10/13/2019

1

Pain and Addiction Treatment—Best Practices

Kirk Moberg, MD, PhD, FASAMUnityPlace Illinois Institute for Addiction Recovery

Clinical Professor of Internal Medicine and PsychiatryUniversity of Illinois College of Medicine

Appalachian Addiction and Drug Abuse ConferenceMorgantown, WVOctober 18, 2019

Disclosures

• Dr. Moberg has disclosed no conflicts ofinterest.

Objectives1- Case studies on best practices for indication of opioids in chronic paintreatment, general characteristics, including toxicities and drug interactions.2- Case studies on risk assessment and tools, examination and evaluation ofthe pain patient.3- Case studies on the initiation and ongoing management of chronic painpatient treated with opioid based therapies, including treatment objectives;monitoring and periodic review; referrals and consultations; informedconsent; prescription of controlled substance agreements, urine screens andpill counts; patient education on safe use, storage and disposal of opioids;discontinuation of opioids for pain due to lack of benefits or increased risks;documentation and medical records.4- Describe and explain the epidemiology of chronic pain and misuse ofopioids including the economic social impact5- To describe the tactics and behaviors of best practices of suspected doctorshopping, drug seeking and drug diversion.6- Understand best practice methods for working with patients suspected ofdrug seeking behavior, diversion and other aberrant behavior

10/13/2019

2

Agenda• Chronic pain• The opioid epidemics• Opioid addiction• Chronic pain treatment

Agenda

• Chronic pain• The opioid epidemics• Opioid addiction• Chronic pain treatment

10/13/2019

3

Pain—anotherco-existing disorder

“ Pain is viewed as a biopsychosocialphenomenon that includes sensory, emotional,cognitive, developmental, behavioral, spiritualand cultural components. ” (IASP website)

“ Pain is whatever the experiencing person saysit is, existing whenever he says it does. ”(McCaffrey 1968)

“ An unpleasant sensory and emotionalexperience associated with actual or potentialtissue damage or described in terms of suchdamage. ” (IASP 1994)

7 | © ASAM 2013

Pain classification

Acute pain Less than three months

Chronic pain Three months or greater

Treede et al. A Classification of Chronic Pain for ICD-11. Pain. 2015;156(6):1003-1007.

But more importantly

Chronic pain Lasts longer than thenormal healing time.

Serves no biologicpurpose.

Treede et al. A Classification of Chronic Pain for ICD-11. Pain. 2015;156(6):1003-1007.

10/13/2019

4

CategoryPain Persistence (Last3 Months)

Pain Bothersomeness (LastTime You Had Pain)

Pain free No pain in last 3 months Not applicable

Category 1 pain

Definition Some days A little pain

Category 2 pain

Definition 1 Most or every day A little pain

Or

Definition 2 Some days Between a little and a lot

Category 3 pain

Definition 1 Some days A lot

Or

Definition 2 Most or every day Between a little and a lot

Category 4 pain

Definition Most or every day A lot of pain

Nahin. Estimates of Pain Prevalence and Severity in Adults: United States, 2012. J Pain. 2015;16(8):769-80.

Pain Prevalence

Nahin. 2015.

Pain Prevalence

10/13/2019

5

Nahin. 2015.

Psychological Impact

Nahin. 2015.

Disability

Nahin. 2015..

Accessing the Health Care System

10/13/2019

6

Pain is costly

All figures in $billion/year in 2010 dollars

$560 – $635ComparisonsCardiovascular disease—$309Cancer—$243Injury and poisoning—$205Endocrine, Nutritional and Metabolic disease—$127Gastrointestinal disease—$112Respiratory disease—$112

Gaskin & Richard. The Economic Costs of Chronic Pain in the United States. J Pain. 2012;13(8):715-24.

Pain is costly

Incremental health care costs of pain—$261 - $300 billion

Lost productivity due to pain—$299 - $334 billion

Gaskin and Richard. 2012.

