Disclaimer. New Technologies for Abuse Prevention and Treatment. Sanford M. Silverman, MD

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1 New Technologies for Abuse Prevention and Treatment Sanford M. Silverman, MD Disclaimer Speaker: Purdue, Depomed, DSI, BDSI, AZ Institute of Pain Management, Pompano Beach, Florida Medical Director, Compassionate Care Clinics of America Member: ASIPP, FAPM, FSIPP, ASAM, FSAM, FMA, BCMA Officer/ Board Position: Past-President Broward County Medical Association, Past-president FSIPP, Board of Directors ASIPP, Board of Directors FSIPP Publications: Articles in Anesthesiology, Canadian Journal of Anesthesia, Pain Physician (Section editor Controlled Substances) No outside funding, no grants for this presentation Some slides borrowed from Joe Pergolizzi, MD 2 1

2 Self Assessment 1. The most common source(s) of diverted controlled substances is/are: a) Multiple doctors b) Street dealers c) Friend or family d) a and b 2. Evidence shows that abuse-deterrent formulation (ADF) OxyContin a) Reduces non-oral use of the drug (snorting and injecting) b) Results in reduced use of other ER formulations of opioids c) Leads to decreased use of heroin use d) All of the above 3. ADFs reduce the need for REMs a) True b) False Nothing is intrinsically good or evil but it s manner of usage may make it so Thomas Aquinas 2

3 Objectives Review data (CDC, SAMHSA) on prescription drug use and overdose Review data on increasing utilization of opioids Understand the shift in usage to other opioids (heroin) Evaluate the use and efficacy of abuse-deterrent formulations (ADFs) The FDA Draft Abuse-Deterrent Opioid Guidance Provides a Path Study Categorization and Abuse-Deterrent Label Study Categories Premarketing Studies Postmarketing Studies Category 1 Category 2 Category 3 Category 4 Preclinical in vitro manipulation and extraction studies Pharmacokinetic (PK) studies Clinical abuse potential (eg, drug liking studies) Epidemiological studies measuring abuse deterrence (overall and route-specific abuse and abuse deterrence) Tiers for Potential Abuse-Deterrent Claims* Tier 1 The product is formulated with physicochemical barriers to abuse Tier 2 The product is expected to reduce or block effect of the opioid when the product is manipulated Tier 3 The product is expected to result in a meaningful reduction in abuse Tier 4 The product has demonstrated reduced abuse in the community 3

4 The FDA Abuse-Deterrent Opioid Guidance Provides a Path for Drug Developers Abuse-Deterrent Opioids Evaluation and Labeling Guidance for Industry Abuse-deterrent technology into 6 categories: 1. Physical/chemical barrier 2. Agonist/antagonist combinations 3. Aversion 4. Prodrug 5. Delivery system 6. Combination of 2 or more of the above 4

5 The FDA recommended collecting data from each of the following premarket studies categories to obtain a full understanding of a product s abuse potential 1. Laboratory-based in vitro manipulation and extraction studies (category 1) 2. Pharmacokinetic studies (category 2) 3. Clinical abuse potential studies (category 3) Recommendations for collecting data from each premarket studies categories to obtain a full understanding of a product's abuse potential The FDA noted that results from category 1 studies may affect the designs of the other 2, and category 2 results may affect the design and need for category 3 studies. The guidance contains postmarket study recommendations for products that may be an exception to these criteria. The FDA recommended that the labeling should include information on a product s abusedeterrent properties which is supported by data to better inform healthcare professionals, patients, and the public about a product s abuse potential. The label should also make it clear that abuse is still possible. 5

6 Opioid Abuse-Deterrent Strategies Hierarchy Combination Mechanisms Increasing Direct Abuse Deterrence Pharmacologic Sequestered antagonist Bioavailable antagonist Prodrug Aversive Component Capsaicin burning sensation Ipecac emetic Denatonium bitter taste Physical Difficult to crush Difficult to extract Deterrent Packaging RFID protection Tamper-proof bottles Prescription Monitoring Morphine Sulfate and Naltrexone Hydrochloride (Embeda ) Extended-release morphine Sequestered naltrexone (antagonist) core Moderate-to-severe pain when a continuous around the clock opioid analgesic is needed for an extended period of time 6 dosage strengths (20 mg to 100 mg morphine sulfate with 0.8 to 4 mg naltrexone hydrochloride) accessed June 2015 FPI Embeda 6

