1 What Pediatric Primary Care Providers Need to Know About Medication Assisted Therapy - PowerPoint Presentation

Slide1

1

What Pediatric Primary Care Providers Need to Know About Medication Assisted Therapy for Adolescent Opioid Addiction

Diana Deister, MS, MDChild and Adolescent PsychiatristAdolescent Substance Use and Addictions ProgramDivision of Developmental MedicineBoston Children’s HospitalOctober 24th, 2017

Slide2

Disclosure

Diana Deister, MS, MD has no relationships with commercial companies to disclose.

2

Slide3

Learning outcomes

Review the neurobiology of opioidsReview the epidemiology of opioid use in adolescents and opioid related deaths in MA

Review the evidence for appropriate use of medication-assisted therapy (MAT) for opioid use disorders in adolescentsUnderstand how to monitor patients on MAT even if they are receiving MAT elsewhere 3

Slide4

4

Slide5

Opiates

Opioids

Oxycodone

20 mg

5

Slide6

Opioid Pharmacology

6

The human body produces m

olecules

called

“endorphin

s”

that bind to

m

u-opioid

receptors.

B

inding

in the CNS results in a sense

of wel

l-being, satisfaction and plea

sure,

all of

which are important for homeostasis.Opioids mimic endorphins and bind to the same receptor.

Op

i

oid µ-receptor and agonist

T

he

hu

m

an

body

a

l

so

has

kappa

and

de

l

ta

op

i

o

i

d

r

ecepto

r

s,

thou

g

h

the

i

r

r

o

l

e

i

n

add

i

ct

i

on

i

s not

w

e

l

l de

f

i

n

ed

.

Slide7

**

The limbic sy

stem is

one

of the

“

o

l

dest”

po

rtions of the brain, is critical for

adapti

ve

m

e

m

ory and plays an important role in addiction.CNS Areas with High Mu-Opioid Receptor Density7Brain

Region

Function

Prefrontal Cortex“Executive Functions”Limbi

c System**

Pl

ea

s

ure

and

R

e

w

ard

B

ra

i

n

St

em

R

e

s

p

i

ra

ti

on,

C

ough

S

p

i

nal

C

ord

P

a

i

n

Slide8

A Dynamic System

8

Immediately after tissue injury, spinal cord receptors become available, allowing injured patients to tolerate large opioid doses without euphoria or overdose.The same large dose could result in overdose in the same individual, once the pain has subsided and receptors are downregulated.Pain patients on appropriate treatment should not experience a euphoric “high,” which reduces the risk of developing an addiction.

Slide9

Physiologic Adaptations: Tolerance and Withdrawal

9

Tolerance is the need for increasing am

ounts of

the

s

ub

s

tan

c

e

to

a

chie

ve the desired effect.Withdrawal is a physiological response

to a rapid

decline in receptor

binding,

due

to either rapidly

decreasing concentrations of the opioid, or presence of a blocking agent. Symptoms are listed on the next slide.

Note

that tol

erance and withdrawal occur whenever

there

has

been

ch

r

on

i

c

e

x

posu

r

e to opioids – whether for long term pain management or in addiction. Tolerance and withdrawal alone are not sufficient to make a diagnosis of addiction..

American Psychiatric Association. DSM IV-TR. Diagnostic and Statistical Manual

of Mental Disorders Text Revision Fourth Edition ed. Washington DC; 2000.

18

Slide10

Opioid Withdrawal

10

The signs listed abov

e a

r

e

a

l

l

cons

i

stent

with opioid withdrawal. T

hese can

be quant

i

f

i

ed using the “Clinical Opioid Withdrawal Scale,” or COWS. A COWS is used to fo

llow

patients

who are detoxing.

Dysphor

i

c

M

ood

I

n

s

o

m

n

i

a

N

ausea/VomitingDiarrheaMuscle aches/crampsSweatingLacrimationRhinorrheaHypertensionTachycardia

Slide11

Length and Timing of Withdrawal Period

11

Short-acting opioids (e.g., heroin, hydrocodone, oxy

codone): w

ithdra

w

al

u

sually

begins

6-12

hours after last dose, peaks at 36-72 hours, and lasts about 5 day

s

Long-acting opioids

(e.g.,

methadone, buprenorphine): withdrawal begins 36-72 hours after last dose, peaks at 4-5 days, and can last up to 2 weeks.

