Pain, Addiction & the Opioid Epidemic 2017

Presented by Stacy Seikel, MDMedical Director, RiverMend Health Center of AtlantaChief Medical Officer of Integrated Treatment, RiverMend Health

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About RiverMend Health

RiverMend Health is a premier provider of scientifically driven, specialtybehavioral health services to thosesuffering from alcohol and drugdependency, eating disorders,dual disorders and chronic pain.

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Introducing the RiverMend Health Portfolio of Recovery Programs

Founded on the belief that addiction and eating disorders are the nation’s most pressing healthcare challenges, we bring together the world’s preeminent experts and

a nationwide network of recovery programs to conduct evidence-based treatment, research and education.

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DISCLAIMER

Stacy Seikel, MD

• Medical Director, RiverMend Health Center- Atlanta

• Member: ASAM, GSAM, AMA, MAG, MAA

• Board Certified, Addiction Medicine, Anesthesiology

• Medical Review Officer (MRO)

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RiverMend Health CD Programs877-879-3312

• RMHC of Atlanta: Dr. Stacy Seikel PHP/IOP-Atlanta, GA

• Bluff Plantation: Dr. William Jacobs Detox/RTC/PHP-Augusta, GA

• Positive Sobriety Institute: Dr. Dan Angres Professional PHP/IOP, CAP-Chicago, IL

• Malibu Beach Recovery Center: Dr. Dave Baron Detox/RTC/PHP/IOP-Malibu & Brentwood, CA

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Dr. Mark Gold’s MonthlyAddiction Research You Can Use

• Dr. Gold reads > 100 peer reviewed addiction related articles, picks the best 10, summarizes and puts into context each month.

• Sign up at : addictionresearchnow.com

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OBJECTIVES

• Understand Pain & Addiction as Co-morbid Disease States

• Use the Prescription Drug Monitoring Program in Treating Patients with Pain and Addiction

• Review CDC Guidelines For Opioid Rx

• Understand Pharmacology of Methadone, Buprenorphine and Naltrexone for the Treatment of Opioid Use Disorders

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Oxycontin-Purdue And Opiate Epidemic

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PAIN

DEFINITION: an unpleasant sensory &

emotional experience associated with actual

tissue damage or described in terms of such

damage.

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Addiction

• … a primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing the development and manifestations. It is characterized by behaviors that include one or more of the following:

• Impaired control over drug use

• Compulsive use

• Continued use despite harm

• Craving

• (ASAM, 2001)

Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitryanalysis. Lancet Psychiatry. 2016;3(8):760–773. doi: 10.1016/S2215-0366(16)00104-8.

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Dopamine D2 Receptors are Lower in Addiction

Cocaine

Alcohol

DA

DA

DA DADA

DA

Reward Circuits

DADA DA

DA

DA

Reward Circuits

DA

DA

DA

DA DA

DA

Heroin

Meth

DA

Kwako LE, Momenan R, Litten RZ, Koob GF, Goldman D. Addictions neuroclinicalassessment: a neuroscience-based framework for addictive disorders. BiolPsychiatry (2016) 80:179–89.10.1016/j.biopsych.2015.10.024

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What Addiction Isn’t:

Physical Dependence

• Pharmacologic effect characteristic of opioids

• Withdrawal or abstinence syndrome manifest on abrupt

discontinuation of medication or administration of

antagonist

• Assumed to be present with regular opioid use for days-

to-weeks

• Becomes a problem if:

– Opioids not tapered when pain resolves

– Opioids are inappropriately withheld

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What Addiction Isn’t:

Tolerance

• Pharmacologic effect characteristic of opioids

• Need to increase dose to achieve the same effect or diminished effect from same dose

• Tolerance to various opioid effects occurs at differential rates

• Tolerance to non-analgesic effects often beneficial to patients (sedation, respiratory depression)

• Analgesic tolerance is rarely the dominant factor in the need for opioid

• Patients requiring dose escalation most often have a change in pain stimulus (disease progression, infection, etc.)

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Remember-

• Limbic system in overdrive

• Prefrontal cortex not working

• “You have to use to survive.”