7 Prolonged-Release Oxycodone and Naloxone (Targinque ) Local Action of Opioid Antagonist and Systemic Action of Opioid Posthepatic circulation Opioid Inactive opioid antagonist Opioid antagonist is subject to extensive first pass metabolism (98%) Prehepatic circulation Opioid Opioid antagonist S. Mercadante & A. Giarratano 164 Expert Opin. Investig. Drugs (2013) 22(1) Thus, opioid antagonist acts only locally in the gut. In the gut, opioid antagonist competes with peripheral opioid actions on the bowel. 2:1 oxycodone/naloxone (OX:N ) ratio Efficacy shown in Two Randomised, Double-blind Clinical Trials for chronic non-cancer pain Oliver Löwenstein; Petra Leyendecker; Eberhard A Lux; Mark Blagden; Karen H Simpson; Michael Hopp; Pharmacol. 2010;10(12):1-9. Björn Bosse; Karen Reimer Disclosures BMC Clin 13 OXYCODONE ER Xtampza Microspheres resistant to manipulation Resistant to grinding, crushing, and extraction Has ADT properties per section 9.2 7

8 Oxymorphone (Opana ER) Physical Deterrent: Crush Resistance Hydrocodone bitartrate technology is designed to be crush resistant and maintain the extended-release characteristics of the formulation Proprietary technology features controlled drug delivery through a polymer matrix designed to be crush resistant The clinical significance of these technologies or its impact on abuse/misuse liability has not been fully established, though recent data shows promise for abuse reduction in recreational users* However, abuse by the intravenous, intranasal, and oral routes is still possible June 2015FPI OPANA ER IR Oxycodone (Oxaydo ) Discourages intranasal abuse 8

9 In a double-blind, active-comparator, crossover study in 40 non-dependent recreational opioid users, drug liking responses and single-dose safety of crushed OXAYDO tablets were compared with crushed immediate-release oxycodone tablets when subjects self-administered the drug intranasally. The presence of sequence effects resulted in questionable reliability of the second period data. First period data demonstrated small numeric differences in the median and mean drug liking scores, lower in response to oxycodone HCl, USP than immediate-release oxycodone. 30% of subjects exposed to oxycodone HCl, USP responded that they would not take the drug again compared to 5% of subjects exposed to immediaterelease oxycodone. Study subjects self-administering oxycodone HCl, USP reported a higher incidence of nasopharyngeal and facial adverse events and a decreased ability to completely insufflate 2 crushed tablets within a fixed time period (21 of 40 subjects). The clinical significance of the difference in drug liking and difference in response to taking the drug again reported in this study has not yet been established. There is no evidence that oxycodone HCl, USP has a reduced abuse liability compared to immediate-release oxycodone. Oxycodone ER/New Formulation (Oxycontin ) Hydrocodone Bitartrate (Same Technology for Hydrocodone Bitartrate ER) Original Tablet Reformulated Tablet Raffa et al in Press

10 Hydrocodone ER (Hysingla ) Once daily Section 9.2 ADT properties Same technology as Oxycontin Hydrocodone ER (Zohydro ) Twice daily dosing Has section 9.2 ADT properties 10

11 Morphine ER (Morphobond ) Matrix resistant to manipulation BID dosing Has section 9.2 ADT properties Arymo Extended release Morphine Has physical properties that resists crushing and syringing Has 9.2 ADP s Taken 2-3 times daily 11

12 Other ADT Prodrugs KP201benzhydrocodone (Kempharm) Transdermal buprenorphine (Butrans ) Implant Probuphine (implanted buprenorphine for opioid use disorder) SL buprenorphine for opioid use disorder Effects of Reformulated Oxycodone ER With Abuse-Deterrent Properties Abuse Therapeutic errors Accidental exposures Prescription trends Dose relationship 12

13 Case Study 1 Study Background Exposure reporting calls Poison centers Data collection by NPDS Exposure changes with reformulated ERO, and comparison with SE oxycodone and heroin Study was a part of formal postmarketing commitment program required by the FDA ERO = extended release oxycodone Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12):

