Indiana(University(Bloomington Indiana CTSI Retreat 2018 · Indiana CTSI Retreat 2018...

transcript

Indiana CTSI Retreat 2018Medical(Science(Solutions(to(Indiana’s(Opioid(Crisis

Indiana(University(Bloomington

Wednesday,(April(25,(2018

Wilson'Compton,'M.D.

Keynote'Lecture'4'Advancing'Addiction'Science'to'Address'the'

Opioid'Crisis:'Science'='Solutions”

Advancing)Addiction)Science)to)Address)the)Opioid)Crisis

Advancing)Addiction)Science

Wilson'M.'Compton,'M.D.,'M.P.E.Deputy'Director

National'Institute'on'Drug'Abuse

Science)=)Solutions

ADDICTIONS)as)Diseases)of)Gene$Environment$Development

Environment))))

Addiction

DRUG/ALCOHOL))

Brain)Mechanisms)))

BiologyGenes/Development

2.3 2.73.5 3.4

0123456789

0 1 2 3 4 ≥5

Adjusted

s3Ratio,3p<.05

ACE+Score

Ever+AddictedN=8613

Adverse'Childhood'Experiences''(ACE)&Associated&with&Increased&Illicit&Drug&Use

SR#Dube,#et#al.#PEDIATRICS#111:#5648572,#2003

IndividuallyHoused

D.0Morgan0et0al.0Nature0Neuroscience0(2002)

S.003 .01 .03 .10

Reinforcers

(per0session)

Cocaine0(mg/kg/injection)

DominantSubordinate

Social0Setting0Can0Change0Neurobiology

Effects0of0a0Social0Stressor on0Brain0Dopamine0D20Receptors0and0Propensity0to0Administer0Drugs

GroupHoused

Becomes0Subordinate

Becomes0Dominant

Stress0remains

No0longer0stressed

Social0Status0Is0Correlatedwith0D2/30Receptor0Binding

Martinez0D.0et0al.,0Bio0Psychiatry02010.

Brody GH, et al. JAMA Pediatr, 2017.

The$Environment$MattersA$recent$study$shows$that$a$Family8Based$intervention$for$

young$teenagers$can$help$brain$development

Science&= Solutions

More%years%in%poverty%as%a%teen%=%smaller%brain%volumes.

With%the%SAAF%intervention,%no%difference%in%brain%volume.%%

Figure: Effect of Family Poverty on Youth Brain Region by Intervention Status. SAAF=Strong African American Families intervention.

Virtually)All#of#the#U.S.#Have)Increased)Drug)Overdoses:))Estimated#Age3adjusted#Death#Rates#per#100,000#for#Drug#Poisoning#by#County

Source:(https://www.cdc.gov/nchs/data5visualization/drug5poisoning5mortality/index.htm

1999 2016

Evolution)of)the)Opioid)OD)Crisis:

Source:(NCHS(WONDER,(NCHS(Data(Brief(294

05,00010,00015,00020,00025,00030,00035,00040,00045,000

Any/OpioidCommonly/Prescribed/Opioids/(natural/&/semisynthetics/and/methadone)HeroinSynthetic/Opioids/Other/Than/Methadone/(i.e.//Fentanyl/and/Related)

42,249/Any/Opioid

17,087/Rx19,413/“Fentanyl”

15,469/Heroin

Analgesics**********Heroin**********Fentanyl

1. Over'prescription'of'opioid'medications'led'to'misuse2. Addiction'to'prescription'opioids'led'to'heroin3. Emergence'of'fentanyl(s),'with'higher'potency'and'greater'profitability'in'

the'black'market'than'heroin.'

Morphine)equivalent0(mg/patient0in0need0of0care),0and0estimated0percentage0of0need0that0is0met

Knaul&FM&Lancet&2017

Over%reliance%on%opioids%for%pain%management

People&Misusing&Analgesics&Obtain&them&Directly)&)Indirectly)by&Prescription&

Source)where)pain)relievers)obtained)for)most)recent)misuse

36%87%

Friend/Relative

Prescription

Their&Prescription

Their&Friend/RelativeOther

Source:((Han,(Compton,(et(al.(Annals(of(Internal(Medicine(2017;167(5):293E301

Source)where)pain)relievers)obtained)for)most)recent)misuse

36%87%

Friend/Relative

Prescription

Their&Prescription

Their&Friend/RelativeOther

Source:((Han,(Compton,(et(al.(Annals(of(Internal(Medicine(2017;167(5):293E301

Doctors'Continue'to'Prescribe'Opioids'for'Ninety5one'Percent'of'Overdose'Patients

