Increasing diversion of prescribed benzodiazepines and Z-drugs to new psychoactive substances.

ABSTRACT: Over the last few years reports have indicated an increase in the number, type and availability of new psychoactive substances belonging to the benzodiazepine class. These molecules may pose high risks to users, since the majority have never undergone clinical trials or tests so their pharmacology and toxicology is largely unknown. However the new drug scenario emerging from the COVID-19 global pandemic seems to play a role in increasing the diversion of prescribed benzodiazepines and Z-drug. A brief presentation of this phenomenon is hereby presented. The awareness and response activities at national and international levels related to this issue should be enforced.

Characterization of diverted buprenorphine use among adults entering corrections-based drug treatment in Kentucky.

BACKGROUND: Illicit, medically unsupervised use of buprenorphine (i.e., "diverted use") among vulnerable and underserved populations, such as corrections-involved adults, remains underexplored. METHODS: Survey data (2016-2017) collected as part of a clinical assessment of incarcerated adults entering corrections-based substance use treatment in Kentucky were analyzed. For years examined, 12,915 completed the survey. Removing cases for participants who did not reside in Kentucky for >6 months during the one-year pre-incarceration period (n = 908) resulted in a final sample size of 12,007. RESULTS: Over a quarter of the sample reported past-year diverted buprenorphine use prior to incarceration and 21.8 % reported use during the 30-days prior to incarceration, using 6.5 months and 14.3 days on average, respectively. A greater proportion of participants who reported diverted buprenorphine use had previously been engaged with some substance use treatment (77.0 %) and reported greater perceived need for treatment (79.4 %) compared to those who did not report use. Use was more likely among participants who were younger, white, male, and who reported rural or Appalachian residence. Diverted buprenorphine users also evidenced extensive polydrug use and presented with greater substance use disorder severity. Non-medical prescription opioid, heroin, and diverted methadone use were associated with increased odds of diverted buprenorphine use while kratom was not. Diverted methadone use was associated with a 252.9 % increased likelihood of diverted buprenorphine use. CONCLUSIONS: Diverted buprenorphine use among participants in this sample was associated with concerning high-risk behaviors and may indicate barriers to accessing opioid agonist therapies for corrections-involved Kentucky residents, particularly those in rural Appalachia.

Long-term medical cannabis use and risk factors for diversion: Report on physician's guidance and patients' behaviour.

OBJECTIVES: Various jurisdictions have legalized cannabis for medical purposes. As with all psychoactive medications, medical cannabis carries a risk of diversion and accidental ingestion. These risks may be particularly high among long-term medical cannabis patients as safety practices may become less salient to patients once the treatment becomes part of everyday life. The current study examines whether patients who have used medical cannabis for longer periods differ from those who have used for shorter periods in terms of sociodemographic background and other key aspects of medical cannabis use. Furthermore, the study examines the relationship between length of medical cannabis treatment and risk factors related to storage and diversion. Finally, the study examines the extent to which oncologists provide information to their patients about safe storage and disposal. METHODS: One hundred twenty-one medical cannabis oncology patients were interviewed face-to-face and 55 oncologists participated in a survey about safe storage and disposal practices related to medical cannabis. RESULTS: Length of medical cannabis treatment was related to administration by smoking and using higher monthly dosages. In terms of risk for unsafe storage and diversion, length of medical cannabis was positively associated with using cannabis outside the home and having been asked to give away medical cannabis. Physicians did not report providing information to patients regarding safe storage and disposal practices in a regular manner. SIGNIFICANCE OF RESULTS: Results suggest that there is an ongoing risk of unsafe storage and diversion over the course of medical cannabis treatment. Oncologists may need to give more consistent and continued training in safe storage and disposal practices, especially among long-term medical cannabis patients.

An Automated Software Application Reduces Controlled Substance Discrepancies in Perioperative Areas.

