Matthew S. Ellis

Effect of abuse-deterrent formulation of OxyContin.

In 2010, an abuse-deterrent formulation of the widely abused prescription opioid OxyContin replaced the original formulation. After the new formulation was introduced, patients reported that they used OxyContin less often and other drugs (including heroin) more often.

Shifting Patterns of Prescription Opioid and Heroin Abuse in the United States

This analysis of data from surveys of patients with opioid dependence who were entering treatment programs in the United States showed that exclusive abuse of prescription opioids declined between 2010 and 2014 and concurrent abuse of heroin and opioids increased.

Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone

BACKGROUND The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin®) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. METHODS Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS®) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. RESULTS OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. DISCUSSION Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years.

Increased use of heroin as an initiating opioid of abuse

INTRODUCTION Given the relatively recent growth in access to heroin and a more permissive atmosphere surrounding its use, we hypothesized that an increasing number of persons with limited experience and tolerance to opioids would experiment with heroin as their first opioid rather than more common prescription opioid analgesics. METHODS Individuals entering substance abuse treatment for an opioid use disorder in the period 2010-2016 (N=5885) were asked about the specific opioid they first regularly used to get high. To limit long-term recall and survival bias, analyses was restricted to opioid initiation that occurred in the past ten years (2005-2015). RESULTS In 2005, only 8.7% of opioid initiators started with heroin, but this sharply increased to 33.3% (p<0.001) in 2015, with no evidence of stabilization. The use of commonly prescribed opioids, oxycodone and hydrocodone, dropped from 42.4% and 42.3% of opioid initiators, respectively, to 24.1% and 27.8% in 2015, such that heroin as an initiating opioid was now more frequently endorsed than prescription opioid analgesics. CONCLUSIONS Our data document that, as the most commonly prescribed opioids - hydrocodone and oxycodone - became less accessible due to supply-side interventions, the use of heroin as an initiating opioid has grown at an alarming rate. Given that opioid novices have limited tolerance to opioids, a slight imprecision in dosing inherent in heroin use is likely to be an important factor contributing to the growth in heroin-related over dose fatalities in recent years.

Factors influencing the selection of hydrocodone and oxycodone as primary opioids in substance abusers seeking treatment in the United States

Summary Selection of hydrocodone and oxycodone as primary opioids of misuse is complexly determined by gender, age, pain, accessibility, drug formulation, and quality of the high. Abstract 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).

Relative preferences in the abuse of immediate-release versus extended-release opioids in a sample of treatment-seeking opioid abusers.

Although differences in the pharmacological properties of immediate‐release (IR) and extended‐release (ER) opioid formulations have been reported, there are few studies comparing the real world abuse and relative preferences for these formulations.

Health outcomes in patients using no-prescription online pharmacies to purchase prescription drugs

Background Many prescription drugs are freely available for purchase on the Internet without a legitimate prescription from a physician. Objective This study focused on the motivations for using no-prescription online pharmacies (NPOPs) to purchase prescription drugs rather than using the traditional doctor-patient-pharmacy model. We also studied whether users of NPOP-purchased drugs had poorer health outcomes than those who obtain the same drug through legitimate health care channels. Methods We selected tramadol as a representative drug to address our objective because it is widely prescribed as an unscheduled opioid analgesic and can easily be purchased from NPOPs. Using search engine marketing (SEM), we placed advertisements on search result pages stemming from the keyword “tramadol” and related terms and phrases. Participants, who either used the traditional doctor-patient-pharmacy model to obtain tramadol (traditional users, n=349) or purchased it on the Web without a prescription from their local doctor (ie, nontraditional users, n=96), were then asked to complete an online survey. Results Respondents in both groups were primarily white, female, and in their mid-forties (nontraditional users) to upper forties (traditional users). Nearly all nontraditional users indicated that their tramadol use was motivated by a need to treat pain (95%, 91/96) that they perceived was not managed appropriately through legitimate health care channels. A majority of nontraditional users (55%, 41/75) indicated they used NPOPs because they did not have access to sufficient doses of tramadol to relieve pain. In addition, 29% (22/75) of nontraditional users indicated that the NPOPs were a far cheaper alternative than seeing a physician, paying for an office visit, and filling a prescription at a local pharmacy, which is often at noninsured rates for those who lack medical insurance (37%, 35/96, of NPOP users). The remainder of participants (16%, 12/96) cited other motivations (eg, anonymity) for using NPOPs. In terms of health outcomes, nontraditional users experienced a significantly (P<.01) greater number and severity of adverse events, including life-threatening seizures: 7% (7/96) of nontraditional users reported seizures, while none of the traditional users reported seizures. Conclusions Although online pharmacies can offer distinct advantages in terms of convenience and cost, users of these “rogue” pharmacies that offer drugs with no prescription or doctor supervision do so at great risk to their health, as evidenced by much higher rates of adverse events. The most logical explanation for these findings is that the lack of physician oversight of dosage schedules, contraindicated conditions, and concomitant medications, were responsible for the increased intensity and frequency of adverse events in the nontraditional users. Although we only examined tramadol, it is logical to postulate that similar results would be observed with dozens of equally accessible prescription drugs. As such, the geometric growth in the use of online pharmacies around the world should prompt intense medical and regulatory discussion about their role in the provision of medical care.

