Ryan A. Black

Abuse Rates and Routes of Administration of Reformulated Extended-Release Oxycodone: Initial Findings From a Sentinel Surveillance Sample of Individuals Assessed for Substance Abuse Treatment

UNLABELLED Oxycodone hydrochloride controlled-release, also known as extended-release oxycodone (ER oxycodone), was reformulated with physicochemical barriers to crushing and dissolving intended to reduce abuse through nonoral routes of administration (ROAs) that require tampering (eg, injecting and snorting). Manufacturer shipments of original ER oxycodone (OC) stopped on August 5, 2010, and reformulated ER oxycodone (ORF) shipments started August 9, 2010. A sentinel surveillance sample of 140,496 individuals assessed for substance abuse treatment at 357 U.S. centers between June 1, 2009, and March 31, 2012, was examined for prevalence and prescription-adjusted prevalence rates of past-30-day abuse via any route, as well as abuse through oral, nonoral, and specific ROAs for ER oxycodone and comparators (ER morphine and ER oxymorphone) before and after ORF introduction. Significant reductions occurred for 8 outcome measures of ORF versus OC historically. Abuse of ORF was 41% lower (95% CI: -44 to -37) than historical abuse for OC, with oral abuse 17% lower (95% CI: -23 to -10) and nonoral abuse 66% lower (95% CI: -69 to -63). Significant reductions were not observed for comparators. Observations were consistent with the goals of a tamper resistant formulation for an opioid. Further research is needed to determine the persistence and generalizability of these findings. PERSPECTIVE This article presents preliminary findings indicating that 8 outcome measures of abuse of a reformulated ER oxycodone were lower than that for original ER oxycodone historically, particularly through nonoral ROAs that require tampering (ie, injection, snorting, smoking), in a sentinel sample of individuals assessed for substance use problems for treatment planning.

Abuse risks and routes of administration of different prescription opioid compounds and formulations

BackgroundEvaluation of tamper resistant formulations (TRFs) and classwide Risk Evaluation and Mitigation Strategies (REMS) for prescription opioid analgesics will require baseline descriptions of abuse patterns of existing opioid analgesics, including the relative risk of abuse of existing prescription opioids and characteristic patterns of abuse by alternate routes of administration (ROAs). This article presents, for one population at high risk for abuse of prescription opioids, the unadjusted relative risk of abuse of hydrocodone, immediate release (IR) and extended release (ER) oxycodone, methadone, IR and ER morphine, hydromorphone, IR and ER fentanyl, IR and ER oxymorphone. How relative risks change when adjusted for prescription volume of the products was examined along with patterns of abuse via ROAs for the products.MethodsUsing data on prescription opioid abuse and ROAs used from 2009 Addiction Severity Index-Multimedia Version (ASI-MV®) Connect assessments of 59,792 patients entering treatment for substance use disorders at 464 treatment facilities in 34 states and prescription volume data from SDI Health LLC, unadjusted and adjusted risk for abuse were estimated using log-binomial regression models. A random effects binary logistic regression model estimated the predicted probabilities of abusing a product by one of five ROAs, intended ROA (i.e., swallowing whole), snorting, injection, chewing, and other.ResultsUnadjusted relative risk of abuse for the 11 compound/formulations determined hydrocodone and IR oxycodone to be most highly abused while IR oxymorphone and IR fentanyl were least often abused. Adjusting for prescription volume suggested hydrocodone and IR oxycodone were least often abused on a prescription-by-prescription basis. Methadone and morphine, especially IR morphine, showed increases in relative risk of abuse. Examination of the data without methadone revealed ER oxycodone as the drug with greatest risk after adjusting for prescription volume. Specific ROA patterns were identified for the compounds/formulations, with morphine and hydromorphone most likely to be injected.ConclusionsUnadjusted risks observed here were consistent with rankings of prescription opioid abuse obtained by others using different populations/methods. Adjusted risk estimates suggest that some, less widely prescribed analgesics are more often abused than prescription volume would predict. The compounds/formulations investigated evidenced unique ROA patterns. Baseline abuse patterns will be important for future evaluations of TRFs and REMS.