14 Methods 1-year prior to reformulated ERO was used as a baseline Poisson regression was used to calculate percent change and 95% confidence intervals (CI) in the average number of exposures per quarter Pre-formulation period (3Q2009 2Q2010) ERO reformulation ((3Q2010) Transition period (3Q2010) Quarterly analysis of exposures reported with ERO, SE oxycodone excluding ERO, and heroin Study Model Post-formulation period (4Q2010 3Q2012) Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12): All Exposure Types Decreased With Reformulated ERO All ERO exposure types, abuse, therapeutic errors, and accidental exposures were decreased after reformulation Exposures for other SE oxycodone products increased or remained unchanged PRODUCT ERO SE Oxycodone Heroin 26% 15% 37% EXPOSURES 693 to to to 807 Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12):

15 All exposures (for all reasons) Intentional abuse exposures 100% ERO Other SE oxycodone Heroin 120% ERO Other SE oxycodone Heroin % change from baseline 80% 60% 40% 20% 0% -20% Pre-reformulation period Post-reformulation period % change from baseline 100% 80% 60% 40% 20% 0% -20% -40% Pre-reformulation period Post-reformulation period -40% -60% ERO reformulation -60% -80% ERO reformulation Time period Time period Changes in calls reporting brand ERO, other SE oxycodone products, and heroin between 3Q 2009 and 3Q Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12): Changes in Abuse Exposures ERO showed 36% decrease in 2 years after reformulation, but showed 59% decrease with 80 mg tablets Results are consistent with the intended role of physicochemical barriers Reduces the desirability of tablets for the purpose of abuse and the preference of higher dosage strengths for abuse PRODUCT ERO SE Oxycodone Heroin 36% 20% 42% EXPOSURES 130 to to to 505 Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abusedeterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12):

16 Changes in Unintentional Therapeutic Errors Includes unintentional deviation from the recommended treatment regimen that results in wrong dosage Therapeutic errors for ERO declined steadily after reformulation, except for a spike in 3Q 2012 PRODUCT ERO 20% SE Oxycodone 19% EXPOSURES 161 to to 265 Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12): Changes in Accidental Exposures Include unintentional ingestion by children gaining access for nonmedical use ERO (all strengths) showed 39% decrease, and 57% decrease with 80 mg dose Among children of 1 to 2.5 years of age, exposures decreased from 63% in preformulation to 51% postformulation period PRODUCT ERO SE Oxycodone Heroin 39% 0% 21% EXPOSURES 75 to to to 27 Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12):

17 Significant Reduction of Prescription Adjusted Rates for All ERO Exposures Changes from baseline in ERO exposures had consistent decreases for number of exposures per quarter, population-adjusted rates, and prescription-adjusted rates ERO First year: 2% Second year: 9% Prescription Changes Second year: 51% SE oxycodone Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12): Decrease in All Types of ERO Exposures Were Greater With Increasing Dose ERO 80 mg dose showed largest decrease in abuse and accidental exposures ERO 40 mg showed greater decrease for unintentional therapeutic error exposure type when compared with <40 mg Change in average number of ERO exposures per quarter by tablet strengths All Exposures Pre-reformulation (3Q2009 2Q2010) Post-reformulation (4Q2010 3Q2012) % change in numbers All strengths % mg % mg % 80 mg % Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12):

18 Increased Heroin Abuse Exposures Seen ERO Postreformulation Heroin abuse increased sharply starting 4 to 6 months after reformulation Net pre vs post changes in abuse exposures Significant increase in slope, from 3.4% quarterly increase prereformulation vs 5.8% quarterly increase postreformulation is seen ERO Abuse Quarterly -8.3% Quarterly 2.3% Heroin Abuse Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12): Switching Heroin abuse exposures preand postoxycodone reformulation introduction Raw data and trend lines # of intentional abuse exposures per quarter Trend line with a knot at 2Q2010 Heroin Intentional abuse exposures Time period ERO reformulation 1Q2007 2Q2007 3Q2007 4Q2007 1Q2008 2Q2008 3Q2008 4Q2008 1Q2009 2Q2009 3Q2009 4Q2009 1Q2010 2Q2010 3Q2010 4Q2010 1Q2011 2Q2011 3Q2011 4Q2011 1Q2012 2Q2012 3Q2012 Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12):

