Virginia Opioid Addiction ECHO*

Virginia Opioid Addiction ECHO* Project ECHO: July 27th *ECHO: Extension of Community Healthcare Outcomes

Agenda

Introductions Clinical Director Administrative Medical Director ECHO Hubs and Principal Investigator Clinical Expert VCU Team Mishka Terplan, MD, MPH, FACOG, FASAM Vimal Mishra, MD, MMCi Lori Keyser-Marcus, PhD Program Manager Practice Administrator IT Support Nanah Fofanah, MPH, CPH David Collins, MHA Vladimir Lavrentyev, MBA

Opioid Epidemic and Virginia At least 1,420 people died last year due to drug overdose Fatal drug overdose has been the leading cause of unnatural death in Virginia since 2013

Opioid Epidemic and Virginia SAMHSA Buprenorphine Treatment Practitioner Locator Data Project ECHO will likely build capacity and create access to high-quality addiction care at local communities

Statewide Administrator Academic hub Academic hub Academic hub Clinical hub will rotate every 12-16 weeks Bi-Weekly 2 hour tele-echo Clinics Every tele ECHO clinic includes a 30-minute talk followed by case discussions Talks will be developed and delivered by inter-professional experts in substance use disorder https://www.vcuhealth.org/explore-vcu-health/for-medical-professionals/project-echo

Clinical Directors Project ECHO Clinical Leadership Mishka Terplan, MD, MPH, FACOG, FASAM (VCU) Administrative Medical Director ECHO Hub and Principal Investigator Program Manager Practice Administrator IT Support Administrative Team Richard Lawrence Merkel, MD, PhD (UVA) Cheri W. Hartman, PhD (Virginia Tech Carilion) Vimal Mishra, MD, MMCi Nanah Fofanah, MPH, CPH David Collins, MHA Vladimir Lavrentyev, MBA

Benefits to Participating Clinicians Free continuing education credit Opportunity to present actual patient cases, in a de-identified format, and receive specialty input Addiction treatment training, including management of naloxone/ buprenorphine (e.g. Suboxone) Access to a virtual learning community for access to treatment guidelines, tools, and patient resources Professional interaction with colleagues with similar interest

Helpful Reminders Recording: By participating in this clinic you are consenting to be recorded. If you do not wish to be recorded, please email ProjectECHO@vcuhealth.org Protect Patient Privacy Participation and discussion is welcomed

Helpful Reminders Rename your ZOOM screen: Please rename your screen with your full name All participants are Muted during the call, Please Unmute yourself before speaking. If you have a question, use the hand-raised future in ZOOM or type your question in the Chat box. Speak to the Camera, avoid distractions and for ZOOM issues (such as echoing, audio level etc.), use the chat function to speak with the clinic IT team (Vlad)

What to Expect I. Overview II. Introductions III. Didactic Presentation IV. Case presentations I. Case1 I. Case summary II. Clarifying questions III. Recommendations II. Case 2 I. Case summary II. Clarifying questions III. Recommendations Lets get started! Didactic Presentation V. Closing and questions

Virginia Opioid Addiction ECHO: Didactic Presentation Open to all practicing and licensed M.D.s, D.O.s, and Community-based clinicians

Disclosures Dr. Mishka Terplan and Dr. Lori Keyser-Marcus have no financial conflicts of interest to disclose There is no commercial or in-kind support for this activity.

Objectives Compare and contrast the medications commonly used for treatment of Opioid use disorders including indications, side effects, and regulatory concerns Plan strategies to integrate medication for Opioid use disorders into practice

Pharmacotherapy for OUD Medications for the Treatment of OUD Presenter: Dr. Mishka Terplan

Not everyone who uses drugs becomes addicted

Heroin addiction is a disease a metabolic disease of the brain with resultant behaviors of drug hunger and drug selfadministration, despite negative consequences to self and others. Heroin addiction in not simply a criminal behavior or due along to antisocial personality or some other personality disorder

Why do people use opioids? Withdrawal Normal Euphoria To feel good Acute use To feel better Tolerance and Physical Dependence Chronic use

Maintenance Treatment for Severe Opioid Use Disorder Withdrawal Normal Euphoria Chronic use Maintenance

Overtime Addiction from Reward Seeking to Relief Seeking

Opioid Efficacy: Full Agonist, Partial Agonist, Antagonist 100 90 80 Full Agonist (Methadone) % Efficacy 70 60 50 40 30 20 10 0 Partial Agonist (Buprenorphine) Antagonist (Naloxone) -10-9 -8-7 -6-5 -4 Log Dose of Opioid

