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Confronting the Opioid Epidemic:Office-Based Buprenorphine Treatment
Alain Litwin, MD, MPH
Vice Chair of Academics and Research
Executive Director, Addiction Research Center
Professor of Medicine, Department of Medicine
Prisma Health
University of South Carolina School of Medicine - Greenville
Clemson University School of Health Research
February 1, 2020
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Bayer Pharmaceuticals - Heroin
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Slide courtesy of Zibbell, CDC
More than 72,000 Americans died from drug
overdoses in 2017.
THE OPIOID EPIDEMIC
Wave 1: Pill Mills
A small number of physicians prescribed an outsized number of pills.
THE OPIOID EPIDEMIC
Wave 2: Heroin
Compton, N Engl J Med 2016;374:154-63
• Import from Mexican cartels• Marketing directly to suburban
white customers
• Heroin deaths on the rise
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THE OPIOID EPIDEMIC
Wave 3: Fentanyl
• 50 times more potent than heroin
• Manufactured in China and elsewhere
• Mixed with heroin and other drugs to increase “high”
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500% Increase in 2014Fentanyl-Related Deaths in Ohio
(Slide courtesy of Zibbell, CDC)
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Wave 4: Polydrug use including stimulants
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Case Study
• 33 yo female presents to Prisma Health Recovery Program – “having hard time stopping on her own” and “her best friend died of an overdose"
• Started using oxycodone in her late 20s followed by Norcos 10 mg
• 2 years ago, she started snorting heroin 1 gram daily to “get high” but lately using 2 grams daily just to feel “normal”. No injection drug use
• 2 part-time jobs (gas station clerk and waiting tables) - she has recently been showing up late to work and is worried that she may lose her jobs. Seeking and using heroin is becoming “full time job”
• High school graduate who used to enjoy hiking on weekends – has not hiked in 3 years
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Case Study
• Tried to quit “cold turkey” but has withdrawal symptoms (yawning, flu-like symptoms, and abdominal pain), and unable to quit long-term. Has quit 3 times over last 6 months the longest 1.5 days
• “Craves” using heroin when she is not using
• Verbal fights with mom who is always pleading for her to get help
• She reports unprotected sex with male partners who using heroin and - chlamydia 6 months ago
• Diagnosed with depression as teenager (on sertraline), and depression worse when she is recovering from heroin use
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Why Do People Use Opioids?W
ith
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Chronic use
Tolerance and Physical Dependence
To feel good
To feel better
Acute useSlide courtesy of Drs. Alford and Walley
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Defining Addiction
• Primary, chronic brain disease characterized by compulsive drug seeking and use despite
harmful consequences
• Involves cycles of relapse and remission
• 40‐60% genetic
• Without treatment addiction is progressive and can result in disability or premature death
American Society of Addiction Medicine. April 12, 2011. www.asam.orgNIDA. August, 2010. http://www.drugabuse.gov/publications/science‐addiction
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Defining Chronic Illness
• Long in duration—often with protracted clinical course
• Associated with persistent and recurring health problems
• Multi‐factorial in etiology, often heritable
• No definite cure
• Requires ongoing medical care
Goodman RA, et al. Prev Chronic Dis 2013;10:120239.Martic CM. Can Fam Physician. 2007 Dec; 53(12): 2086–2091.
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SUD Meets Criteria for Chronic Illness
• Common features with other chronic illnesses:
– Heritability
– Influenced by environment and behavior
– Responds to appropriate treatment
– Without adequate treatment can be progressive and result in substantial morbidity & mortality
– Has a biological/physiological basis, is ongoing and long term, can involve recurrences
https://archives.drugabuse.gov/about/welcome/aboutdrugabuse/chronicdisease/de long‐term lifestylemodificationhttp://www.asam.org/quality‐practice/definition‐of‐addiction
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Addiction Changes Brain Structure and Function
Healthy Brain
Decreased Brain Metabolism inAddiction
Diseased BrainDiseased Heart
Decreased Heart Metabolism in Coronary Artery Disease
Healthy heart
High
NIDA
Addiction Is a Brain Disease
• Drugs hijack brain reward circuits
• Develop tolerance and withdrawal
• Learned behavior “Habit”
THE OPIOID EPIDEMIC
Volkow, N Engl J Med 2016; 374:363-371 Lewis, N Engl J Med 2018; 379:1551-1560
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A Treatable Disease
NIDA. Principles of Drug Addiction Treatment. 2012. McLellan et al., JAMA, 284:1689‐1695, 2000 .
