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.

Drug product dispensing and estimates of use in a general population survey as a signal detection problem.

PURPOSE: Understanding potential bias due to rarity of the outcome is important when monitoring newly approved drugs and drugs with low availability to the general public. Although there is an increasing use of online surveys to investigate health outcomes, the limits of inference due to drug availability have not been studied. The goal of this study was to quantify the relationship between dispensing of prescription drugs and estimates of use in an online general population survey. METHODS: An online repeated, cross-sectional survey from 2018 to 2020 was used to estimate the number of adults in the United States who used prescription drugs in the general population and compared to estimated number of prescriptions dispensed over an equivalent time period. Joinpoint regression was used to quantify thresholds. A sample of respondents was retested to estimate reliability statistics. RESULTS: A model with a single threshold was the best fit, with the estimated threshold of 565 000 (95% CI: 9500-11 600 000) prescriptions dispensed per year. Above the threshold, there was a significant association between dispensing and estimates (p < 0.001); below the threshold, the relationship was not significant (p = 0.912). Above the threshold, responses were more reliable than random chance, and reliability steadily increased with increased dispensing. CONCLUSIONS: These results suggest the threshold demarcates two distinct pharmacoepidemiological paradigms when investigating drug use in general population surveys. Dispensing can be used as a guide to determine the epidemiological paradigm that is best suited.

Consistency Between Opioid-Related Mortality Trends Derived From Poison Center and National Vital Statistics System, United States, 2006-2016.

OBJECTIVES: To determine the association between poison center opioid exposure calls and National Vital Statistics System (NVSS) deaths. METHODS: We categorized Centers for Disease Control and Prevention NVSS mortality and the Researched Abuse, Diversion and Addiction-Related Surveillance System poison center program cases from 2006 to 2016 by International Classification of Diseases, Tenth Revision, codes (heroin [T40.1]; natural or semisynthetic opioids [T40.2]; methadone [T40.3]; synthetic opioids, other than methadone [T40.4]). We scaled rates by 100 000 population and calculated Pearson correlation coefficients. Sensitivity analysis excluded polysubstance cases involving either heroin or synthetic opioids as well as natural and semisynthetic opioids. RESULTS: The NVSS mortality and poison center program exposure rates showed similar trends from 2006 to 2012, and diverged after 2012 for all opioids combined, natural and semisynthetic opioids, and synthetic opioids (r = -0.37, -0.12, and 0.30, respectively). Sensitivity analysis with removal of heroin or synthetic opioid polysubstance deaths markedly improved correlations for all opioids combined and natural and semisynthetic opioids (r = 0.87 and 0.36, respectively). CONCLUSIONS: The NVSS mortality and poison center exposure rates showed similar trends from 2006 to 2012 then diverged, with sensitivity analysis suggesting polysubstance cases also involving heroin or illicit fentanyl as the cause. Public Health Implications. The NVSS and poison center program may provide complementary data when trends diverge. Public health interventions must include both licit and illicit opioids for maximal impact.

Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States.

BACKGROUND: Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. METHODS: Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. RESULTS: From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (p<0.001). CONCLUSIONS: Between 2009 and 2015, IR opioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations.

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.).

Seasonal variation in suicidal behavior with prescription opioid medication.

BACKGROUND: Suicide attempts by self-poisoning utilizing prescription opioids account for more than half of prescription drug abuse and misuse emergency calls received by poison centers. Additionally seasonal suicidal behavior using other means is a commonly replicated finding. We hypothesized seasonal behavior would exist in individuals using opioid medication as a suicide means, and that this pattern would change at different latitudes in the United States. METHODS: We used a harmonic regression strategy to investigate sinusoidal seasonal variations of suicidal behavior utilizing prescription opioids, and to contrast changes in seasonal behavior by latitude within the United States. Further, we investigated associations between suicide frequency utilizing opioid medication and frequency of dispensed opioid prescriptions. RESULTS: Seasonal patterns were identified; overall, all harmonic terms were significant (p<0.05). Interaction terms of harmonic by latitude and harmonic by gender also were significant (p<0.05). After stratification, females had significant harmonic terms at all latitudes. A changing peak time period with latitude also was observed, such that the peak appeared later at more southern latitudes. Additionally, increased dispensed prescriptions rates per population were associated with increased suicidal behavior utilizing prescription opioids. LIMITATIONS: This study has limitations due to its ecological nature and to missing data that may inform our understanding of suicide risk factors, such as marital status and socio-economic status. CONCLUSION: Suicidal behavior with prescription opioids follows a seasonal pattern that changes with latitude within the United States. Further, increased accessibility may contribute to increased suicidal attempt rates utilizing prescription opioids.

Pregnancy and race/ethnicity as predictors of motivation for drug treatment.

While drug use during pregnancy represents substantial obstetrical risks to mother and baby, little research has examined motivation for drug treatment among pregnant women. We analyzed data collected between 2000 and 2007 from 149 drug-using women located in Baltimore, Maryland. We hypothesized that pregnant drug-using women would be more likely than non-pregnant drug-using women to express greater motivation for treatment. Also, we explored race/ethnicity differences in motivation for treatment. Propensity score analysis was used to match a sample of 49 pregnant drug-using women with 100 non-pregnant drug-using women. The first logistic regression model indicated that pregnant women were more than four times as likely as non-pregnant women to express greater motivation for treatment. The second logistic regression analysis indicated a significant interaction between pregnancy status and race/ethnicity, such that white pregnant women were nearly eight times as likely as African-American pregnant women to score higher on the motivation for treatment measure. These results suggest that African-American pregnant drug-using women should be targeted for interventions that increase their motivation for treatment.

Interaction of cognitive performance and knowing someone who has died from AIDS on HIV risk behaviors.

This study examined the association among knowledge of someone who has died from AIDS, cognitive functioning, and performance of protective health behaviors to reduce the risk of contracting HIV. Baseline data were analyzed from a sample of 229 injection drug users (IDUs) of heroin, a subset of the respondents from the Baltimore site of the International Neurobehavioral HIV Study. Multivariate logistic regression equations were fitted to predict risky injection drug use practices and sexual behavior based on cognitive performance scores and knowledge of someone who had died from AIDS. Among IDUs with lower cognitive reserves, knowing someone who had died from AIDS was associated with increased risk. This finding indicates that more intensive efforts may be required to reduce the risky behaviors among those IDUs with lower cognitive scores in higher risk social groups. Among IDUs with greater cognitive reserves, knowing someone who had died from AIDS was associated with decreased risk. This suggests that cognitive performance can provide protection to individuals in riskier social environments. These findings can aid in targeting HIV prevention efforts toward higher risk individuals within the IDU population.