19 Other Possibilities for Decreased ERO Exposures Besides Reformulation Effects At poison centers: Passive surveillance system Changes in reporting processes Possible misclassification between original and reformulated ERO exposures Changing opioid trends: Reductions in ERO prescriptions Changes in the population coverage Secular trends in prescription Opioid abuse and misuse due to other interventions Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12): Conclusion Abuse-deterrent formulations, with physicochemical barriers appear to be promising at reducing abuse and adverse outcomes from misuse. More consistent abuse-deterrent properties and addressing heroin availability may be necessary to improvise public health benefit. Abuse, therapeutic errors, and accidental exposures reported to NDPS were decreased for ERO reformulation but not with other opioid agents. The clinical significance of these technologies or its impact on abuse/misuse liability has not been fully established, though recent data shows promise for abuse reduction in recreational users. Reformulating one opioid alone to have abuse-deterrent properties does not meet the public health benefit. Coplan PM, Kale H, Sandstrom L et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf. 2013;22(12):

20 Case Study 2 Methods 5 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 oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol The programs gather data from drug-diversion investigators, poison centers, substanceabuse treatment centers, and college students 20

21 Case Study 3 21

22 Methods An observational design compared the prevalence, prescription-adjusted prevalence rates, and ROA (routes of administration) patterns of past-30-day abuse of ORF in the period after its introduction to that of OC before ORF introduction Abuse patterns for 2 comparator opioid compounds (ER morphine and ER oxymorphone) were assessed during the same pre- and post-orf periods. The primary route of non-oral abuse of ER oxymorphone is by snorting and of ER morphine is by injecting, 2 thus providing relevant controls for route-specific comparisons A sensitivity analysis was conducted to account for number of prescriptions dispensed using data from the Vector One National database Results 22

23 Pre- and Postreformulation of Oxycodone Pre- and Postreformulation of Oxycodone (cont d) 23

24 Pre- and Postreformulation of Oxycodone (cont d) Case Study 4 24

25 Reformulated oxycodone was associated with a significant reduction of past-month abuse after its introduction (45.1% [95% CI, 41.2%-49.1%] apparently owing to a migration to other opioids, particularly heroin However, this reduction leveled off, such that 25% to 30% of the sample persisted in endorsing past-month abuse from 2012 to 2014 Among the 88 participants who indicated experience using pre-adf and ADF oxycodone, this residual level of abuse reflects the following 3 phenomena: (1) a transition from non-oral routes of administration to oral use (38 participants [43%]); (2) successful efforts to defeat the ADF mechanism leading to a continuation of inhaled or injected use (30 participants [34%]) (3) exclusive use of the oral route independent of formulation type (20 participants [23%]) Abuse-Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the United States Lessons Learned From OxyContin. Theodore J. Cicero, PhD; Matthew S. Ellis, MPE JAMA Psychiatry. 2015;72(5): doi: /jamapsychiatry Published online March 11, The Wrong Message Abuse Deterrent Oxycodone Won t Solve US Opioid Epidemic; Megan Brooks 25

26 Methods Survey of Key Informants Patients (SKIP) program, a key element of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) system, a comprehensive series of programs that collect and analyze post-marketing data on the misuse and diversion of prescription opioid analgesics and heroin. Clients older than 18 years who were entering their substance abuse treatment program with a primary diagnosis of opioid abuse, as defined by DSM-V criteria. (11,782 participants) A subset of respondents indicated by a mail-in postcard provided with the SKIP survey that they were willing to give up their anonymity and participate in the interview-based Researchers and Participants Interacting Directly (RAPID) program. The purpose of the RAPID program was to supplement and add context to the structured SKIP survey by establishing a 2-way exchange of information with participants in which questions were developed, administered, and answered within a short period. (244 participants) Respondents Who Endorsed Past-Month Use of Oxycodone or Heroin Before and After the Introduction of an Abuse-Deterrent Formulation (ADF) 26

27 Effect of Abuse-Deterrent Formulation (ADF) of Oxycodone in Subsamples of Respondents Drugs Used to Replace Oxycodone After the Introduction of the Abuse-Deterrent Formulation (ADF) 27