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Relapse & Chronic Disease
NIDA. Principles of Drug Addiction Treatment. 2012. McLellan et al., JAMA, 284:1689‐1695, 2000 .
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Single Screening Question for Drug Use (Smith et al, 2010)
• “How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?”
• Brief, validated in primary medical care settings• 93% sensitive and 94% specific for any drug use
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Single Screening Question for Alcohol Use (Smith et al, 2009)
• “How many times in the past year have you used have you had X or more drinks in a day?”• X is 5 for men and 4 for women• Response of ≥ 1 is considered positive
• Brief, validated in primary medical care settings• 82% sensitive and 79% specific for detection of
unhealthy alcohol use
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DSM V Criteria for Substance Use Disorder
• Loss of Control
▪ Larger amounts, longer time
▪ Inability to cutback
▪ More time spent, getting, using, recovering
▪ Craving
• Physiologic
▪ Tolerance
▪ Withdrawal
• Consequences
▪ Social or interpersonal problems related to
use
▪ Neglected major roles to use
▪ Activities given up to use
▪ Hazardous use
▪ Continued use after significant problems
• A substance use disorder
is defined as having 2 or
more of these symptoms in
the past year
• Tolerance and withdrawal
alone don’t necessarily
imply a disorder.
• Severity is related by the
number of symptoms.
2-3 = mild
4-5 = moderate
6+ = severe
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Medication Saves Lives
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Kakko et al. The Lancet, Volume 361, Issue 9358, 2003, 662 -668
Buprenorphine Maintenance More Effective than Detox + Counseling
• Buprenorphine Maintenance• 75% retained in treatment • 75% abstinent by toxicology
• Detoxification•0% retained in treatment •20% died
All Cause Mortality Rates In and Out of Methadone and Buprenorphine Treatment,1974-2016
THE OPIOID EPIDEMIC
All Cause Mortality rates per 1000
Methadone vs. No Rx11.3 vs. 36.1
Buprenorphine vs. No Rx4.3 vs. 9.5
Luis Sordo et al. BMJ 2017;357:bmj.j1550
Adjusted* Hazard for Opioid-Related MortalityBy Monthly Receipt of Treatment in Post-Overdose Period
THE OPIOID EPIDEMIC
*Adjusted for: age, sex, depression DX, anxiety DX, incarceration, detoxification, baseline opioid and benzodiazepine RX, and monthly post-overdose receipt of benzodiazepines, opioids, detoxification and short- and long-term residential treatment. LaRochelle, Ann. Int Med 2018
Massachusetts - Population Study
Buprenorphine
Methadone
0.3 (0.2-0.5)
0.5 1 2 3 4 5
Naltrexone
0.1
0.3 (0.2-0.6)
0.5 (0.1-2.1)
On Treatment
N=17,568
Buprenorphine
Medications for OUD Treatment
Goals• Alleviate physical withdrawal
• Opioid blockade
• Alleviate drug craving
• Normalized brain changes
Options• Naltrexone (opioid antagonist)
• Opioid Agonist Therapy
– Methadone (full opioid agonist)
– Buprenorphine (partial opioid agonist)
Buprenorphine Still Blocks Opioids as It Dissipates
Courtesy of NAABT, Inc. (naabt.org)
Imperfect Fit –Limited Euphoric Opioid Effect
Buprenorphine
Opioid
Empty Receptor
Withdrawal Pain
Receptor Sends Pain Signal to
the Brain
Perfect Fit - Maximum Opioid Effect
Empty Receptor
Euphoric Opioid Effect
No Withdrawal Pain
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What is Buprenorphine (Bupe)?• Bupe is an opioid partial agonist approved by the FDA in 2002 to treat
adults with opioid use disorder
• Lower potential for misuse (ceiling effect)
• Reduce withdrawal symptoms and cravings
• Lower risk of overdose
• Can be prescribed or dispensed in physicians offices, unlike methadone treatment
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Why Do People Use Opioids?W
ith
dra
wa
lN
orm
al
Eu
ph
oria
Chronic use
Tolerance and Physical Dependence
To feel good
To feel better
Acute useSlide courtesy of Drs. Alford and Walley
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Opioid Agonist Maintenance Treatment for Moderate - Severe Opioid Use Disorder
With
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Chronic use Maintenance
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Who is Eligible for Bupe Treatment in Primary Care?
