Abuse of tapentadol compared to other atypical opioids among individuals entering treatment for opioid use disorders.

OBJECTIVE: Tapentadol is an atypical opioid analgesic thought to have dual mechanisms of action: µ-receptor agonism and inhibition of norepinephrine reuptake. Unlike other atypical opioids, tapentadol is a schedule II-controlled substance. We compared the prevalence of abuse (use to get high) of tapentadol to other atypical opioids used to treat pain (buprenor-phine and tramadol). DESIGN: An observational, serial cross-sectional study. SETTING: Individuals enrolling in treatment programs for opioid use disorder in 2019. Each completed a self-administered, paper questionnaire assessing prescription drug abuse and illegal drug use within 1 week of enrollment. MAIN OUTCOME MEASURES: Indication of past month abuse of tapentadol or comparator drugs on a self-administered ques-tionnaire. RESULTS: There were 6,987 respondents. Unadjusted and utilization-adjusted logistic regression models were used to compare odds of endorsement of tapentadol to tramadol and buprenorphine products indicated for the management of pain. Unadjusted abuse prevalence was 0.20 percent for total tapentadol (0.03 percent for NUCYNTA® and 0.06 percent for NUCYNTA ER). Relative to total tapentadol, the odds of abuse of buprenorphine for pain was 2.9 times greater (95 percent CI: 1.6 to 5.3, p < 0.001), and for tramadol, 43.1 times greater (95 percent CI: 25.3 to 73.3, p < 0.001). Adjusting for prescriptions dispensed, differences in odds of abuse were not statistically significant (odds ratio (OR) = 1.6, 95 per-cent CI: 0.9 to 3.0, p = 0.108 for buprenorphine for pain and OR = 0.7, 95 percent CI: 0.4 to 1.2, p = 0.209 for tramadol). CONCLUSIONS: Tapentadol use to get high is less frequent than other atypical opioids. Findings suggest tapentadol is rarely the primary drug abused by an individual.

Differences in Self-identification of Opioid Overdose Risk and Naloxone Perceptions Between Therapeutic and Nontherapeutic Opioid Populations.

OBJECTIVES: Efforts to improve low naloxone uptake to mitigate the current opioid crisis have included coprescribing naloxone with opioid medications and, more recently, expansion through over-the-counter availability, the latter of which necessitates self-identification of overdose risk by consumers. This study sought to understand perceptions of opioid overdose risk and naloxone among distinct opioid populations at elevated risk for overdose. METHODS: A cross-sectional, online survey was provided to 2 opioid populations in June 2020. First, chronic pain opioid managed (CPOM; n = 190) individuals currently treated with an opioid prescription (either >50 daily morphine milligram equivalents [73.2%] or benzodiazepine co-use [52.6%]), restricted by confounders. Second, individuals with a history of opioid use disorder (OUD; n = 152) previously participating in a national opioid surveillance study of new entrants to substance use treatment centers. RESULTS: Risk perceptions significantly differed, with 60.0% (CPOM) versus 28.9% (OUD) reporting that they were "not at all concerned about overdosing," and 62.1% (CPOM) versus 19.1% (OUD) perceiving themselves as having "no risk" of overdose. Perceived need for naloxone was lower among CPOM versus OUD patients (48.3% and 71.8%, respectively), whereas 22.6% and 35.0%, respectively, indicated any likelihood of obtaining naloxone in the future. CONCLUSIONS: Results suggest that a significant proportion of both samples lacked the ability to self-identify their risk of overdose and self-select themselves as needing naloxone, with gaps being more prominent in the CPOM sample. A multi-intervention framework that addresses distinct pathways of behavioral change between unique opioid populations should be considered in conversations surrounding potential transitions to over-the-counter naloxone.

Association between recent overdose and chronic pain among individuals in treatment for opioid use disorder.

Chronic pain increases risk for opioid overdose among individuals with opioid use disorder. The purpose of this study is to evaluate the relationship between recent overdose and whether or not chronic pain is active. 3,577 individuals in treatment for opioid use disorder in 2017 or 2018 were surveyed regarding recent overdoses and chronic pain. Demographics from the 2017 Treatment Episode Data Set, which includes all U.S. facilities licensed or certified to provide substance use care, were used to evaluate the generalizability of the sample. χ2 tests and logistic regression models were used to compare associations between recent overdoses and chronic pain. Specifically, active chronic pain was associated with opioid overdose among people in treatment for opioid use disorder. Individuals with active chronic pain were more likely to have had a past month opioid overdose than those with no history chronic pain (adjusted OR = 1.55, 95% CI 1.16-2.08, p = 0.0003). In contrast, individuals with prior chronic pain, but no symptoms in the past 30 days, had a risk of past month opioid overdose similar to those with no history of chronic pain (adjusted OR = 0.88, 95% CI 0.66-1.17, p = 0.38). This suggests that the incorporation of treatment for chronic pain into treatment for opioid use disorder may reduce opioid overdoses.