BACKGROUND: Perioperative controlled substance diversion and tracking have received increased regulatory focus throughout the United States. The authors' institution developed and implemented an automated web-based software application for perioperative controlled substance management. The authors hypothesized that implementation of such a system reduces errors as measured by missing controlled substance medications, missing controlled substance kits (a package of multiple controlled substance medications), and missing witness signatures during kit return. METHODS: From December 1, 2014 to March 31, 2017, the authors obtained missing controlled substance medication, controlled substance kit, and witness return signature data during the preimplementation, implementation, and study period of the controlled substance management application at a single university hospital. This before and after study was based on a QI project at the authors' institution. The authors included all cases requiring anesthesia services. The primary outcome of this study was the rate of missing controlled substance medications. Secondary outcomes included rates for kits not returned to pharmacy and missing kit return witness signatures. RESULTS: There were 54,302 cases during the preimplementation period, 57,670 cases during the implementation period, and 65,911 cases during the study period. The number of missing controlled substance medication (difference 0.7 per 1,000 cases; 95% CI, 0.38-1.02; P < 0.001) and kit return errors (difference 0.45 per 1,000 cases; 95% CI, 0.24-0.66, P < 0.001) declined after implementation of the application. There was no difference in the number of missing witness return signatures (difference 0.09 per 1,000 cases; 95% CI, -0.08 to 0.26, P = 0.350). A user survey with 206 of 485 (42%) response rate demonstrated that providers believed the new application managed controlled substances better than the previous system. CONCLUSIONS: A software application that tracks perioperative controlled substance kits with deep integration into the electronic health record and pharmacy systems is associated with a decrease in management errors.

Pharmacy-related theft of controlled substances: RxPATROL® findings.

OBJECTIVE: To characterize pharmacy-related theft data reported to the Rx Pattern Analysis Tracking Robberies and Other Losses (RxPATROL®) database during the time periods before (2007-2010) and after (2011-2016) the August 2010 switch to reformulated OxyContin® (oxycodone hydrochloride) extended-release tablets (Purdue Pharma L.P.). METHODS: The RxPATROL® database was queried to identify characteristics associated with theft of drug products. Variables analyzed included incident counts, drugs involved (OxyContin or other oxycodone products), pharmacy-security features, and other incident-related information. The data captured from 2007 to 2010, defined as the original formulation period, were compared with those captured from 2011 to 2016, defined as the post-reformulation period. RESULTS: A total of 6,905 incidents were reported from 2007 to 2016, with robbery (51.8 percent) and burglary (26.4 percent) being the most commonly reported incidents. The number of total robbery incidents reported peaked in 2010 and remained steady. Incidents reported as robberies that involved OxyContin initially increased from 2007 to 2010 and then steadily decreased from 296 in 2010 to 13 in 2016. Total burglary reports decreased from 2009 to 2015 and slightly increased from 2015 to 2016. Total burglary reports that involved OxyContin decreased after 2009. Total burglary reports that involved oxycodone remained steady from 2009 to 2014, decreased from 2014 to 2015, and remained steady from 2015 to 2016. The majority of reported incidents occurred on weekdays and involved suspects who entered and exited through the front door at pharmacies without security features such as alarms, dead bolts, and cameras. CONCLUSION: Following replacement of the original formulation of OxyContin with a new formulation that has abuse-deterrent properties in 2010, pharmacy thefts of OxyContin reported to the RxPATROL® database decreased. The decreases were not fully explained by concurrent trends in total robbery or burglary incidents reported to the RxPATROL® database over the same time period.

The source and diversion of pharmaceutical drugs for non-medical use: A systematic review and meta-analysis.

