1. The Opioid Epidemic NOVEMBER 29, 2018 Jane Liebschutz, MD, MPH, FACP
PROFESSOR OF MEDICINE
Chief, DIVISION OF GENERAL INTERNAL MEDICINE
Upmc, university of Pittsburgh
@liebschutz

2. Learning
Objectives
Historical perspective on opioid prescribing and addiction
Criteria for diagnosis of opioid use disorder
Impact of opioid epidemic
Treatment of opioid use disorder
The opioid epidemic

3. Discovery of Morphine, 1806
Friedrich Wilhelm Adam Serturner,
Morphine is named for Morpheus, God of Sleep and Dreams
15 mg standard dose
The opioid epidemic

4. Michael S. 1864: Civil War battle injury Morphine treated his pain
The opioid epidemic

5. Michael S. 1899: Chronic cough from industrial exposure
Di-acetylmorphine from Bayer
The opioid epidemic

6. Harrison Act of 1914
Combat addictive properties of medicinal opioids (heroin, morphine, codeine)
Regulate nonmedical opioid use
Made possession without prescription illegal
The opioid epidemic

7. Opioids Natural and Semi-synthentic Synthetic Morphine
Diacetylmorphine
(Heroin)
Oxycodone
Hydrocodone
Hydromorphone
Oxymorphone
So let’s talk a little bit about opioids in terms of their pharmacology so we get a better appreciation for the efficacy and safety of opioids, and are they all the same or are they different? It really starts with the opiates, morphine and codeine, which come from opium. And when you take these molecules, you take them to the lab, and you alter them some, you can create semi-synthetic opioids like hydrocodone, hydromorphone, oxycodone, oxymorphone, and diacetylmorphine, which is heroin.
The important thing to remember is that when we check urine drug tests, we ask the lab to check whether or not there are opioids or opiates in the urine. And we’re checking for morphine and codeine. However, the semi-synthetics that came from morphine and codeine can revert back to morphine and codeine and turn your urine positive for an opiate.
That’s different, however, than the synthetic opioids like methadone, meperidine, and fentanyl. These never came from an opiate, namely morphine and codeine, and they will never convert back to morphine and codeine, and they will never turn your urine positive for an opiate.
All of these opioids, whether they’re semi-synthetic or synthetic, can be tested for specifically with immunoassays. And you’re going to hear much more about urine drug testing in the next presentation.
Synthetic
Methadone
Meperidine (Demerol)
Fentanyl
Buprenorphine
The opioid epidemic

8. 1974:
Michael S.
Exposed to heroin and drugs during deployment in Vietnam
Treated with methadone
The opioid epidemic

9. Heroin, 1960s – 1970s Mostly minority communities
Returning Vietnam vets
Methadone approved 1972
The opioid epidemic

10. Undertreatment of Pain
1970s-1980s
Undertreated cancer pain
The opioid epidemic

11. “Addiction Rare in Patients Treated with Narcotics”
January 10, 1980
N Engl J Med 1980; 302:123
The opioid epidemic

12. Wave 1: Increase Opioid Prescribing
1996: Oxycontin marketed aggressively by Purdue
2001 Joint Commission: Pain as a 5th vital sign
Compton 2006 Drug Alc Depend 81:
The opioid epidemic

13. Michael S. 1997: Chronic back pain from construction accident Disabled
Prescribed OxyContin to help with pain
The opioid epidemic

14. Parallel Rise in Opioid Prescriptions, Addiction, and Overdose
MMWR November 4, (43);
The opioid epidemic

15. Addiction Is a Brain Disease
Drugs hijack brain reward circuits
Develop tolerance and withdrawal
Learned behavior “Habit”
Volkow, N Engl J Med 2016; 374:
Lewis, N Engl J Med 2018; 379:
The opioid epidemic

16. What Is Opioid Use Disorder? DSM-V criteria
Use in larger amounts or over a longer period than intended
Unsuccessful efforts to cut down/persistent use
A great deal of time spent getting, using, or recovering from use
Craving, or a strong desire to use
Recurrent use resulting in failure to fulfill major obligations at work, school, or home
Continued use despite social or interpersonal problems caused by use
The opioid epidemic

17. What Is Opioid Use Disorder? (Continued)
Social, work, recreational activities given up or reduced
Use in situations in which it is physically hazardous
Continued use despite physical or psychological harm
Withdrawal
Classic withdrawal
Opioids relieve withdrawal symptoms
Tolerance
Need for increased amount to achieve same effect
Decreased effect with same amount
2 or more in 12 months; 2-3=mild, 4-5=moderate, 6 or more=severe
The opioid epidemic