Changes in Prevalence of Prescription Opioid Abuse after Introduction of an Abuse-Deterrent Opioid Formulation

OBJECTIVE The reformulation of oxycodone hydrochloride controlled-release (CR) tablets in August 2010 created a natural experiment at a national scale, providing an opportunity to evaluate patterns of abuse of prescription opioids and other drugs before and after introduction of this abuse-deterrent formulation (ADF). DESIGN Observational, cross-sectional study SETTING Sentinel sample of adults assessed for substance abuse treatment within the NAVIPPRO® surveillance system SUBJECTS Two hundred thirty-two thousand and eight hundred seventy-four adults at 437 facilities during January 1, 2008 through December 31, 2011. METHODS Time-series analysis using logistic regression to estimate quarterly prevalence of past 30-day abuse (adjusted for covariates and prescription volume) and changes in abuse pre-and post-ADF introduction. RESULTS Increases in abuse prevalence occurred for all prescription opioids as a class and for extended-release (ER) opioids. Significantly greater abuse of ER oxymorphone and buprenorphine occurred in the post-ADF period (relative risk [RR] = 2.91, 95% confidence interval [CI] = 2.59-3.27 and RR = 1.85, 95% CI = 1.74-1.96). Increases in abuse for these two compounds were significant among groups who reported abuse via preferential routes of administration (oral only, snorting only, injection only) post-ADF introduction. CONCLUSIONS Replacement of a widely prescribed opioid formulation known for its abuse potential alone may have had little impact on overall rates of prescription opioids as a class. However, changes in abuse levels of certain opioids coinciding with ADF introduction suggest possible switching of abuse among this study sample to specific long-acting opioid analgesics. Additional follow-up studies will be important to monitor changing abuse patterns and their public health impact as new opioid formulations are developed and introduced to market.

Typologies of Prescription Opioid Use in a Large Sample of Adults Assessed for Substance Abuse Treatment

Background As a population, non-medical prescription opioid users are not well-defined. We aimed to derive and describe typologies of prescription opioid use and nonmedical use using latent class analysis in an adult population being assessed for substance abuse treatment. Methods Latent class analysis was applied to data from 26,314 unique respondents, aged 18-70, self-reporting past month use of a prescription opioid out of a total of 138,928 cases (18.9%) collected by the Addiction Severity Index-Multimedia Version (ASI-MV®), a national database for near real-time prescription opioid abuse surveillance. Data were obtained from November 2005 through December 2009. Substance abuse treatment, criminal justice, and public assistance programs in the United States submitted data to the ASI-MV database (n = 538). Six indicators of the latent classes derived from responses to the ASI-MV, a version of the ASI modified to collect prescription opioid abuse and chronic pain experience. The latent class analysis included respondent home ZIP code random effects to account for nesting of respondents within ZIP code. Results A four-class adjusted latent class model fit best and defined clinically interpretable and relevant subgroups: Use as prescribed, Prescribed misusers, Medically healthy abusers, and Illicit users. Classes varied on key variables, including race/ethnicity, gender, concurrent substance abuse, duration of prescription opioid abuse, mental health problems, and ASI composite scores. Three of the four classes (81% of respondents) exhibited high potential risk for fatal opioid overdose; 18.4% exhibited risk factors for blood-borne infections. Conclusions Multiple and distinct profiles of prescription opioid use were detected, suggesting a range of use typologies at differing risk for adverse events. Results may help clinicians and policy makers better focus overdose and blood-borne infection prevention efforts and intervention strategies for prescription opioid abuse reduction.

A Randomized Trial of a Web-based Intervention to Improve Migraine Self-Management and Coping

Objective.— To test the clinical efficacy of a web‐based intervention designed to increase patient self‐efficacy to perform headache self‐management activities and symptom management strategies, and reduce migraine‐related psychological distress.

