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Objective: The majority of prescription drugs, including prescription stimulants, are marketed using multiple brand names, doses, and formulations. There is limited research on the extent to which individuals correctly identify medication by brand name or packaging, but such identification is important for epidemiological studies especially among youth. Testing the ability of youth to identify medications was one aim of the National Monitoring of Prescription Stimulants Study, which focused on the prevalence of prescription stimulant use among youth., Methods: Using the entertainment venue intercept method, youth 10 to 18 years of age (n = 11,048) were recruited across 10 metropolitan areas throughout the United States, shown pictures of eight formulations of prescription stimulants, and asked to identify them by name, dosage, and formulation., Results: Overall, 27% of youth reported having seen one of the eight stimulant formulations and between 2% and 70% correctly identified name, dose, and formulation. Youths' reports of having seen and correctly identifying medication increased with age except for Daytrana ® . Specifically, while 2.8% of youth reported using Adderall ® in the past 30 days, only 71.4% correctly identified it., Conclusions: These results provide strong evidence of the need for more stringent methods for youth to report drug use., (© 2021 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

Rural areas of the United States have been disproportionately impacted by the opioid epidemic, exacerbated by COVID-19-related economic upheavals. While polysubstance use is an important determinant of overdose risk, variability in polysubstance use as a result of numerous factors (e.g., access, preference) has yet to be described, particularly among rural persons with opioid use disorder (PWOUD). Survey data on past-month use of prescription and illicit opioids and 12 non-opioid psychoactive drug classes were analyzed from a national sample of rural (n = 3872) and urban (n = 8153) residents entering treatment for OUD from 2012 to 2019. Trend analyses for opioid and stimulant use were compared between rural and urban PWOUD. Latent class analyses assessed substance use trends through identified typologies of rural/urban PWOUD, which then underwent comparative analyses. By 2019, prescription opioid use remained greater in rural versus urban PWOUD, and methamphetamine use showed greater growth in rural, compared to urban areas. Latent class analyses identified variability in polysubstance use, with five identical subgroups in rural/urban PWOD: high polysubstance, polyprescription, prescription opioid-focused, prescription opioid-focused with polysubstance use, and illicit opioid-focused. Polyprescription was highest in rural areas, with illicit opioid-focused use highest in urban areas. Demographic characteristics, co-morbid conditions and healthcare coverage were all associated with between-group differences. There is significant variability in polysubstance use that may identify specific prevention and treatment needs for subpopulations of OUD patients: interventions focused on reducing opioid prescriptions, early engagement with mental health resources, wider distribution of naloxone, and screening/treatment plans that take into account the use of multiple substances., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives. To understand important changes in co-occurring opioid and nonopioid drug use (i.e., polysubstance use) within the opioid epidemic in the United States. Methods. We analyzed survey data on the past month co-use of prescription and illicit opioids and 12 nonopioid psychoactive drug classes from a national sample of 15 741 persons entering treatment of opioid use disorder. Results. Past-month illicit opioid use increased from 44.8% in 2011 to 70.1% in 2018, while the use of prescription opioids alone dropped from 55.2% to 29.9%, yet overall remained high (94.5% to 85.2%). Past-month use of at least 1 nonopioid drug occurred in nearly all participants (> 90%), with significant increases in methamphetamine (+85%) and decreases across nonopioid prescription drug classes (range: -40% to -68%). Conclusions. Viewing opioid trends in a "silo" ignores the fact not only that polysubstance use is ubiquitous among those with opioid use disorder but also that significant changes in polysubstance use should be monitored alongside opioid trends. Public Health Implications. Treatment, prevention, and policymaking must address not only the supply and demand of a singular drug class but also the global nature of substance use overall.

