China, eBay, & Lincoln’s Beard

Clinical Review of the Opioid Epidemic and Opioid Use Disorder

Outline

• Statistics of opioid epidemic

• Synthetic Opioids

• Addiction Treatment Models

• Treatment options

• Resources

CDC: Opioid Overdose Deaths

IMF: illegally manufactured fentanyl – laced with heroin, counterfeit pills, or cocaine

CDC: Overdoses Most common drugs involved in prescription opioid overdose deaths:

Methadone (pill form)OyxcodoneHydrocodone

Heroin Overdoses

CDC:Fentanyl Deaths in 2016:Up 540% in 3 Years (provisional data)

Worse than HIV

2000 2015

Increase in deaths from

Cocaine & meth use

(often involve opiates)

Deaths involving synthetic

opioids, mostly fentanyl,

jumped from

3,000 to 20,000 in 3 yrs.

More Overdose Data

• SAMHSA – 5/18: Research Letter, JAMA

• Overdoses involving synthetic opioids

• 2010: 14% of all ODs

• 2016: 46% of all ODs

• Suicides?

• Very challenging to ascertain

• Estimate 25% - 45% of all overdose deaths

Connecticut Data

• CT is in the top ten states for highest opioid-related overdose deaths.

• 2015: CT prescribers wrote 2.3 million Rxsfor opioid pain relievers, or 64.0 prescriptions for every 100 persons – 9.3 percent decline since 2013

– less than the national rate of 71 Rxs/100 persons

Synthetic Opiates

Question

• Where are the majority of synthetic opiates and designer drugs developed?

– A) US– clandestine labs in the Southwest (ie Breaking Bad)

– B) Mexico – highly organized drug cartel (ie El Chapo)

– C) China – chemists browsing old chemistry journals

– D) Middle East – corrupt pharmaceuticals

“Flatline, Drop Dead, Bud Ice”Fentanyl-laced heroin/cocaine/oxy

• New Haven, CT: public health emergency

– 6/23/16: ~20 OD, 3 deaths in 6 hours

– Seeking cocaine

• Cincinnatti: 174 OD in 6 days

• Pittsburgh: 22 OD in 10 days

• Massachusetts: 66% OD deaths in 2016

Fentanyl

• Fentanyl – 50-100x more potent than heroin

– Very fast-acting, victims OD w/ needle still in arm

• Colorless, odorless

• Per users:

– Looks concrete/gray (vs powder white)

– Tastes bitter

– Sometimes identified by stamp –ladybug

• Laced blotter paper

Question:Can you spot the fake??

A. B.

Courtesy of California Poison Control, San Francisco DivisionHydrocodone vs fentanyl/promethazine/cocaine

Legal Illegal

Profits for Traffickers

• 1 kilogram of Fentanyl costs $2,000-$3000.

Cutting supply does NOT stop addiction.

Carfentanil

• Analog of fentanyl

• 10,000x more potent than morphine

• 100x more potent than fentanyl

• Schedule II narcotic, not intended for human use

• Used to tranquilize elephants and other large mammals – Wildnil

• Lethal amount – 2mg

– Lincoln’s beard on penny

Carfentanil• Case report of veterinarian splashed in face

– Drowsy within minutes and required narcan

• Transported from China and Mexico

• Confirmed cases in several states

• First responders, law enforcement

– Must wear protective gear

– Require several doses of Narcanto revive

• Urine Drug Screen $$$

Black Tar vs White Powder Heroin

GumsCheekingBodypacking

Non-narcotic Drugs of Abuse/Cocktails (often taken with opiates to augment euphoria)

• Gabapentin – next slide• Pregabalin (Lyrica)

• Controlled substance, Schedule V

• Clonidine– Similar to BZD high

• Promethazine– Often used in conjunction w/ opiates for euphoria

• Loperamide (Imodium)– High doses can cause euphoria– Serious side effects

Gabapentin• Controlled substance, schedule V

– Kentucky is the first state

– Several states now report on PMP

• Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study - T Gomes et al, PLoS 10/3/2017

– Canada, 1997 – 2013

– Cases defined as opioid users who died of an opioid-related cause

• Concomitant gabapentin and opioid exposure– associated with a 49% higher risk of dying from an opioid overdose

– Seen w/moderate (900 - 1,799mg daily) and high (>1,800mg daily) gabapentin doses

Addiction Treatment Models

• Harm reduction– set of practical strategies and ideas aimed at reducing negative

consequences associated with drug use– a movement for social justice built on a belief in, and respect for the rights

of people who use drugs– Moderation Management

• Abstinence – complete cessation of alcohol and drugs.

