel technologies are one part of a comprehensive intervention strategy that can deter abuse of prescription opioid analgesics without creating barriers to the safe use of prescription opioids. The maximal public health contribution of OADP will probably occur only when all opioids have FDA-recognized abuse-deterrent properties and label claims.

Polysubstance use and misuse or abuse of prescription opioid analgesics: a multi-level analysis of international data.

Increasing mortality and morbidity associated with opioid analgesics has led to concerns about their misuse and abuse, even when obtained through a prescription. These concerns have been most pronounced in the United States, but limited data make it difficult to determine whether it is a problem in other countries. We investigated opioid analgesic misuse and abuse in participants from the Global Drug Survey 2015 resident in the United States (N = 1334), United Kingdom (N = 1199), France (N = 1258), Germany (N = 866), and Australia (N = 1013) who had used at least 1 prescription opioid analgesic medication in the past year. We also investigated the relationship with polysubstance use, one of the most consistent predictors of problematic opioid analgesic use. Data included misuse and abuse of codeine, hydrocodone, oxycodone, and tramadol; ability to obtain a prescription; different sources for obtaining drugs; and past-year use of benzodiazepines and illicit drugs. In multilevel models, country of residence accounted for less than 3% of the variance in opioid analgesic misuse or abuse. Adjusting for country of residence and sociodemographic factors, use of illicit drugs and benzodiazepines was associated with 4-fold greater odds of misuse (odds ratio 4.36, 95% confidence interval 3.29-5.93) and 6-fold greater odds of abuse compared with not using either drug (odds ratio 6.49, 95% confidence interval 4.0-10.48), although the strength of the association with abuse varied by country. Misuse and abuse by those prescribed opioid analgesics seem to be a problem that is not limited to the United States and warrant attention on an international scale.

Trends in Opioid Analgesic Abuse and Mortality in the United States

BackgroundThe use of prescription opioid medications has increased greatly in the United States during the past two decades; in 2010, there were 16,651 opioid-related deaths. In response, hundreds of federal, state, and local interventions have been implemented. We describe trends in the diversion and abuse of prescription opioid analgesics using data through 2013.MethodsWe used five programs from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System to describe trends between 2002 and 2013 in the diversion and abuse of all products and formulations of six prescription opioid analgesics: oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol. The programs gather data from drug-diversion investigators, poison centers, substance-abuse treatment centers, and college students.ResultsPrescriptions for opioid analgesics increased substantially from 2002 through 2010 in the United States but then decreased slightly from 2011 through 2013. In general, RADARS System programs reported large increases in the rates of opioid diversion and abuse from 2002 to 2010, but then the rates flattened or decreased from 2011 through 2013. The rate of opioid-related deaths rose and fell in a similar pattern. Reported nonmedical use did not change significantly among college students.ConclusionsPostmarketing surveillance indicates that the diversion and abuse of prescription opioid medications increased between 2002 and 2010 and plateaued or decreased between 2011 and 2013. These findings suggest that the United States may be making progress in controlling the abuse of opioid analgesics. (Funded by the Denver Health and Hospital Authority.)

Opioids induce dissociable forms of long-term depression of excitatory inputs to the dorsal striatum

As prescription opioid analgesic abuse rates rise, so does the need to understand the long-term effects of opioid exposure on brain function. The dorsal striatum is an important site for drug-induced neuronal plasticity. We found that exogenously applied and endogenously released opioids induced long-term depression (OP-LTD) of excitatory inputs to the dorsal striatum in mice and rats. Mu and delta OP-LTD, although both being presynaptically expressed, were dissociable in that they summated, differentially occluded endocannabinoid-LTD and inhibited different striatal inputs. Kappa OP-LTD showed a unique subregional expression in striatum. A single in vivo exposure to the opioid analgesic oxycodone disrupted mu OP-LTD and endocannabinoid-LTD, but not delta or kappa OP-LTD. These data reveal previously unknown opioid-mediated forms of long-term striatal plasticity that are differentially affected by opioid analgesic exposure and are likely important mediators of striatum-dependent learning and behavior.