Background/aims: Adolescents and young adults have the highest rates of opioid use, and despite shared risk-factors such as mental health and social pressures, there is little information on the relationship between education and opioid use disorder. In this study, we sought to assess differences in educational attainment between opioid users and the general population, and the impact of opioid use on one's education., Methods: Patients (N = 14,349) entering opioid treatment programs across the United States were surveyed on educational attainment from 2010 to 2018. Data were compared to estimates from an annual survey administered by the US Census. A follow-up sub-set of opioid users (N = 240) was interviewed to add context and expand on the structured survey., Results: Nearly one-third (32.2%) of the US population is estimated to have earned a bachelor's/advanced degree, compared to just 7.8% of treatment-seeking opioid users. Over half of follow-up respondents (57.5%) reported initiating regular opioid use while attending an educational institution. The majority (68.0%) also indicated opioids negatively impacted their education, with drug-seeking behavior prioritized over attendance and academic performance. Perceived benefits included cognitive enhancement and therapeutic value for anxiety/depression., Conclusions: Our data suggest that opioid users achieve lower levels of education, which may result in both individual and economic costs. Prevention programs need to not only include education-specific risk factors (e.g., social norms), but underlying precipitators such as mental health, stigma, and the myth of risk-free cognitive enhancement. Opioid specific services should be available and disseminated to student populations, including certification of campus physicians to provide buprenorphine maintenance., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Opioids with abuse-deterrent properties may reduce widespread abuse, misuse, and diversion of these products. This study aimed to quantify misuse, abuse, dependence, and health resource use of extended-release morphine sulfate with sequestered naltrexone hydrochloride (ER-MSN; EMBEDA®), compared with non-abuse-deterrent extended-release morphine (ERM) products in Medicaid non-cancer patients., Methods: Administrative medical and pharmacy claims data were analyzed for 10 Medicaid states from 1 January 2015, to 30 June 2016. Patients were included if they received a prescription for ER-MSN or any oral, non-abuse-deterrent ERM. Index date was the date of first prescription for an ER-MSN or ERM. Abuse/dependence, non-fatal overdose, emergency department (ED) visits, and ED/inpatient readmissions were determined for each participant. An overall measure of misuse and abuse was also calculated. To account for differences in follow-up, all counts are expressed per 100 patient-years., Results: There were 4,857 patients who received ER-MSN and 10,357 who received an ERM. The average age in the two cohorts was approximately 45 years old. From pre-index to follow-up, the number of patients per 100 patient-years with a diagnosis code indicating abuse or dependence increased by 0.91 (95% confidence interval [CI]: 0.85, 0.97) in the ER-MSN cohort and 2.23 (95% CI: 2.14, 2.32) in the ERM cohort. The number of patients per 100 patient-years with an opioid-related non-fatal overdose increased by 0.05 (95% CI: 0.04, 0.06) in the ER-MSN cohort compared with 0.11 (95% CI: 0.09, 0.13) in the ERM cohort. The opioid abuse overall composite score increased by 1.36 (95% CI: 1.24, 1.48) in the post-index period in the ER-MSN cohort compared to 3.21 (95% CI: 3.10, 3.32) in the ERM cohort., Conclusion: Misuse, abuse, and dependence events were numerically lower in patients receiving ER-MSN compared with those receiving ERM products.

Purpose: Oral use is the primary route of administration among non-medical prescription opioid users. While progression to non-oral routes and shifts to stronger opioids have been previously studied as ways to cope with tolerance, the prevalence and patterns of those who cope by increasing the number of pills/tablets ingested at one time (ie, multi-pill use) has not been assessed., Methods: A subset (N = 231) of treatment-seeking opioid users from a national opioid surveillance system, participating in the Researchers and Participants Interacting Directly (RAPID) Program, completed an online survey centered on multi-pill use., Results: Over two-thirds of non-medical prescription opioid users had a history of multi-pill use (67.7%), defined as ingesting four or more of the same pill, intact and at the same time. Among these (n = 154), the median maximum number of pills taken at one time was eight, with over 20% ingesting 11 or more pills in a single instance. Nearly half engaged in multi-pill ingestion more than once a day in the past month (43.8%), with accessibility to lower dose pills being the primary motivator (85.4%). Hydrocodone immediate-release (IR) compounds were by far the most frequently endorsed (90.3%), followed by oxycodone IR tablets with acetaminophen (76.0%) and oxycodone IR tablets containing no acetaminophen/ibuprofen (56.5%)., Conclusions: These results indicate that the ingestion of multiple opioid pills/tablets is extremely common among treatment-seeking opioid users. This, and other forms of non-medical oral use of prescription opioids, should be taken under consideration when developing prevention and intervention efforts targeting the opioid epidemic., (© 2018 John Wiley & Sons, Ltd.)