• Individualized approach– Safety sensitive occupations

• Healthcare professionals• Airline pilots• Construction

– Risk/benefit ratio

Changing the Language of Addiction

Psych – “schizophrenic”

Med – “diabetic”

• JAMA October 2016• Case vignette – substance abuser vs person with SUD• Punitive vs therapeutic measures

“Addict” “Dirty” or “clean” urine“Alcoholic” “Crackhead”

Changing the Language of Addiction

• Office of Drug Control and Policy• Draft – guidance on how to do this

• Clinical, non stigmatizing language• First person language

• Less shaming words

• National Press Foundation

• Pts often refer to themselves with these terms• Teaching opportunity

“Addict” vs person who uses drugs (PWUD)“Alcoholic” vs someone who has alcohol use disorder“Crackhead” vs someone who uses cocaine

“Dirty” or “clean” urine vs positive or negative for…“Abuse” vs misuse

DSM-5 Criteria for Opiate Use Disorder

11 Criteria –Presence of at least 2 for OUD

• Missing work or school

• Using in hazardous situations

• Using despite social or personal problems

• Craving for opiates

• Build up of tolerance

• Withdrawals when trying to quit

Mild: 2-3; Moderate: 4-5; Severe: 6 or >

• Using more than intended

• Trying to quit without success

• Increased drug-seeking behavior

• Interference with important activities

• Continued use despite health problems

Medication Assisted Treatment and other Tx considerations

MAT: Pharmacotherapy plus counseling and behavioral therapies

MAT for Opiate Use Disorder – Options

Buprenorphine/naloxone – 1st • Partial opioid agonist• Ceiling effect – resp depression,

sedation• Films/Pills/Implantable• Office based tx – requires federal

waiver to Rx• Stable pts – no poly drug use,

support system in place, psychiatrically stable

• MUST be in withdrawal to start• Robust data to support efficacy

Methadone maintenance (MMTP) – 1st• Full opioid agonist• Higher risk for OD, sedation• Liquid form, daily dosing• Federally qualified OTP (opiate tx

program)• Highly regulated, structure • Counseling mandated• Pts in need of monitoring, lack of

support system, psychiatrically unstable, Failed bupe

• Withdrawal not necessary to start • Robust data to support efficacy

Naltrexone – 2nd• Opioid blocker• NO risk for OD from Nal; risk

trying to override blockade• Pill or injection (Vivitrol)• Office based • Pts w/cravings, not experiencing

withdrawal, not currently using• Stable pts - no poly drug use,

support system in place, psychiatrically stable (? for pts who have failed MMTP/bupe)

• MUST be in withdrawal to start• Limited data

Opiate replacement treatment is associated with reduced mortality, lower HIV transmission, improved social functioning, and reduced criminal behavior.

Naltrexone• Not a new drug, but –

• increase in marketing for OUD: “non-addictive medication”• gaining interest from patients

• FDA approved for OUD, NOT 1st line • FDA approved for AUD, 1st line• Not FDA approved for other SUDs

• FDA approved for weight loss: Contrave (nal/buproprion)• Off label for self-injurious behavior

• Oral formulation – daily dosing• Extended release

– Injection: monthly– Implant: 2 months (not FDA approved)

Naltrexone for OUD

• Opiate Use Disorder – approved 2010 • Mu - opiate receptor antagonist

– Blocks exogenous opiates; blocks endogenous opiate peptides– prevent the increased dopamine release pleasurable reinforcing effects of drugs