Safe Opioid Prescribing: A Long Way to Go

Safe Opioid Prescribing: A Long Way to Go

Acetaminophen modulation of hydrocodone reward in rats

Abuse of prescription opioid analgesics in non-medical context has been on the rise over the past decade. The most commonly abused analgesic in this drug class consists of a combined formulation of hydrocodone and acetaminophen. The present study was aimed to determine the rewarding effects of hydrocodone, acetaminophen, and their combination using the conditioned place preference (CPP) paradigm. Using a 6-day CPP paradigm, rats were paired with hydrocodone (0.5, 1.0 or 5.0mg/kg) or acetaminophen (50, 100 or 300mg/kg) to determine whether the drugs given alone would produce a CPP. Rats conditioned with the highest dose of hydrocodone exhibited place preference, whereas rats conditioned with acetaminophen did not demonstrate place preference. In a second experiment, varying doses of hydrocodone and acetaminophen were combined to determine whether acetaminophen would enhance hydrocodone reward. Acetaminophen (100mg/kg) enhanced the rewarding effects of hydrocodone (1mg/kg), although the effect was unique to this particular dose combination. Higher or lower doses of acetaminophen combined with hydrocodone did not alter hydrocodone CPP. The present findings suggest that acetaminophen has a limited potential of modulating the rewarding properties of hydrocodone in rats.

Prescription Drug Monitoring Programs and Death Rates from Drug Overdose

Drug overdoses resulting from the abuse of prescription opioid analgesics and other controlled substances have increased in number as the volume of such drugs prescribed in the United States has grown. State prescription drug monitoring programs (PDMPs) are designed to prevent the abuse of such drugs. This study quantifies the relation of PDMPs to rates of death from drug overdose and quantities of opioid drugs distributed at the state level. Observational study of the United States during 1999-2005. Rates of drug overdose mortality, opioid overdose mortality, and opioid consumption by state. PDMPs were not significantly associated with lower rates of drug overdose or opioid overdose mortality or lower rates of consumption of opioid drugs. PDMP states consumed significantly greater amounts of hydrocodone (Schedule III) and nonsignificantly lower amounts of Schedule II opioids. The increases in overdose mortality rates and use of prescription opioid drugs during 1999-2005 were significantly lower in three PDMP states (California, New York, and Texas) that required use of special prescription forms. While PDMPs are potentially an important tool to prevent the nonmedical use of prescribed controlled substances, their impact is not reflected in drug overdose mortality rates. Their effect on overall consumption of opioids appears to be minimal. PDMP managers need to develop and test ways to improve the use of their data to affect the problem of prescription drug overdoses.

Source of Drugs for Prescription Opioid Analgesic Abusers: A Role for the Internet?

There has been a sharp increase in the abuse of prescription opioid analgesics in the United States in the past decade. It has been asserted, particularly by several governmental and regulatory agencies, that the Internet has become a significant source of these drugs which may account to a great extent for the surge in abuse. We have studied whether this is correct. We asked 1,116 prescription drug abusers admitted for treatment, through standardized questionnaires, where they obtained their drugs. We also attempted to purchase scheduled II and III drugs from a random sample of Internet sites offering such sales. Dealers, friends or relatives, and doctors' prescriptions were listed as a source of drugs with equal frequency ( approximately 50-65%), with theft and forgery far behind at 20%. The Internet was mentioned by fewer than 6% of the total responders. Because these data suggest either lack of availability or that our sample has not yet realized that the Internet is a potential source, we attempted to purchase scheduled II and III opioids and the unscheduled opioid, tramadol, from a random sample of 10% of the sites listing such sales. We were unsuccessful in purchasing a single scheduled opioid analgesic, but found that tramadol, as an unscheduled drug, was freely available. The assertion that the Internet has become a dangerous new avenue for the diversion of scheduled prescription opioid analgesics appears to be based on no empirical evidence and is largely incorrect.