10/13/2019

7

Agenda

• Chronic pain• The opioid epidemics• Opioid addiction• Chronic pain treatment

A Triphasic Epidemic

PrescriptionOpioids

Heroin Fentanyl

10/13/2019

8

SOURCE: CDC, Prescription Opioid Data

Prescription Opioids

Opioid Overdose US Prescribing Rate Maps. cdc.gov/drugoverdose/maps/rxrate-maps.html

<64.164.1-82.983-107.1>107.1

Prescriptions per 100 people—2016

126 96

47,600

WV

US2017

2014

81

Prescribing Rates (per 100 people)

2016 2017

Opioid Prescribing Rates & Overdose Deaths

833WV2017

https://www.cdc.gov/drugoverdosehttps://www.kff.org/state-category/health-status/opioids/

Opioid Overdose Deaths

10/13/2019

9

Past Year Misuse of Prescription Pain Reliever Subtypes amongPeople Aged 12 or Older: 2017

Bose et al. Key Substance Use and Mental Health Indicators in the United States: Results from the 2017 National Surveyon Drug Use and Health. 2018. samhsa.gov/data/

Heroin then…

Ciccarone. Heroin in Brown, Black and White: Structural Factors and MedicalConsequences in US Heroin Market. Int J Drug Policy. 2009;20(3):277-82.

…and now

10/13/2019

10

McCance-Katz. The National Survey on Drug Use and Health: 2017. US Department of Health and Human Services.

Fentanyl

Armenian et al. Fentanyl, Fentanyl Analogs and Novel Synthetic Opioids: A Comprehensive Review.Neuropharmacology. 2018;134:121-132.

10/13/2019

11

Lethal dose

McDermott. N.H. Medical Examiner: At Least 10 Overdose Deaths in 2017 Traced to Carfentanil. New Hampshire PublicRadio, July 13, 2017. nhpr.org.Callejas. Opioid Epidemic Part 2: Stronger and Deadlier. July 29, 2017. inmaricopa.com.

Agenda• Chronic pain• The opioid epidemic?• Opioid addiction• Chronic pain treatment

Opioid Use Disorder in the Past Year among People Aged 12or Older, by Age Group: 2017

Bose et al. Key Substance Use and Mental Health Indicators in the United States: Results from the 2017 National Survey onDrug Use and Health. 2018. samhsa.gov/data/

10/13/2019

12

The Cost of Opioid Addiction(2013 dollars)

$78.5 billion

Florence et al. The Economic Burden of Prescription Opioid Overdose, Abuse and Dependence In the United States.Medical Care. 2016;54(10):901-906.

The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States,2013.Florence, Curtis; Zhou, Chao; Luo, Feijun; Xu, LikangMedical Care. 54(10):901-906, October 2016.DOI: 10.1097/MLR.0000000000000625

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Publishedby Lippincott Williams & Wilkins, Inc.

But it’s more than opioids

10/13/2019

13

The Addictions“Certain People Use Certain Substances

in Certain WaysThought at Certain Times

to Be Unacceptableby Certain Other People

for Reasons Both Certain and Uncertain.”

Burglass & Shaffer. Diagnosis in the Addictions I: Conceptual Problems. Adv Alc Subst Abuse. 1984;3(1-2):19-34.

Substance Use Disorders in Perspective

• Substance Use Disorder—20.1 million• Alcohol Use Disorder—15.1 million• Alcohol Related Deaths—100,000 per year• Past month tobacco use—63.4 million• Tobacco Related Deaths—450,000 per year• Opioid Use Disorder—2.1 million

Ahrnsbrak et al. 2017.Tobacco Related Mortality. 2016. cdc.gov.Alcohol Facts and Statistics. 2017. niaaa.nih.gov.

It’s your fault

10/13/2019

14

Agenda• Chronic pain• The opioid epidemic?• Opioid addiction• Chronic pain treatment

False dichotomies

…or else what?

OR

10/13/2019

15

Depression, Catastrophic ThinkingInfluence Pain

Pain catastrophizing:predictor of pain intensity and interference

Depression:predictor for perceived disability

based on physical functioningBaxter et al. The Role of Psychosocial Factors in the Pain Experience: the Relationship Between Depression, Catastrophizingand Chronic Pain. Pain. 2016;17(4S):S97-S98.

