The Opioid Crisis in Erin Zerbo, MD Assistant Professor, Department of Psychiatry Rutgers New Jersey Medical School

Transcription

1 The Opioid Crisis in 2017 Erin Zerbo, MD Assistant Professor, Department of Psychiatry Rutgers New Jersey Medical School

2 Outline Neurobiology of addiction Epidemiology of the opioid crisis Medication-assisted treatment Pain management

3 Neurobiology of Addiction

4 Reward Pathway n Neurons start in the VTA à release DA in the nucleus accumbens n Baseline: steady DA n Drugs: burst of DA (pleasure/salience) DA = dopamine

5 Effects of Drugs on Dopamine Levels % of Basal Release MORPHIN E Dose mg/kg hr % of Basal Release COCAINE hr % of Basal Release NICOTINE % of Basal Release ALCOHOL Dose (g/kg ip) hr hr Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of Nora D Volkow, MD 0 5

6 Effects of Drugs on Dopamine Levels 1100 % of Basal Release AMPHETAMINE DA hr Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of Nora D Volkow, MD

7 Acute drug effects n Extra DA release à changes in cell signaling n D1 DA receptor stimulation à camp-dependent protein kinase (PKA) à phosphorylation of CREB à immediate early gene products such as cfos à short-term neuroplastic changes for a few hrs/days But this does not explain long-lasting behavioral changes

8 How to explain end-stage addiction? n Overwhelming desire to obtain drug n Diminished ability to control drug seeking n Reduced pleasure from biological rewards

9 Transition to addiction n Repeated use à brain changes that last for days-weeks n Long-acting proteins involved n FosB = transcriptional regulator, increases AMPA glutamate receptor subunits n Create new circuits based on glutamate, not dopamine

10 New circuits created from prefrontal cortex (glutamate)

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13 Volkow ND, Baler RD. Addiction science: Uncovering neurobiological complexity. Neuropharmacology 2014;76:

14 And to make matters worse NIDA

15 Addiction Chronic drug consumption = decreased DA activity So even though you care more about the drug now - You don t get as much pleasure when you actually do it - You don t care about things in your everyday life Volkow, Fowler, et al. The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies. Neuropharmacology 2004;47:3-13.

16 Blue = mature state

17 Blue = mature state

18 Opioids

19 Definitions Opium = mixture of alkaloids from the poppy plant, Papaver somniferum Opioid = any naturally occurring, semi-synthetic or synthetic compound that binds specifically to opioid receptors; shares the properties of 1 or more of the naturally occurring endogenous opioids Opiate = any naturally occurring opioid derived from opium

20 Endogenous vs Exogenous Opioids

21 Opioid receptors/ligands µ (mu) -- endorphin ( endogenous morphine ) Addictive liability, euphoria, analgesia, miosis, respiratory depression, reduced GI motility K (kappa) -- dynorphin Dysphoria, psychedelic effects (salvia divinorum = kappa agonist), analgesia δ (delta) -- enkephalin Mood/euphoria, analgesia, convulsant effects NOP -- nociceptin, orphanin FQ Anxiety, depression, appetite, tolerance to µ agonists

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23 Classification of Opioids Traditional Origin Function Strong morphine fentanyl remifentanil Intermediate buprenorphine pentazocine butorphanol Weak codeine Naturally occurring morphine, codeine, papavarine, thebaine Semisynthetic oxycodone, hydrocodone, hydromorphone, buprenorphine Synthetic fentanyl methadone Tramadol Pure agonists morphine, fentanyl, remifentanil Partial agonist buprenorphine Agonists-antagonists pentazocine nalbuphine Pure antagonists naloxone naltrexone

24 Opioid Intoxication Euphoria experienced as a rush of intensely pleasurable feelings Reduced psychological pain: Anxiety, depression, anger, paranoid ideation/psychosis GI: nausea, vomiting, constipation Miosis (pinpoint pupils) Respiratory suppression

25 Opioid Withdrawal Dysphoric mood Nausea/vomiting Muscle aches Lacrimation Rhinorrhea Pupil dilation Pilorection Sweating Diarrhea Yawning Fever Insomnia

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27 A (Very) Brief History of Opioids Opium used for centuries 1800s: morphine isolated, needle/syringe invented 1898 = Heroin (Bayer) 1914: Harrison Narcotics Tax Act 1960s = Methadone maintenance 2002 = Buprenorphine (Suboxone, Subutex, etc)

28 Since that time

29 Admissions: 1999 Primary non-heroin opioid admission rates (per 100,000) 29

30 Admissions: 2001 Primary non-heroin opioid admission rates (per 100,000) 30

31 Admissions: 2003 Primary non-heroin opioid admission rates (per 100,000) 31

32 Admissions: 2005 Primary non-heroin opioid admission rates (per 100,000) 32

33 Admissions: 2007 Primary non-heroin opioid admission rates (per 100,000) 33

34 Admissions: 2009 Primary non-heroin opioid admission rates (per 100,000) 34

35 New York Times June 5, 2017 New York Times June 5 th, 2017 J Katz: Drug Deaths in America Are Rising Faster than Ever, NYT

36 March 2016

37 J Katz: Short Answers to Hard Questions About the Opioid Crisis, NYT

38 New York Times June 5, 2017 J Katz: Short Answers to Hard Questions About the Opioid Crisis, NYT

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40 Monitoring the Future Survey

41 Monitoring the Future Survey

42 Fentanyl: The New Kid on the Block J Katz: Short Answers to Hard Questions About the Opioid Crisis, NYT

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44 DEA Intelligence Brief, July Counterfeit Prescription Pills Containing Fentanyls: A Global Threat.