Background/aims: Recent supply-side efforts enacted to curb the opioid epidemic have had both positive (i.e., prescription opioid abuse is on the decline) and negative outcomes (i.e., shifts to other drugs). Given methamphetamine is notably increasing in use across the United States, we sought to understand whether use of methamphetamine has increased among opioid users and whether there is an association between these two epidemics., Methods: Patients (N = 13,521) entering drug treatment programs across the United States completed an anonymous survey of drug use patterns from 2011 to 2017. A subset of these patients (N = 300) was also interviewed to add context and expand on the structured survey., Results: Past month use of methamphetamine significantly increased among treatment-seeking opioid users (+82.6%, p < .001), from 18.8% in 2011 to 34.2% in 2017. The Western region had the greatest increase in past month methamphetamine use (+202.4%, p < 0.001) and the highest prevalence rate in 2017 (63.0%). Significant increases (p < .001) in methamphetamine use were seen among males (+81.8%), females (+97.8%), whites (+100.6%), urban residents (+123.0%) and rural residents (+93.7%)., Conclusions: Our studies show that there has been a marked increase in the past month use of methamphetamine in individuals with a primary indication of opioid use disorder. Qualitative data indicated that methamphetamine served as an opioid substitute, provided a synergistic high, and balanced out the effects of opioids so one could function "normally". Our data suggest that, at least to some extent, efforts limiting access to prescription opioids may be associated with an increase in the use of methamphetamine., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Abuse-deterrent opioid formulations have been suggested as one way to decrease the abuse, addiction, and overdose of orally prescribed opioids. Ten oral opioid formulations have received abuse-deterrent labeling by the U.S. Food and Drug Administration (FDA). Their properties consist of physical and/or chemical means by which the pills resist manipulation and create a barrier to unintended administration, such as chewing, nasal snorting, smoking, and intravenous injection. In this review, we describe the mechanisms of abuse-deterrent technology, the types of premarketing studies required for FDA approval, the pharmacology of the currently approved abuse-deterrent opioid formulations, and the evidence for and against their influence on opioid abuse. We conclude that there is currently insufficient evidence to indicate that the availability of abuse-deterrent opioid formulations has altered the trajectory of opioid overdose and addiction; however, postmarketing studies are in their infancy, and novel deterrent formulations are continually being developed and submitted for marketing approval.

Importance: In an effort to reduce wide-scale abuse of the proprietary oxycodone hydrochloride formulation OxyContin, an abuse-deterrent formulation (ADF) was introduced in 2010. Although the reformulation produced an immediate drop in abuse rates, a definite ceiling effect appeared over time, beyond which no further decrease was seen., Objective: To examine the factors that led to the initial steep decline in OxyContin abuse and the substantial levels of residual abuse that have remained relatively stable since 2012., Design, Setting, and Participants: We used data from the ongoing Survey of Key Informants' Patients program, part of the Researched Abuse, Diversion and Addiction-Related Surveillance system that collects and analyzes postmarketing data on misuse and diversion of prescription opioid analgesics and heroin. For our survey study, patients with a DSM-V diagnosis of opioid use disorder and primary drug of abuse consisting of a prescription opioid or heroin (N = 10,784) at entry to 1 of 150 drug treatment programs in 48 states completed an anonymous structured survey of opioid abuse patterns (surveys completed from January 1, 2009, through June 30, 2014). A subset of these patients (n = 244) was interviewed to add context and expand on the structured survey., Main Outcomes and Measures: In addition to key demographic measures, past-month abuse of opioids was the primary measure in the structured surveys. In the interviews, the effect of the introduction of the ADF on drug-seeking behavior was examined., Results: Reformulated OxyContin was associated with a significant reduction of past-month abuse after its introduction (45.1% [95% CI, 41.2%-49.1%] in January to June 2009 to 26.0% [95% CI, 23.6%-28.4%] in July to December 2012; P < .001; χ(2) = 230.83), apparently owing to a migration to other opioids, particularly heroin. However, this reduction leveled off, such that 25% to 30% of the sample persisted in endorsing past-month abuse from 2012 to 2014 (at study end [January to June 2014], 26.7% [95% CI, 23.7%-29.6%]). Among the 88 participants who indicated experience using pre-ADF and ADF OxyContin, this residual level of abuse reflects the following 3 phenomena: (1) a transition from nonoral routes of administration to oral use (38 participants [43%]); (2) successful efforts to defeat the ADF mechanism leading to a continuation of inhaled or injected use (30 participants [34%]); and (3) exclusive use of the oral route independent of formulation type (20 participants [23%])., Conclusions and Relevance: Abuse-deterrent formulations can have the intended purpose of curtailing abuse, but the extent of their effectiveness has clear limits, resulting in a significant level of residual abuse. Consequently, although drug abuse policy should focus on limiting supplies of prescription analgesics for abuse, including ADF technology, efforts to reduce supply alone will not mitigate the opioid abuse problem in this country.

Background: The 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., Methods: We 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., Results: Prescriptions 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., Conclusions: Postmarketing 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.).

