The National Opioid Epidemic The Scope of the Problem and Treatment for Teens and Young Adults Steven C. Matson, MD Chief, Division of Adolescent Medicine Nationwide Children’s Hospital

DISCLOSURE The speaker and members of the planning committee do not have a conflict of interest in this topic. There is no commercial support for this program.

Outline What is Addiction? Drugs that teens are using Epidemiology of opioid abuse General evaluation/treatment of opioid use disorder Medication assisted treatment Outcomes of treatment

Brain (Neurobiological) “Drug Abuse is a Chronic, Relapsing Brain (Neurobiological) Disease”

DA Concentration (% Baseline) In Search of the Dopamine High Food Sex 200 200 150 150 DA Concentration (% Baseline) % of Basal DA Output 100 100 Empty 50 Natural rewards stimulate dopamine neurotransmission. Eating something that you enjoy or being stimulated sexually can cause dopamine levels to increase. In these graphs, dopamine is being measured inside the brains of animals. Its increase is shown in response to food or sex cues. This basic mechanism of controlled dopamine release and reuptake has been carefully shaped and calibrated by evolution to reward normal activities critical for our survival. Box Feeding Female Present 1 2 3 4 5 6 7 8 60 120 180 Sample Number Time (min) Adapted from: Di Chiara, Neuroscience, 1999; Fiorino and Phillips, J Neuroscience, 1997. 6

Drugs of Abuse Increase Dopamine Levels Di Chiara and Imperato, Proc. Natl. Acad. Sci. USA,Vol. 85, pp. 5274-5278, July 1988,Neurobiology.

Drug Use Changes the Brain Weakens the Brain Dopamine System

Dopamine D2 Receptors are Lower in Addiction

U.S. Department of Health and Human Services (HHS), Office of the Surgeon General, Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS, November 2016.

The Three Stages of the Addiction Cycle Brain Regions Associated with Them

Definition of Addiction American Society of Addiction Medicine A primary, chronic disease of brain: Reward Motivation Memory and related circuitry. Dysfunction leads to pathological pursuit of reward or relief by substance use and other behaviors.

Definition of Addiction American Society of Addiction Medicine Like other chronic diseases, addiction often involves cycles of: Relapse and Remission Without treatment addiction is progressive and can result in: Disability or Death

Addiction is a Developmental Disease That Starts in Adolescence

90% of Those Hooked on Alcohol, Tobacco, or Drugs Started Using Them Before Age 18 25% of Americans who began using any addictive substance before age 18 are addicted. Only 4% of Americans who started using an addictive substance when they were 21 or older are addicted.

Trends in Lifetime Prevalence of Use of Various Drugs in Grade 12 2015

% of Ohio Students Who Used Cigarettes or Marijuana During The Past Month 2003‐2013

Changes in US High School Tobacco Use 2011 to 2015 Percent Using

12th Grade Substance Use Ohio 2013 2013 Ohio Youth Risk Behavior Survey (YRBS)

Overdose Death Rates In US Counties

Deaths per 100,000 Population 4 8 12 16 20 4 2003 2014 CDC/NCHS Nation al Vital Statistics System

U.S. Opioid Overdose Deaths 2014

2014 Opioid Overdose Death Rates per 100,000 Population (Age-Adjusted) West Virginia 31.6 Ohio 19.1 Kentucky 16.8

All Opioid Overdose Deaths 1999-2014 2,590 in 2015

Overdose Deaths by Drug Type 2014 Location Natural and Semisynthetic Opioids (e.g. oxycodone, hydrocodone) Synthetic Opioids, other than Methadone (e.g. fentanyl, tramadol) Methadone Heroin Total Opioid Overdose Deaths Kentucky 344 179 59 228 (31%) 729 Ohio 618 590 107 1208 (57%) 2106 West Virginia 363 122 35 163 (29%) 554

Ohio Overdose Deaths Unintentional drug overdoses caused the deaths of 3,050 Ohio residents in 2015 Highest number on record, compared to 2,531 in 2014. The number of overdose deaths increased 20.5% from 2014 to 2015 Fentanyl-related overdose deaths in Ohio more than doubled from 503 in 2014 to 1,155 in 2015

Fentanyl-Related Drug Overdoses, Ohio, 2012-15

Relative Potency Morphine Heroin: 3 times stronger Fentanyl 80 times stronger Carfentanyl 10,000 times stronger

Number of Opioid Doses Dispensed to Ohio Patients 2011-2015

Neonatal Abstinence Syndrome (NAS) Incidence Rates 25 States, 2012–2013 http://dx.doi.org/10.15585/mmwr.mm6531a2

Neonatal Abstinence Syndrome Ohio 2004-2014 Babies with NAS 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Recognizing Possible Drug Abuse Change in appearance New friends, secretive about the new peers Loss of interest in old hobbies/sports Lying about new interests and activities Demanding more privacy; locking doors; avoiding eye contact; sneaking around Money/valuables missing from home

Matching Significant Drug Abuse to Level of Treatment All patients require a full substance abuse assessment The assessment drives the level of care Alcohol Marijuana Best treatment for an patient with severe opioid use disorder: Residential placement Intensive counseling with Medication Assisted Treatment (MAT)

Progression of Use END Begin

Treatments for Opioid Use Disorder Non-Pharmacologic Residential Treatment Intensive Outpatient Programs 12-Step Fellowships Individual/Group/ Family Therapy Therapeutic community