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The Perfect Storm for Opioid Epidemic• Pain is the 5th Vital Sign-Joint Commission

• Big Pharma Marketing- Purdue & Oxicodone

• “Pseudo-Addiction” = Undertreated Pain

• Medicare- based hospital payments on low patient complaints scores (keep pain complaints low)

• Then………in 2017, one person dies every 10 minutes from opioid overdose and surpasses MVA as #1 preventable cause of death in the US

• US has 5.7% of world’s population and consumes 90% of world’s hydrocodone

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John Oliver---- Opioid Epidemic

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A call to action

• In 2016 the United States Office of the Surgeon General issued a report on the current state of addiction in America

• Large treatment gap: approximately 10% of individuals with SUDs receive treatment

• Many reasons for disparities in treatment, but lack of access is common

• Surgeon General’s report called for greater dissemination and implementation of all evidence based treatments

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Opioid Addiction

• Opioid addiction is a chronic, progressive, relapsing medical condition

• Profound neurobiological changes accompany the transition from opioid use to opioid addiction

• Pharmacologic treatments are effective in normalizing the neurobiological status, decreasing illicit opioid use, medical and social complications

Current Trends and Practices

• NIDA recommends that pharmacotherapy should be considered for every patient

• Even so, only ~15% of treatment facilities use evidence based pharmacotherapy

– Philosophy of treatment program

– Personal biases

– Lack of training

– Specialty of physician prescribing

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Treating Pain and Addiction

• All pain is real

• Emotions drive the experience of pain

• Opioids don’t always make chronic pain better

• Focus on improving function

• Expectations influence outcome

Mel Pohl, MD

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Opioid Therapy

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Adjunct Meds and Treatments

• NSAIDS- ketoralac (Toradol), naproxen, acetaminophen

• AED- pregabalin (Lyrica), gabapentin (Neurontin)

• SRI, SNRI- milnacipran (Savella), duloxetine (Cymbalta)

• Amitriptyline (Elavil)

• Topicals- local anesthetics, NSAIDS, etc

• Exercise, yoga, Pilates, meditation, hypnosis, acupuncture, TPI’s, ESI, RFA, FB, TENS unit, chiropractic care, massage

• 12 Step Recovery for Chronic Pain

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WE ASK A LOT OF OUR PATIENTS!!!

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CDC Guidelines for Prescribing Opioids for Chronic Pain

• Try non-pharmacologic and non-opioid treatment first

• Establish realistic pain and function goals

• Discuss risk/benefits

• Start short-acting not long-acting opioids first

• Use lowest effective dose

• Acute pain: prescribe 3 days worth or less

• Re-evaluate R/B at 4 weeks and every 3 months

• Offer Naloxone Rescue

• Check PDMP

• Drug test patients

• Avoid benzodiazepines with opioids

• Use buprenorphine or methadone for patients with pain and addiction (if absolutely needed)

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BENZODIAZEPINES

• Valium (diazepam)

• Xanax (alprazolam)

• Ativan (lorazepam)

• Klonopin (clonazepam)

• Dalmane (flurazepam)

• Serax (oxazepam)

• Librium (chlordiazepoxide)

• Benzo-like: Lunesta (eszopiclone), Ambien (zolpidem), Sonata (zaleplon)

• Soma (carisoprodol): a muscle relaxant that breaks down to meprobamate

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Benzodiazepines

• Opiates + Benzos = respiratory arrest and accidental OD

• Disinhibiting effects, like alcohol, can contribute to aggressive behavior (benzos

are alcohol in a pill form, binding to gaba receptor)

• Even short-term use at prescribed doses can be associated with an increased risk

for cognitive problems (amnesia is a side effect of benzos)

• Does NOT fix the depression, insomnia, &/or anxiety symptoms – “a temporary

bandaid”

• Tolerance develops and higher and higher doses are needed to get the same effect

• Eventually, they stop working, then there is physical dependence with no clinical

benefit

• Stopping benzos suddenly can result in seizures and death

• Asking someone with a substance use disorder to take a benzodiazepine as

prescribed is an unrealistic request, IMHO

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DON’T FEED THE BEARS!!!!!

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BENZO PRESCRIBER’S

WAITING ROOM

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Risk of OD

• 84% of all methadone related deaths had

benzos, sedatives or alcohol in their system

(2004, CSAT)

• 100% of buprenorphine related deaths had

benzos, alcohol or other sedative in their

system

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Methadone & Buprenorphine

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Methadone 101

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Federal laws governing addiction treatment

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Methadone and Pain

• Methadone may be prescribed for the treatment

of pain in any patient by any physician with a

DEA number

• This includes pain patients without addiction

and pain patients with a history of addiction

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Methadone for Addiction

• In order to use Methadone for Opioid

Addiction Therapy (OAT), one must obtain a

special federal license and be affiliated with an

opioid addiction treatment program, OTP,

(“methadone clinic”)

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Restrictions on OTP’s- Federal and State

• OTP’s- dispense methadone (do not prescribe it)

• Patients typically dose daily at clinic

• “Once a Day” dosing the norm

• Counseling & UDS required

• To deviate from above requires and “exception” from the State Methadone Authority” (SOTA)

