Nabarun Dasgupta

An Analysis of the Root Causes for Opioid-Related Overdose Deaths in the United States

OBJECTIVE A panel of experts in pain medicine and public policy convened to examine root causes and risk factors for opioid-related poisoning deaths and to propose recommendations to reduce death rates. METHODS Panelists reviewed results from a search of PubMed and state and federal government sources to assess frequency, demographics, and risk factors for opioid-related overdose deaths over the past decade. They also reviewed results from a Utah Department of Health study and a summary of malpractice lawsuits involving opioid-related deaths. RESULTS National data demonstrate a pattern of increasing opioid-related overdose deaths beginning in the early 2000s. A high proportion of methadone-related deaths was noted. Although methadone represented less than 5% of opioid prescriptions dispensed, one third of opioid-related deaths nationwide implicated methadone. Root causes identified by the panel were physician error due to knowledge deficits, patient non-adherence to the prescribed medication regimen, unanticipated medical and mental health comorbidities, including substance use disorders, and payer policies that mandate methadone as first-line therapy. Other likely contributors to all opioid-related deaths were the presence of additional central nervous system-depressant drugs (e.g., alcohol, benzodiazepines, and antidepressants) and sleep-disordered breathing. CONCLUSIONS Causes of opioid-related deaths are multifactorial, so solutions must address prescriber behaviors, patient contributory factors, nonmedical use patterns, and systemic failures. Clinical strategies to reduce opioid-related mortality should be empirically tested, should not reduce access to needed therapies, should address risk from methadone as well as other opioids, and should be incorporated into any risk evaluation and mitigation strategies enacted by regulators.

Project Lazarus: Community-Based Overdose Prevention in Rural North Carolina

BACKGROUND In response to some of the highest drug overdose death rates in the country, Project Lazarus developed a community-based overdose prevention program in Western North Carolina. The Wilkes County unintentional poisoning mortality rate was quadruple that of the states in 2009 and due almost exclusively to prescription opioid pain relievers, including fentanyl, hydrocodone, methadone, and oxycodone. The program is ongoing. METHODS The overdose prevention program involves five components: community activation and coalition building; monitoring and surveillance data; prevention of overdoses; use of rescue medication for reversing overdoses by community members; and evaluating project components. Principal efforts include education of primary care providers in managing chronic pain and safe opioid prescribing, largely through the creation of a tool kit and face-to-face meetings. RESULTS Preliminary unadjusted data for Wilkes County revealed that the overdose death rate dropped from 46.6 per 100,000 in 2009 to 29.0 per 100,000 in 2010. There was a decrease in the number of victims who received prescriptions for the substance implicated in their fatal overdose from a Wilkes County physician; in 2008, 82% of overdose decedents received a prescription for an opioid analgesic from a Wilkes prescriber compared with 10% in 2010. CONCLUSIONS While the results from this community-based program are preliminary, the number and nature of prescription opioid overdose deaths in Wilkes County changed during the intervention. Further evaluation is required to understand the localized effect of the intervention and its potential for replication in other areas.

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.

Ethics in a Pandemic: A Survey of the State Pandemic Influenza Plans

A pandemic of highly pathogenic influenza would threaten the lives of hundreds of thousands in the United States and confront governments and organizations, with ethical issues having wide-ranging implications. The Department of Health and Human Services and all states have published pandemic influenza plans. We analyzed the federal and state plans, available on the Internet, for evidence of ethical guidance as judged by the presence of ethical terms. The most striking finding was an absence of ethical language. Although some states acknowledged the need for ethical decisionmaking, very few prescribed how it should happen. If faced by a pandemic in the near future, we stand the risk of making many unjust and regrettable decisions.

Breaking the news or fueling the epidemic? Temporal association between news media report volume and opioid-related mortality.