• Clinically: – Help with cravings– Relapse prevention

• Oral formulation (50mg daily): poor adherence, high dropout rate, increased mortality

• Injectable XR (monthly): decent amount of studies have shown efficacy vs placebo/TAU• Incarceration – data supporting use; methadone/bupe not options

XR Naltrexone vs Buprenorphine JAMA Psychiatry 10/18/17

Open-label, randomized clinical trial x 12 wksN=159, (Norway)

Primary Outcomes

– Retention in study

– # of UDTs negative for illicit opiates

– # of days of heroin/illicit opiate use

Secondary Outcomes

– # of days of THC, amphet, cocaine, BZDs, EtOH

– # of days of injecting

– # degree of opiate cravings

– Life/treatment satisfaction

– Mental health

XR Naltrexone vs Buprenorphine • Noninferior to buprenorphine/naloxone

– Primary outcome results:

• retention rate

• # neg UDTs

• # days of OPI use

– Secondary outcome results:

• significantly less heroin craving

• significant reduction in BZD use

• significantly higher life/treatment satisfaction

• Can we extrapolate this to US population?

–Enrollment followed detox–Avg buprenorphine dose ~ 11mg–No follow up data re: overdose after stopping the medication

XR Naltrexone Guidelines

• SAMHSA - Clinical Use of Extended-Release Injectable Naltrexone in the treatment of OUD: A Brief Guide

• Office based addiction tx

– Comprehensive tx approach

• Counseling

• Psychiatric treatment as needed

• Social support: AA, NA, mutual-help programs

Ideal Candidates

• S/p opiate detoxification– No withdrawal sxs– Co-occurring alcohol use disorder– Short or less severe addiction history– Highly motivated:

• Professionals demonstrate sobriety to licensing boards, criminal justice officials– HCP, attorneys, pilots

• Agonist therapy for professionals is banned in some states

– Unsuccessful tx with buprenorphine or methadone • Depends on reason for failure

– Successful tx with agonist – but would like ‘more freedom’

Not Ideal Candidates

• Unable to complete/tolerate w/d

• PAWS: post acute withdrawal syndrome – see next slide

• Unstable psychiatric sxs

• Chronic pain which requires opioid tx

• Advanced liver disease, impending liver failure, acute hep

– Tolerated in stable chronic HBV, HCV, elevated LFTs

Post-acute withdrawal syndrome (PAWS)

• 4-8 weeks after detox; may last 6-12 months• Less physical sxs, more psychological sxs

– Insomnia, irritability, anxiety, mood changes, memory issues, anhedonia – Seen BZDs, EtOH, OPI, stimulants

• Impairment in reversal learning“WHEN I USE DRUGS I FEEL GOOD”

needs to change to“WHEN I USE DRUGS BAD THINGS HAPPEN”

– Inability to adapt to new understanding – Involves dopamine and glutamate

• Lack of evidence to support DSM-5 diagnosis

XR Naltrexone

• 380mg IM injection

• Gluteal muscle every 28-30 days

• 2 peak levels following injection

– 2 hours after

– 2-3 days later

• After 14 days, blood level slowly declines in linear fashion

• Reach steady state at the end of the first dosing interval

Contraindications/Warnings

• Hypersensitivity reactions

• Hepatotoxicity

• Depression/suicidality – relative

• Precipitated opioid withdrawal

– More severe than natural withdrawal

• Overdose may result from trying to overcome the opiate blockade

Warning: Opioid Overdose

• No comprehensive mortality data yet available for injectable

• Cases of fatal opioid overdose have been reported in pts who:

– Used opioids at or near the end of the 1-month dosing interval.