Risk behaviors and drug use: a latent class analysis of heavy episodic drinking in first-year college students

Examining individual characteristics may not yield an understanding of the complex array of factors that affect college student alcohol use. Utilizing a latent class analysis, the present study investigated an alcohol and drug use database of first-year college students at 89 U.S. colleges and universities (N = 21,945). These data were collected between December, 2010 and September, 2011. This study identified: (1) classes based on alcohol consumption, alcohol-related behaviors, and past-year use of illegal drugs and nonmedical use of prescriptions medications (NMUPM); (2) demographic covariates of these classes; and (3) differential social norms awareness, perceived harmfulness of illegal drugs and NMUPM, and protective strategies. Four classes were identified: (1) Low Risk Drinking/Low Prevalence Drug Use (Class 1); (2) Lower Intake Drinking/Moderate Prevalence Drug Use (Class 2); (3) Moderate Risk Drinking/Moderate Prevalence Drug Use (Class 3); and (4) High Risk Drinking/High Prevalence Drug Use (Class 4). Classes differed in self-reported typical week drinking, estimated peak blood alcohol content over the past 2 weeks, high-risk alcohol use, negative alcohol-related consequences, driving under the influence or riding with drinking drivers, alcohol-related protective behaviors, and past-year substance use. Of particular interest was the identification of a latent class (Class 2) composed primarily of females with a relatively low alcohol intake, but with a high probability of past-year other substance use. This group reported negative alcohol-related consequences despite their relatively low intake. To our knowledge, this is the first latent class analysis of college student alcohol use that includes a drug use indicator and compares social norms awareness, harmfulness perceptions, and alcohol-related protective behaviors between classes.

Tapentadol abuse potential: a postmarketing evaluation using a sample of individuals evaluated for substance abuse treatment.

OBJECTIVE Abuse of prescription opioid pain relievers continues to be a serious public health concern. In contrast to opioids such as oxycodone or morphine, tapentadol, a prescription analgesic, has two mechanisms of action: μ-opioid receptor agonism and norepinephrine reuptake inhibition. As a result of differences in its receptor pharmacology, there may be differences in its abuse profile. As an initial step toward testing this hypothesis, we present a postmarketing examination of tapentadols abuse liability relative to comparators. METHODS A sentinel sample of 113,914 individuals assessed for substance abuse treatment as part of the NAVIPPRO ASI-MV(®) surveillance system at 624 facilities in 38 states from January 2011 to September 2012 was examined for prevalence and prescription-adjusted prevalence of past 30-day abuse of tapentadol as a compound and its immediate-release (IR) and extended-release (ER) formulations with oxymorphone, hydromorphone, hydrocodone, morphine, fentanyl, oxycodone, tramadol, and buprenorphine as comparators. RESULTS Tapentadol abuse was reported significantly less often (P < 0.001) than all comparator compounds. Tapentadol IR abuse prevalence was significantly lower than all comparators except fentanyl IR, which had the next lowest unadjusted abuse prevalence. Prevalence of tapentadol ER abuse was lower than comparators except hydromorphone ER. Low prescription-adjusted estimates were observed for tapentadol as a compound as well as its IR and ER formulations, which were among the lowest observed and the lowest of the Schedule II comparators. Prescription-adjusted risk for tapentadol ER was less than comparators except hydromorphone ER (P = 0.06). CONCLUSIONS Tapentadol abuse was seen infrequently in this study and, on a prescription basis, was less likely to be abused than most of the examined Schedule II analgesics.

Monitoring of internet forums to evaluate reactions to the introduction of reformulated OxyContin to deter abuse.