Non-pharmacologic techniques

Cognitive BehavioralTherapy

MotivationalInterviewing

Mindfulness RelaxationTechniques

Chronic pain is not monolithic

10/13/2019

16

Highly COX-1Selective

Relatively COX-1 Selective

EquallySelective

Relatively COX-2 Selectivee

Highly COX-2Selective

Flurbiprofen Fenoprofen Aspirin Diclofenac MK-966(Refecoxib)

Ketoprofen Piroxicam Ibuprofen Etodolac SC-58635(Celecoxib)

Sulindac Indomethacin Meloxicam L-743,337

Ketorolac Nabumetone NS-398

Naproxen Nimesulide SC-58125

Oxaprosin 6-MNA

Tenoxicam

Tolmetin

Table 3. General Ranges of COX Isoform Selectivity of Currently Available NSAIDsand of COX-2 Selective Inhibitors in Development

Cryer & Dubois. The Advent of Highly Selective Inhibitors of Cyclooxygenase—A Review. Prosta-glandins &Other Lipid Mediators. 1998;56:341-61.

Case Discussion: Jacob

Jacob, a 30 year old man who sufferswith fibromyalgia.

What is the best opioid for him?

10/13/2019

17

Name Substance Class Mechanism ofAction

RecommendedDosage

Grade ofRecommen-dation

Amitriptyline TCA Inhibition of NEand 5HTtransporter (1);*

10-50 mg/day Weak for

Cyclobenzaprine TCA derivative 1; ** 10-40 mg/day Weak for

Duloxetine SNRI 1 20-120 mg/day Weak for

Milnacipran SNRI 1 100-200 mg/day Weak for

Pregabalin Anti-convulsant Modulation ofa2d subunit ofpresynaptic Cachannel (2);

300-450 mg/day Weak for

Gabapentin Anti-convulsant 2; increasedGABA turnover

1200 mg/day Weak for

Tramadol Opioid m agonist; 1 150 mg/day Weak for

*5-HT2A, 5-HT2C, 5-HT6, 5-HT7 receptor antagonism**5-HT2A receptor antagonism

GRADE system for making recommendations

modified from Schmidt-Wilcke & Diers. 2017.

Case Discussion: Jacob

Jacob, a 30 year old man who sufferswith fibromyalgia.

What is the best opioid for him?

What if he suffers with alcohol use disorder?

Gabapentin and Opioids

Low dose < 900 mg/dayModerate dose 900-1799 mg/dayHigh dose > 1800 mg/day

Gomes et al. Gabapentin, Opioids, and the Risk of Opioid-Related Death: A Population-Based Nested Case-ControlStudy. PLOS Medicine. 2017;14(10):e1002396.

10/13/2019

18

Gabapentin and Opioids

Low dose < 900 mg/dayModerate dose 900-1799 mg/day (1.56)High dose > 1800 mg/day (1.58)

Very high dose > 2500 mg/day (1.83)

Gomes et al. 2017.

Gabapentin and Opioids

Low dose < 900 mg/dayModerate dose 900-1799 mg/day (1.56)High dose > 1800 mg/day (1.58)

Very high dose > 2500 mg/day (1.83)

Age, opioid dose, other medications (pregabalin, SSRIs, other anti-depressants, benzodiazepines, other psychotropic drugs, long-actingopioids, methadone, buprenorphine), number of medications prescribed,alcohol use disorder, COPD, DM, Charlson index, number of opioidprescribers, number of pharmacies, NSAID use.

Gomes et al. 2017.

10/13/2019

19

Summary of 2016 CDC guidelines• Non-pharmacologic and non-opioid treatments preferred.• Establish treatment goals• Immediate release first• Lowest dose preferable; caution when exceeding 50

Morphine Milligram Equivalents• Avoid exceeding 90 MME• For acute pain only prescribe what is expected• Evaluate response to opioids one 1-4 weeks after initiation

for chronic pain• If benefits do not outweigh harms taper and discontinue

Frieden TR & Houry D. Reducing the Risks of Relief—The CDC Opioid-Prescribing Guideline. NEJM. 2016;374(16):1501-4.Dowell D, Haegerich TM, Chou R. CDC Guidelines for Prescribing Opioids for Chronic Pain-United States 2016. MMWRRecomm Rep. 2016;65(1):1-49.

Mitigate Risk

Refer for…

…Treatment

10/13/2019

20

Prescription Drug Monitoring Program

PDMP Outcomes

Opioid Prescribing Behavior (2/6)

Opioid Diversion and Supply (2/2)

Opioid Misuse (1/1)

Opioid Related Morbidity/Mortality (3/6)

Finley et al. Evaluating the Impact of Prescription Drug Monitoring Program Implementation: A Scoping Review. BMCHealth Serv Res. 2017;17(1):420.