– Used opioids after missing a dose

– Attempted to overcome the opioid blockade

– Upregulation of opioid receptors increases sensitivity to opiate effects

• 1/3 of pts will “test” blockade, within 1-2 days after 1st injection

• Very few patients try to intentionally “override the blockade”

How to Prescribe

• Opiate free for 7-10 days– 2 weeks for bupe or methadone

• Screen – LFTS, renal function then Q6-12 mos

• Rec Check 3-4 months • LFTs increase mild and self-limiting, resolves with

continuation

– UDS w/ethyl glucuronide, HCG• Then random UDS

• Check PMP

• Tolerance test -PO naltrexone for 2 wks– Some insurance dictates 30 day trial with

compliance failure

• Challenge test– Narcan dose and/or po challenge test: 25mg

naltrexone, wait 1 hour

• Injection: upper outer quad of gluteal region, alternate side monthly– Physician, Nurse, or PA can administer

• Housekeeping items– Ordered via specialty pharmacy

– Delivered to clinic

– Stored in fridge– F/u medication monitoring can be

billed/performed by an RN.

Length of Pharmacotherapy??

• Highest risk of relapse follows detox – first 30-90 days

• Beyond 90 days– Very individualized

• Safe to stay on indefinitely – Side effects of MAT fairly minimal

• Pts request to stop– Stable

– Buprenorphine/methadone• Slow taper recommended

Long term treatment results in higher rates of recovery

Acudetox

• Evidence

• reduce: cravings for alcohol, drugs, nicotine, sugar, withdrawal symptoms, relapse episodes, anxiety, insomnia, and agitation.

• Auricular points

– 5 points in the ear

• Needles vs seeds

– Vaccaria plant

5 Points -Ear

• ShenMen (Heavenly Gate) –calms the spirit, helps decrease anxiety, insomnia and pain.

• Sympathetic – balances the sympathetic nervous system, calms the fight/flight response.

• Kidney – addresses the emotion of fear.

• Liver – detoxifies and unblocks stuck energy (both emotional and physical), addresses the emotion of anger.

• Lung – “let go,” associated with the emotions of grief and sadness.

Prescription Heroin

• Canada, Europe (UK, 1926)• Diacetylmorphine • Clinics with “Injection rooms”• better health outcomes, reductions in drug-related crimes, and

improvements in social functioning - stabilized housing and employment– sharp drops in street heroin use among people in the treatment.

• Insite : Vancouver, BC; 1st injection site in NA. – Exemption from prosecution under Canadian federal drug laws

• SPOT Clinic – Boston Healthcare for the Homeless

Comprehensive Treatment Approach

• Counseling

• Psychiatric treatment as needed

• OUD suicide risk: 10% vs 1.3% in the gen population

• Social support: Alcoholics Anonymous

Narcotics Anonymous

Refuge Recovery

Recovery Yoga

Mutual-help programs

Naloxone (Narcan)• Opiate antagonist – reverses opiate overdoses

– Nasal spray

– Intramuscular injection – auto injector

– Nasal atomizer

– Takes effect within 2-5 min, lasts 45-90 minutes. Rare side effects

• Fentanyl often needs multiple, consecutive doses

– PrescribeToPrevent.org

Narcan Efficacy Study

• American College of Emergency Physicians Conf, 10/30/17– B&W Hospital, S. Weiner

• Massachusetts Department of Health– ambulance, hospital, and death records– 12,192 people administered naloxone by EMS ; 7/1/13 thru 12/31/15

• 93% survived the overdose– 6.5% died the day they received the medication.

• Of those who survived, 9.9% died within a year. – Median age was 54.

• Of those who died, 40% did so outside of the hospital and more than half passed away in the first month.

• “You have a 1 in 10 chance of dying if we don’t get you into treatment.”

Resources-SAMHSA

PCSS-O website

• Providers’ Clinical Support System for Opioid Therapies

• ‘National training and mentoring project developed in response to the prescription opioid overdose epidemic.’

• FREE CME: webinars and archived modules

– FREE Buprenorphine Waiver training

– Fulfill state CME requirements for addiction/opiate Rx training

• Free mentoring/support

• PCSS-O.org

Resources

• ASAM - American Society of Addiction Medicine

• AAAP – American Academy of Addiction Psychiatry

• SAMHSA – Substance Abuse Mental Health Services Administration

• NIDA – NDEWS (National Drug Early Warning System)

• CDC – up-to-date data

• Opioidprescribing.org – Boston University SOM

• PrescribeToPrevent.org