Slide12

Civil War

1914

VIETNAM

WAR

1970’s

1974

METHADONE

HARRISON DRUG ACT

1999

“PAIN” AS THE 5

th

VITAL SIGN

1860’s

12

Slide13

Increase in Opioid Rx, 1991-2013

13

Volkow ND. America’s Addiction to Opioids: Heroin and Prescription Drug Abuse. Natl. Inst. Drug Abus. 2014. Available at: http://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2014/americas-addiction-to-opioids-heroin-prescription-drug-abuse. 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

No. of Rx’s (millions)

Slide14

Monitoring the Future 2015 survey

Slide15

Monitoring the Future 2015

– 8/10/12th graders, Past Month Use

Courtesy of NIDA: https://teens.drugabuse.gov/teachers/infographics

Slide16

Monitoring the Future 2015 survey

– 12th graders, Past Year Use

Courtesy of NIDA: https://teens.drugabuse.gov/teachers/infographics

Slide17

Source:

Johnston LD, et al., Monitoring the Future – National Results on Adolescent Drug Use: Overview of Key Findings,

2016Rates of opioid misuse by 12th graders17

Slide18

Slide19

Mass Opioid Death Rate

Slide20

Slide21

Confirmed Unintentional/Undetermined1 Opioid-related Deaths Compared to All Deaths by Age: January 2016-December 2016

http://www.mass.gov/

eohhs/docs/dph/stop-addiction/current-statistics/opioid-demographic-february-2017.pdf

Slide22

Reason for Opioid Misuse

22

Lifetime

opio

i

d

m

i

suse

r

ates

r

ose dramatically between 1993 and 2003,

and has

subsequ

e

nt

l

y leveled off near 13%. Nearly half of all new recreational users of prescripti

on p

ain

medications are under 18.Part

nership

f

o

r

a

D

r

ug

-Fr

e

e

Am

erica. The Partnership Attitude Tracking Study(PATS): Teens in grades 7 through 12 2005; May 16, 2006Easy to get from medicine cab

inet62%Available everywhere52%Not illegal

51%Easy to get through other people’s prescription50%

C

a

n

c

l

a

i

m

y

o

u

h

a

v

e

a

p

r

esc

ri

p

t

io

n

i

f

ca

ught

49%

C

hea

p

43%

Sa

f

e

r

to

u

s

e

t

h

a

n

ill

e

g

a

l

d

r

ug

35%

L

es

s

s

h

am

e

a

tt

ac

h

e

d

to

u

s

i

n

g

33%

Ea

s

y

t

o

pu

r

c

ha

s

e

o

v

e

r

t

h

e

I

n

t

e

r

ne

t

32%

F

e

w

e

r

s

i

d

e

e

ff

ec

ts

t

h

a

n

s

t

r

ee

t

d

r

ug

s

32%

Pa

r

e

n

ts

don

’

t

ca

r

e

a

s

m

u

c

h

i

f

y

o

u

g

e

t

ca

ught

21%

Slide23

Heroin

23

Heroin (di-acetyl morphine) rapidly cross

es the blood brain barrie

r

,

w

here

it is

m

etaboliz

ed

to morphine, resulting in very rapid delivery of morphine to the central ner

vous s

ystem.

B

e

c

ause it is potent and relatively inexpensive, individuals who have become addicted to opioids may switch to

heroin to co

mbat toleranc

eIncreased purity of heroin since the 1990s has

made snorting or

s

m

o

king

pra

ctical

alternati

v

es

to

injecting

, thus

lowering the barrier to initiate use.

Slide24

Age of onset of non-medical use of prescription

drugs

24Source: McCabe SE et al. Does early onset of non-medical use of prescription drugs predict subsequent prescription drug abuse and dependence? Results from a national study. Addiction 2007 102(12):1920-1930.