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Methadone Induction

• Start Low - Go Slow

• 5 days until steady state obtained

• Peaks 2-3 hours after dosing

• See patients frequently to monitor for over sedation

• Consider dosing in office/clinic and observing the patient for 3 hours

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Methadone Induction

• Opiate intolerant- Day 1: 10mg-15mg max

• Opiate tolerance unknown- Day 1: 15mg max

• Opiate tolerant- Day 1: 25mg- 40mg max

• Increase every 5 days

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Methadone for pain and addiction

• Potent mu agonist

• Useful for addiction and pain

• Need federal license for addiction only management

• D isomer inactive but NMDA antagonist

• Long T1/2, good oral bioavailability

• Analgesic T1/2 4-8 hours

• 5 days to steady state

• Overdose potential great due to long T1/2

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Buprenorphine 101

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Buprenorphine:

• Federal law prohibits physicians from

prescribing methadone (or other DEA Schedule

II medications) for maintenance therapy or

opiate addiction* EXCEPT in a federally

licensed opiate treatment program (OTP) (this

includes methadone maintenance).

• 8 hour course and application for a DEA waiver

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Pharmacology: Partial Opioid Agonists

• Bind to and activates opiate mu receptor

• Increasing dose does not produce as great an

effect as does increasing the dose of a full

agonist (less of a maximal effect is possible)

• “Ceiling effect” on respiratory depression

• Example: buprenorphine

• Mu opioid receptor partial agonist

• Useful for treating opioid withdrawal or as maintenance drug

• “Ceiling effect”: blocks any extra opioids ingested

• Can be combined with naloxone as an abuse deterrent

• Requires a waiver to prescribe with limits on patients per physician

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Intrinsic Activity: Full Agonist (Morphine), Partial

Agonist (Buprenorphine), Antagonist (Naloxone)

-10 -9 -8 -7 -6 -5 -4

0

10

20

30

40

50

60

70

80

90

100

Intrinsic Activity

Log Dose of Opioid

Full Agonist

(Morphine)

Partial Agonist

(Buprenorphine)

Antagonist (Naloxone)

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Duration of Action

• Onset of action: 30 – 60 minutes (after SL administration)

• Peak effects: 1 – 4 hours

• Half-life ~24 to 36 hours or longer

• Analgesic half life 4-8 hrs

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Buprenorphine/Naloxone Combination

(Suboxone®, Zubsolv ,Bunavil)

• Addition of naloxone to buprenorphine to

decrease abuse potential of tablets/film

• If taken as medically directed (dissolve under

tongue), predominant buprenorphine effect

• If opioid dependent person dissolves tablet and

injects, predominant naloxone effect (and

precipitated withdrawal)

Probuphine

• 6 month implantable formulation of Buprenorphine

• Possibly comparable abstinence rates (non inferiority) to sublingual buprenorphine

• Cost $4950/6 months

Buprenorphine implants (probuphine) for opioid dependence. Jama. 2016;316(17):1820-1.Rosenthal R. (2017). Sensitivity analysis of a comparative trial of 6 month buprenorphine implants (probuphine) and sublingual buprenorphine in stable opioid-dependent patients. Drug and Alcohol Dependence. 171. p.e179.

Buprenorphine (and Methadone)

• Both improve abstinence and treatment retention (MTD>Bup)

• Both reduce transmission of Hepatitis C and HIV• Both are safe in pregnancy

• Methadone has better treatment retention rates• Buprenorphine has a less protracted Neonatal

Abstinence Syndrome • When either is stopped, relapse rates dramatically increase

Connery HS. Medication-assisted treatment of opioid use disorder: review of the evidence and future directions. Harvard review of psychiatry. 2015;23(2):63-75

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Perioperative Pain Management in

Buprenorphine Maintained Patients

• For anticipated moderate to severe pain- May stop

buprenorphine 3 days before surgery, and it’s business as usual

for anesthesiologist

• May need to bridge with tramadol or short acting opiate if they

have pain or withdrawal issues

• Or continue buprenorphine treatment and use higher than usual

doses of fentanyl or hydromorphone (Dilaudid) for peri-

operative pain management

• May increase dose of buprenorphine and use it in divided doses

for post-op pain management

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Chronic Pain in Patients taking

Buprenorphine

• Analgesic ½ life is 4-8 hours

• Usually need TID dosing

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REMEMBER:

These patients often have:

• high opiate tolerance

• low pain tolerance

Naltrexone/Vivitrol

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Naltrexone for Opioid Use Disorders and Alcohol Use Disorders

• Option for maintenance treatment to prevent relapse in opioid use disorder via opioid receptor blockade and anti-craving properties

• Opioid antagonist: prevents user from experiencing opioid intoxication or physiologic dependence with subsequent use

• Reinforces abstinence– Naltrexone- oral daily pill– Vivitrol-once a month injection

• Also used as anti-craving medication for Alcohol Use Disorders

Naltrexone

• Oral formulation has poor compliance rates, increased severity of relapse

• Less evidence for IM formulation (one RCT with open label extension for opioids)

• No abuse potential; does not decrease respiratory drive

Naltrexone for Alcohol Use Disorders

• Mu opioid receptor antagonist

• Variable effects in different studies

• Consistent findings of delays in returning to drinking after abstinence

• Reduction in heavy drinking days

• Available in IM formulation to improve compliance

Courtesy: NIAAA

Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: A systematic review and meta-analysis. Jama. 2014;311(18):1889-900.