Importance: Over the past several years, there have been a number of mainstream media reports that the abuse of heroin has migrated from low-income urban areas with large minority populations to more affluent suburban and rural areas with primarily white populations., Objective: To examine the veracity of these anecdotal reports and define the relationship between the abuse of prescription opioids and the abuse of heroin., Design, Setting, and Participants: Using a mixed-methods approach, we analyzed (1) data from an ongoing study that uses structured, self-administered surveys to gather retrospective data on past drug use patterns among patients entering substance abuse treatment programs across the country who received a primary (DSM-IV) diagnosis of heroin use/dependence (n = 2797) and (2) data from unstructured qualitative interviews with a subset of patients (n = 54) who completed the structured interview., Main Outcomes and Measures: In addition to data on population demographics and current residential location, we used cross-tabulations to assess prevalence rates as a function of the decade of the initiation of abuse for (1) first opioid used (prescription opioid or heroin), (2) sex, (3) race/ethnicity, and (4) age at first use. Respondents indicated in an open-ended format why they chose heroin as their primary drug and the interrelationship between their use of heroin and their use of prescription opioids., Results: Approximately 85% of treatment-seeking patients approached to complete the Survey of Key Informants' Patients Program did so. Respondents who began using heroin in the 1960s were predominantly young men (82.8%; mean age, 16.5 years) whose first opioid of abuse was heroin (80%). However, more recent users were older (mean age, 22.9 years) men and women living in less urban areas (75.2%) who were introduced to opioids through prescription drugs (75.0%). Whites and nonwhites were equally represented in those initiating use prior to the 1980s, but nearly 90% of respondents who began use in the last decade were white. Although the "high" produced by heroin was described as a significant factor in its selection, it was often used because it was more readily accessible and much less expensive than prescription opioids., Conclusion and Relevance: Our data show that the demographic composition of heroin users entering treatment has shifted over the last 50 years such that heroin use has changed from an inner-city, minority-centered problem to one that has a more widespread geographical distribution, involving primarily white men and women in their late 20s living outside of large urban areas.

Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants' Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ("unique recipients of a dispensed drug," URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

The purpose of the present study was to identify the factors that influence the selection of hydrocodone and oxycodone as primary drugs of abuse in opioid-dependent subjects (n = 3520) entering one of 160 drug treatment programs around the country. Anonymous, self-administered surveys and direct qualitative interviews were used to examine the influence of demographic characteristics, drug use patterns, and decision-related factors on primary opioid selection. Our results showed that oxycodone and hydrocodone were the drugs of choice in 75% of all patients. Oxycodone was the choice of significantly more users (44.7%) than hydrocodone (29.4%) because the quality of the high was viewed to be much better by 54% of the sample, compared to just 20% in hydrocodone users, who cited acetaminophen as a deterrent to dose escalation to get high and hence, its low euphoric rating. Hydrocodone users were generally risk-averse women, elderly people, noninjectors, and those who prefer safer modes of acquisition than dealers (ie, doctors, friends, or family members). In contrast, oxycodone was a much more attractive euphorigenic agent to risk-tolerant young, male users who prefer to inject or snort their drugs to get high and are willing to use more aggressive forms of diversion. Prevention and treatment approaches, and pain physicians, should benefit from these results because it is clear that not all drug abusers share the same characteristics, and the decision to use one drug over another is a complex one, which is largely attributable to individual differences (eg, personality, gender, age, and other factors)., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Purpose: The present study was undertaken to assess the degree to which key informants' perceptions of relative abuse liability of opioids in their communities correspond to actual drug use in their patients., Methods: Key informants (n = 49) and their patients (n = 738) were asked to complete anonymous, independent paper surveys about perceived or actual abuse of nine targeted opioid drugs: buprenorphine, fentanyl, heroin, hydrocodone, hydromorphone, methadone, morphine, oxycodone and tramadol., Results: There was a strong correspondence (R = 0.98) between KI rankings of relative abuse of opioids in their patient population and the actual rank order calculated from their patients' selection of a primary euphorigenic opioid. The patient surveys not only validated the KI's conclusions, but also provided a great deal of important information about the nature of the abuse patterns. Notably, significant co-morbidity was found in the patient population: 55% had a history of psychiatric problems; chronic pain of moderate intensity was common; 67% were nicotine dependent; and 43% were diagnosed alcoholics., Discussion: Our results demonstrate that KI's perceived rank order of drugs of choice correlated almost perfectly with their patients' choice of a primary drug. These data suggest that key informants, as they have for decades in epidemiological research, provide a reliable, high-level view of substance abuse in their catchment area. As such, KIs provide valid and reliable information on scope and patterns of abuse, but if more detail is required about the characteristics of abuse, such as that required for FDA-mandated Risk Evaluation and Mitigation Strategies, then direct interviews with the abusers themselves seem more appropriate., (Copyright © 2010 John Wiley & Sons, Ltd.)

