Challenges and Controversies Pain and Addiction Challenges and Controversies Mel Pohl, MD, FASAM Medical Director Las Vegas Recovery Center 1 1

5 Key Facts: All pain is real. Emotions drive the experience of chronic pain. Opioids often make pain worse. Treat to improve function. Expectations influence outcomes. 2

Pain Definition “An unpleasant sensory and emotional experience associated with actual or potential tissue damage ….” The International Association for the Study of Pain (Mesky,1979) 3

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Structural Remodeling How does acute pain become chronic pain? CNS Neuroplasticity Hyperactivity Structural Remodeling Sustained Activation Peripheral Nociceptive Fibers Sensitization Surgery or injury causes inflammation Peripheral Nociceptive Fibers Transient Activation Sustained currents CHRONIC PAIN ACUTE PAIN Woolf CJ, et al. Ann Intern Med. 2004;140:441-451; Petersen-Felix S, et al. Swiss Med Weekly. 2002;132:273-278; Woolf CJ. Nature.1983;306:686-688; Woolf CJ, et al. Nature. 1992;355:75-78. 5 5 5 Petersen-Felix S, Curatolo M. Neuroplasticity--an important factor in acute and chronic pain. Swiss Med Wkly. 2002;132(21-22):273-478. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140(6):441-451.

Pain is influenced by: Culture Context Anticipation and previous experience Emotional and cognitive factors 6

Pain Switchboard – Lower Threshold GENETICS TRAUMA N O C I E P T P A I N COMT Pain is what the patient says it is. Nociception does not necessarily translate directly into pain. There are a number of “switchboards” in the pain pathways from peripheral nociceptors to the brain, which can influence how much pain gets through to higher brain centres as well as the response to pain in the brain. For example the enzyme catechol-O- methyl transferase (COMT)… SEE APPENDIX # 16 IN HANDOUT FOR AN EXPLANATION. There are at least 20 splice variants of the Mu opioid receptor (MOR) which respond differently to the various opioids. The melanocortin-1 receptor (MC1R) has been recently discovered to predict responsiveness to Kappa opioids – as well as coding for red hair and freckled skin. One of the “hottest” areas in pain research today is the pharmacogenetics of pain. The response to many pain medications, such as gabapentin and pregabalin, is increasingly being found to be under genetic influence. Suffering, the net result of pain on the patient’s quality of life, is further influenced by psychosocial factors such as cognition (the meaning of the pain), emotions (most often depression) and the patient’s environment (family, work, etc). As clinicians, we are really in the business of treating suffering rather than just pain. 7 7 7

NORMAL PAIN RESPONSE 8 8

CENTRAL SENSITIZATION 9 9

So he feels two pains, physical and mental. “…When touched with a feeling of pain, the ordinary uninstructed person sorrows, grieves, and laments, beats his breast, becomes distraught. So he feels two pains, physical and mental. Just as if they were to shoot a man with an arrow and, right afterward, were to shoot him with another one, so that he would feel the pains of two arrows…” The Buddha 10 10

Chronic Pain Syndrome Pain > 6 months Depression, anxiety, anger, fear Restriction in daily activities Excessive use of medications and medical services Multiple, non-productive tests, treatment, surgeries No clear relationship to organic disorder 11

unless proven otherwise” Pain Assessment Scale: Clinical definition of pain: “Whatever the patient says it is... unless proven otherwise” 12 12

Reasonable Goals of Pain Management: Enhance Quality of Life!! Maintain function Improve function Reduce discomfort by 50% 13

Pharmacologic Non-Opioid NSAID’S, COX 2S Tricyclics, SNRI’S Anticonvulsants Muscle Relaxants— (AVOID SOMA/carisoprodol) Topicals 14

Promoting More Conservative Prescribing Think beyond drugs Practice more strategic prescribing Heightened vigilance regarding adverse effects Caution and skepticism regarding new drugs Shared agenda with patients Weigh longer-term broader effects Schiff GD, Galanter WL. JAMA. 2009;301(8):865-867. 15

Barriers to Conservative Prescribing Time pressure. Income bonuses linked to patient satisfaction. Industry-funded research promotes bias towards prescribing. Ethical qualms about withholding adequate pain treatment. Schiff GD, Galanter WL. JAMA. 2009;301(8,):865-867. 16

Treating Chronic Pain with Opioids Clinical Trial Ongoing Assessment Need exit strategy 17

Entry Strategy: Screening Before Prescribing SOAPP – Screener and Opioid Assessment for Patients in Pain (5, 14, and 24 items – 5 point scale) CAGE-AID Questionnaire (4 items) ORT – Opioid Risk Tool (5 items – weighted) Psychological/psychiatric screening Awareness of chemical coping styles Family history of addiction/mental illness Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14. Butler SF, et al. J Pain. 2008;9:360-372.