BACKGROUND: The non-medical use (NMU) of pharmaceutical drugs is an increasing public health concern. This systematic review consolidates current knowledge about how pharmaceutical drugs are obtained for NMU and the processes and people involved in diversion. METHODS: Peer-reviewed and grey literature databases were searched for empirical studies published between 1996 and 2017 that examined the source or diversion of pharmaceutical opioids, sedatives or stimulants for NMU in countries with reported misuse problems. Pooled prevalence meta-analyses using random effects models were used to estimate the prevalence of medical and non-medical sourcing reported by end-users, and gifting, selling and trading by various populations. RESULTS: This review synthesizes the findings of 54 cross-sectional studies via meta-analyses, with a remaining 95 studies examined through narrative review. Pharmaceutical drugs are primarily sourced for NMU from friends and family (57%, 95% CI 53%-62%, I2 = 98.5, n = 30) and despite perceptions of healthcare professionals to the contrary, illegitimate practices such as doctor shopping are uncommon (7%, 95% CI 6%-10%, I2 = 97.4, n = 29). Those at risk of diversion include patients displaying aberrant medication behaviors, people with substance use issues and students in fraternity/sorority environments. Sourcing via dealers is also common (32%, 95% CI 23%-41%, I2 = 99.8, n = 25) and particularly so among people who use illicit drugs (47%, 95% CI 35%-60%, I2 = 99.1, n = 15). There is little to no organized criminal involvement in the pharmaceutical black market. CONCLUSION: Pharmaceutical drugs for NMU are primarily sourced by end-users through social networks. Future research should examine how dealers source pharmaceutical drugs.

Medical prescriptions falsified by the patients: a 12-year national monitoring to assess prescription drug diversion.

Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a comparative analysis of falsified prescriptions collected during three periods from 2001 to 2012. The data recorded in a national program which records all falsified prescriptions presented to community pharmacies were studied. Included data regarded: subjects, prescription forms, and drugs. Description of the dataset in three periods (2001-2004, 2005-2008, and 2009-2012) was completed with clustering analyses to characterize profiles of prescriptions and subjects associated with the most reported drugs. The 4469 falsified prescriptions concerned most often females (51.6%). Average age was 46.5 years. Zolpidem, bromazepam, and buprenorphine were the most frequent drugs. Alone, 13 drugs (1.7%, 13/772) represented more than 40% of the total reports (3055/7272). They were associated with three diversion profiles: (i) buprenorphine, flunitrazepam, and morphine were mentioned on overlapping secure prescription forms presented by young men; (ii) alprazolam, bromazepam, zolpidem, codeine/acetaminophen were mentioned on simple prescription forms presented by experienced women; and (iii) acetaminophen and lorazepam were mentioned on modified prescription forms presented by elderly subjects. Clonazepam, clorazepate, dextropropoxyphene, zopiclone moved between those profiles. The patterns of falsified prescriptions provided in this study contribute to enhance the scientific knowledge on the most diverted prescription drugs. The latter follow distinct trajectories across time depending on their pharmacology (including their abuse/addiction potential) and on their regulation's history. The close and continuous analysis of falsified prescriptions is an excellent way to monitor prescription drug diversion.

Increasing diversion of methadone in Vancouver, Canada, 2005-2015.

BACKGROUND AND AIM: Although methadone, an opioid agonist, has been an effective medication used to treat opioid use disorder for over 40years, recent studies have found that methadone was identified in more than a quarter of prescription opioid-related deaths among people who use illicit drugs in Vancouver, Canada. Thus, we sought to longitudinally examine the availability of diverted methadone among people who inject drugs (PWID). DESIGN AND METHODS: Data were collected from three prospective cohorts of PWID in Vancouver, Canada between December 2005 and May 2015. Multivariable generalized estimating equation logistic regression was used to identify temporal trends in the immediate availability of diverted methadone (defined as the ability to acquire illicit methadone in <10min). RESULTS: A total of 2092 participants, including 727 (34.8%) women, were included in the present study. In the multivariable analyses after adjusting for a range of potential confounders, later calendar year (adjusted odds ratio [AOR]=1.21 per year; 95% confidence interval [CI]: 1.19-1.23) was independently and positively associated with reporting immediate availability of diverted methadone. CONCLUSIONS: We observed a significant increase in the reported availability of diverted methadone among PWID over a ten-year follow-up period. Further research is needed to identify strategies to limit methadone diversion and assess the impact of alternative medications that are equally effective but safer, such as buprenorphine/naloxone.

Law enforcement-derived data on gabapentin diversion and misuse, 2002-2015: diversion rates and qualitative research findings.

