Opioid Addiction Treatment ECHO

This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under contract number HHSH250201600015C. This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements

be inferred by HRSA, HHS or the U.S. Government.

Introduction to Opioid Use DisorderDevelopers/Contributers: Miriam Komaromy, MD, The ECHO Institute™

Joe Merrill, MD, University of Washington

R. Andrew Chambers, MD, IUSM, DirectorIU Addiction Psychiatry Training Program robchamb@iupui.eduThe 2 x 4 Model: A neuroscience based blueprint for the modern integrated

addiction and mental health Treatment System CRC press, 2018, New York. https://www.amazon.com/Model-Neuroscience-Based-Blueprint-Integrated-Addiction/dp/1498773052

Disclosures

Miriam Komaromy and Joe Merrill have no financial conflicts of interest to disclose

Dr. Chambers*Enfoglobe : Medical data analytics and education software *Indigobio : Biological Fluids testing and data analytics.*Proniras: Biotech start up/CNS active orphan drug development

What are opioids?

“Natural”, referred to as “opiates”

• Derived from opium poppy• Morphine, codeine, opium

Synthetic (partly or completely):

• Semisynthetic: heroin, hydrocodone, oxycodone

• Fully Synthetic: fentanyl, tramadol, methadone

“Opioid” refers to endogenous, natural and synthetic members of this drug class:Quite broad, generally any molecule active at brain opioid receptors

Opiates: natural and synthetics.

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Opioids

Heroin $50-200 K /kg 30-70% pure

Oxycontin:

Rx Street

10 mg $1.25 $5-20

80 mg $6.00 $65++

Morphine

codeine

methadone

fentanyl

heroin

oxycodone

hydrocodone

Buprenorphine

tramadol

Use of opiates for acute pain is one of the major miracles of modern medicine.

Dilaudid

Vicodin, LorcetLortab, Norco

6 -MAM

Codeine

Morphine

Heroin

Oxycodone(oxycontin, percoset, endocet, roxicet)

Oxymorphone(OPANA, Numorphan)

Methadone EDDP

Opioid Intoxication General Effects• Drowsy, sedated (“nodding”)• Speech and movement may be slowed• May appear confused or incoherent• May appear euphoric (“high”)• Pupils are constricted (“pinpoint”)

• Addiction• Pain relief (analgesia)• Cough suppression• Constipation• Sedation (sleepiness)• Respiratory suppression (slowed

breathing)• Respiratory arrest (stopping breathing)• Death

Opioid WithdrawalGenerally opposite of the above : Cold Turkey, increase Vitals, tremor

Sweating, crying, nasal discharge, agitation,dysphoria

Also kappa and delta opiate receptorsEndorphins (18+)

Prodynorphin

Proenkephalin

Proopimelanocortin

Dynorphins enkephalins(Substance P)

striatum

G protein mechanism…mu’s inhibit Adenylate cyclase and activate K+ channels (out of the cell)

Image from Neuropsychiatry, Fogel, Shiffer & Rao, 1993

MU RECEPTOR is primary Receptor active in analgesia,Addiction, Euphoria and CNS/respiratory depression

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Acute DA discharge has intracellular effects in the NAc

DA

DA DA

OPI

OPI

MU

D2

D2Gi

Gi

Adenylate cyclasecAMP

pKA

Inside a NAc neuron

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What does cAMP/PKA do in the Cell?

NucleusCytoplasm

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What does this mean for Neuronal Form and Function?