Although prescription drugs are readily available on the Internet, little is known about the prevalence of Internet use for the purchase of medications without a legitimate prescription, and the characteristics of those that obtain non-prescribed drugs through online sources. The scientific literature on this topic is limited to anecdotal reports or studies plagued by small sample sizes. Within this context, the focus of this paper is an examination of five national data sets from the U.S. with the purpose of estimating: (1) how common obtaining prescription medications from the Internet actually is, (2) who are the typical populations of "end users" of these non-prescribed medications, and (3) which drugs are being purchased without a prescription. Three of the data sets are drawn from the RADARS (Researched Abuse Diversion and Addiction-Related Surveillance) System, a comprehensive series of studies designed to collect timely and geographically specific data on the abuse and diversion of a number of prescription stimulants and opioid analgesics. The remaining data sets include the National Survey on Drug Use and Health (NSDUH) and the Monitoring the Future (MTF) survey. Our analysis yielded uniformly low rates of prescription drug acquisition from online sources across all five data systems we examined. The consistency of this finding across very diverse populations suggests that the Internet is a relatively minor source for illicit purchases of prescription medications by the individual end-users of these drugs., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

A variety of surveys and studies are examined in an effort to better understand the scope of prescription drug diversion and to determine whether there are consistent patterns of diversion among various populations of prescription drug abusers. Data are drawn from the RADARS System, the National Survey of Drug Use and Health, the Delaware School Survey, and a series of quantitative and qualitative studies conducted in Miami, Florida. The data suggest that the major sources of diversion include drug dealers, friends and relatives, smugglers, pain patients, and the elderly, but these vary by the population being targeted. In all of the studies examined, the use of the Internet as a source for prescription drugs is insignificant. Little is known about where drug dealers are obtaining their supplies, and as such, prescription drug diversion is a "black box" requiring concentrated, systematic study.

Purpose: Integrate statewide rankings of abuse across different drugs and/or signal detection systems to summarize prescription drug abuse in each state in 2007., Methods: Four signal detection systems (Opioid Treatment Programs, Key Informants, Drug Diversion, and Poison Centers) that covered heterogeneous populations collected data on the abuse of nine opioids: hydrocodone, immediate-release oxycodone, tramadol, extended-release [ER] oxycodone, fentanyl, morphine, methadone, hydromorphone, and buprenorphine). We introduce here linearized maps which integrate nine drugs within each system; four systems for each drug; or all drugs and systems., Results: When rankings were integrated across drugs, Rhode Island, New Hampshire, Maine, West Virginia, and Michigan were in the highest tertile of abuse in three systems. When rankings were integrated across signal detection systems, there was a geographic clustering of states with the highest rates for ER oxycodone (in Tennessee, Mississippi, Kentucky, Ohio, Indiana, Michigan, and in Massachusetts, New Hampshire, Maine, and Vermont) and methadone (Massachusetts, Rhode Island, New Hampshire, Maine, Vermont, Connecticut, and New Jersey). When rankings were integrated across both drugs and signal detection systems, states with 3-digit ZIP codes below 269 (i.e., from Massachusetts to West Virginia): Massachusetts, New Hampshire, Maine, Vermont, Washington DC, Virginia, and West Virginia were in the highest tertile and only Delaware was in the lowest tertile., Conclusions: We have presented methods to integrate data on prescription opioid abuse collected by signal detection systems covering different populations. Linearized maps are effective graphical summaries that depict differences in the level of prescription opioid abuse at the state level.

Generic drugs account for half of all prescription drug purchases in the United States. Although they are bioequivalent to their branded counterparts, they are typically sold at substantial discounts from the branded price. Given this, the purpose of this analysis is to examine the impact of the introduction of generic forms of selected opioids on their diversion to the illicit marketplace. The analgesics in this analysis include oxycodone ER (extended release), and the fentanyl transdermal patch. The data were collected through a post-marketing surveillance initiative supported by the Researched Abuse Diversion and Addiction-Related Surveillance (RADARS) System risk management program, gathered on a quarterly basis from a national sample of police and regulatory agencies. The results indicate that with oxycodone ER and the fentanyl transdermal patch, the diversion of their generic formulations occurs less often than that of the branded products, and that the introduction of the generic formulations did not significantly increase the overall levels of diversion during the period covered by this analysis. Although diversion did not increase in the short-term, the need for longer term monitoring appears warranted.