45 What about in New Jersey?

46 More than guns, car accidents, and suicides combined NJ.com: The death toll from drugs just reached a grim new high in NJ. July 21, 2017.

47 NJ.com: The death toll from drugs just reached a grim new high in NJ. July 21, 2017.

48 Treatment Admissions 1. Newark 2. Jersey City 3. Paterson 4. Camden 5. Atlantic City 6. Elizabeth 7. Toms River 8. Brick 9. Trenton 10. Vineland 11. Egg Harbor Township 12. Plainfield 13. Lacey 14. Jackson 15. Middletown 16. Millville 17. Old Bridge 18. East Orange 19. Asbury Park 20. Howell 21. Lower Township 22. New Brunswick 23. Keansburg 24. Edison 25. Woodbridge DMHAS, 2013

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50 1. Newark 2. Jersey City 3. Paterson 4. Camden 5. Atlantic City 6. Elizabeth 7. Toms River 8. Brick 9. Trenton 10. Vineland DMHAS, Egg Harbor Township 12. Plainfield 13. Lacey 14. Jackson 15. Middletown 16. Millville 17. Old Bridge 18. East Orange 19. Asbury Park 20. Howell 21. Lower Township 22. New Brunswick 23. Keansburg 24. Edison North Central South 25. Woodbridge

51 September 14, 2014 nj.com

52 90% in NJ from Colombia nj.com

53 How did we get here?

54 Porter and Jick, N Engl J Med, January 10, 1980.

55 Art Van Zee, MD. American Journal of Public Health, 2009

56 Marketing of OxyContin Sales force: risk of addiction less than 1% Starter coupon 7-30d supply: 34,000 redeemed nationally 1996: 316,000 Rx at $44 million : 14 million Rx at over $3 billion May 2007: Purdue Frederick Co. + 3 company executives: criminal charges of misbranding, $634 million in fines Purdue s own testing in 1995: 68% of oxycodone extracted from OxyContin when crushed

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58 CDC 2011

59 August 15, 2015

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61 The Opioid Epidemic Today Compton, NEJM, 2016.

62 Cicero et al 2014: The changing face of heroin use in the U.S. (JAMA)

63 Annual prescribing rates by overall and high-dosage prescriptions CDC 2017

64 How the Heroin Market Has Changed $3,500 $3,000 $2,500 $2,000 $1,500 $1,000 $500 $- "Retail" Price Per Pure Gram Source: National Drug Control Strategy--Data Supplement

65 So what can be done?

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67 Naloxone (Narcan ) High-affinity opioid receptor antagonist Inactive in absence of opioid Part of coma cocktail administered to unconscious patients for decades (in ED and by EMTs)

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70 Take-home naloxone kit

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73 Heroin users and overdose Many studies: >2/3 have witnessed o/d >1/2 have overdosed themselves Most o/d in company of others Applying ice or water Painful stimuli Shaking or trying to walk the victim Injecting salt and/or milk First aid (CPR or rescue breathing) in only minority Nearly 100% would like to call 911 if no risk from police Tracy, Melissa et al. (2005) "Circumstances of witnessed drug overdose in New York City: implications for intervention," Drug and Alcohol Dependence, 79:

74 Chicago Recovery Alliance Opioid overdose deaths

75 Ocean + Monmouth Counties: Narcan Pilot Program April 2014: Law Enforcement Narcan Program Funded by confiscated property from drug dealers First month: 10 reversals First reversal 3 days after training

76 NJ Prescription Monitoring Program Mandatory reporting as of March 2015 Data-sharing with multiple other states

77 NJ PMP Aware

78 Medication-Assisted Treatment (MAT) 1) Methadone Federally-regulated methadone maintenance programs (1960s) Decreases overdose deaths, improves psychosocial adjustment, reduces criminal activity, decreases rates of HIV/HCV mg daily 2) Buprenorphine Used since 2002 DATA 2000 Waiver allows office-based prescriptions 8mg BID 3) Naltrexone (or Vivitrol injection) Opioid antagonist (blocks receptor) 380mg IM q 4 wks

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80 Buprenorphine: Partial agonist

81 How buprenorphine works

82 Buprenorphine vs Methadone Buprenorphine has: - decreased risk of respiratory depression - relative safety in overdose - decreased sedation - more mild withdrawal symptoms (some patients disagree)

83 JAMA 2000 Is OMT better?

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85 JAMA 2000

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88 Lancet mg buprenorphine vs. 6-day taper and placebo

89 Mortality: 4/20 in placebo group, 0/20 in buprenorphine group

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92 Opioids are different Protracted abstinence syndrome à high relapse rates (we need our endogenous opiates) Overdose death most likely after period of abstinence Inpatient rehab Incarceration 129x more likely to die of drug overdose in first 2 wks s/p release from incarceration (Binswanger 2007)

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95 Schwartz, RP et al. Opioid agonist treatments and heroin overdose deaths in Baltimore, Maryland, Am J Public Health 2013.

96 Naltrexone and Vivitrol Naltrexone is a mu opioid antagonist Vivitrol (Naltrexone XR) is a monthly injection

97 Vivitrol 380mg IM every 4 weeks

98 Dunbar et al. Alcohol Clin Exp Res 2006;30:

99 What about our treatment system?

100 Across the U.S.

101 371 Facilities in NJ in 2016: Pharmacotherapy offered? SAMHSA: National Survey of Substance Abuse Treatment Services,

102 KnowAddiction.nj.gov

103 KnowAddiction.nj.gov

104 For those managing pain

105 JAMA, March 2017

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107 Thank you NJMS.Rutgers.edu/Psychiatry