25 X

100 X

400 X

Axon

Apical dendrite

Basilar dendritic spines

Pyramidal cell bodymPfC

Li, Acerbo and Robinson, 2004 Europ J Neurosci

12Robinson et al. (2002) Synapse

Neuronal changes due to chronic morphine administration

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DSM-V: Substance Use Disorder (Addiction)Problematic pattern of use causing clinically significant impairment or distress within a year

including 2 or more of:

1. Escalation in amounts of drug or time spent using

2. Persistent Desire to quit and/or failed attempts to quit

3. Great time spent acquiring or recovering from the substance

4. Escalation of/ significant craving and desire to use

5. Recurrent use causes occupational , educational and family role failures

6. Recurrent use disrupts relationships

7. Recurrent use reduces or eliminates social, occupational or recreational activities

8. Recurrent use creates physical danger

9. Recurrent use persists despite knowledge that use is causing physical or mental health problems

10. Tolerance

11. Withdrawal

Motivational

Injury

Nicotine, alcohol, cannabis, cocaine, amphetamine, opiates (2-3 Mild, 4-5 Moderate, 6+ Severe)

Why Have Opioids Become Such a Big Problem in the US?

• 1990s: New norm that all pain should be eliminated• pain as the “5th vital sign”

• Pharmaceutical company promotion• Opioid over-prescribing• Diversion, and widespread non-medical use of opioids,

especially among youth• Heroin widely available and less costly• Limited access to medication treatment

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The Iatrogenic Opioid Addiction Epidemic

CDC, MMWR, 60:43 2011

-In 2010, narcotics were prescribed in the U.S. at levels equivalent to medicating every single adult with a 5 mg hydrocodone 6 x/day for a month.

-By 2008, an American adult is as likely to die from a prescription opioid overdose than either suicide or a motor vehicle accident.

?#2

?#1

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?#1 “Pseudoaddiction”“iatrogenic syndrome that mimics the behavioral symptoms of addiction” … in patients receiving inadequate doses of opioids forpain. A syndrome caused by doctors withholding opioids (due to fear of causing addiction) that must be treated with more

and higher doses of opioids. -(Weissman and Haddox, 1989)

‘Pseudoaddiction’ proliferated and was accepted widely in the medical literature, penetrating medical dictionaries, textbooks,

and being the subject of at least 224 peer-review publications. About 10% of this literature listed funding sponsorship by pharmaceutical companies (e.g. Purdue Pharma) that are the industry leaders in the manufacturing and saleof prescription opioids (oxycodone, meperidine, morphine, hydromorphone, oxymorphone, tramadol, etc.) - (Greene & Chambers, 2015, Curr Addiction Reports)

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“Follow the Money.”

‘Deep throat’ to Bob Woodward-- In “All the President’s Men” (1976)

PAIN As 5th Vital Sign, VA+ JAACHO Pain InitiativeSponsored by Purdue Pharm and other companies

?#2

Compton WM et al. N Engl J Med 2016;374:154-163

Age-Adjusted Overdose Death Rates Related to Prescription Opioids and Heroin in the United States, 2000–2014

Comptom N Engl J Med. 2016 Jan 14;374(2):154-63

What Can Primary Care Teams do to Address Opioid Use Disorder?

• Prevention: Responsible opioid prescribing (CDC Guideline 2016)• Includes 3 main principles:

• Use non-opioid therapies:• Use non-pharmacologic therapies and non-opioid pharmacologic therapies• Establish and measure goals for pain and function• Don’t routinely use opioids to treat chronic pain

• Start low and go slow:• Start with lowest possible effective dose• Start with immediate release, rather than long-acting• Only prescribe amount needed for expected duration of pain• Taper and discontinue if no improvement or risks of harms outweigh benefits

• Close follow-up:• Check prescription monitoring program and urine drug tests• Avoid concurrent benzos and opioids• Arrange treatment for opioid use disorder if needed

What Can Primary Care Teams do Besides Prevention to Address Opioid Use Disorder?

• Screening: detection and early intervention for risky use• Prevent diversion: close monitoring of patients on opioids, use of

prescription monitoring programs and urine drug screens• Harm reduction: overdose prevention, infection prevention through syringe

exchange and vaccination• Treatment: Medication treatment for Opioid Use Disorder is highly effective

in reducing relapse, overdose, and other harms. Behavioral treatments and peer support also help to prevent relapse.