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ELIGIBILITY CRITERIA
• Age > 18 years able to consent for medical and substance use treatment
• Diagnosed with an opioid use disorder by DSM-5 criteria and desiring pharmacotherapy
• Able to adhere with buprenorphine treatment program policies
• Currently receiving primary care or willing to start primary care at treatment clinic
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EXCLUSION CRITERIA
• Severe hepatic dysfunction (i.e. AST or ALT ≥ 5x ULN)
• Methadone or opioid analgesic doses exceeding levels allowing safe transition to buprenorphine (i.e. methadone > 30 – 40 mg
• Acute or chronic pain syndrome requiring chronic use of opioid analgesics
• Known allergy or hypersensitivity to buprenorphine or naloxone
• Active suicidal ideation
• Unstable or uncontrolled psychiatric disorders
• Impaired ability to provide informed consent (i.e. dementia, delusional, actively psychotic)
• Requires higher level of care than can be offered at primary care site (i.e. patient needs methadone maintenance or mental illness chemical addiction/MICA program)
• *DSM-5 criteria for benzodiazepine use disorder
• *DSM-5 criteria for alcohol use disorder
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Case Study
Is our patient eligible for buprenorphine treatment?
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What to Expect for Bupe Treament in Primary Care?
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Treatment Timeline
Initial Referral and Intake
Treatment initiation and stabilization
Treatment maintenance and monitoring
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Initial Evaluation
• Review substance use and psychosocial history
– Ascertain diagnosis of opioid use disorder
– Identify comorbid substance use, psychiatric disorders, social history,
housing or legal issues, adverse childhood experiences (ACEs) etc
• Identify comorbid medical conditions that need tailored management
– Screen for liver disease, HIV, viral hepatitis, TB, STIs (chlamydia,
gonorrhea, and syphilis), acute on chronic pain syndromes,
pregnancy
– Check for medications that may interact (CYP34A inhibitors)
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Substance Use History:
Patterns
▪ Substance use history:
• Ask about all substances:
− Nicotine
− Opioids: prescription opioids,
non-prescribed opioids,
heroin, fentanyl
− Alcohol, marijuana
− Hallucinogens,
sedative/hypnotics
(benzodiazepines),
stimulants, other
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Substance Use History:
Patterns▪ Substance use history:
• Age at first use
• Determine patterns of use over time:
− Frequency
− Amount
− Route
• Assess recent use (past several
weeks)
• Cravings and control:
− Assess temporality and
circumstances
− Determine if patient sees loss of
control over use
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Initial Evaluation• Obtain baseline urine drug screen
- Expect opiate positive
- Do urine results match patient’s self report?
• Review treatment agreement
– Adhere to follow up appointments
– No walk in or emergency refills
– Urine drug screens at each visit
– Complimentary or alternative treatment options may be
recommended
• Do not come to first visit in withdrawal!