Objective: 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., Design: 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., Results: 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., Conclusions: 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.

Background: A great deal of previous work on the pharmacoeconomics of alcohol, tobacco and illicit drug abuse indicates that as cost decreases, abuse increases and vice versa. The application of these cost principles to the abuse of prescribed medications is largely unknown. In this paper we assessed whether the introduction of generic products in the U.S. increased the therapeutic use and illicit abuse of extended release oxycodone products and the fentanyl patch., Methods: As an index of therapeutic use, we purchased prescription data for each of the ZIP codes in which we had corresponding abuse data. To gather information about prescription drug abuse, we elicited cases with quarterly questionnaires completed by a key informant network., Results: The introduction of generic extended release (ER) oxycodone and fentanyl patch did not significantly change the total prescriptions written for these products, but markedly altered the composition of sales: branded sales dropped precipitously over a very short time and this was compensated for by a corresponding increase in sales of generics. Surprisingly, the introduction of generic products did not increase the abuse of ER oxycodone or fentanyl products; the branded version was the drug of choice for at least 2 years., Conclusions: Our data suggest that drug costs alone do not increase the overall likelihood that a prescription opioid analgesic will be used therapeutically or abused. However, while generics are rapidly endorsed by insurance companies as a prescribed entity, abuse of the branded versions of ER oxycodone and fentanyl remains predominant for some time.

Buprenorphine was approved in late 2004 for the treatment of opioid abuse and dependence in specially trained and certified physicians' offices. At the time of the approval, there was a regulatory concern that given the anticipated wide exposure there would be unexpectedly high levels of abuse in the high-risk population for which it was intended. To assess its abuse potential, the authors recruited more than 1000 individuals seeking treatment for prescription opioid abuse from 100 stand-alone (i.e., self-pay or insurance) drug abuse treatment programs around the country to determine whether they misused buprenorphine in the past 30 days to get high. The results indicate that there was a time-related increase in the number of subjects who used buprenorphine to get high, reaching 30-35 percent of individuals completing a questionnaire in the second quarter of 2006. At this time, it was equivalent to the misuse of methadone, both of which, however, were considerably lower than hydrocodone and oxycodone. Thereafter, the number of individuals using buprenorphine to get high dropped in a near linear fashion to less than 20 percent of those completing a questionnaire in the second quarter of 2007, significantly lower than that for methadone, oxycodone, and hydrocodone. The most likely interpretation of these data is that the poly-substance-abusing population, for whom buprenorphine is intended, experimented with this medication for its mood-altering effects for a period of time, but presumably because of its lack of euphorogenic properties, its use has now dissipated. Additionally, support for this conclusion is the very rare endorsement of buprenorphine as a primary drug (<3 percent of the total sample). Thus, the results indicate that it is unlikely that buprenorphine abuse will ever reach the epidemic that was feared by some regulatory groups and that its use in opioid detoxification and maintenance should continue.

Purpose: The goal of these studies was to determine the relationship between prescribed use of opioid analgesics and their non-medically related use (abuse) at a regional level across the country., Methods: To gather information about prescription drug abuse, we asked 233 drug abuse treatment specialists to provide us Quarterly reports on the number of cases of prescription opioid analgesic abusers who used opioid analgesics to get high in the past 30 days., Results and Conclusions: We found that there was a very strong correlation between therapeutic exposure to opioid analgesics, as measured by prescriptions filled, and their abuse. There were, however, geographical loci that represented outliers in which abuse was disproportionately high relative to therapeutic use (>95th percentile), most of which were in very small urban, suburban, and rural areas. The rank order of abuse shows that buprenorphine products, extended release (ER) oxycodone and methadone are the most intensely abused prescription opioid analgesics, with hydrocodone the least abused, when the data are corrected for degree of exposure, i.e., cases/1000 persons filling a prescription. If, on the other hand, one uses the number of cases/100 000 population, hydrocodone ranked as high as ER oxycodone and all other drugs grouped together at very low levels of abuse. Since the latter conclusion ignores therapeutic exposure, we conclude that the rate of abuse of highly efficacious opioid analgesics is best expressed as cases of abuse/1000 persons filling a prescription, which yields the best possible estimate of the risk-benefit ratio of these drugs.

