Lessons Learned from the US Prescription Opioid Abuse Epidemic

Transcription

1 Lessons Learned from the US Prescription Opioid Abuse Epidemic Michelle Lofwall, M.D. University of KY, Dept. of Psychiatry Center on Drug and Alcohol Research October 3, 2012

2 Outline for today s talk Background on worrisome trends in the U.S. The context: Lessons learned? Responses including naloxone overdose programs Summary

3 Global consumption of narcotics (defined daily doses/million inhabitants/day) USA Canada Aus + NZ 7284 EU 6450 Japan 662 Eastern Europe 191 All others 116 WORLD Courtesy of Dr. Jayadeep Patra, Centre for Addiction and Mental Health, University of Toronto, under review.

4 Rates of prescription (rx) opioid sales, deaths and substance abuse treatment admissions ( ) *In 2010 there were enough rx opioids prescribed to medicate every American around the clock for 1 month.

5 A brief US history of Rx opioids FDA approved to treat all types of pain Limited data on long term use and efficacy particularly with non-cancer chronic pain Some data showing hyperalgesia with chronic opioids 1980 s: push to more aggressively treat pain 1990 s: More opioids coming to market (e.g., 1996 OxyContin) & 1999 pain = 5 th vital sign Financial punishments if do not address pain 2000 s: Growth of pill mills (doctors and pharmacies) & adverse consequences

6 Broward Palm Beach New Times, Volume 13, Number 6, December 10-16, 2009.

7 Lesson #1- A few unethical doctors & pharmacists can cause great harm Early 2011: top 90 oxycodone-purchasing doctors and top 53 oxycodone-purchasing pharmacies were located in South Florida. Cases prosecuted: mobile clinics/bullet-proof pharmacies change locations within days, cash only (no insurance) burning $1 dollar bills, over 500 prescriptions within a day for one doctor Lesson #2- Greed and many profiteers Airlines offering very cheap flights to Florida Advertising makes clear where to get easy pills Pharmaceutical companies govt. investigations

8 Amount (kg) of rx opioids sold by state Hydrocodone products most commonly prescribed followed by oxycodone products

9 Who gets prescribed the opioid analgesics? ~80% of patients prescribed low doses (<100 mg morphine equivalent dose per day) by a single practitioner ~10% of patients are prescribed high doses ( 100 mg morphine equivalent dose per day) of opioids by single prescribers ~10% of patients are getting scripts from multiple doctors = prescribed high daily doses These latter two groups account for 80% of overdoses Center for Disease Control Grand Rounds: Prescription Drug Overdoses a US Epidemic, January 13, 2012 / 61(01);10-13

10 Source of pain relievers for misuse Source Percentage From 1 doctor 18 From > 1 doctor 2 From friend/relative for free 56 From friend/relative for $ 9 Stole from friend/relative 5 Forged prescription <1 Stole from clinic/pharmacy <1 Internet <1 From drug dealer/stranger for $ 4 Other 4 85% of friends/relati ves get from 1 or more doctors National Household Survey on Drug Use & Health ( )

11 Prevalence of opioid use disorders Heroin: approximately 1 million addicted Prescription opioids: National Survey of Drug Use and Health million meet DSM-IV abuse or dependence criteria

12 Rx drug overdose rates by state >14k deaths in 2008 due to prescription drugs (mostly opioids) that now outnumber fatal car crashes in many US states. In Kentucky in 2011, ~5k hospital admissions for non-fatal overdose and 730 newborns treated for drug withdrawal syndromes (KY ODCP).

13 Risk factors for prescription opioid overdoses Demographics characteristics: Male years old Less urban Living in area without a naloxone overdose program Low income/medicaid Prescription history: Multiple scripts Multiple prescribers High daily opioid dose (> 120 mg of morphine equivalents per day) Paulouzzi 2012, Populations at risk for opioid overdose, CDC April 12, 2012

14 Summary so far Clear + relationship between opioid prescribing and overdose deaths and addiction Most common source of misused rx opioids is doctors and pharmacies Challenge = how to strike the right balance between opioid access for pain treatment vs. these opioid-related harms

15 What is the connection between between pain and addiction? Prescription opioids are prescribed for pain so there is a legal supply of medication that is easily and readily prescribed and results in increased availability and exposure Long-acting opioids are supposed to have a more gradual onset of effects, which was supposed to result in less risk for misuse and abuse than immediate-release, fast-onset opioids

16 Not a simple connection Treat Pain With Opioid Opioid Addiction Myth: Everyone who has pain and takes pain pills will misuse or develop opioid abuse and addiction BUT does pain offer any protection against the euphorigenic properties of opioids?

