Trends in Opioid Analgesic Abuse and Mortality in Europe

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Current Challenges of Opioids EAPCCT Annual Congress 26 May 2016 Trends in Opioid Analgesic Abuse and Mortality in Europe Jody L. Green, PhD, CCRP Denver Health Rocky Mountain Poison & Drug Center

Disclosure 2 The RADARS System is supported by subscriptions from pharmaceutical manufacturers for surveillance, research and reporting services. RADARS System is the property of Denver Health and Hospital Authority, a political subdivision of the State of Colorado. Denver Health retains exclusive ownership of all data, databases and systems. Subscribers do not participate in data collection or analysis, nor do they have access to the raw data.

Objective 3 Drug utilization trends European mosaic network Abuse/misuse trends

Europe Opioid Dosage Units per Population 4 80 Norway UK France 0 2011 2012 2013 2014 2015 Spain Germany Italy Includes: buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, oxycodone, sufentanil, tapentadol, tramadol

Europe Dosage Units per Population 5

European Mosaic for Prescription Drug Misuse/Abuse 6 Acute Health Events GTNet Drug Transactions Drug Diversion Entering Treatment EUROPAD Illicit Market Price StreetRx General Population NMU-Rx Chatter on the Web Web Monitoring 6

European Opiate Addiction Treatment Association (EUROPAD) 7 Population Patients entering treatment, either inpatient or outpatient, for opioid addiction. Definition/Type of Cases Self-reported use of prescription or illicit opioids to get high in the past 30 days. The data collected will include, but is not limited to, patient s drug(s) of choice, route of administration, drug use in the past month, lifetime drug abuse, age at first use and the primary source of the abused drugs Methodology Patients entering treatment, either inpatient or outpatient, for opioid addiction are asked to volunteer to complete the questionnaire. Questionnaires are sent to data coordination site for quality review and data entry.

EUROPAD Partners 8 Francina Fonseca Gaetano Deruvo Lorenzo Somaini Didier Touzeau Marc Auriacombe Jean-Pierre Daulouède Pierre Villèger Amine Benyamina Norbert Scherbaum Thomas Clausen Duncan Hill Oscar D Agnone Kevin Ratcliffe

EUROPAD Primary Drug Used to Get High 9 UK n=199 Spain n=62 Norway n=78 Italy n=86 Germany n=148 France n=187 codeine buprenorphine heroin THC-not Rx heroin other heroin heroin heroin 0.0% 20.0% 40.0% 60.0% 80.0%

10 EUROPAD All Endorsements to get high Germany Italy United Kingdom Heroin Heroin Heroin Methadone THC-not Rx Benzo Benzo Benzo Codeine THC-Rx THC-Rx THC-not Rx Amphet-not Rx Methadone THC-Rx THC-not Rx Bup Methadone

EUROPAD Route of Abuse 11 Endorsements 80 70 60 50 40 30 20 10 0 Germany: Mentions by Route Heroin Methadone Benzodiazepine Top 3 Matrix Drugs Chewed then swallowed Smoked Snorted Injected

EUROPAD Route of Abuse 12 Endorsements 60 50 40 30 20 10 0 Heroin Italy: Mentions by Route THC, cannabinoid, marijuana- not Rx Top 3 Matrix Drugs Benzodiazepine Chewed then swallowed Smoked Snorted Injected

EUROPAD Route of Abuse 13 Endorsements 160 140 120 100 80 60 40 20 0 United Kingdom: Mentions by Route Heroin Benzodiazepine Codeine Top 3 Matrix Drugs Chewed then swallowed Smoked Snorted Injected

Global Toxicosurveillance Network (GTNet) 14 Population young children, adolescents, young adults, adults, elderly Definition/Type of Cases Spontaneous reports of intentional and unintentional exposure mentions of acute medical events associated with one or more prescription drug of interest through data collection at poison centers. Methodology Standardized data are collected during routine daily management of acute medical events then queried for cases involving drugs of interest

GTNet Partners 15 Country Name Member Poison Centre Australia Naren Gunja Jared Brown New South Wales Poisons Information Centre Victorian Poisons Information Centre Queensland Poisons Information Centre Western Australia Poisons Information Centre Centre Antipoisoin et de Toxicovigilance de Paris France Bruno Megarbane Robert Garnier Germany Andreas Schaper GIZ-Nord Poisons Centre (Göttingen) Martin Ebbecke Italy Fabrizio Sesana Poison Control Centre of Milan The Irma de Vries National Poisons Information Centre Netherlands Switzerland Hugo Kupferschmidt Swiss Toxicological Information Center United Kingdom Simon Thomas John Thompson National Poisons Information Service, Newcastle National Poisons Information Service, Cardiff National Poisons Information Service, Birmingham National Poisons Information Service, Edinburgh