Slide25

Prescribed opioid use

Opioid misuse

Slide26

Prescribed pain relief

AOR: 1.33

(95% CI 1.04-1.70)Source: Miech, et al. Pediatrics. (2015). 136(5):e1169-77.Association between prescribed opioids and opioid misuse

Slide27

Alc/MJ/tobacco use

Prescribed opioid use

Opioid misuse

Slide28

Lifetime Cigarette use

AOR

: 1.25(95% CI 1.16-1.36)Lifetime Marijuana useAOR: 2.44(95%

CI 2.22-2.67)

Source

:

Fiellin

et al.

(2013) Prior use of alcohol, cigarettes, and marijuana and subsequent abuse of prescription opioids in young

adults.

Lifetime Alcohol use

AOR

: 1.23

(95% CI

1.11-1.36)Gateway to Opioid Misuse

Slide29

Alc/MJ/tobacco use

Prescribed opioid use

Opioid misuse

Mental health disorders

Genetic vulnerability

Opioid addiction

Younger age

Motivation

Prescribed opioid use

Slide30

Younger age*

*AOR decreases by 5% each year that non-medical use is delayed (after one year,

AOR: 0.95 with 95% CI 0.94-0.97)Sources: McCabe et al. Addiction. (2007). 102(12):1920-30

Slide31

Familial alcohol problem/drug use

Drug abuse/DependenceOR: 7.89-7.92

PTSDDrug abuse/Dependence OR: 8.68Major depression, anxiety disorder, or panic disorderOpioid use OR: 4.43 (95% CI 3.64-5.38)Sources: 1) Kilpatrick DG, Acierno R, Saunders B, Resnick HS, Best CL, Schnurr PP (2000). 2)

Risk Factors for Adolescent Substance Abuse and Dependence:Data From a National Sample. J Consult and Clin

Psych 63(1):19-30.

3)

Sullivan

MD,

Edlund

MJ, Zhang L,

Unützer

J, Wells

KB (2006).

Association Between Mental Health Disorders, Problem Drug Use, and Regular Prescription Opioid Use. 

Arch Intern Med 166(19):2087-2093.

Mental health and opioid use

Slide32

Motivations for opioid misuse

Source:

McCabe et al. Add Behav. 2012. 37(5):651-6.

Slide33

Recreational use

AOR: 3.42

(95% CI 1.45-8.07)Unprescribed pain reliefAOR: 1.8 (95% CI 1.20-2.60)

Sources : 1) Boyd et al. J. Addict Dis. 2009.

28(3):

232-42. 2) Boyd

et al

.

Pediatrics.

(2006). 118(6):2472-80.

Association between motivation for use and Opioid Use Disorder

Slide34

DSM-5 Criteria for Substance Use Disorder

Use in larger amounts or for longer periods of time than intended

Unsuccessful efforts to cut down or quit.Excessive time spent taking the drugFailure to fulfill major obligationsContinued use despite knowledge of problemsImportant activities given upRecurrent use in physically hazardous situationsContinued use despite social or interpersonal problemsToleranceWithdrawalCraving

Severity is designated according to the number of symptoms endorsed: 0 - 1: No diagnosis

2

- 3: mild SUD

4 - 5

: moderate SUD

6

or more: Severe SUD

34

Slide35

Overview of Treatment for Opioid Addiction

35

Opioid depe

ndence i

s

a

ch

r

on

i

c,

r

elapsing neurological conditi

on;

patients

w

ho

remain in long-term treatment generally do best. Supportive therapy combin

ed

with pha

rmacologic treatment seems

to pr

oduce

the

best outco

m

e

s.

M

ost

e

f

ficacy studies have been done with adults, and little is known about the effects of treating developing adolescents with opioid agonists.Non-pharmacologicPharmacologicResidential TreatmentDetoxmethadone,

buprenorphine, clonidine, “comfort meds”Intensive Outpatient/Partial12-Step Fellowships and other Peer support groupsAntagonist Therapynaltrexone PO or IM

Individual, Group, or Family TherapyAgonist Therapymethadone, buprenorphineTherapeutic School/Community

Slide36

Pharmacologic Treatment Options

Detoxification: eases discomfort associated with withdrawal. Can be achieved with opioids or non-opioid “comfort meds” such as ibuprofen, trazodone and clonidine for symptomatic relief.