Unlabelled: OBJECTIVE. Beginning in the late 1990's a marked increase in abuse of OxyContin emerged, which led to the development and establishment of a proactive surveillance program to monitor and characterize abuse, named the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS) System. The main goal of RADARS was to develop proactive, timely and geographically sensitive methods to assess the abuse and diversion of OxyContin, along with a number of other Schedule II and III opioids with the aim of using this information to guide risk reduction interventions. Thus, its major focus was the detection of abuse of OxyContin and other commonly prescribed opioid analgesics at the three-digit ZIP code level across the country utilizing a number of different detection systems., Methods: The detection systems selected were: (1) Quarterly-surveys of drug abuse experts who are knowledgeable about cases of prescription drug abuse; (2) Surveys of law enforcement agencies that detect diversion of prescription drugs; and (3) Poison Control Center reports of intentional misuse or abuse of prescription opioids. Collectively, the three systems provide overlapping coverage of over 80% of the nation's 973 three-digit ZIP codes., Results: Preliminary results indicate that prescription drug abuse is prevalent nationwide, but it seems to be heavily localized in rural, suburban and small urban areas. Our results also indicate that hydrocodone and extended and immediate release oxycodone products are by far the most widely abused drugs in the country, but the abuse of all prescription opioids seems to have grown over the 14 quarters since the inception of RADARS., Conclusion: The next step in these studies is to develop regionally specific, risk-minimization-strategies, which is the goal of all risk-management programs. If successful, RADARS will serve as a prototype of such programs for any new drug approved that has measurable abuse potential.

Increased abuse and diversion of prescription opioids has been a consequence of the increased availability of opioids to address the widespread problem of undertreated pain. Opioid risk management refers to the effort to minimize harms associated with opioid therapy while maintaining appropriate access to therapy. Management of these linked public health issues requires a coordinated and balanced effort among a disparate group of stakeholders at the federal, state, industry, practitioner, and patient levels. This paper reviews the principles of opioid risk management by examining the epidemiology of prescription opioid abuse in the United States; identifying key stakeholders involved in opioid risk management and their responsibilities for managing or monitoring opioid abuse and diversion; and summarizing the mechanisms currently used to monitor and address prescription opioid abuse. Limitations of current approaches, and emerging directions in opioid risk management, are also presented.

Ultram (tramadol HCL) was approved by the Food and Drug Administration in 1994 as a non-scheduled drug under the Controlled Substance Act. The non-scheduled status was contingent on the development and implementation of a comprehensive post-marketing surveillance program by an Independent Steering Committee external to Ortho-McNeil Pharmaceutical charged with monitoring abuse and recommending scheduling if unexpectedly high abuse occurred. The program developed by this committee was composed of a variety of studies, and the results of the first three years of the surveillance efforts revealed that the rate of Ultram abuse was low. At a meeting of the FDA in 1998 to reexamine the scheduling status of Ultram, it was recommended that the scope of the postmarketing surveillance program be broadened to include data on diversion. After a 1-year pilot study, by January 2002, a nationwide diversion survey was fully operational. This brief communication describes the experiences of this diversion study, and compares the findings on the diversion of Ultram and other tramadol HCL products with that of more widely abused drugs. Survey data suggest that the diversion of Ultram and other tramadol products is low, and overall, diversion investigators did not consider tramadol to be a problem in their respective jurisdictions.

Purpose: The analgesic Tramadol HCl (Ultram) was approved in 1994 as a non-scheduled drug under the CSA provided that a novel risk-management program would be developed by an Independent Steering Committee (ISC). The risk-management program began in 1995 with the launch of Ultram, and has been modified over the past decade to accommodate Ultracet (Ultram and acetaminophen) in 2001 and generic tramadol in 2002. This provided a unique opportunity to study the potential changes in abuse as the generic and combination products became available., Methods: To proactively detect cases of abuse and diversion, the ISC developed a comprehensive questionnaire which was completed quarterly by an extensive network of drug abuse experts (n = 309) and police agencies (n = 100) who were asked to indicate how many diversion cases involving Ultram, Ultracet, and generic tramadol were identified during the preceding 3 months and what were the ten most commonly diverted drugs in their catchment area during that period., Results and Conclusions: The data generated demonstrate that the abuse of tramadol remained very low despite new branded and generic formulations. Contrary to the hypothesis that cheaper generic drugs would lead to higher rates of abuse, we found no increase in abuse with the introduction of generic tramadol. Ultracet abuse rates, unlike those found with other widely used hydrocodone and oxycodone combination products, have been even lower than that observed for tramadol. Since the FDA has now mandated that proactive risk-management plans be implemented for new drugs, the tramadol risk-management plan may be useful as a prototypic model which can be modified to accommodate other drugs with abuse potential., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