10/13/2019

21

Non-fatal and Fatal Overdoses

Fink et al. Association Between Prescription Drug Monitoring Programs and Nonfatal and Fatal Drug Overdoses: ASystematic Review. Ann Int Med. 2018;168(11):783-790.

Evidence insufficient

even for heroin

Recent Use

Drug Screen ResultsOpiates present

A. FentanylB. MorphineC.NaltrexoneD.CodeineE. MethadoneF. BuprenorphineG.HydrocodoneH.MeperidineI. OxycodoneJ. 6-monoacetyl-morphineK.Propoxyphene

10/13/2019

22

Drug Screen ResultsOpiates present

A. FentanylB. MorphineC.NaltrexoneD.CodeineE. MethadoneF. BuprenorphineG.HydrocodoneH.MeperidineI. OxycodoneJ. 6-monoacetyl-morphineK.Propoxyphene

Case: Henry, UDT

Henry is 42 years old and was injured in an MVA several years ago.He underwent a THR with 2 revisions later on because of infectiouscomplications. He has been prescribed 40 mg oxycodone ER twice dailyand an “occasional diazepam.” He is switching primary care providers andpresents asking for an oxycodone refill.

He denies the use of any other drugs.

You order a UDT.

Case: Henry, UDT

10/13/2019

23

Case: Henry, UDT

He states,

“Your lab screwed up.It’s not my urine. I’ll doanother test right now.”

Case: Henry, UDT

EXAMPLES OF OPIOIDMETABOLISM

*6-MAM=6-Monoacetylmorphine

CODEINE MORPHINE 6-MAM* HEROIN

HYDROCODONE HYDROMORPHONE

OXYCODONE OXYMORPHONE

T½=25 – 30 Min T½=3 – 5 Min

POPPY SEEDS

10/13/2019

24

“ OK, doc. I did use cocaine twice.Once on Jan 1 and once on Feb 1. Noother times.”

What is going on?

What do yourecommend?

Abuse deterrent opioids• Oxycodone/naloxone ER

– Targiniq ER®• Buprenorphine/naloxone

– Generic– Suboxone®– Zubsolv®– Bunavail®

• Morphine sulfate/naltrexone ER– Embeda®

• Oxycodone/naltrexone ER– Troxvca ER®

10/13/2019

25

Abuse deterrent opioids• Hydrocodone ER

– Hysingla ER®– Zohydro ER®– Vantrela ER®

• Hydromorphone ER– Embeda®

• Oxycodone ER* and IR**– *Oxycontin®– *Xtampza®– **Oxaydo®– **Roxybond® (4/20/2017)

• Morphine sulfate ER– Arymo ER®

2010

Cicero & Ellis. Abuse Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the United States LessonsLearned from OxyContin. JAMA Psychiatry. 2015;72(5):424-430.

Deprescribing

10/13/2019

26

Deprescribing

Deprescribing

DeprescribingWithdrawal Treatment

Clonidine/LofexidineDicyclomine

AntihistaminesAntiemetics

AntidiarrhealsNSAIDS

10/13/2019

27

Loperamide

St. Louis. Addicts Who Can’t Find Painkillers turn to Anti-Diarrhea Drugs. New York Times, 5/10/2016Eggleston et al. Loperamide Abuse Associated with Cardiac Dysrhythmia and Death. Ann Emerg Med. 2017;69(1):83-86.Katselou et al. “Poor Man’s Methadone” Can Kill the Poor Man. Extra-medical Uses of Loperamide: A Review. ForensicToxicology. 2017;35(2):217-231.

KratomMitragyna speciosa

Summary

• Chronic pain is pervasive and complex.

10/13/2019

28

Summary

• Chronic pain is pervasive and complex.• Opioids are not first-line medications for

chronic pain.

Summary

• Chronic pain is pervasive and complex.• Opioids are not first-line medications for

chronic pain.• Opioids can be prescribed safely.

Summary

• Chronic pain is pervasive and complex.• Opioids are not first-line medications for

chronic pain.• Opioids can be prescribed safely.• Opioid addiction is part of a larger epidemic.

10/13/2019

29