SAMHSA/CSAT TIP #40 page13 How does buprenorphine work? High affinity, but low activity at the mu opioid receptor Low activity is enough activity to TREAT WITHDRAWAL and REDUCE CRAVINGS Low activity results in a CEILING EFFECT Euphoria is unusual Overdose occurs only with other drugs of abuse Opioid dependent patients FEEL NORMAL High affinity means it is a BLOCKER, more active opioids can not stimulate the receptor in presence of buprenorphine Death Respiratory depression Euphoria Withdrawal relief Pain relief

Goals of medication treatment for opioid use disorder 1. Relief of withdrawal symptoms Low dose methadone (30-40mg), buprenorphine 2. Reduce opioid craving High dose methadone (>60mg), buprenorphine, naltrexone 3. Opioid blockade High dose methadone (>60mg), buprenorphine, naltrexone Target Blocking withdrawal Plasma BUP levels for target effects Plasma Concentration MOR binding >1ng/mL > 50% 4. Restoration of reward pathway Long term (>6 months) methadone, buprenorphine, naltrexone Opioid blockade > 2-3 ng/ml > 70%

How do buprenorphine + naloxone work? Buprenorphine has good sublingual and IV bioavailabilty but poor GI bioavailability Naloxone (Narcan) has good IV bioavailabilty, but poor GI and sublingual bioavailability The combination results in decreased abuse and diversion for IV use

Medication saves lives. People die when medication stops. ALL CAUSE MORTALITY RATE PER 1000 PERSON YEARS, IN AND OUT OF TREATMENT In Treatment Out of Treatment 4.3 9.5 11.3 36.1 BUPRENORPHINE METHADONE Sordo L, Barrio G, Bravo MJ, Indave BI, Degenhardt L, Wiessing L, Ferri M, Pastor-Barriuso R. Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of cohort studies. BMJ 2017 Apr 26;357:j1550.

Deaths per 100-person-years

Naltrexone Pure opioid antagonist Injectable naltrexone (Vivitrol ) Monthly IM injection FDA approved 2010 Patients must be opioid free for a minimum of 7-10 days before treatment Oral naltrexone Well tolerated, safe Duration of action 24-48 hours FDA approved 1984 2008 Cochrane Review No clear benefit in treatment retention or relapse at follow up over placebo Physicians > 80% abstinence at 18 months Outcomes NTX placebo Trial completion 53% 38% Abstinence at 24 weeks 90% 35% Change in craving score -10.1 0.7 Krupitsky E, et al. Lancet, 2011

Opioid Detox Outcomes Low rate of retention in treatment High rates of relapse post treatment < 50% abstinent at 6 months < 15% abstinent at 12 months Increased rates of overdose due to decreased tolerance So, how long should maintenance treatment last? Long enough O Connor PG JAMA 2005 Mattick RP, Hall WD. Lancet 1996 Stimmel B et al. JAMA 1977

Matching Patients to Pharmacotherapy The choice between methadone, buprenorphine or naltrexone depends upon: Patient preference - Past experience Access to treatment setting Ease of withdrawal Risk of overdose Care = Evidence-Based and Person-Centered

New Formulations

For patients stable on SL bupe for 7+ days 300 mg SQ/ month for 2 months followed by 100mg SQ/month (Increase monthly dose to 300mg for patients in whom benefits outweigh risks)

SQ Bupe Blockade Positron Emission Tomography (PET) study with SUBLOCADE in 2 subjects (one subject receiving 200 mg SC injections and one subject receiving 300 mg SC injections): 75 to 92% occupancy of the muopioid receptors in the brain was maintained for 28 days following the last dose under steady-state conditions.

SQ Bupe PK At steady state (generally achieved 4-6 months after starting therapy), average plasma buprenorphine concentrations with once-monthly Sublocade 100 mg are about 10% higher than those with 24 mg/day of sublingual buprenorphine tablets.

Efficacy

Cost

Diversion

Relative Risks/Strengths Diverted Opioids

Relative Risks/Strengths Diverted Opioids OxyContin Methadone Buprenorphine

Questions?

Reference Mattick RP, Breen C, Kimber J, Davoli M.,Buprenorphine maintenance versus placebo ormethadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD002207. DOI: 10.1002/14651858.CD002207.pub4.

Case #1

Case #2

Scheduled TeleECHO Clinics Bi-Weekly Fridays 12-2pm 1. May 18: Introduction to Opioid Use Disorder 2. June 1: Harm Reduction of Opioids 3. June 15: Counselling and Other Support for Treatment of Opioid Use Disorders 4. June 29: Introduction to Motivational Interviewing 5. July 13: Identifying Addiction in Primary Care 6. July 27: Medications for Treatment of Opioid Use Disorders

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