Ongoing Assessment 5 A’s PDMP’s Patient agreements Urine toxicology Affect Analgesia Aberrant behaviors Adverse effects Addiction PDMP’s Patient agreements Urine toxicology

EXIT STRATEGY Discuss options - continuation of conversation from entry Be consistent, supportive, informative, nonjudgmental and firm DO NOT BE PUNITIVE Gather resources for support Discuss detoxification options

Problems with Opioids Side Effects Tolerance and physical dependence Loss of function Perceive emotional pain as physical pain (chemical copers) Hyperalgesia 21

NEJM, Ballantyne & Mao Nov 2003 22

Pendulum Swings 23

80 mg pills of oxycodone (OxyContin) are being abused by increasing numbers of users. Users crush the time-release tablets to get the drug full force. The sensation is described as similar to a heroin rush. Diversion of the drug is fairly common. This drug originally came in 160 mg tablets, but the amount of abuse and number of overdoses caused by the 160 mg tablets caused the manufacturer pull them from the market. Image courtesy of the Drug Enforcement Administration OxyContin 80mg 24 24

So, by 2012: New Oxycontin® Formulation to Mitigate Abuse April 2010 1. Freeze Oxy or 2. Opana® New formulation added clumping substance making harder to liquefy for injection abuse or crush to circumvent the time release coating and snort to abuse. Reports of increasing number of Oxy addicts now turning to heroin addicts. Oxycodone Oxymorphone 25 25

Emergence of an Epidemic

Primary non-heroin opiates/synthetics admission rates, by State (per 100,000 population aged 12 and over) 27

Primary non-heroin opiates/synthetics admission rates, by State (per 100,000 population aged 12 and over) 28

Primary non-heroin opiates/synthetics admission rates, by State (per 100,000 population aged 12 and over) 29

Primary non-heroin opiates/synthetics admission rates, by State (per 100,000 population aged 12 and over) 30

Primary non-heroin opiates/synthetics admission rates, by State (per 100,000 population aged 12 and over) 31

Primary non-heroin opiates/synthetics admission rates, by State (per 100,000 population aged 12 and over) 32

U.S. Rates of Death from Unintentional Drug Overdoses Okie S. N Engl J Med 2010;363:1981-1985. U.S. Rates of Death from Unintentional Drug Overdoses and Numbers of Deaths, According to Major Type of Drug. Shown are nationwide rates of death from unintentional drug overdoses from 1970 through 2007 (Panel A) and the numbers of such deaths from opioid analgesics, cocaine, and heroin from 1999 through 2007 (Panel B). Data are from the National Vital Statistics System, Centers for Disease Control and Prevention. 33 33

U.S. Numbers of Deaths, According to Major Type of Drug. U.S. Rates of Death from Unintentional Drug Overdoses and Numbers of Deaths, According to Major Type of Drug. Shown are nationwide rates of death from unintentional drug overdoses from 1970 through 2007 (Panel A) and the numbers of such deaths from opioid analgesics, cocaine, and heroin from 1999 through 2007 (Panel B). Data are from the National Vital Statistics System, Centers for Disease Control and Prevention. U.S. Numbers of Deaths, According to Major Type of Drug. Okie S. N Engl J Med 2010;363:1981-1985. 34 34

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Hazard Ratio of Serious Overdose Dunn, et al. 2010 9940 patients; 1997-2005 Results: Morphine Dose Hazard Ratio of Serious Overdose None 0.19 1 - <20 mg /day 1.00 20 - <50 mg/day 1.19 50 - <100 mg/day 3.11 100 + mg/day 11.18 36

High Opioid Dose and Overdose Risk 11.18 3.11 1.19 1.00 This slide from Group Health shows the distribution opioid usage in a population being prescribed opioids with diagnoses of chronic pain. It therefore represents a population obtaining opioids by prescription for a legitimate reason. It shows that risk of overdose increased steadily with increasing dosage to nearly a nine-fold increase at dosages of 100+ mg/day. This suggests that a high-risk strategy concentrating on people getting higher dosages might be most cost-efficient for patients using opioids under medical supervision. People with dosages of 20+ mg/day represented only 21.7% of patients but accounted for almost half of the overdoses. * Overdose defined as death, hospitalization, unconsciousness, or respiratory failure. Dunn et al. Opioid prescriptions for chronic pain and overdose. Ann Int Med 2010;152:85-92. 37