PURPOSE: Recent limited epidemiologic and case reports suggest that gabapentin is being misused, especially among prescription opioid misusers. However, no apparent studies have reported data from law enforcement on the diversion and misuse of gabapentin. METHODS: Case report data are drawn from a quarterly survey of prescription drug diversion completed by a national sample of law enforcement and regulatory agencies who engage in drug diversion investigations. Rates of gabapentin diversion per 100 000 population were calculated for each quarter from 2002 through 2015. Qualitative data are drawn from a brief questionnaire completed by a subsample of survey respondents and were organized and presented by theme. RESULTS: In total, 407 new cases of diverted gabapentin were reported during the time period, with diversion rates steadily increasing from zero cases in the first 2 quarters of 2002 to a high of 0.027 cases per 100 000 population in the fourth quarter of 2015. Qualitative data suggest that gabapentin is being misused in conjunction with prescription opioids and that gabapentin and heroin are being combined and consumed together. Law enforcement reporters found these drug use trends to be contributing to gabapentin diversion. CONCLUSIONS: The recent increase in gabapentin diversion appears to be related to the opioid epidemic, based on law enforcement descriptions of gabapentin being misused in combination with opioids. Yet epidemiological data related to this finding is limited and research conducted among gabapentin misusers is needed to understand this problem in more depth. Greater monitoring of gabapentin abuse and diversion appear warranted.

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.

Non-prescription sale and dispensing of antibiotics in community pharmacies in Zambia.

BACKGROUND: In Zambia, antibiotics are categorized as prescription-only medicines. Antibiotics dispensed without a prescription pose a public health threat, which is a concern. Consequently, the aim is to ascertain the extent of non-prescription sales and dispensing of antibiotics in community pharmacies in Zambia. METHODS: The practice of non-prescription sale and dispensing were assessed in 73 randomly selected community retail pharmacies, using a structured interviewer-administered questionnaire with simulated case scenarios. RESULTS: Majority (97%) stated that clients frequently requested non-prescribed antibiotics. Interviewees usually asked clients' indications (94%), counselled on dosing (96%) and suggested changes to antibiotic choices (97%). All (100%) dispensed non-prescribed antibiotics. Commonly dispensed antibiotics included amoxicillin (52%), cotrimoxazole (25%) and metronidazole (23%). Non-prescription sale and dispensing of antibiotics was significantly associated with interviewees' professional qualification in four out of five simulations. CONCLUSION: Non-prescription sale and dispensing of antibiotics is widespread in Zambia. Concerted public and professional interventions are needed coupled with stronger regulatory enforcement to reduce this.

Decreased diversion by doctor-shopping for a reformulated extended release oxycodone product (OxyContin).

BACKGROUND: Doctor-shopping (obtaining prescriptions from multiple prescribers/pharmacies) for opioid analgesics produces a supply for diversion and abuse, and represents a major public health issue. METHODS: An open cohort study assessed changes in doctor-shopping in the U.S. for a brand extended release (ER) oxycodone product (OxyContin) and comparator opioids before (July, 2009 to June, 2010) versus after (January, 2011 to June, 2013) introduction of reformulated brand ER oxycodone with abuse-deterrent properties, using IMS LRx longitudinal data covering >150 million patients and 65% of retail U.S. prescriptions. RESULTS: After its reformulation, the rate of doctor-shopping decreased 50% (for 2+ prescribers/3+ pharmacies) for brand ER oxycodone, but not for comparators. The largest decreases in rates occurred among young adults (73%), those paying with cash (61%) and those receiving the highest available dose (62%), with a 90% decrease when stratifying by all three characteristics. The magnitude of doctor-shopping reductions increased with increasing number of prescribers/pharmacies (e.g., 75% reduction for ≥2 prescribers/≥4 pharmacies). CONCLUSIONS: The rate of doctor-shopping for brand ER oxycodone decreased substantially after its reformulation, which did not occur for other prescription opioids. The largest reductions in doctor-shopping occurred with characteristics associated with higher abuse risk such as youth, cash payment and high dose, and with more specific thresholds of doctor-shopping. A higher prescriber and/or pharmacy threshold also increased the magnitude of the decrease, suggesting that it better captured the effect of the reformulation on actual doctor-shoppers.

Evidence of slow-release morphine sulfate abuse and diversion: epidemiological approaches in a French administrative area.