Source:(Larochelle et(al.(Ann#Intern#Med.(2016;164(1):179.

high(dose moderate(doselow(dose none

63%$of$high*dose$opioid$pts$still$on$high$dose$31*90$days$after$OD$

17%of'high5 dose'

patients'overdosed'again'within'two'years

In#a#25year'follow5up'of'2848'commercially'insured'patients'who'had'a'nonfatal'opioid'overdose during#long0term#opioid#therapy#:

!33539%'of'those'with'active'opioid'prescriptions'during'follow5up'also'were'prescribed'benzodiazepines.

Analgesic*Mechanisms*of*Mu*Opiate*Drugs*(Heroin,*Vicodin,*Morphine)

Thalamus(pain)

ACC(pain)

PAG(pain)

Accumbens(reward)

ECONOMICS:))Heroin'Increases'Due'to'Lower'Price'and'Greater'Availability

!$1,000

!$1,500

!$2,000

!$2,500

!$3,000

!$3,5001981

"Retail"!Price!Per!Pure!Gram

National(Drug(Control(Strategy11Data(Supplement(2014.(https://www.whitehouse.gov/sites/default/files/ondcp/policy1and1research/ndcs_data_supplement_2014.pdf

ECONOMICS:))CHEAP&Fentanyl&Precursor&Chemicals

Heroin'Contaminated'with'Fentanyl'Dramatically'

Enhances'Brain'Hypoxia

Solis&et&al.,&2017,&eNeuro

Fentanyl’s*higher*potency*contributes*to*its*lethality*and*when*combined*with*heroin this*might*enhance*their*toxicity

National'Forensic'Laboratory'Information'System'(NFLIS).''Fentanyl'ORANGEFentanyl'analogues'RED

More'than'double'of'the'drugs'seized'by'DEA'tested'positive'for'fentanyl'from'2015'to'2016

Counties)Deemed)Highly)Vulnerable to)Rapid)Dissemination)of)HCV)or)HIV

Source:)Van)Handel)et)al,)JAIDS)2016

Rising)rates)of)HCV

HIV (and%Hepatitis)C)%Outbreak%Linked%to%Oxymorphone Injection%

Use%in%Indiana,%2015Peters%et%al.%%

The New England Journal ofMedicine 2016;375:229I239

20002002200420062008201020122014

Number-of-cases

National(Notifiable(Diseases(Surveillance(System((NNDSS)

• ~31,000%new%HCV%infections%in%2015

• 1:1%male:%female%ratio,%predominantly%white

Science&=&Solutions:"NIDA,"CDC,"SAMHSA,"ARC"Partnering"to"Combat"HIV"and"Viral"Hepatitis"in"Rural"Areas

New$England

West$Virginia

Kentucky

North$Carolina

Illinois

WisconsinOregon

Science&=&Solutions&:""Opioid"Use"and"Misuse"During"Pregnancy"

Increasing*NICU*Admissions*for*Neonatal*Abstinence*Syndrome*NAS*(per%1000%%

Admissions)

Source:((Tolia VN,(Patrick(SW,(et(al.,(NEJM 2015;372:2118=2126.

Buprenorphine resulted(in(a(shorter,durationof,NAS,treatment,and(length,of,hospital,stay

than(treatment(with(morphineSource:((Kraft(WK(et(al.,(NEJM 2017;376:2341=2348.

Buprenorphine*for*NAS*Tx

Source:((Winkelman(TNA,(Villapiano N,(Kozhimannil KB,(Davis(MM,(Patrick(SM..(Pediatrics.+2018;141(4):e20173520

Increasing&Costs&for&Neonatal&Exposure

Prevention)

Research(on(the(Neurobiology(of(Pain

• Males&had&higher&K&opioid&receptor&availability&than&females&presumably&from&increased&dynorphin.&&• Could&this help&explain&gender&differences&in&pain&catastrophizing??

Vijay&et&al.,&Am(J(Nucl(Med(Mol(Imaging. 2016&6(4):2055214.