17 Sustained release?

18 Lesson learned from the original sustained release OxyContin formulation Introduced in US in Introduced 160 mg dose in 2000 but soon withdrawn Easily crushed and with crushing the long acting nature is gone so just because it says it is extended release does not mean it is always it actually becomes immediate release Recently reformulated in 2011 to become very hard to crush

19 Crushed OxyContin pharmacokinetics Concentration (ng/ml) Oxycodone plasma concentration (n=8 subsample; 4 males/4 females) IV oxycodone 5 mg/70 kg IN OxyContin 15 mg/70 kg IN OxyContin 30 mg/70 kg **IN bioavailability was ~80% compared to IV route * Detectable within 5 min in blood after snorting Time (hrs) Lofwall et al Pharmacokinetics of intranasal crushed oxycontin and IV oxycodone in nondependent prescription opioid abusers J Clinical Pharmacology. 54:

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21 Does cold water produce pain? Yes Do opioids reduce pain? Yes How much physical pain do you have right now? IN OxyContin 0 mg/70 kg IN OxyContin 30 mg/70 kg IN OxyContin 15 mg/70 kg Score *Warm dose conditions not displayed because pain scores ~ BL Time relative to drug administration (hours) Lofwall et al. 2012, Effects of cold pressor pain on the abuse liability of intranasal oxycodone in male and female prescription opioid abusers, Drug and Alcohol Dependence

22 Does being in pain alter the abuse liability of crushed OxyContin? How HIGH Are You? Score Cold= Pain Warm= No Pain Oxycontin (IN) 0 mg/70 kg 15 mg/70 kg 30 mg/70 kg Time (hrs) Time (hrs) No main effect of pain or dose x pain interaction, but significant dose effect

23 More lessons Just because it says extended or sustained release doesn t mean it always has these properties under all conditions No clear data demonstrating that pain modulates the abuse liability of opioid analgesics If the health care providers and industry can t fix the problems of the related harms from increased opioid analgesic prescriptions there will likely be more regulation

24 Responses Pharmaceutical industry Abuse deterrent and tamper resistant formulations (e.g., hard to crush, adds an opioid antagonist), but older and less expensive formulations remain on the market (ex: generic oxycodone) and widely prescribed US Food and Drug Administration mandates: Risk Evaluation and Mitigation Strategies (REMS) for new opioids coming to market Pharmaceutical companies marketing long acting (but not short acting) opioids now required to provide $ to fund education for doctors

25 Individual State Responses Prescription monitoring programs Doctors must query for every rx opioid prescribed Pharmacists may also query, but must enter for every dispensed dose into database Medical licensure boards develop proactive prescribing patterns to watch for and where filled can be combined with state overdose death records Mandated standards for opioid prescribing Random urine drug testing Random medication pill counts Screening for addiction Medical license potentially in jeopardy if do not follow

26 Naloxone overdose prevention programs Opioid antagonist reversal agent for overdoses Programs provide basic life support training, identification of overdose, kits for either intravenous or intranasal naloxone Several US states have programs no randomized studies to date BUT states that have programs have lower rates of overdose deaths than states without No evidence of increased drug use (Walley et al. College on Problems of Drug Dependence meeting, June 2012.)

27 Project Lazarus North Carolina Wilkes County: First to distribute naloxone to patients receiving high dose opioids for pain. Educated patient and family in clinics/hospitals. Public health doctors also trained in addiction to provide suboxone for those that were reporting having an overdose with naloxone administered Police, emergency departments, schools all involved in combatting the overdose deaths 71% decrease in OD deaths over first 2-years Brason, F.W., Sanford, C.P., Albert, S., Dasgupta, N. Positive results from Project Lazarus community-based prescription opioid overdose prevention. Poster presentation at the College on Problems of Drug Dependence meeting, June 2012.

28 Pharmacy role in naloxone overdose programs Pharmacies currently an untapped resource in these programs but have clear potential for involvement: As potential sites for distribution of kits Kit refills and/or education Educators/screening sites regarding addiction and addiction treatment

29 Summary? Decreased access to legitimate pain treatment 1980 s Increased need for pain treatment Increase pain prescribing over last several decades How can increasing access and decreasing barriers to addiction treatment and naloxone overdose programs affect this cycle? 2012: Clamp down on opioid prescribing 2012: Increased misuse, OD, addiction

30 Australia an emerging problem? Oxycodone (OxyContin and Endone ) 1 : : 4-fold in # scripts across all of Australia May April 2012: 709k oxycodone prescriptions (Pharmaceutical Benefits Schedule) : 465 oxycodone-related deaths Comments from within Australia: Doctors becoming better at treating pain Remember USA: more people misusing and abusing, too. Not mutually exclusive to improve pain treatment and unintentionally increase/create other problems 1. Victoria Alcohol and Drug Association News July 25, 2012

31 Naloxone overdose program resources

32 Acknowledgements National Institute on Drug Abuse University of Kentucky Investigational Drug Pharmacy (Steve Sitzlar, Pharm.D.) University of Kentucky Inpatient Research Unit and Nursing staff (Linda Rice, Lisa Chamblin) Sharon Walsh, Ph.D. Paul Nuzzo