18. A small number of physicians prescribed an outsized number of pills.
Pill Mills
A small number of physicians prescribed an outsized number of pills.
The opioid epidemic

19. Prescription Drug Monitoring Programs
State based - – to “catch” the patients who are “doctor shopping”
2000s
2010: 27 states
2018: 49 states
Law enforcement aggressively pursue prescribers
Shut down pill mills
The opioid epidemic

20. Michael S. 2010: Unemployed coal miner
When OxyContin supply cut off, started buying heroin
Injects 3-4 times daily
Two overdoses
Girlfriend works as a nurse
Watches kids when girlfriend works
The opioid epidemic

21. Wave 2: Heroin Import from Mexican cartels Heroin deaths on the rise
Marketing directly to suburban white customers
Heroin deaths on the rise
Compton, N Engl J Med 2016;374:154-63
The opioid epidemic

22. Heroin Use Climbed Then Stablized
The opioid epidemic

23. Wave 3: Fentanyl 50 times more potent than heroin
Manufactured in China and elsewhere
Mixed with heroin and other drugs to increase “high”
The opioid epidemic

24. Michael S. 2016: Multiple nonfatal overdoses
No treatment slots in his rural county
Died of fentanyl overdose
The opioid epidemic

25. >72,000 drug overdose deaths 2017
The opioid epidemic

26. Mortality Rates Rise for U.S. Whites
All-cause mortality, ages for U.S. White non-Hispanics (USW), U.S. Hispanics (USH), and six comparison countries:
France (FRA)
Germany (GER)
United Kingdom (UK),
Canada (CAN)
Australia (AUS)
Sweden (SWE)
Deaths of Despair:
Overdose
Alcoholism
Suicide
Anne Case, and Angus Deaton PNAS 2015;112:49:
The opioid epidemic
©2015 by National Academy of Sciences

27. Impact on Families
2.8 million custodial grandparents raising 4.5 million children
Increase of 7% since 2009
Parent support groups:
The opioid epidemic

28. Neonatal Withdrawal Syndrome (NOWs)
Hyperactivity of central and autonomic nervous system and gastrointestinal tract
2009: 1.19/1000 live births
2012: 5.63/1000 live births
Rural > Urban
West Virginia: 50/1000 live births
The opioid epidemic

29. Types of Treatments: Medications Behavioral Therapies
The opioid epidemic

30. Medication Treatments:
Full Agonists
Methadone
Morphine*
Partial Agonists
Buprenorphine (Suboxone)
Antagonists
Naltrexone (Vivitrol)
*off-label
Naloxone (Narcan)
The opioid epidemic

31. Buprenorphine (Partial Agonist) Naltrexone (Antagonist)
Clinical Setting
Clinical Setting
Methadone (Agonist)
Buprenorphine (Partial Agonist)
Naltrexone (Antagonist)
Any outpatient setting
DEA waiver for outpatient
Up to 30 day supply
Federally licensed facility
Daily observed dosing
Any licensed prescriber
Oral (daily), injectable (4 weeks)
The opioid epidemic

32. All Cause Mortality Rates In and Out of Methadone and Buprenorphine Treatment,
All Cause Mortality rates per 1000
Methadone vs. No Rx
11.3 vs. 36.1
Buprenorphine vs. No Rx
4.3 vs. 9.5
Luis Sordo et al. BMJ 2017;357:bmj.j1550
The opioid epidemic

33. Massachusetts Chapter 55
Adjusted* Hazard for Opioid-Related Mortality
By Monthly Receipt of Treatment in Post-Overdose Period
N=17,568
Buprenorphine
0.3 ( )
Methadone
0.3 ( )
0.5 ( )
Naltrexone
*Adjusted for: age, sex, depression DX, anxiety DX, incarceration, detoxification, baseline opioid and benzodiazepine RX, and monthly post-overdose receipt of benzodiazepines, opioids, detoxification and short- and long-term residential treatment.
0.1
0.5 1 2 3 4 5
On Treatment
LaRochelle, Ann. Int Med 2018
The opioid epidemic

34. Cognitive Based Therapy Contingency Management
Behavioral Therapies –
Adjunct to
Pharmacotherapy
Cognitive Based Therapy
Contingency Management
The opioid epidemic

35. Adjuvant Psychosocial Rx/CBT Risk Ratio: 1.03 (0.98-1.07)
Amato 2011 Cochrane Systematic Review
The opioid epidemic

36. Key Points: OPIOIDS Balance between therapeutic use and addiction
Brain adaptation
Bending the mortality curve
Impacts children and families
Medication treatment saves lives
The opioid epidemic

37. Thank You Twitter: @Liebschutz
The opioid epidemic