Opioid Dosage Levels, Concurrent Risk Factors and Self-Perceptions among Chronic Pain, Opioid-Managed Individuals at Elevated Risk for Opioid Overdose.

While current opioid prescribing guidelines highlight a dose-response relationship between therapeutic management and overdose risk, other concurrent risk factors have also been identified. However, there is little data in assessing the relationship between risk factor prevalence, associated provider communication, and subsequent perceptions of overdose risk among chronic pain, opioid-managed (CPOM) patients. An online questionnaire was distributed in June 2020 to a sample of CPOM individuals (n = 190) treated with an opioid prescription at or above 50 daily MME, or any dosage alongside benzodiazepines. CPOM individuals reported a mean daily MME of 470, with half (52.6%) receiving a concurrent benzodiazepine prescription. All patients reported past month alcohol use, and 67.4% indicated a risk-elevating diagnosed medical condition. In assessing provider communication, 41.6% reported no discussion focusing on the risks of one's opioid therapy. Subsequently, 62.1% perceived themselves as having "no risk", and 60.0% were "not at all concerned" (60.0%) about experiencing an opioid overdose. Organizational policies should focus on implementing consistent methods of patient education regarding overdose risk, as well as assessments of behaviors or characteristics that my increase an individual's risk of opioid overdose. These policies should also include other forms of evidence-based overdose risk prevention such as co-prescriptions of naloxone.

Polysubstance use trends and variability among individuals with opioid use disorder in rural versus urban settings.

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.

Prescription stimulant brand name recognition among a national sample of 10- to 18-year-old youth.

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.

The impact of opioid use disorder on levels of educational attainment: Perceived benefits and consequences.

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.

Polysubstance Use: A Broader Understanding of Substance Use During the Opioid Crisis.

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.

An ethnographic decision model of the initiation of gabapentin misuse among prescription and/or illicit opioid (mis)user.

AIMS: Gabapentin is used in the treatment of seizures and neuralgia, and it is prescribed off-label to treat substance use disorders and withdrawal symptoms. Recent research documents misuse of gabapentin, especially among prescription opioid misusers. The present study contributes to this literature by examining the initiation of gabapentin misuse. METHODS: Qualitative interviews were conducted with prescription and/or illicit opioid (mis)users who reported a history of gabapentin misuse (N = 62) and who did not (N = 29). During semi-structured interviews, respondents provided descriptions of the first time they misused gabapentin. An ethnographic decision model was constructed to illustrate the factors that influence the initiation decision. RESULTS: Multiple individual, social, and environmental factors influence the decision to initiate gabapentin misuse. Respondents described the initiation decision related to: a) wanting to feel a psychoactive high during times of limited access to one's preferred drug because of institutional barriers (e.g., substance abuse treatment; jail; transitional living facility; N = 18); b) the desire to use multiple drugs, including for experimentation or to potentiate another substance (N = 18); and c) the need to self-treat withdrawal symptoms during periods of opioid nonuse or when opioids were unavailable (N = 16). Respondents also initiated gabapentin misuse to self-treat physical pain (N = 10). CONCLUSIONS: Multiple approaches are needed to mitigate gabapentin misuse, including limiting availability in institutional settings and informal channels as well as addressing the needs of drug users who experience physical pain and withdrawal symptoms. Continued research is needed to examine therapeutic uses of gabapentin and behaviors related to misuse.

Gabapentin prescribed during substance abuse treatment: The perspective of treatment providers.