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Treatment Agreements –
Example of Key Components
▪ Arriving at appointments punctually
▪ Courteous in the office
▪ Refrain from arriving intoxicated or
under the influence of drugs
▪ Agree not to sell, share, give any
medication to others
▪ Agree not to deal, steal or conduct other illegal or disruptive activities
▪ Medications will be provided during scheduled office visits
▪ Responsible safe storage of medications
▪ Agree not to obtain medications from other providers, physicians,
pharmacies, or other sources without informing my treating provider
▪ Agree to follow the prescription instructions
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Treatment Initiation & Stabilization
• Recommend initial Bupe dosage
• Office Induction scheduled or
• Home induction patient instructions provided
• Review treatment agreement
• Adjust Bupe dosage on follow up visits
• Relapse prevention counseling at each visit
• Urine drug screen at each visit
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Clinical Opiate Withdrawal Scale
(COWS)
▪ Resting Pulse
▪ Sweating
▪ Restlessness
▪ GI Upset
▪ Tremor
▪ Pupil Size
▪ Bone or Joint Aches
▪ Yawning
▪ Anxiety or Irritability
▪ Gooseflesh
▪ Runny Nose
or Tearing Eyes
Wesson and Ling, 2003
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Clinical Opiate Withdrawal Scale
(COWS)
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Buprenorphine Dosing: Efficacy
Ling et al., 1998
%
Wit
h 1
3 C
on
secu
tive
Op
iate
Fre
e U
rin
es
25
20
15
10
5
0
Buprenorphine dose (mg)
1
4
8
16
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Treatment Maintenance & Monitoring
• Review Bupe use history
• Identify cravings, triggers, relapses
• Tailor relapse prevention plan if appropriate
• Facilitate referrals if appropriate
• Urine drug screen to be expected at each visit
• Monthly visits
• Substance Use Counselor and/or Recovery Coach
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Case Study
• Our patient starts on buprenorphine with home induction and over the 1st
week increases to Suboxone (buprenorphine/naloxone 16 mg SL daily)
• At week 3, screening urine toxicology is positive for opiates and benzodiazepines
• She denies using heroin, prescription opioids, or benzodiazepines
• GC-MS is + for morphine (600 ng/ml) and codeine (16 ng/ml)
• GC-MS is negative for benzodiazepines
How do we interpret these urine toxicology tests?
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Examples of Screening and Confirmatory Tests
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Common Tests
Substances vary in the duration of time they remain detectable in urine. Below are approximate times for some common substances:
Moeller et al., 2017
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False Positives
▪ A number of substances can cross-react with common immunoassays and produce false positive results on screening tests
▪ Screening tests for amphetamines are most prone to false positive results, while those for cocaine metabolites are among the most specific
▪ Most false positive results can be distinguished by confirmatory testing, which will show absence of the tested substance. Exceptions include poppy seeds in opiate tests (discussed more later) and some over-the-counter nasal sprays in tests for amphetamines
▪ A few examples of false positives are shown on the next slide, but there are many more and published tables can be helpful, e.g. Mayo Clinic Proceedings92(5):774-796
Moeller et al., 2017
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Examples of False Positives
Moeller et al., 2017
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Poppy Seeds and Opioids
▪ Poppy seeds can contain codeine and morphine in amounts detectable on UDT after ingestion, including after eating poppy-seeded baked goods such as bagels or pastries
▪ Because morphine and codeine are actually present in the seeds, positive results due to poppy seeds are chemically indistinguishable from those due to use of opiates, even with confirmatory testing
▪ Hence, patients being tested for opioids should be advised to avoid poppy seeds and foods containing them, and abstinence from poppy seed-containing foods may be included as part of a treatment agreement in order to allow informative testing for opioid use
▪ Concentrations of codeine and morphine > 2000 ng/ml are generally considered to suggest opioid use rather than poppy seed ingestion
SAMHSA, 2012
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Testing for Opioids
▪ Common opioids and metabolites are interconverted during metabolism as shown below, so multiple products can be detected after use of a single opioid
▪ An additional metabolite, 6-acetylmorphine, is a specific marker of heroin use but is metabolized rapidly to morphine and detectable only for 8 hours or less after using heroin
Moeller et al., 2017SAMHSA, 2012
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Case Study
Our patient agrees to on-site counseling with substance use counselor (Phoenix Center) once a month.
However, she declines on-site group counseling and cognitive behavioral therapy (CBT).
She asks if counseling or other psychosocial interventions will help her?