Background Historical studies of news media have suggested an association between reporting and increased drug abuse. Period effects for substance use have been documented for different classes of legal and illicit substances, with the suspicion that media publicity may have played major roles in their emergence. Previous analyses have drawn primarily from qualitative evidence; the temporal relationship between media reporting volume and adverse health consequences has not been quantified nationally. We set out to explore whether we could find a quantitative relationship between media reports about prescription opioid abuse and overdose mortality associated with these drugs. We assessed whether increases in news media reports occurred before or after increases in overdose deaths. Methodology/Principal Findings Our ecological study compared a monthly time series of unintentional poisoning deaths involving short-acting prescription opioid substances, from 1999 to 2005 using multiple cause-of-death data published by the National Center for Health Statistics, to monthly counts of English-language news articles mentioning generic and branded names of prescription opioids obtained from Google News Archives from 1999 to 2005. We estimated the association between media volume and mortality rates by time-lagged regression analyses. There were 24,272 articles and 30,916 deaths involving prescription opioids during the seven-year study period. Nationally, the number of articles mentioning prescription opioids increased dramatically starting in early 2001, following prominent coverage about the nonmedical use of OxyContin. We found a significant association between news reports and deaths, with media reporting preceding fatal opioid poisonings by two to six months and explaining 88% (p<0.0001, df 78) of the variation in mortality. Conclusions/Significance While availability, structural, and individual predispositions are key factors influencing substance use, news reporting may enhance the popularity of psychoactive substances. Albeit ecological in nature, our finding suggests the need for further evaluation of the influence of news media on health. Reporting on prescription opioids conforms to historical patterns of news reporting on other psychoactive substances.

Observed transition from opioid analgesic deaths toward heroin

BACKGROUND In the United States, overdose mortality from controlled substances has increased over the last two decades, largely involving prescription opioid analgesics. Recently, there has been speculation on a transition away from prescription opioid use toward heroin, however the impact on overdose deaths has not been evaluated. METHODS Time series study of North Carolina residents, 2007 through 2013. Monthly ratio of prescription opioid-to-heroin overdose deaths. Non-parametric local regression models used to ascertain temporal shifts from overdoses involving prescription opioids to heroin. RESULTS There were 4332 overdose deaths involving prescription opioids, and 455 involving heroin, including 44 where both were involved (total n = 4743). A gradual 6-year shift toward increasing heroin deaths was observed. In January, 2007, for one heroin death there were 16 opioid analgesic deaths; in December, 2013 there were 3 prescription opioid deaths for each heroin death. The transition to heroin appears to have started prior to the introduction of tamper-resistant opioid analgesics. The age of death among heroin decedents shifted toward younger adults. Most heroin and opioid analgesic deaths occurred in metropolitan areas, with little change between 2007 and 2013. CONCLUSIONS The observed increases in heroin overdose deaths can no longer be considered speculation. Deaths among younger adults were noted to have increased in particular, suggesting new directions for targeting interventions. More research beyond vital statistics is needed to understand the root causes of the shift from prescription opioids to heroin.

Crowdsourcing Black Market Prices For Prescription Opioids

Background Prescription opioid diversion and abuse are major public health issues in the United States and internationally. Street prices of diverted prescription opioids can provide an indicator of drug availability, demand, and abuse potential, but these data can be difficult to collect. Crowdsourcing is a rapid and cost-effective way to gather information about sales transactions. We sought to determine whether crowdsourcing can provide accurate measurements of the street price of diverted prescription opioid medications. Objective To assess the possibility of crowdsourcing black market drug price data by cross-validation with law enforcement officer reports. Methods Using a crowdsourcing research website (StreetRx), we solicited data about the price that site visitors paid for diverted prescription opioid analgesics during the first half of 2012. These results were compared with a survey of law enforcement officers in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System, and actual transaction prices on a “dark Internet” marketplace (Silk Road). Geometric means and 95% confidence intervals were calculated for comparing prices per milligram of drug in US dollars. In a secondary analysis, we compared prices per milligram of morphine equivalent using standard equianalgesic dosing conversions. Results A total of 954 price reports were obtained from crowdsourcing, 737 from law enforcement, and 147 from the online marketplace. Correlations between the 3 data sources were highly linear, with Spearman rho of 0.93 (P<.001) between crowdsourced and law enforcement, and 0.98 (P<.001) between crowdsourced and online marketplace. On StreetRx, the mean prices per milligram were US

Evolution and Convergence of State Laws Governing Controlled Substance Prescription Monitoring Programs, 1998-2011

3.29 hydromorphone, US

Surveillance of Diversion and Nonmedical Use of Extended-Release Prescription Amphetamine and Oral Methylphenidate in the United States

2.13 buprenorphine, US

Signal detection in post-marketing surveillance for controlled substances

1.57 oxymorphone, US