Estimated Costs of Prescription Opioid Analgesic Abuse in the United States in 2001: A Societal Perspective

Estimated Costs of Prescription Opioid Analgesic Abuse in the United States in 2001: A Societal Perspective

Estimated Costs of Prescription Opioid Analgesic Abuse in the United States in 2001

This study estimates the costs to society of prescription opioid analgesic (RxO) abuse in the United States. Costs associated with RxO abuse were grouped into healthcare, criminal justice, and workplace categories. Costs were estimated by either (1) a quantity method that multiplies the number of RxO abusers derived from various national surveys by the estimated per abuser cost, or (2) an apportionment method that starts with overall (ie, prescription and nonprescription) drug abuse costs for a cost component (eg, police protection) and apportions the share of costs based on the prevalence of RxO abuse relative to overall drug abuse. Medical costs in excess of those for otherwise similar nonabusers were based on an analysis of a large administrative claims database for an employed population using multivariate regression methods. A lower bound estimate of the costs of RxO abuse in the United States was 8.6 billion dollars in 2001 (or 9.5 billion dollars in 2005 dollars). Of this amount, 2.6 billion dollarswere healthcare costs, 1.4 billion dollars were criminal justice costs, and 4.6 billion dollars were workplace costs. The costs of RxO abuse represent a substantial economic burden. Rising trends of RxO abuse suggest an escalating economic and public health burden in coming years in the United States, and potentially, elsewhere.

Office-Based Buprenorphine Treatment for Opioid-Dependent Patients

Opioid dependence is epidemic in the United States, with increasing numbers addicted to heroin and burgeoning abuse of prescription opioid analgesics. Buprenorphine, the most recent addition to the pharmacotherapies available to treat opioid dependence, is novel among the opioid pharmacotherapies because of its partial agonist properties. It has been placed on Schedule III and is available by prescription from a physician's office-based practice. This review briefly summarizes the research supporting buprenorphine as a treatment for opioid dependence--including its clinical pharmacology, formulation with naloxone to prevent diversion, clinical use in treatment of opioid dependence, and issues regarding its use in special populations.

Costs of prescription opioid analgesic abuse in the United States in 2001: a societal perspective

Purpose Estimate the total costs to society of prescription opioid analgesic (RxO) abuse in the United States in 2001. Methods For this analysis, “drug abuse” refers to any nonmedical use of a drug, including that which meets the DSM-IV criteria for substance abuse or dependence disorders. The costs associated with RxO abuse were grouped into three major cost categories: health care, lost productivity, and criminal justice. Each category has multiple underlying components. Relying primarily on published data, we used varying methods, depending on the cost component considered. In general, cost estimates were obtained by either (i) a quantity method, which multiplies the relevant number of RxO abusers based on various national surveys (e.g., National Household Survey on Drug Abuse, Treatment Admissions Data Set, Drug Abuse Warning Network) by the per abuser cost, or (ii) an apportionment method, which starts with the overall costs of drug abuse for a particular cost component (e.g., prevention programs) and apportions the share solely due to RxO abuse based on the prevalence of RxO abuse relative to overall (i.e., licit plus illicit) drug abuse. An additional data source (for excess medical costs) was an administrative claim database for an employed population of approximately 600,000 lives. Results Total costs of RxO abuse in the United States in 2001 were $9.2 billion. Of these costs, $2.8 billion were health care costs, $4.6 billion were lost productivity costs, and $1.8 billion were criminal justice costs. These estimates are lower-bound estimates, in that some cost categories and components—such as diversion—were not included. Sensitivity analyses found that costs for the estimated cost categories and components could range up to $11.5 billion. Conclusion The costs of RxO abuse in the United States impose a substantial economic burden to society. Rising trends of prescription opioid abuse suggest an escalating economic and public health burden in coming years.