28 ABUSE Section Health Economics Research Permanent replacement of OxyContin with Oxy ERO could potentially reduce the societal economic costs of prescription opioid abuse, without causing the loss of health benefits accruing to legitimate users of the drug. Skinner BJ (2012). Net societal economic impact in Canada from withholding regulatory approval for generic OxyContin 28

29 Opioid Abuse Gets Insurers Attention Relieving chronic pain while preventing opioid abuse requires vigilance Enter health plans Some identify at-risk members as well as prescribers who write an unusually high number of opioid prescriptions Question is who should pay for ADFs Evaluation and Data Sources for Key Opiate Risks Clinical trials Epidemiology studies Pharmacology Formulation Company safety database 1 Drug abuse 2 Physical dependence 3 Psychological dependence 4 Overdose 5 Respiratory depression 29

30 Classification of Opioids Full opioid agonist Agonist fits neatly into the receptors site and activates it Morphine, Oxycodone, Codeine, Fentanyl, Hydromorphone, Meperidine, Oxymorphone, Hydrocodone, Levorphanol, Methadone Propoxyphen Partial opioid agonist Mixed agonist-antagonist Agonist fits neatly into the receptors site, but not quite as well as the full agonist Buprenorphine Pentazocin Butorphanol Nalbuphine Opioid antagonist Agonist fits into the receptors site, but is not the right shape to activate it Naloxone Naltrexone Trescot AM, et al. Pain Physician 2008;11(2 Suppl):S133 Buprenorphine DEA Classification: Schedule III Schedule III class drugs have: Less abuse potential than the drugs or other substances in: Schedule I (eg, heroin, PCP, marijuana) and Schedule II (eg, fentanyl, morphine, oxycodone) Moderate or low physical dependence Source: US Department of Justice Drug Enforcement Administration Web Site. Available at: usdoj.gov/schedules/index.html. Accessed October 4,

31 Scientific Literature Supports That There May Be Low Abuse Liability with Buprenorphine In a double-blind, placebo-controlled, in-patient study of morphine maintained abusers, buprenorphine injection produced: Little good effect with subjects moderately interested in product Increased ratings of bad drug Not self-administered above placebo at any dose tested Comer SD, et al. Neuropsychopharmacol. 2008;33: Consistent Message In 1978 the head of the dependence potential testing program the United States Addiction Research Center was Dr. Donald R. Jasinski. Dr. Jasinski conducted historic studies of buprenorphine. He concluded the following: Buprenorphine has a unique pharmacology with immediately obvious therapeutic applications as an analgesic of low abuse potential He recommended the least restrictive scheduling to distinguish buprenorphine from much stronger dependence producing drugs such as morphine, fentanyl, and oxycodone. We now have 3 additional decades of research and ¼ century of clinical experience to confirm that Dr. Jasinski was correct. 31

32 Buprenorphine Products Approved by the FDA Product Formulation Approval Date Buprenex Subutex Suboxone Butrans Injectable buprenorphine Sublingual buprenorphine Sublingual buprenorphine + naloxone Transdermal buprenorphine patch Indication 1981 Moderate to severe pain 2002 Opioid dependence 2002 Opioid dependence 2010 Moderate to severe chronic pain Zubsolv Sublingual tablet 2013 Opioid dependence Bunavail Buccal strip 2014 Opioid dependence Belbuca Buccal strip 2016 Moderate to severe chronic pain Buprenorphine Dosing Analgesic dose range Dose range for drug substitution Efficacy 0.2 < 7 mg 8-32 mg Dose Walsh SL et al. J Pharmacol Exp Ther 1995;274:

33 Low Abuse/Physical Dependency Risk Partial μ-receptor agonist Decreased abuse potential High receptor binding affinity and slow dissociation from the μ- receptor Slow onset but relatively long duration of analgesic action Low risk of physical dependency and analgesic tolerance compared with full mu-receptor agonists Milder withdrawal symptoms compared with full mu-receptor agonists Kress HG. Euro J Pain. 2009;13: Buprenorphine DEA Classification: Schedule III Schedule III class drugs have: Less abuse potential than the drugs or other substances in: Schedule I (eg, heroin, PCP, marijuana) and Schedule II (eg, fentanyl, morphine, oxycodone) Moderate or low physical dependence Source: US Department of Justice Drug Enforcement Administration Web Site. Available at: usdoj.gov/schedules/index.html. Accessed October 4,