GTNet Trends of Intentional Misuse & Self-harm (per 100,000 population) 16 Germany Italy United Kingdom Bucher Bartelson B, Desel H, Schaper, A, Davanzo, F, Sesana F, Cooper G, Thompson JP, Johnson DJG, Green JL. Trends over time in population rates of intentional misuse and selfharm mentions with buprenorphine, methadone, and oxycodone as reported to poison centres in Germany, Italy, and the United Kingdom. Clinical Toxicology 2015; 53(4):374.

Web Monitoring 17 Population Youth and adults posting information on the internet. Definition/ Type of Cases Qualitative measure of prescription drug abuse reported via the internet. Monitoring the content of various blogs, news articles, tweets and forums. Methodology Systematic search is conducted on a regular schedule to identify posts related to the drugs of interest. A web crawler is used to conduct the search, remove duplicate posts and organize the data. Algorithms, supplemented by manual reviews by trained coders, are used to identify common themes and assess sentiment.

Web Monitoring Partners 18 Paul Dargan David Wood

Web Monitoring Program Daily Posts by Drug Substance - UK (1Q2014-1Q2015) 19

Web Monitoring Program Sentiment by Drug Substance - UK (1Q2014-1Q2015) 20 Sentiment Positive (anti-abuse) Buprenorphine N=3,924 % Codeine N=55,526, n=3,979 % (95% CI) 16.4 18.7 (17.4, 19.9) Neutral 14.7 40.6 (39.0, 42.1) Negative (pro-abuse) 7.2 30.3 (28.9, 31.8) Tramadol N=29.948, n=3,852 % (95% CI) 24.2 (22.0, 26.4) 34.5 (31.1, 38.1) 30.0 (27.0, 33.1)

Web Monitoring Program Addiction, Overdose, and Death by Drug Substance - UK (1Q2014-1Q2015) 21 Buprenorphine N=3,924 % Codeine N=55,526, n=3,979 % (95% CI) Tramadol N=29.948, n=3,852 % (95% CI) Addiction 1.2 1.4 (1.1, 1.8) 2.6 (2.0, 3.4) Overdose 0.0 0.7 (0.5, 1.0) 0.4 (0.2, 0.7) Death 0.0 <0.1 (<0.1, 0.3) 0.1 (<0.1, 0.3)

Germany Summary 22 Oxycodone and hydromorphone utilization increasing Patients entering substance abuse treatment most often report heroin, benzodiazepines as their primary drug of abuse most mentions of heroin (smoked & injected), methadone (chewed), and benzodiazepines (chewed) Intentional misuse & self-harm reported to poison centre increasing for methadone and oxycodone

Italy Summary 23 Codeine most commonly utilized opioid, oxycodone utilization increasing Patients entering substance abuse treatment most often report heroin and THC (not Rx) as their primary drug of abuse most mentions of heroin (smoked), THC/cannabinoid/marijuana not Rx (smoked), and benzodiazepines (chewed) Intentional self-harm reported to poison centre increasing for oxycodone

United Kingdom Summary 24 Codeine most commonly utilized opioid, morphine utilization increasing Patients entering substance abuse treatment most often report heroin and codeine as their primary drug of abuse most mentions of heroin (smoked & injected), benzodiazepines (chewed), and codeine (chewed) Intentional self-harm reported to poison centres by healthcare professionals for methadone, oxycodone, and buprenorphine decreasing Pro-abuse chatter more likely for tramadol than buprenorphine Minimal chatter detected on the web for addiction, overdose or death associated with buprenorphine, codeine or tramadol

Conclusion 25 A mosaic approach to surveillance provides valuable insight from multi-dimensional perspectives Each of the programs target different facets of prescription opioid abuse, misuse, and diversion While magnitude and patterns vary heroin, THC, prescription opioids and benzodiazepines commonly abused/misused in many countries alternate routes of abuse often reported (smoked, injected, chewed)

Thank You! Questions? Jody.Green@rmpdc.org