Females

Gender(Differences(in(Kappa(Opioid(Receptor(Availability

New$Target$for$Pain$Control• Congenital+analgesia:+rare+condition,+individuals+cannot+feel+pain+–Mutation+identified+in+gene+that+encodes+for+Nav1.7+– sodium+channel+that+regulates+pain>sensing+neurons

• Targeting+Nav1.7+to+produce+analgesia–Several+companies+now+have+drugs+in+pipeline+to+block+channel• Targeting+complications–Understanding+what+happens+when+Nav1.7+is+blocked

Science$= Solutions

Soergel DG,*et*al.,*Pain 2014.**Manglik A, et al., Nature 2016. DeWire SM, et al., JPET 2013. Bohn LM, et al., Science 1999

A"Promising"New"Generation"Of"Pain"Therapeutics

Science&= Solutions

Biased&Mu0Opioid&Receptor&Ligands

Resources(for(Medical(Students,(Resident(Physicians(&(Faculty

Web(training(on(pain(assessment(and(treatment

Archived(NIDA(CME(Courses:

Safe(Prescribing(for(PainManaging(Pain(Patients(Who(Abuse(Rx(Drugs

Opioid&Education&

Upcoming(NIDA(CME(Course:

Adolescent(Substance(Use((Prescription(Opioid(Module)

Bringing(NIDA(research(to(

clinical(practice

Medical(schools(have(developed(innovative(curriculum(resources(about(how(to(identify(and(treat(patients(with(substance(use(disorders

Universal*Drug*Abuse*Prevention*Reduces'Opioid'(and'other)'Prescription'Drug'Misuse

Notes:*General=Misuse*of*narcotics*or*CNS*depressants*or*stimulants.**Source:**R*Spoth et*al.*American*Journal*of*Public*Health*2013

In*this*study,*for*100*young*adults*in*general*population*starting*Rx*abuse,*only*35*young*adults*from*an*intervention*community**started.*

1.2**0.6***

5.4**4.7**

9.38.7

Age1211General Age1211Narcotics Age1251General Age1251Narcotics

Family1Program

Control

**p<.01;1***p<.001;1RRRs1=165G93%

Overall,*three*studies*now*suggest*the*impact*of*universal*prevention*on*prescription*drug*abuse.**

Science&="Solutions

Naloxone(Distribution for$opioid$overdose$victims.$$The$potential for$direct$intervention$to$save$lives.$$

! Nasal(spray(and$Auto3injector formulations$now$approved$by$the$FDA

Next(steps• Longer(acting(agents(to(

address(fentanyl(risks?• Respiratory(stimulation?(• Device(development?

Science(=(Solutions:$Direct$Overdose$Intervention

I,#Surgeon#General#of#the#United#States#Public#Health#Service,#VADM#Jerome#Adams,#am#emphasizing#the#importance#of#the#overdoseBreversing#drug#naloxone.#For#patients#currently#taking#high#doses#of#opioids#as#prescribed#for#pain,#individuals#misusing#prescription#opioids,#individuals#using#illicit#opioids#such#as#heroin#or#fentanyl,#health#care#practitioners,#family#and#friends#of#people#who#have#an#opioid#use#disorder,#and#community#members#who#come#into#contact#with#people#at#risk#for#opioid#overdose, knowing'how'to'use'naloxone'and'keeping'it'within'reach'can'save'a'life.

BE#PREPARED.#GET#NALOXONE.#SAVE#A#LIFE.

April#5,#2018Surgeon#General’s#Advisory#on#Naloxone#and#Opioid#Overdose

Retail'Pharmacy'Prescriptions'for$Naloxone$Increase$Markedly

• Retail'prescriptions'show'an'increase'of'9520% from'the'4thquarter'of'2013'to'2nd quarter'2016.''

• Outpatient'prescribing'of'naloxone'may'complement'communityAbased'distribution'and'first'responder'access.''