BACKGROUND: Gabapentin, a prescription medication approved for the treatment of seizures and neuralgia, is often prescribed off-label for substance use treatment, mental health problems, and pain. Emerging reports also suggest it is misused for the purpose of getting high. The present study examines substance abuse treatment provider key informants' experiences with gabapentin prescribed to clients in treatment. The focus of this exploratory study is to ascertain how gabapentin is used in these settings and the benefits and risks for clients. METHODS: Key informants from South Florida participated in confidential, in-depth interviews (N = 12). Data analyses included descriptive and in vivo coding schemes and employed a descriptive qualitative approach. RESULTS: All key informants recognized the benefits of prescribing gabapentin to clients in treatment for problems related to withdrawal symptoms, mental distress and pain. At the same time, half of participants described gabapentin misuse among clients and four key informants described such misuse as a first marker of relapse. Key informants also stated that more research must be done about how to use gabapentin effectively in treatment settings. CONCLUSIONS: These findings illustrate the lack of clarity about the efficacy of administration of gabapentin in treatment settings. Additional research about how to best use gabapentin, for whom it may be beneficial, and the effect of prescribed gabapentin on addiction recovery is needed.

Real-world misuse, abuse, and dependence of abuse-deterrent versus non-abuse-deterrent extended-release morphine in Medicaid non-cancer patients.

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.

Understanding multi-pill ingestion of prescription opioids: Prevalence, characteristics, and motivation.

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.

Twin epidemics: The surging rise of methamphetamine use in chronic opioid users.

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.

Understanding the use of diverted buprenorphine.

BACKGROUND: Buprenorphine is approved in many countries for the treatment of opioid use disorder (OUD), but problems with diversion and abuse exist. There is a need to understand how and why patients use diverted buprenorphine, and whether barriers to access contribute to illicit use. METHODS: Adults >18 years with DSM-IV criteria for substance use disorder and primarily using an opioid completed the online Survey of Key Informants' Patients (SKIP) between August and September 2016. The survey included closed- and open-ended questions regarding reasons for buprenorphine use with and without a prescription, sources of buprenorphine, route of administration, and barriers to treatment. RESULTS: Of 303 respondents, 175 (58%) reported a history of diverted buprenorphine use, 65 (37%) of whom reported never receiving a prescription. The most common reasons for illicit buprenorphine use were consistent with therapeutic use: to prevent withdrawal (79%), maintain abstinence (67%), or self-wean off drugs (53%). Approximately one-half (52%) reported using buprenorphine to get high or alter mood, but few (4%) indicated that it was their drug of choice. Among respondents who had used diverted buprenorphine, 33% reported that they had issues finding a doctor or obtaining buprenorphine on their own. Most (81%) of these participants indicated they would prefer using prescribed buprenorphine, if available. CONCLUSIONS: Although 58% of survey respondents reported a history of using diverted buprenorphine, the most frequently cited reasons for non-prescription use were consistent with therapeutic use. Diversion was partially driven by barriers to access, and an unmet need for OUD treatment persists.

Increased use of heroin as an initiating opioid of abuse: Further considerations and policy implications.

INTRODUCTION: Previously, we reported a marked increase in the use of heroin as an initiating opioid in non-tolerant, first time opioid users. In the current paper, we sought to update and expand upon these results, with a discussion of the policy implications on the overall opioid epidemic. METHODS: Opioid initiation data from the original study were updated to include surveys completed through 2017 (N = 8382) from a national sample of treatment-seeking opioid users. In addition, past month abuse of heroin and prescription were analyzed as raw numbers of treatment program entrant in the last five years (2013-2017), drawing from only those treatment centers that participated every year in that time frame. RESULTS: The updated data confirm and extend the results of our original study: the use of heroin as an initiating opioid increased from 8.7% in 2005 to 31.6% in 2015, with increases in overall Ns per initiation year reflecting a narrowing of the "treatment gap", the time lag between opioid initiation from 2005 to 2015 and later treatment admission (up to 2017). Slight decreases were observed in treatment admissions, but this decline was totally confined to prescription opioid use, with heroin use continuing to increase in absolute numbers. CONCLUSIONS: Given that opioid novices have limited tolerance, the risk of fatal overdose for heroin initiates is elevated compared to prescription opioids, particularly given non-oral administration and often unknown purity/adulterants (i.e., fentanyl). Imprecision of titrating dose among opioid novices may explain observed increases opioid overdoses. Future policy decisions should note that prescription opioid-specific interventions may have little impact on a growing heroin epidemic.

Assessment of Tapentadol API Abuse Liability With the Researched Abuse, Diversion and Addiction-Related Surveillance System.

Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted. PERSPECTIVE: This article presents the results from an examination of tapentadol API across the Researched Abuse, Diversion and Addiction-Related Surveillance System: a broad and carefully designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion, and Treatment Centers combined suggest a low, but present public health burden related to tapentadol.

Abuse-deterrent Opioid Formulations.

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.