Rates of prescription painkiller sales, deaths and substance abuse treatment admissions (1999-2010) SOURCES: National Vital Statistics System, 1999-2008; Automation of Reports and Consolidated Orders System (ARCOS) of the Drug Enforcement Administration (DEA), 1999-2010; Treatment Episode Data Set, 1999-2009 38

Industry-influenced “Education” on Opioids for Chronic Non-Cancer Pain Emphasizes: Physicians are needlessly allowing patients to suffer because of “opiophobia.” Opioids are safe and effective for chronic pain. Opioid therapy can be easily discontinued. Opioid addiction is rare in pain patients. 39

“Only four cases of addiction among 11,882 patients treated with opioids.” Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med. 1980 Jan 10;302(2):123 Cited 693 times (Google Scholar) 40

N Engl J Med. 1980 Jan 10;302(2):123. 41

Total Sales & Prescriptions for OxyContin (1996-2002) Source: United States General Accounting Office: Dec. 2003, “OxyContin Abuse and Diversion and Efforts to Address the Problem.” 2013 – US sales of Rx painkillers = $12 Billion (IMS Health) 42 42 42 42

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FDA used to permit drug manufacturers to advertise opioids as safe and effective for chronic pain. 44

Photo taken at the7th International Conference on Pain and Chemical Dependency, June 2007 45

Methadone (Dolophine, Methadose) Leading Cause of Rx OD Deaths 2010-2011

Heroin: making a big comeback since 2010! Texas “Cheese Heroin”: Black Tar Mixed with Tylenol PM Black Tar heroin

Medication Assisted Treatment Methadone Buprenorphine Naltrexone Naloxone 49

Suboxone tablets (RB)

Naloxone Handheld Device That Delivers Opioid Overdose Treatment Approved by FDA

ASAM Short Definition of Addiction Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors... 52

This is a false dichotomy Aberrant drug use behaviors are common in pain patients 63% admitted to using opioids for purposes other than pain1 Pain Patients “Drug Abusers” 35% met DSM V criteria for addiction2 92% of opioid OD decedents were prescribed opioids for chronic pain. 1. Fleming MF, Balousek SL, Klessig CL, Mundt MP, Brown DD. Substance Use Disorders in a Primary Care Sample Receiving Daily Opioid Therapy. J Pain 2007;8:573-582. 2. Boscarino JA, Rukstalis MR, Hoffman SN, et al. Prevalence of prescription opioid-use disorder among chronic pain patients: comparison of the DSM-5 vs. DSM-4 diagnostic criteria. J Addict Dis. 2011;30:185-194. 3. Johnson EM, Lanier WA, Merrill RM, et al. Unintentional Prescription Opioid-Related Overdose Deaths: Description of Decedents by Next of Kin or Best Contact, Utah, 2008-2009. J Gen Intern Med. 2012 Oct 16.

Emotional Intensifiers Guilt Anger – Resentments Loneliness Helplessness Fear 54

Cycle of Uncontrolled Pain and Fear Avoidance Behaviors FEAR FEAR Decreased Mobility Pain FEAR FEAR Social Limitations Altered Functional Status Diminished Self- Efficacy FEAR FEAR 55 55 55 55

Ways to reduce pain intensity Cognitive/Behavioral Therapy (CBT) DBT/ACT Attention/Distraction Control/Placebo effect Fear reduction 56

Reversal of Cycle of Fear and Pain Exercise Increased Mobility Pain Less Pain Improved Function Enhanced Self- Efficacy 57 57 57 57

Pain Pearls Conditioning Increases Pain. Pain Patients Are A Pain. Secondary Gain Prevents Getting Well. 58

Pain Recovery – Develop Balance Mental Emotional Physical Spiritual RESULTING CHANGES Relationships Positive actions and behaviors 59

Non-Medication Treatments at LVRC Exercise – Physical Therapy Chiropractic Treatments Therapeutic Massage Reiki Acupuncture Nutrition Individual + group therapy Mindfulness-Based Stress Reduction (Kabat-Zinn) Yoga - Chi Gong 60

5 Key Facts: All pain is real. Emotions drive the experience of chronic pain. Opioids often make pain worse. Treat to improve function. Expectations influence outcomes. 61

THANK YOU Mel Pohl, MD, FASAM 702-515-1373 mpohl@centralrecovery.com adaywithoutpain.com 62