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.

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.

Overcoming Impediments to OTP Expansion in the United States and Abroad.

By all published accounts and federal government reports, the United States is experiencing a serious opioid use epidemic. Additional treatment resources are needed in order to provide access to evidence based medical care for untreated individuals with substance use disorders. The focus of this commentary is increasing access to more opioid treatment programs and overcoming the significant impediments, which block such efforts.

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.

Challenges and Opportunities for the Use of Medications to Treat Opioid Addiction in the United States and Other Nations of the World.

There has been a well documented increase in the use and abuse of prescription opioids and heroin in the United States and other parts of the world. There has also been an increasing focus to increase access to the use of medications (methadone, buprenorphine, Naltrexone/Vivitrol) for opioid addicted individuals under legal supervision. As policymakers engage in strategic initiatives to better prevent and effectively treat chronic opioid addiction, both in the United States and other countries, there are a number of unintended consequences, complicating how best to increase access to effective treatment.

Trends in opioid analgesic abuse and mortality in the United States.

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.).

Distance traveled and cross-state commuting to opioid treatment programs in the United States.

This study examined commuting patterns among 23,141 methadone patients enrolling in 84 opioid treatment programs (OTPs) in the United States. Patients completed an anonymous one-page survey. A linear mixed model analysis was used to predict distance traveled to the OTP. More than half (60%) the patients traveled < 10 miles and 6% travelled between 50 and 200 miles to attend an OTP; 8% travelled across a state border to attend an OTP. In the multivariate model (n = 17,792), factors significantly (P < .05) associated with distance were, residing in the Southeast or Midwest, low urbanicity, area of the patient's ZIP code, younger age, non-Hispanic white race/ethnicity, prescription opioid abuse, and no heroin use. A significant number of OTP patients travel considerable distances to access treatment. To reduce obstacles to OTP access, policy makers and treatment providers should be alert to patients' commuting patterns and to factors associated with them.

Validity of self-reported misuse of prescription opioid analgesics.

AIM: To determine concurrent validity of self-reported misuse of prescription opioids. DESIGN AND SETTING: Cross-sectional study in five U.S. methadone maintenance programs. PARTICIPANTS: 92 addicts. MEASUREMENTS: Self-reported questionnaire assessing past-month misuse of 14 opioid analgesics, and color photographs of five opioid analgesics with instructions to mark those used in the past month "to get high." Concordance between self-report and photograph endorsement was assessed via Kappa statistic. FINDINGS: 29 respondents completed both questionnaire and photograph endorsements. Kappas were 0.62 (OxyContin), 0.59 (methadone), 0.49 (Dilaudid), and 0.46 (generic extended-release oxycodone). CONCLUSIONS: Good-to-fair concurrent validity of self-reported abuse was seen for OxyContin, methadone, Dilaudid, and generic extended-release oxycodone.

Post-marketing surveillance of methadone and buprenorphine in the United States.

INTRODUCTION: There have been recent increases in the use of methadone and buprenorphine in the United States. Methadone is increasingly being used for pain management, and buprenorphine use has expanded to include treatment for opioid addiction, leading to exposures of these drugs in new populations. There is a debate about the relative safety of these two drugs in routine outpatient medical use. METHODS: Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Programs were used to analyze rates of abuse, misuse, and diversion using the Drug Diversion, Key Informant, Poison Center and Opioid Treatment Programs, 2003-2007. National rate and rate ratios were calculated using population and person-time exposed denominators. Detailed data are presented on severity of medical outcome and drug formulations. RESULTS: Between 2003 and 2007, there were steady increases in the rates of abuse, misuse, and diversion of both methadone and buprenorphine. Rate ratios (per 100,000 population per quarter) of abuse, misuse, and diversion were consistently higher for methadone than buprenorphine. RADARS System poison centers received 7,476 calls for methadone and 1,117 calls for buprenorphine. After accounting for availability, there were higher rates of calls for methadone misuse, abuse, and diversion than buprenorphine in three of the four programs. The numbers of exposures requiring medical attention correspond to 46.8% and 25.8% of all calls, for methadone and buprenorphine, respectively. The most commonly diverted form of methadone was solid oral tablets (which are typically dispensed at pharmacies, not at opioid treatment programs), comprising 73% of cases. CONCLUSIONS: Buprenorphine appears to have a better safety profile than methadone during routine outpatient medical use. However, both medications have roles in the treatment of pain and opioid addiction, and further research into their respective benefits and risks should be conducted.

Variation among state-level approaches to addressing alcohol abuse in opioid treatment programs.

In view of their role in licensing opioid treatment programs (OTPs), state opioid treatment authorities (SOTAs) are in a unique position to influence how OTPs address their patients' alcohol abuse. Using data from a telephone survey of SOTAs from the District of Columbia and states that have at least one OTP (n = 46), this study examines the extent to which SOTAs address alcohol abuse in their respective state policies and guidelines for OTPs. Findings indicate that 27 states have overall measures on how to address patients' problematic alcohol use, 23 states require or recommend alcohol education to be provided to all patients, and 17 states have stipulations that address specific actions to be taken if patients present at daily dosing under the influence of alcohol. Although SOTAs generally rate alcohol of at least moderate importance in formulating regulations, many of their policies and guidelines do not deal with various alcohol-related services and issues.

Alcohol education provided to opioid treatment program patients: results of a nationwide survey.

Alcohol-related problems are especially common among opioid treatment program (OTP) patients, suggesting that educating OTP patients about alcohol and its harmful effects needs to be a priority in OTPs. Using data collected in interviews with a nationwide U.S. sample of OTP directors (N = 200) in 25 states, we identified factors that differentiate OTPs that provided this education to all OTP patients from those that did not. Findings indicate that these factors include (1) providing this education in a greater variety of ways, (2) having a larger percent of staff knowledgeable about alcohol-related issues, (3) having a director who views alcohol issues as a high priority, and (4) having a written OTP policy.

Integrating nine prescription opioid analgesics and/or four signal detection systems to summarize statewide prescription drug abuse in the United States in 2007.

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.

The "black box" of prescription drug diversion.

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.

Prescription opioid abuse among enrollees into methadone maintenance treatment.

A multi-state survey of 5663 opioid dependent persons enrolling in 72 methadone maintenance treatment programs (MMTPs) was conducted to determine the prevalence of prescription opioid (PO) abuse, factors associated with PO abuse and sources for POs. Regions where PO abuse was believed to be prevalent were oversampled; primary opioid was defined as the drug used the most before coming to the MMTP. Among primary heroin abusers, 69% reported abusing POs. Opioid abuse frequencies among primary PO abusers were oxycodone (79%), hydrocodone (67%), methadone (40%), morphine (29%), heroin (13%), hydromorphone (16%), fentanyl (9%) and buprenorphine (1%). Correlates (p < or = .01) of PO abuse, using general estimating equations, were: low urbanicity (MMTPs located in comparatively low population density counties), white ethnicity, no history of injecting primary drug, no previous methadone treatment, younger age, chronic pain, and pain as a reason for enrollment. The most frequent sources of POs were dealer, friend or relative, and doctor's prescription; least frequent were Internet and forged prescription. One-third of PO abusers reported a history of injecting their primary drug. PO abuse is highly prevalent among MMTP patients. Future studies should describe HIV/HCV needle injection practices, characteristics that predict treatment outcomes, and factors that contribute to higher prevalence of persistent pain among PO abusers.