Opioid Antagonist Therapy: “blocks” opioid receptor so patients cannot get high. Naltrexone used for long-term treatment can be given PO or IM.Opioid Agonist Therapy: long-term treatment aimed at quelling cravings, improving functioning and reducing relapse rates. Options include methadone (full agonist) and buprenorphine (partial agonist).36

Slide37

37

Detoxification

Adult studies have recurrently found high relapse rates after detoxification without subsequent treatment. An NIH consensus statement regarding treatment of opioid dependent adults indicated detoxification alone is insufficient treatment.

Woody, GE., et al. Extended vs. Short-term Buprenorphine-Naloxone for Treatment of Opioid-Addicted Youth.

JAMA

300(17) :2003-2011, 2008.

National Institute of Health Consensus Development Conference Statement, 1997.

Kosten

TR,

Schottenfeld

R,

Ziedonis

D,

Falcioni

J. Buprenorphine versus methadone maintenance for opioid dependence. Journal of Nervous and Mental Disease 1993;181(6):358-64.;

Mattick

et al., Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients.,

Addiction,

2003 Apr;98(4):441-52.;

Gowing

, L., Buprenorphine for the management of opioid withdrawal.,

Cochrane Database Syst Rev. 2000;(3):CD002025.

Slide38

Medication Assisted Treatment

38

Slide39

39

Slide40

Opioid Function at Receptors

Different exogenous molecules have varying levels of “fit” at the opioid receptor, resulting in different levels of receptor activity with bindingSubstances are divided into three groups: full agonists, partial agonists and antagonists.

In general, antagonists have the highest receptor affinity and full agonists the lowest.40

Slide41

Methadone

Methadone – very limited options for patients under age 18Schedule IIHighly regulatedCan only be prescribed through “methadone clinics”; very few can take patients under 18 years old.

Methadone programs are highly structured, which offers an advantage for patients, especially with limited social supportSome patients who are not successful with the partial agonist buprenorphine can be successful with methadone.41Studies in

adults

co

m

pa

ri

ng

m

etha

d

o

ne to buprenorphine have

found

nearly

i

dent

ical treatment retention and outcomes

Slide42

Partial Agonist Therapy: Buprenorphine

Partial agonists occupy the receptor and blocks binding of full strength opioids.Receptors are only partially activated even with full occupancy

Less reinforcing and less commonly abused than full agonists. The potential for misuse is not zero42

Slide43

Buprenorphine

Buprenorphine – FDA indication for treating patients > 16 yearsSchedule III

Can be prescribed from physician officesCombination product (with naloxone) limits misuse potentialAntagonist properties may be therapeutically usefulSafer than methadone in overdoseMildly reinforcing which may support medication adherence43Studies in

adul

ts

co

m

pa

ri

ng

m

etha

d

one to buprenorphine have

found nea

rly

i

dent

i

cal treatment retention and outcomes

Slide44

BuprenorphinePreparations

Buprenorphine/naloxone combination product is the recommended formulation for treatment of opioid dependenceNaloxone is present only to reduce diversion to injected abuse

When taken sublingually, naloxone is poorly absorbed and has no physiologic effectPatients who use the combination product IV or IN get primarily blocking from naloxone (and can precipitate withdrawal) rather than euphoria from a large dose of buprenorphine44

B

up

r

eno

r

phine

N

aloxone

Slide45

Research Trials with

AdolescentsExtended vs. Short-term Buprenorphine-Naloxone for

Treatment of Opioid-Addicted Youth: A Randomized Trial 45

Study design

Participants 15-21 years old with opioid dependence via DSM-IV, N=152

Randomly assigned to 1 of 2 groups:

2-week detox

w/ max dose of 14 mg/day buprenorphine (n=78)

12-week treatment

buprenorphine-naloxone

w/ max dose of 24 mg/day for 5-7 days/ week for 12 weeks (n=74)

All participants received group and individual counseling each week

for 12 weeks

Woody, GE., et al.