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Psychosocially Assisted Pharmacotherapy
“Of all the treatments, opioid agonist maintenance
treatment is most effective… psychosocial services should be made available to all patients,
although those who do not take up the offer should not be
denied effective pharmacological treatment.”
http://www.who.int/substance_abuse/publications/opioid_depende nce_guidelines.pdf
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Buprenorphine and Counseling: Brief counseling by nurse plus weekly dispensing is as good as enhanced counseling and thrice weekly dispensing (NEJM, 2006)
AdjuvantPsychosocialRx/CBT
THE OPIOID EPIDEMIC
Risk Ratio: 1.03 (0.98-1.07)
Amato 2011 Cochrane Systematic Review
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Case Study
• On evaluation visit, our patient had negative urine pregnancy test
• Four weeks into treatment, she states she believes that she is pregnant. Repeat urine pregnancy test is positive
• She currently is maintained on Suboxone (buprenorphine/naloxone) 16 mg and doing well.
She wants to stop taking Suboxone or decrease the dose. How do you counsel her?
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Pregnancy – increase bupe dose and frequency
Mean Neonatal Morphine Dose, Length of Neonatal Hospital Stay, and Duration of Treatment for Neonatal Abstinence Syndrome
Jones HE et al. N Engl J Med 2010;363:2320-2331
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Case Study
Our patient is referred to the Prisma Health Magdalene Clinic; she has a successful pregnancy and delivers a healthy baby boy.
She has been in treatment now for 10 months, and asks if she can taper off the buprenorphine.
How do we counsel her about how long treatment should last?
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From: Primary Care–Based Buprenorphine Taper vs Maintenance Therapy for Prescription Opioid Dependence:
A Randomized Clinical TrialJAMA Intern Med. 2014;174(12):1947-1954. doi:10.1001/jamainternmed.2014.5302
Treatment Retention and Mean Buprenorphine Dosage for Patients With Prescription Opioid Dependence Patients were assigned to the taper or the
maintenance condition. Buprenorphine treatment was administered as a tablet formulation of buprenorphine hydrochloride and naloxone hydrochloride
in a 4:1 ratio.
Figure Legend:
DAT Recovery
with prolonged
abstinence from
methamphetamine
[C-11]d-threo-methylphenidate
Volkow et al., J. Neuroscience, 2001.
low
high
Normal Control
Methamphetamine Abuser
(1 month abstinent)
Methamphetamine Abuser
(14 months abstinent)
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Extended Abstinence is Predictive of Sustained Recovery
It takes a year of
abstinence before
less than half
relapse
Dennis et al, Eval Rev, 2007
After 5 years – if you are sober,
you probably will stay that way.
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How Long Should Treatment Last?Long Enough
“In most cases, treatment will be required in the long term or even throughout life. The aim of treatment services is not only to reduce or stop opioid use, but also to improve health and social functioning, and to help patients avoid some of the more serious consequences of drug use. Such long‐term treatment, common for many medical conditions, should not be seen as treatment failure, but rather as a cost‐effective way of prolonging life and improving quality of life, supporting the natural and long‐term process of change and recovery.”
World Health Organization http://apps.who.int/iris/bitstream/10665/4 3948/1/9789241547543_eng.pdf
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Increased Access to Narcan Saves Lives
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Date of download: 1/26/2020
Copyright 2019 American Medical Association.
All Rights Reserved.
From: Association Between State Laws Facilitating Pharmacy Distribution of Naloxone and Risk of Fatal
Overdose
JAMA Intern Med. 2019;179(6):805-811. doi:10.1001/jamainternmed.2019.0272
).
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Prisma Health Resources
• Prisma Health IMC Recovery Program
• Core Team: 2 NPs, 1 MD, 1 Substance Use Counselor, and 1 Recovery Coach
• Referrals• Epic – “IMC Recovery Program”
• Call Michelle Bublitz (NP) at 864-270-6087 or IMC clinic at 864-455-5848
• On-site MAT Training to obtain X License – prescribe buprenorphine
• April 1, 2020 and April 2, 2020
• Email: [email protected]