Sources:'Jones'CM,'Lurie'PG,'Compton'WM.'Am'J'Public'Health.'2016;106(4):689J690;

Science&='Solutions

1Q2010

3Q2010

1Q2011

3Q2011

1Q2012

3Q2012

1Q2013

3Q2013

1Q2014

3Q2014

1Q2015

3Q2015

1Q2016

20142015

Medications+are+Effective+for$Opioid$Use$Disorder

Medication+Assisted+Treatment+(MAT)+can$DECREASE:• Opioid$use• Opioid4related$overdose$deaths• Criminal$activity• Infectious$disease$transmission

And$INCREASE• Social$functioning• Retention$in$treatment

Kakko J+et+al.,+The+Lancet+2003.

Jones&C&et&al.,&Am&J&Public&Health&2015.

In#48#states#and#D.C.,#Opioid#Use#Disorder#Rates#Exceed#Buprenorphine#Treatment#Capacity#

Medications+are+Underused

9%16% 19%

0%10%20%30%40%50%60%70%80%90%100%

Buprenorphine

Methadone

Tablet<naltrexone

Injectable<naltrexone

Disulfiram

Acamprosate

%<Treatment<Programs<Offering<FDAJapproved

SUD<Medications

Knudsen&et&al.,&J&Addict&Med&2011

In#2014,#only#25%#of#opioid#admissions#had#treatment#plans#that#included#receiving#medications.

Treatment&Episode&Data&Set&

(TEDS):&2004H2014.

MAT No+MAT

• Initiating'buprenorphine'treatment'in'the'emergency(department(improves'treatment'engagement'and'reduces'illicit'opioid'use

• Extended'release'naltrexone'initiated'in'criminal(justice settings'lowers'relapse'rates'and'overdoses

• XR:Naltrexone'and'BUP:Nx Equally(Safe(and(Effective((After'Induction)

• Lofexidine for'opioid'withdrawal'treatment'recommended'by'FDA'Advisory'Committee'March'29,'2018

Science(=(Solutions:""Improving"Addiction"Treatment

Lee'JD,'et'al.,''Addiction'2015;100:1005:1014'

and'New'Eng J'Med'2016;374:1232:1242

Relapse6free"survival

Lee#JD#et#al.,#The$Lancet Nov.#14,#2017

Antibodies*reduce*amount*of*drug*in*the*brain

CapillaryBlood*Flow

Targets(drugs,(not(receptors

CapillaryBlood*Flow

AntibodiesVaccine

Binding(sites

Immunotherapies(for(Opioid(Use(Disorder

Hwang&et&al.,&Efficacious&Vaccine&against&Heroin&Contaminated&with&Fentanyl.&ACS&Chem.&Neurosci.&2018&

Non$Pharmacological.Treatments.for$Addiction

Salling and$Martinez,$2016.

Transcranial Direct$Current$Simulation$(tDCS)

Deep$Brain$Stimulation$(DBS)Implanted$electrodes$emit$electrical$stimulation$to$targeted$brain$region

Transcranial Magnetic$Stimulation$(TMS)

Using&Research&to&End&the&Opioid&CrisisNIH$Opioid$Research

PAIN$MANAGEMENTSafe,$effective,$non=addictive$strategies

OPIOID$ADDICTION$TREATMENT

New,$innovative$medications$and$technologies

OVERDOSE$REVERSAL

Interventions$to$reduce$mortality$

and$link$to$treatment

Non=Opioid$Analgesics

Biomarkers$For$Pain$

Opioid$Vaccines

Nonpharmacological$Treatments$(e.g.$TMS)

Respiratory$Stimulation$Devices

New$NIH$Initiative$to$Address$the$Crisis:$HEAL:$Helping$to$End$Addiction$Long:term

• Collaborative,,cross/cutting,research• From,basic,to,behavioral,– and,everything,between• Innovative,partnerships,– across,agencies,,sectors,,

organizations,– will,ensure,rapid,progress,• $500M%just%added%by%Congress• Adds,to,$600M,current,funds,=,$1.1B,for,FY18• Will,propel,HEAL,

• Advances,national'priorities'for'pain,'addiction'research

• Complex(biological,(developmental(and(social(aspects(of(substance(use(and(addiction(suggest(multipronged-responses.• The(severity(of(the(opioid(crisis(demands(urgent-action.-

Summary:Advancing)Addiction)Science

www.drugabuse.gov

www.nih.gov/opioid7crisis

Science)="Solutions

Indiana(University(Bloomington Indiana CTSI Retreat 2018 · Indiana CTSI Retreat 2018...

Documents