JAMA 300(17)

:2003-11, 2008

Slide46

Research Trials with

AdolescentsExtended vs. Short-term Buprenorphine-Naloxone for

Treatment of Opioid-Addicted Youth: A Randomized Trial 46

Summary of Findings

Fewer Opioid positive urine screens in 12-week-treatment group

Higher retention rates in 12-week-treatment group

Woody, GE., et al.

JAMA 300(17)

:2003-11, 2008

Slide47

47

Buprenorphine Waiver Training:

The Half and Half Course – specifically for Pediatricians and Family Physicians in addressing adolescent specific issueshttp://www.cvent.com/d/l4q2mj

Slide48

Treatment with Naltrexone: Overview

FDA indication for Naltrexone is a long-acting, high affinity, competitive opioid receptor antagonist with an active metabolite (6-β-naltrexol

)Naltrexone blocks the euphoric effects of opioid use.A study with adults aged 18 and over found that compared to placebo, patients who received naltrexone had less opioid use, better treatment retention and fewer cravings.There are no data regarding the efficacy or adverse effects profile in children.48Krupitsky et

al.,

201

Slide49

Naltrexone: Pharmacology

5-40% bioavailability when administered orallyMetabolized in the liver, renal excretionEffective opioid blockade lasts from 1-3 days depending on

doseRecommended adult dose is 50 mg daily or 380 mg IM monthlyNaltrexone can precipitate opioid withdrawal; start after the withdrawal period is completed – generally 7 days, longer if patient had been using long acting opioid such as methadone49

Slide50

Efficacy of Naltrexone: oral vs. XR injection

Retention in treatment is used as a primary outcome of treatment with NTX as a great majority of patients retained on NTX are abstinent from opioids

Treatment retention rate in groups treated with XR preparations is twice that of the oral group, approximating 50-70% at 6 months50

Slide51

How long will my patient

be on MAT?SUD’s are like any chronic illness requiring maintenance treatment. Early sobriety

Longer sobrietyRelapseEarly Sobriety, etcPatient response to treatment is individual, but should be multi-modal Changes to lifestyle / diet / exercise helpPsychosocial support should start with MAT and continue after its discontinuationIndividual medication needs vary in short term and long term

Slide52

Monitor

52

Slide53

MAT with outside provider

Get a release to speak with the provider that specifically states substance abuse treatment is part of the information being communicatedNotify external provider about critical medical updates

Monitoring patients who get MAT somewhere elseDrug tests – you can order them!Buprenorphine/norbuprenorphine should be in the sample if patient is taking this medication

Slide54

Conclusions

Opioid use among adolescents and young adults is a serious problem with potentially life-threatening consequences

Pediatric health care providers can have a significant impact on this problem by:Recognizing that adolescents can develop opioid use disordersUsing caution in prescribing opioids Counseling patients and parents about prescription drug misuseSupporting medication-assisted treatment for patients with severe opioid use disorders54

Slide55

Acknowledgements

Teaching CollaboratorsPamela Burke, PhD, RN, FNP, PNP, FSAHM, FAAN

Linda Malone, DNP, RN, CPNPSarah Pitts, MDMarianne Pugatch, MSW, LICSWJennifer Putney, PhD, LICSWResearch CollaboratorsCo-principal investigators: Elissa Weitzman, ScD, Msc & Sharon Levy, MD, MPHElizabeth Harstad, MD, MPH  Lauren Wisk, PhDResearch Project ManagementJulie Lunstead, MPH, Program ManagerErin Huang, MPH, Data ManagerPCSS MAT Training Providers' Clinical Support System for Medication Assisted Treatment

CliniciansDiana

Deister

, MD

, MS

Leslie Green, MSW, LICSW

Scott Hadland, MD, MPH

Sharon

Levy, MD, MPH

Shannon Mountain-Ray, MSW, LICSW

Patricia

Schram

,

MDJesse Schram, LICSWNicholas Chadi, MDResearch Assistants Dylan Kaye, BALily Rabinow, MSParissa Salimian, BAMeghana Vijaysimha, MPHRosemary Ziemnik, BS55Adolescent Substance Abuse Program (ASAP)

Slide56

Questions?

56