A tale of 2 ADFs: differences in the effectiveness of abuse-deterrent formulations of oxymorphone and oxycodone extended-release drugs.

Abstract The introduction of extended-release opioid analgesics helped initiate an epidemic of prescription opioid abuse in the United States. To make access to the drug by crushing or dissolution more difficult, abuse-deterrent formulations (ADFs) of OxyContin (Purdue Pharma, Stamford, CT) and Opana ER (Endo Pharmaceuticals Inc., Malvern, PA), which use the same foundation technology (Intac, Grunenthal, Aachen, Germany), were introduced in 2010 and 2012, respectively. To examine their relative effectiveness, we used a structured survey of 12,124 individuals entering treatment for opioid use disorder followed by a more focused online survey with a subset of these patients (N = 129) using both structured and open-ended questions. Data showed that the OxyContin ADF was highly effective in reducing nonoral abuse (91.4% before the ADF, 47.9% afterwards), particularly with insufflation (78%-28.8%) and intravenous injection of the active drug (42.7%-21.4%). However, although the Opana ER ADF was effective in reducing insufflation (80%-37.1%), injection (60.0%-51.4%), and overall nonoral abuse (94.3%-77.1%), it showed no significant decrease over time. Bearing in mind that the Opana ER sample was smaller in size than that for OxyContin, our results nonetheless suggest disparate outcomes resulting from the introduction of the ADFs, which could indicate that an ADFs effectiveness may be drug-specific. Given the public health impact of prescription opioids and the considerable effort being expended to develop ADFs as a partial solution to the problem, our preliminary studies suggest that each ADF must be evaluated on its own merits even if the same proprietary technology is used.

Psychoactive substance use prior to the development of iatrogenic opioid abuse: A descriptive analysis of treatment-seeking opioid abusers

Physicians are frequently thought to be a major source of opioids diverted for non-therapeutic purposes, largely because it is so difficult for them to discern which patients might abuse them. In this study we sought to determine whether those who were first exposed to an opioid through a physicians prescription, and subsequently developed a substance use disorder, had a history of using psychoactive drugs prior to abusing opioids. Patients entering one of 125 drug treatment programs across the country for opioid abuse were asked to provide detailed histories of psychoactive drug use prior to their initial opioid exposure. Nearly half (47.1%, N=4493) indicated they were first exposed to opioids through a prescription from their physician to treat pain. Of these, 94.6% indicated experience with at least one other psychoactive substance (mean=4.55±0.05) prior to, or coincident with, their first exposure to an opioid from a physician. Alcohol (92.9%), nicotine and/or tobacco (89.5%), and marijuana (87.4%) were used by nearly all patients prior to, or coincident with, their first opioid prescription. If one excludes these drugs, 70.1% (N=2913) still reported some psychoactive drug use of licit or illicit stimulants (77.8%), benzodiazepines (59.8%) or hallucinogens (55.2%). Our results indicate that pain patients who developed a substance use disorder were rarely drug naïve prior to receiving their first opioid prescription. Rather, most have an extensive history of psychoactive drug use. As such, physicians should routinely ascertain complete licit and illicit drug histories in patients for whom they prescribe opioids.

Abuse Deterrent Formulations of Prescription Opioids—Reply

Abuse-Deterrent Formulations of Prescription Opioids To the Editor Cicero and Ellis1 reported that 25% to 30% of individuals entering a group of substance abuse treatment centers endorse the reformulated OxyContin as a drug they had abused in the previous 30 days. Although Cicero and Ellis1 reported that the rate of endorsement of OxyContin fell from 46% to 25%, the popular press has portrayed the report as evidence that abuse-deterrent formulations are ineffective. The Survey of Key Informants’ Patients (SKIP) program on which Cicero and Ellis1 reported is one part of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) system, a national multicomponent surveillance system focusing specifically on the abuse and diversion of prescription drugs.2 The analysis omitted that the number of OxyContin endorsements by individuals in the SKIP program has fallen from an average of 0.273 abuse endorsements per 100 000 population 1 year prior the reformulation to 0.157 per 100 000 population in the second quarter of 2014, indicating a 42% decline. Another RADARS program, the Opioid Treatment Program (OTP), shares with SKIP identical questions regarding drugs the respondent has abused in the previous 30 days. The OTP represents a slightly different population—individuals entering substance abuse programs that use medical substitution therapy such as methadone or buprenorphine. In the OTP, the number of OxyContin endorsements has fallen from an average of 0.593 abuse endorsements per 100 000 population 1 year prior to the reformulation to 0.172 per 100 000 population, marking a 71% decline. We conclude that the abuse-deterrent formulations are indeed effective at reducing diversion and abuse. This conclusion is also supported by evidence from other research.3,4 Finally, the RADARS system also includes surveillance programs including drug diversion and poison centers.2 In these programs, diversion and intentional abuse of OxyContin have decreased 53% and 38%, respectively, in the first 2 years after reformulation and have subsequently decreased further.5 Abuse-deterrent formulations of prescription opioids are one effective measure to reduce prescription drug abuse. They are not a panacea, but they offer the promise of discouraging individuals who decide to crush their medication for the purpose of abuse.