34 A flowchart illustrating the clinical effect of buprenorphine-naloxone (bup/nal) on various categories of patients with chronic pain Buprenorphine-Naloxone Therapy in Pain Management. Chen, Kelly; Chen, Lucy; Mao, Jianren nesthesiology. 120(5): , May DOI: /ALN A potential novel strategy to separate therapeutic - and side-effects that are mediated via the same receptor: b-arrestin2/g-protein coupling antagonists Buprenorphine and its b-arrestin 2 effect Members of arrestin/beta-arrestin protein family are thought to participate in agonistmediated desensitization of G protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals Strategy for the design of novel drugs that would amplify the therapeutic effect and simultaneously attenuate the unwanted effects mediated by the same receptor Raffa RB et al. Journal of Clinical Pharmacy and Therapeutics (2006) 31,

35 Trying to Avoid Opioids All Together Drugs: Long acting local anesthetics NSAID/Coxibs MOR/NRI (tapentadol) Other agonists (kappa) Interventional techniques Medical devices (laser, TENS, pumps, stims) Cognitive behavioral therapy Physical therapy Surgery Bottom line avoid opioids if you can! Study: Opioid Abuse May Be Waning in the United States Reuters (1/15, Emery) reports that according to an analysis (1/15) published Jan. 15 in the New England Journal of Medicine, opiate-based prescription painkiller abuse may be waning in the US. Researchers attribute the decline to new laws, policies, the reformulation of oxycodone, and programs including the prescription tracking system. Data used for the study were collected between 2002 and 2013 from substance-abuse treatment centers, poison centers, college students, and drug-diversion investigators. HealthDay (1/15, Norton) reports that although the US epidemic of prescription-painkiller abuse may be starting to reverse course, researchers believe this could be due, in part, to a disturbing trend: Heroin abuse and overdoses are on the rise. MedPage Today (1/15, Fiore) also reports on the study generally. Delving further into the increasing rates of heroin abuse in the US, CNN (1/15, Kounang) reports that the number of deaths from heroin use over the past 2 decades is up by 39%, and this is the third year in a row that heroin deaths have increased. CNN s Dr. Sanjay Gupta believes that the success of the federal, state, and local government initiatives to crack down on illegal prescription drug sales...may have a connection to the rise in problems with heroin. While a 60-milligram [painkiller] pill will cost $60 for people without insurance, CNN points out that one can obtain the equivalent amount of heroin for about onetenth the price. According to the National Institute on Drug Abuse, almost half of young people who use heroin today started with prescription opioids. Reuters January

36 The CDC Data Reports Regional Reduction in Overdose Deaths CDC Vital Signs July 2014 Conflicting Reports Adds Concerns: Overdose Death Rates Have Increased In 26 States USA Today (6/17, Bowerman, Pager) reports that yesterday, the Trust for America s Health and the Robert Wood Johnson Foundation released a report finding that drug overdose death rates have increased in 26 states and Washington, DC, and overdoses continue to outpace car crashes as the leading cause of injury-related deaths. Reuters (6/18, Kearney) reports that across the US, prescription medication and illicit drug overdoses took the lives of 44,000 people in % of these fatalities are tied to prescription medications. The AP (6/18, Raby, Mattise) reports that West Virginia leads the US in the highest rate of overdose deaths. In fact, the state s drug overdose death rate was more than double the national average, the report says. The report, which cited statistics from the CDC, found that West Virginia experienced about 34 drug overdose deaths per 100,000 people, compared to the US national average of 13.4 deaths per 100,000 people. 36

37 Self Assessment 1. The most common source(s) of diverted controlled substances is/are: a) Multiple doctors b) Street dealers c) Friend or family d) a and b 2. Evidence shows that abuse-deterrent formulation (ADF) OxyContin a) Reduces non-oral use of the drug (snorting and injecting) b) Results in reduced use of other ER formulations of opioids c) Leads to decreased use of heroin use d) All of the above 3. ADFs reduce the need for REMs a) True b) False Sanford M. Silverman, MD Comprehensive Pain Medicine 37

38 Questions & Discussion 38