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Naltrexone for Opioid Use Disorders

• Should not be used prior to the completion of a medically supervised withdrawal from opioids

• Naltrexone causes immediate precipitated withdrawal in an individual with active physical dependence to opioids

• Oral Naltrexone -must take med daily (high motivation)

• Injection-improves adherence-once monthly injection

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Adverse Effects and Cautions

• Few side effects- Nausea is most common

• Liver inflammation-rare and resolves with discontinuation of naltrexone

• Patients who discontinue antagonist therapy and resume opiate use should be made aware of risks (rapid loss of tolerance)

• LFTs should be checked prior to dosing, pregnancy test for females

• Naloxone Challenge test an option (“Suffering Does Not Improve Outcomes.”)

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Pain Management

• Patients should be advised to carry a card to alert medical personnel to the fact that they are taking VIVITROL or oral naltrexone

• In a situation requiring opioid analgesia, the amount of opioid required may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged

– A rapidly acting opioid analgesic which minimizes the duration of respiratory depression is preferred

• In an emergency situation in patients receiving VIVITROL, a suggested plan for pain management is

– Regional analgesia,

– Conscious sedation with a benzodiazepine and non-opioid analgesics, or

– General anesthesiaVIVITROL full Prescribing Information.

Alkermes, Inc.

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Naloxone

• Overdose reversal agent

• Opiate receptor antagonist

• Recently made available in Georgia without prescription via Standing Order from State

• In Georgia, anyone can purchase or use insurance to obtain from a pharmacy

• Please get one

Naloxone – “Narcan” for Overdose Reversal

• 1971- The standard of care for opioid overdose

• Naloxone hydrochloride, the active pharmaceutical ingredient in EVZIO, received FDA approvalin 1971. Over the next 40 years, injectable naloxone became the standard of care used by first responders and within the hospital setting

• 1996-Successful use in pilot programs

• 2013-SAMHSA Opioid Overdose Toolkit is published

• 2014-The first and only naloxone auto-injector, is approved by the FDA

• 2016-Narcan Nasal Spray approved for opioid overdose reversal

• FDA approves new hand-held auto-injector to reverse opioid overdoseFirst naloxone treatment specifically designed to be given by family members or caregivers

• The U.S. Food and drug administration today approved a prescription treatment that can be used by family members or caregivers to treat a person Known or suspected to have had an opioid overdose. Evzio (naloxone hydrochloride injection) rapidly delivers a single dose of the drug naloxone via a hand-held auto-injector that can be carried in a pocket or stored in a medicine cabinet.

• It is intended for the emergency treatment of known or suspected opioid overdose, characterized by decreased breathing or heart rates, or loss of consciousness.

• Evzio is injected into the muscle (intramuscular) or under the skin (subcutaneous). EVZIO (Naloxone Hydrochloride Injection)

Auto-Injector, 0.4 mg/0.4mL Naloxone Hydrochloride solution in a pre-filled auto-injector.

EVZIO is a take-home, hand-held, single-use auto-injector that may be used wherever opioids are present

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Naloxone Nasal Spray

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E-FORCSE

Georgia’s Prescription

Drug Monitoring

Program

(PDMP)

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E-FORCSE

• Legislation recently passed that will require prescribers to use it starting in January, 2018. Some other states already require this.

• Dispensers required to put in dispensing information

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Patient Advisory ReportsPAR

• Obtained in minutes

• Helps rule out doctor shopping

• Improves appropriate prescribing

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Where am I? Where do you want me to go?

Collection

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Take Aways

• Therapeutic alliance is the key-Most of the other stuff does not really matter much.

• Suffering does not improve outcomes.

• “We will not drop you into an abyss of suffering.”

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Dr. Mark Gold’s MonthlyAddiction Research You Can Use

• Dr. Gold reads > 100 peer reviewed addiction related articles, picks the best 10, summarizes and puts into context each month.

• Sign up at : addictionresearchnow.com

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Thank You

Stacy Seikel, MD

Medical Director of RiverMend Health

Center of Atlanta

sseikel@rivermendhealth.com

877-879-3312