• Address co-occurring medical, psychological, and social barriers to health

American Society of Addiction Medicine. (2011). Public Policy Statement: Definition of Addiction. Chevy Chase, MD: American Society of Addiction Medicine. Available at http://www.asam.org/docs/publicypolicy-statements/1definition_of_addiction_long_4-11.pdf?sfvrsn=2

Botticelli MA, Koh HK. Changing the language of addiction. JAMA October 4, 2016;316(13):1361

Broyles LM, Binswanger IA, Jenkins JA, et al. Confronting inadvertent stigma and pejorative language in addiction scholarship: a recognition and response.Subst Abus. 2014;35(3):217-21

Campbell G1, Nielsen S1, Larance B1, et al. Pharmaceutical Opioid Use and Dependence among People Living with Chronic Pain: Associations Observed within the Pain and Opioids in Treatment (POINT) Cohort. Pain Med. 2015 Sep;16(9):1745-58. doi: 10.1111/pme.12773. Epub 2015 May 22.

CDC Guidelines for prescribing opioids for chronic pain: United States 2016. https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm

Chambers, RA, The 2 x 4 Model: A neuroscience based blueprint for the modern integrated addiction and mental health Treatment System CRC press, 2018, New York. https://www.amazon.com/Model-Neuroscience-Based-Blueprint-Integrated-Addiction/dp/1498773052

References

CDC Opioid Overdose Informationhttps://www.cdc.gov/drugoverdose/epidemic/

Compton WM, Jones CM, Baldwin GT Relationship between Nonmedical Prescription-Opioid Use and Heroin Use. N Engl J Med. 2016 Jan 14;374(2):154-63. doi: 10.1056/NEJMra1508490.

Dart RC1, Surratt HL, Cicero TJ, et al. Trends in opioid analgesic abuse and mortality in the United States. N Engl J Med. 2015 Jan 15;372(3):241-8. doi: 10.1056/NEJMsa1406143.

Degenhardt L1, Bruno R2, Lintzeris N3, et al. Agreement between definitions of pharmaceutical opioid use disorders and dependence in people taking opioids for chronic non-cancer pain (POINT): a cohort study. Lancet Psychiatry. 2015 Apr;2(4):314-22. doi: 10.1016/S2215-0366(15)00005-X. Epub 2015 Mar 31.

Megan Crowley-Matoka, Somnath Saha, Steven K. Dobscha et al. Problems of Quality and Equity in Pain Management: Exploring the Role of Biomedical Culture (pages 1312–1324) Pain Medicine: 6 OCT 2009 | DOI: 10.1111/j.1526-4637.2009.00716.

Staton LJ, Panda M, Chen I, et al. When race matters: Disagreement in pain perception between patients and their physicians in primary care. J Natl Med Assoc 2007;99(5):532–8

US Department of Health and Human Services (HHS) Office of the Surgeon General, Facing Addiction in America: the Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC, HHS, November 2016.

Wright, ER, Kooreman, MA, Greene, M, Chambers, RA, Banerjee, A, Wilson, J (2014)”The iatrogenic epidemic of prescription drug abuse: county-level determinants of opioid availability and abuse” Drug and Alcohol Dependence,138, 209-215. PubMed PMID: 24679840.

Hackman, DT, Greene, MS, Fernandes, TJ, Brown, AM, Wright, ER, Chambers, RA (2014) “Prescription drug monitoring program inquiry in psychiatric assessment: Detection of high rates of opioid prescribing to a dual diagnosis population” Journal of Clinical Psychiatry 75(7): 750-756. PubMed PMID: 25093472. PubMed Central PMCID: PMC4401030.

Greene, MS, Chambers, RA (2015) “Pseudoaddiction: Fact or Fiction? An Investigation of the Medical Literature” Current Addiction Reports, 2:310-317.