Slow-release oral morphine sulfate (SM) is one of the most abused prescription opioids in France. However, the regional feature of the abuse of morphine is poorly documented. To investigate the abuse of SM in a French administrative region, a multisource approach was applied. The first approach was based on SM exposition at national and regional level using the OPPIDUM survey. In a second approach, we analyzed a drug reimbursement database to assess the magnitude of SM abuse in Languedoc-Roussillon (LR) region. A clustering method was applied to classify patients and to describe the profile of deviant patients. The third approach was based on a self-administered anonymous questionnaire, proposed to patients seen in addiction care centers in the LR region and consuming oral SM. The OPPIDUM study showed that in most regions, where the prevalence of heroin use is higher than the national average of 9.1%, SM consumers were fewer. With the clustering method, three subgroups were identified. One of them gathered 35 users (3.2%) with a deviant behavior characterized by significantly more dispensations, dispensing pharmacies, and prescribers. These subjects were mainly men, younger, and more consumers of benzodiazepines and opioid maintenance therapy than the others. The third study allowed specifying that SM was mainly injected (93.7%), bought in the street (80%), and used because of unavailability and the poor quality of heroin (33.9%). The three proposed approaches are complementary and help to clarify the abuse of oral SM, while assessing the motivations of this abuse.

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.).

The effects of North Carolina's prescription drug monitoring program on the prescribing behaviors of the state's providers.

State-level prescription drug monitoring programs (PDMPs) show promise as a key strategy to respond to the epidemic of the misuse and abuse of controlled substances (CS), particularly opioid analgesics, in the United States. Undocumented concerns have been expressed that these PDMPs may have a "chilling effect" on providers' willingness to prescribe these substances to their patients. Using data from North Carolina's PDMP for the 3-year period from 2009 through 2011, we examined whether rapid increases in (1) the number of providers who queried the system, and (2) the number of days on which they queried it, would be related to their prescribing practices in regards to CS. We hypothesized that neither marker of PDMP utilization would be associated with a decrease in either patients receiving CS prescriptions or CS prescriptions filled. We found no association between either of these variables and the number of patients who filled prescriptions for CS or the number of prescriptions for CS filled. However, we did find a slight positive relationship between the growth in the utilization of the PDMP and the number of prescriptions filled for opioid analgesics. Concerns that PDMPs may constrain prescribing behavior with regards to CS are not supported.

Deception for drugs: self-reported "doctor shopping" among young adults.

BACKGROUND: Pharmaceutical abuse is a burgeoning problem, and various forms of drug diversion are becoming more common. At present, little is known about those who attempt to deceive physicians to receive medications, and even less is known about those who successfully avoid detection and abuse-related repercussions. The goal of this study is to assess the prevalence of attempted physician deception in a general population, explore common motives, and evaluate risk factors associated with the behavior. METHODS: A stratified random sampling technique was used to obtain a locally representative sample of 2349 young adults. The sample was 48.4% male, 68.9% white, 24.4% black, and 2.8% Hispanic. Selected individuals were surveyed using a self-report instrument (80.4% response rate). RESULTS: Of the respondents, 93 (4.0%) self-reported having attempted to deceive a physician to obtain a pharmaceutical. Most of these indicated that they were at least partially motivated by their own abuse. Approximately half reported that selling a portion of the prescription was a motivating factor. Alcohol use, marijuana use, and pharmaceutical misuse each were risk factors associated with attempted deception. Although no traits were definitively linked to the behavior, attempted deception was more commonly reported by men, Hispanics, self-identified lesbian/gay/bisexual/transgender individuals, and those at the lowest and highest extremes of the income spectrum. Logistic regression models of rare events indicated that past substance use along with sexual orientation and family income were related to attempted deception when controlling for other factors. CONCLUSION: Results suggest that attempted physician deception may be more common than previously believed. Practicing physicians should attempt to use risk factor information presented within this study, albeit very cautiously. This study identifies general characteristics of young people who might divert medications but notes that only a small minority of any patient group will do so. Awareness should not equal bias in the treatment of these patients; instead, it should reinforce the need for careful clinical interviewing and the utilization of prescription drug monitoring programs and local law enforcement databases.