Pain, Opioids, and Addiction

1. Pain, Opioids, and Addiction A Medical Primer Quinnipiac University Opioid Summit November 9, 2018 Daniel G. Tobin, M.D., F.A.C.P. Associate Professor of Medicine

2. Terminology • Acute pain: pain associated with injury, illness, or active inflammation, potentially life saving, usually self-limited • Chronic Pain: a pain syndrome that has persisted beyond resolution of tissue injury, usually 3 months or more • Opioids: naturally occurring “opiates” or synthetic “opioids” that block pain and affect brain and nervous system function • Misuse: use of medication differently than prescribed or for different reasons • Physical Dependence: the body’s normal adaptation to chronic opioid exposure characterized by tolerance and withdrawal • Addiction: a brain disease characterized by drug cravings, compulsive drug use, loss of control, and continued use despite evidence of harm

3. Opioids predate modern medicine • 3400 B.C.: • the opium poppy was used by the Sumerians and later the Assyrians and Egyptians to induce a sensation of joy • 1800s: • opium, laudanum, morphine, and cocaine were marketed to parents to help soothe their irritable or teething children • 1861-1865: • During the Civil War, morphine was used as a battlefield anesthetic. Many soldiers developed morphine addiction • 1898: • Heroin is first produced commercially by the Bayer Company; used to treat morphine addiction

4. Current understanding of pain and opioids

5. Prevalence of chronic pain • Affects over 100 million Americans (1 in 3 people) • 25 million American adults suffer from daily pain • 40 million American adults have severe chronic pain • Costs over $600 billion each year in treatment costs, lost wages, and productivity • Moderate to severe pain is one of the most common chief complaints in primary care

6. America’s recent focus on chronic pain • 1990’s - Pain felt to be significantly undertreated • 1996 - The American Pain Society promoted “pain as the 5th vital sign” • 2000 - The Veterans Health Administration (VHA) implemented a Pain as a 5th Vital Sign Mandate at all VHA Hospitals • 2001 - The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) released new pain management standards, further promoting the concept • 2006 - The Centers for Medicare Services (CMS) linked reimbursement to patients’ satisfaction with pain management in their Hospital Consumer Assessment of Healthcare Providers and Systems survey (HCAHPS)

7. Providers turned (again) to opioids • Poorly trained prescribers: In 2011, only 5 of the 133 medical schools had a mandatory course on pain • Insufficient pain specialist support: • There are only 4 board-certified pain specialists for every 100,000 patients with chronic pain • Many pain specialists focus only on procedures or do not work with certain payers (e.g., Medicaid) • Limited insurance coverage for non-opioid pain management • Pharmaceutical companies inappropriately promoted opioid analgesics to prescribers as “non-addictive” • Unintended consequence of JCAHO and CMS policies

8. Opioid overprescribing in America • Americans • Consume more opioids than the rest of the world • Use 99% of the world’s hydrocodone • Opioid prescriptions • Over 236 million opioid prescriptions in 2016 • Quadrupled since the 1990’s • In 2016, hydrocodone was the 4th most prescribed medication Sources: United Nations International Narcotics Control Board, March 2017; US Department of Health and Human Services, June 2016; IQVIA Institute for Human Data Science 2018

9. Opioid prescribing in Connecticut • 2.16 million prescriptions for opioids written in CT in 2017 • There are 27784 licensed prescribers in CT • 19062 prescribers wrote at least one controlled substance prescription • In 2015, Approximately 10% of CT prescribers (2707) wrote more than 500 controlled substance prescriptions each Sources: Connecticut Department of Consumer Protection, CPMRS Statistics, May 2018 and Connecticut Department of Consumer Protection DCD. Prescription Monitoring Program: Snapshot of legal controlled substance usage throughout Connecticut, 2015

10. Opioid overdose deaths • Increase in deaths from opioid overdose tracks with increases in opioid prescribing • Many deaths occur in those who were not prescribed opioids due to oversupply and diversion • 115 Americans die each day from unintentional opioid overdose1 1 MMWR Morbidity and Mortality Weekly Report (MMWR) 2018;67(12):349-358

11. Overdose risk • Overdose risk increases with: • Increasing dose and potency • When co-prescribed with benzodiazepines • When used with alcohol • When injected or adulterated • After prior non-fatal overdose • When tolerance is low • With sleep disordered breathing Daily Dose in Morphine Milligram Equivalents (MME’s) Source: Bohnert AS et al., JAMA 2011

12. Overdose deaths in Connecticut • Overdose deaths in 2017 • 1038 accidental drug deaths, majority from opioids • 568 in 2014 • 357 in 2012 • Most overdoses were not from prescription drugs • 474 deaths involved heroin • 677 deaths involved fentanyl (up from 14 in 2012) • 333 deaths involved both heroin and fentanyl Map Source: CT Patch Source: CT Medical Examiners Office, as of March 1, 2018

13. Opioid misuse and addiction • Misuse: Opioid use different than prescribed • Misuse Rates: 21% - 29% ([95%CI]: 13%-38%) • Addiction: Compulsive drug seeking and use, despite harmful consequences • Addiction Rates: 8% - 12% ([95% CI]: 3%-17%) • More than half of nonmedical prescription opioid use comes from diversion (given, bought, or stolen from a friend or relative) Sources: Vowles KE et al. Pain. 2015; 156(4):569-576 Systematic review from 38 studies, 26% primary care settings, 53% pain clinics; SAMHSA. (2017). Results from the 2016 National Survey on Drug Use and Health

14. Addictive medications: initial euphoria • The brain as a mesolimbic “reward pathway” • Related to the neurotransmitter dopamine • Promotes life-sustaining activities such as eating and having sex • Opioids stimulate and hijack the reward pathway • In animal models • Having sex raises dopamine levels twice as much as food • Using cocaine or morphine raises dopamine ten to hundred-fold

15. Addiction: brain changes over time • Brain changes • Dopamine less effective at stimulating reward pathway • Blunted pleasure response • Intense cravings due to brain changes can lead to binge behaviors Source: www.drugabuse.gov

16. Natural history of opioid use disorder Initial opioid use driven by euphoria Later opioid use driven by cravings and withdrawal

17. Opioid agonist addiction treatment • Methadone and buprenorphine • Block drug-induced euphoria • Reduce cravings and binge behaviors • Prevent withdrawal symptoms

18. Advantages of opioid agonist treatment • Reduction in illicit substance use • Less viral hepatitis and HIV • Reduction in risk of opioid overdose and death • Reduction in injection drug use complications • Skin infections, endocarditis • Increased engagement in behavioral treatments and primary care • Reduction in risky behaviors • Stealing, violent crime, prostitution, drug-dealing • Reduced risk of legal consequences • Arrest and incarceration • More time available to • Have sustainable relationships • Find gainful employment • Deal with other medical problems Not simply trading one addiction for another MAT is the gold standard in evidence-based opioid addiction care

19. Thank You! • Contact me with additional questions at daniel.tobin@yale.edu • For more information: • https://www.linkedin.com/in/danieltobinmd • https://medicine.yale.edu/intmed/people/daniel_tobin.profile