Background Reformulating opioid analgesics to deter abuse is one approach toward improving their benefit-risk balance. To assess sentiment and attempts to defeat these products among difficult-to-reach populations of prescription drug abusers, evaluation of posts on Internet forums regarding reformulated products may be useful. A reformulated version of OxyContin (extended-release oxycodone) with physicochemical properties to deter abuse presented an opportunity to evaluate posts about the reformulation in online discussions. Objective The objective of this study was to use messages on Internet forums to evaluate reactions to the introduction of reformulated OxyContin and to identify methods aimed to defeat the abuse-deterrent properties of the product. Methods Posts collected from 7 forums between January 1, 2008 and September 30, 2013 were evaluated before and after the introduction of reformulated OxyContin on August 9, 2010. A quantitative evaluation of discussion levels across the study period and a qualitative coding of post content for OxyContin and 2 comparators for the 26 month period before and after OxyContin reformulation were conducted. Product endorsement was estimated for each product before and after reformulation as the ratio of endorsing-to-discouraging posts (ERo). Post-to-preintroduction period changes in ERos (ie, ratio of ERos) for each product were also calculated. Additionally, post content related to recipes for defeating reformulated OxyContin were evaluated from August 9, 2010 through September 2013. Results Over the study period, 45,936 posts related to OxyContin, 18,685 to Vicodin (hydrocodone), and 23,863 to Dilaudid (hydromorphone) were identified. The proportion of OxyContin-related posts fluctuated between 6.35 and 8.25 posts per 1000 posts before the reformulation, increased to 10.76 in Q3 2010 when reformulated OxyContin was introduced, and decreased from 9.14 in Q4 2010 to 3.46 in Q3 2013 in the period following the reformulation. The sentiment profile for OxyContin changed following reformulation; the post-to-preintroduction change in the ERo indicated reformulated OxyContin was discouraged significantly more than the original formulation (ratio of ERos=0.43, P<.001). A total of 37 recipes for circumventing the abuse-deterrent characteristics of reformulated OxyContin were observed; 32 were deemed feasible (ie, able to abuse). The frequency of posts reporting abuse of reformulated OxyContin via these recipes was low and decreased over time. Among the 5677 posts mentioning reformulated OxyContin, 825 posts discussed recipes and 498 reported abuse of reformulated OxyContin by such recipes (41 reported injecting and 128 reported snorting). Conclusions After introduction of physicochemical properties to deter abuse, changes in discussion of OxyContin on forums occurred reflected by a reduction in discussion levels and endorsing content. Despite discussion of recipes, there is a relatively small proportion of reported abuse of reformulated OxyContin via recipes, particularly by injecting or snorting routes. Analysis of Internet discussion is a valuable tool for monitoring the impact of abuse-deterrent formulations.

A randomized, controlled trial to test the efficacy of an online, parent-based intervention for reducing the risks associated with college-student alcohol use

Alcohol consumption among college students remains a major public health concern. Universal, Web-based interventions to reduce risks associated with student alcohol consumption have been found to be effective in changing their alcohol-related behavior. Recent studies also indicate that parent-based interventions, delivered in booklet form, are effective. A parent-based intervention that is also Web-based may be well suited to a dispersed parent population; however, no such tool is currently available. The purpose of this study was to test the efficacy of an online parent-based intervention designed to (1) increase communication between parents and students about alcohol and (2) reduce risks associated with alcohol use to students. A total of 558 participants, comprising 279 parent-teen dyads, were enrolled in the study. The findings suggested that parents who participated in the online intervention were more likely to discuss protective behavioral strategies, particularly those related to manner of drinking and stopping/limiting drinking, with their teens, as compared with parents in an e-newsletter control group. Moreover, students whose parents received the intervention were more likely to use a range of protective behavioral strategies, particularly those related to manner of drinking and stopping/limiting drinking, as compared with students whose parents did not receive the intervention. A universal, online, parent-based intervention to reduce risks associated with student alcohol consumption may be an efficient and effective component of a colleges overall prevention strategy.

Associations between public health indicators and injecting prescription opioids by prescription opioid abusers in substance abuse treatment

OBJECTIVE To determine what, if any, public health and societal impacts are associated specifically with injection of prescription opioids. DESIGN Cross-sectional observational study. SETTING Five hundred forty treatment facilities in 35 states across the United States performing Addiction Severity Index-Multimedia Version (ASI-MV) assessments. PARTICIPANTS Adult patients (29,459) who reported past 30-day abuse of any prescription opioid on the ASI-MV assessment between January 2007 and January 2011. MAIN OUTCOME MEASURES The public health indicators selected for this study were liver disease, HIV/AIDS status, recent visit to an emergency room, treatment for pain, treatment for overdosing, homelessness, residence with alcohol/substance abuser, and unemployment. RESULTS Prescription opioid injection was significantly associated with health problems, psychosocial problems, and utilization of medical services. CONCLUSIONS This study demonstrates an approach to measure the potential impact of injecting prescription opioids on public health indicators. Findings indicate a positive association between injection of prescription opioids and public health indicators suggesting a need for prescription opioid formulations that may inhibit injection of these medications.