Treatments for Opioid Use Disorder Pharmacologic Withdrawal/Maintenance Replacement therapy (MAT) Methadone Buprenorphine/Naloxone Withdrawal based treatment Supervised withdrawal (Comfort meds, Methadone, Buprenorphine) Opiate antagonism Naltrexone (PO/IM)

Why Choose Medication Assisted Treatment (MAT)? Relapse without MAT is high Opiate addiction has high cue response Exposure to opiates can rekindle addiction Cravings and preoccupation with use limit ability to develop coping skills MAT Without Psychosocial Treatment is Unlikely to Yield Good Results

Buprenorphine Treatment Goals Suppress withdrawal Block or decrease euphoric affect of illicit opiates Minimize/eliminate craving for opioids Decrease overdose/death Eliminate IV use/Risk HCV, HBV,HIV Improve function in all spheres of life

Benefits of Office Based Treatment Confidential, safe, effective in a doctor’s office Fits lifestyle: No daily clinic visits Stay local Avoid costly residential treatment Allows for parental involvement Quickly improves functional status: School Work Family and Other Activities

Dopamine-Addiction-Withdrawal 1. Opioids bind to mu receptors, dopamine released, causing pleasurable feelings to be produced. 2. As opioids leave the receptors, pleasurable feelings fade and withdrawal symptoms (and possibly cravings) begin. 3. Opioids continue leaving mu receptors until the person is in withdrawal.

Buprenorphine Treatment Buprenorphine attaches to the empty opioid receptors, suppressing withdrawal symptoms and cravings and producing a limited euphoria or "high “ 5. Buprenorphine attaches firmly to the receptors. At adequate maintenance doses, it fills most receptors and blocks other opioids from attaching.

What is the Medication? Buprenorphine Naloxone

Buprenorphine Formulations X

Generic Buprenorphine Longer acting forms coming

Integrating Substance Use Disorder Services and Mainstream Health Care Substance use, mental/medical disorders often interconnected Integrated services can be: Cost-effective Reduce intake/treatment wait times for those wanting help Integration can lead to improved health outcomes through better care coordination.

Medical Provider – Initial Visit Complete Substance Abuse Assessment Physical exam Injection track marks Murmur of endocarditis Abscesses Skin excoriations due to “picking” Hepatomegaly Signs of withdrawal

Medical Provider – Initial Visit Initial Laboratory Testing Screening for STI Gonorrhea, Chlamydia, HIV, RPR Hepatitis Panel Hep A IgM, IgG Hep B core antibody, surface antibody, surface antigen Hep C antibody, quantitative Hep C PCR If liver enlarged LFTs

Medical Provider – Initial Visit Review Urine Drug Screen Any presumptive positives are sent for MS/GC confirmation Review Prescription Monitoring Program (PMP) Report Required in Ohio to Document at Each Visit)

Medical Provider – Initial Visit Induction/Detoxification onto to BUP/NAL Determine last opioid use Most opioids clear system in 36-48 hrs Can start BUP/NAL 12-24 hrs after last use Methadone has longer half life and initiation of BUP/NAL is delayed until it clears the system

Medical Provider – Initial Visit Common induction dose is 16-4 mg daily 8-2mg sublingual film BID Can prescribe medications to help transition Ondansetron for nausea Clonidine for anxiety/withdrawal Trazodone 50-200 mg PO QHS for insomnia Imodium for diarrhea

Medical Provider – Initial Visit Home “lock down” – allow only school, work, rehab attendance Confiscate phone, delete contacts Explain proper medication technique Trusted adult hold BUP/NAL and give 1 film at a time to patient – observe each dose Keep BUP/NAL in lock box Save all empty film wrappers to return to clinic Warn that lost/stolen doses will not be replaced

Medical Provider Follow Up Visit Initially follow up every 7-10 days Visits Q 2 weeks for the first 2-3 months Once consistently attending treatment maintaining abstinence, visits every 3 weeks Finally, transition to monthly visits

Medical Provider Follow Up Visit Mental Health Assessment After 3-6 weeks of sobriety Mental health disorder vs. depression and anxiety associated with drug use Treating depression, anxiety, insomnia helps maintain abstinence ADD

Medical Provider Long Term Care Plan to have on lowest dose possible to maintain sobriety Once stable for 10-14 months consider taper Decrease by 2-0.5 mg BUP/NAL as tolerated Wean to 2-0.5 mg daily or every other day, then off – usually by 2-3 years Some patients may a need consistent dose for years/life to maintain sobriety

The Brain Takes Time to Heal 1 MONTH OF SOBRIETY 12 MONTHS OF SOBRIETY NORMAL

Medical Provider Long Term Care Stop taper if feeling vulnerable Increase if necessary in times of stress No rush to wean off ! Continue follow-up if off MAT

2009-2012

Tips to Improve Outcomes Welcome patients Minimal requirements to start Truthfulness over perfection Motivational interviewing Contingency management Decreasing BUP dose for chronic relapses or failure to engage in behavioral therapy Incentive programs Integrated care

 90% @ Second Visit  40% @ 4 months  37% @ 6 months  27% @ 1 year

Alternatives to SL Buprenorphine Methadone Vivitrol® (Naltrexone) Probuphine Depot-Buprenorphine

Emergency Overdose Protection