Unlabelled: OxyContin (Purdue Pharma L.P., Stamford, Conn) was approved by the Food and Drug Administration (FDA) in 1995 as a sustained-release preparation of oxycodone hydrochloride and was thought to have much lower abuse potential than immediate-release oxycodone because of its slow-release properties. However, beginning in 2000, widespread reports of OxyContin abuse surfaced. In response, Purdue Pharma L.P. sponsored the development of a proactive abuse surveillance program, named the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) system. In this paper, we describe results obtained from one aspect of RADARS--the use of drug abuse experts (ie, key informants)--as a source of data on the prevalence and magnitude of abuse of prescription drugs. The results indicate that prescription drug abuse has become prevalent, with cases reported in 60% of the zip codes surveyed. The prevalence of abuse was rank ordered as follows: OxyContin >or= hydrocodone > other oxycodone > methadone > morphine > hydromorphone > fentanyl > buprenorphine. In terms of the magnitude of abuse (>or=5 cases/100,000 persons in a 3-digit zip code), modest growth was seen with all analgesics over the 10 calendar quarters we monitored, but was most pronounced with OxyContin and hydrocodone. These results indicate that OxyContin abuse is a pervasive problem in this country, but that it needs to be considered in the context of a general pattern of increasing prescription drug abuse., Perspective: Over the past 5 years, there have been reports, frequently anecdotal, that opioid analgesic abuse has evolved into a national epidemic. In this study, we report systematic data to indicate that opioid analgesic abuse has in fact increased among street and recreational drug users, with OxyContin and hydrocodone products the most frequently abused. Steps need to be taken to reduce prescription drug abuse, but very great care needs to be exercised in the nature of these actions so the legitimate and appropriate use of these drugs in the treatment of pain is not compromised as a result.

In 1994, the Drug Abuse Advisory Committee (DAAC) of the Food and Drug Administration (FDA) concluded that Ultram (tramadol hydrochloride) could be marketed as an analgesic drug without scheduling under the Controlled Substances Act based upon extensive pre-clinical, clinical and European epidemiological data. However, to guard against unexpectedly high levels of abuse in the United States, the DAAC recommended that an independent steering committee (ISC) be appointed to proactively monitor abuse/dependence. In the event that high rates of abuse were found, this ISC was given the authority to immediately recommend to the FDA that Ultram be scheduled. In the course of the surveillance project, the ISC received reports of withdrawal following abrupt discontinuation of Ultram and in some instances, following dose reductions. In most cases, the withdrawal symptoms consisted of classical opioid withdrawal, but in some cases were accompanied by withdrawal symptoms not normally observed in opiate withdrawal, such as hallucinations, paranoia, extreme anxiety, panic attacks, confusion and unusual sensory experiences such as numbness and tingling in one or more extremities. Withdrawal symptoms of either type were one of the more prevalent adverse events associated with chronic Ultram use, comprising nearly 40% of all adverse events reported with Ultram. Most of these consisted of typical opiate withdrawal symptoms, but 1 in 8 cases presented as atypical. These results indicate that physicians and other healthcare professionals need to be aware of the potential of Ultram to induce withdrawal of the classical opioid type, and that atypical withdrawal may also occur.

Tramadol HCl, marketed as Ultram in the USA, was introduced as a non-scheduled drug in April 1995 based on the assumption that the risk of abuse was sufficiently low to warrant a non-scheduled status. However, approval was contingent upon the development of an innovative proactive surveillance program, to be overseen by an independent steering committee, which would detect unexpectedly high levels of abuse. The postmarketing surveillance program consisted of systematic collection and scientific evaluation of reports of suspected abuse in high-risk populations surveyed through an extensive key informant network of drug abuse specialists and all spontaneous reports of abuse received through the FDA MedWatch system. Methods to estimate the number of patients prescribed tramadol were also developed. Monthly rates of abuse were calculated as an index of the risk-benefit ratio (i.e., abuse cases per 100,000 patients prescribed the drug). The data for the 3 years since the drug was introduced show that the reported rate of abuse has been low. Although a period of experimentation seemed to occur in the first 18 months after its introduction--which reached a peak rate of approximately two cases per 100,000 patients exposed--during the 2 year period prior to June 1998, the reported rate of abuse has significantly (P = 0.011) declined, reaching levels of less than one case per 100,000 patients in the last 18 months. The overwhelming majority of abuse cases (97%) have been found to occur among individuals with a history of substance abuse and the abuse has been confined to isolated pockets around the country-notably none of which have significant populations of street drug abusers. Thus, the data support the decision not to schedule tramadol and, furthermore, suggest that a proactive post-marketing surveillance program can be successfully developed to effectively monitor abuse of new medications.