last updated january 2018 - free state social work, llc5 prescription opioid use is a risk factor...

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NationalInstituteonDrugAbuse(NIDA)

PrescriptionOpioidsandHeroin

LastUpdatedJanuary2018

https://www.drugabuse.gov

https://www.drugabuse.gov/

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TableofContents

PrescriptionOpioidsandHeroin

Introduction

Prescriptionopioiduseisariskfactorforheroinuse

Heroinuseisrareinprescriptiondrugusers

Prescriptionopioidsandheroinhavesimilareffects,differentriskfactors

Asubsetofpeoplewhoabuseprescriptionopioidsmayprogresstoheroinuse

Increaseddrugavailabilityisassociatedwithincreaseduseandoverdose

Heroinuseisdrivenbyitslowcostandhighavailability

Emphasisisneededonbothpreventionandtreatment

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Introduction

Drugoverdosedeathsinvolvingprescriptionopioidpainrelievershave

increaseddramaticallysince1999.Concertedfederalandstateeffortshave

beenmadetocurbthisepidemic.In2011,theWhiteHousereleasedan

interagencystrategyforRespondingtoAmerica’sPrescriptionDrugCrisis.

Enactingthisstrategy,federalagencieshaveworkedwithstatestoeducate

providers,pharmacists,patients,parents,andyouthaboutthedangersof

prescriptiondrugabuseandtheneedforproperprescribing,dispensing,use,

anddisposal;toimplementeffectiveprescriptiondrugmonitoringprograms;to

facilitatepropermedicationdisposalthroughprescriptiontake-backinitiatives;

andtosupportaggressiveenforcementtoaddressdoctorshoppingandpill

millsandsupportdevelopmentofabuse-resistanceformulationsforopioidpain

relievers.

Improvementshavebeenseeninsomeregionsofthecountryintheformof

decreasingavailabilityofprescriptionopioiddrugsandadeclineinoverdose

deathsinstateswiththemostaggressivepolicies .However,

since2007,overdosedeathsrelatedtoheroinhavestartedtoincrease.The

CentersforDiseaseControlandPreventioncounted10,574heroinoverdose

deathsin2014,whichrepresentsmorethanafivefoldincreaseoftheheroin

deathratefrom2002to2014 .

Inanefforttocombattheintertwinedproblemsofprescriptionopioidmisuse

andheroinuse,inMarchof2015theSecretaryofHealthandHumanServices

announcedtheSecretary’sOpioidInitiative,whichaimstoreduceaddictionand

mortalityrelatedtoopioiddrugabuseby :

reformingopioidprescribingpractices

expandingaccesstotheoverdose-reversaldrugnaloxone

expandingaccesstomedication-assistedtreatmentforopioidusedisorder

Therelationshipbetweenprescriptionopioidabuseandincreasesinheroin

useintheUnitedStatesisunderscrutiny.Thesesubstancesareallpartofthe

(Johnsonetal.,2014)

(CDC,2015)

(HHStakesstrongsteps,2015)

http://www.whitehouse.gov/sites/default/files/ondcp/issues-content/prescription-drugs/rx_abuse_plan.pdfhttp://www.hhs.gov/news/press/2015pres/03/20150326a.html

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sameopioiddrugcategoryandoverlapinimportantways.Currentlyavailable

researchdemonstrates:

Prescriptionopioiduseisariskfactorforheroinuse.

Heroinuseisrareinprescriptiondrugusers.

Prescriptionopioidsandheroinhavesimilareffects,differentriskfactors.

Asubsetofpeoplewhoabuseprescriptionopioidsmayprogresstoheroin

use.

Increaseddrugavailabilityisassociatedwithincreaseduseandoverdose.

Heroinuseisdrivenbyitslowcostandhighavailability.

Emphasisisneededonbothpreventionandtreatment.

References

CentersforDiseaseControlandPrevention(CDC).Numberandage-

adjustedratesofdrug-poisoningdeathsinvolvingopioidanalgesicsand

heroin:UnitedStates,2000-2014.NationalVitalStatisticsSystem,Mortality

File.http://wonder.cdc.gov/.ReviewedDecember9,2015.Accessed

December10,2015.

HHStakesstrongstepstoaddressopioid-drugrelatedoverdose,deathand

dependence[newsrelease].Washington,DC:U.S.Dept.ofHealthand

HumanServices;March26,2015.

http://www.hhs.gov/news/press/2015pres/03/20150326a.html.Accessed

October8,2015.

JohnsonH,PaulozziL,PorucznikC,MackK,HerterB.Declineindrug

overdosedeathsafterstatepolicychanges–Florida,2010-2012.Morbidity

andMortalityWeeklyReport(MMWR).Atlanta,GA:CentersforDisease

ControlandPrevention;2014.

https://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-heroin-abuse/prescription-opioid-use-risk-factor-heroin-usehttps://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-heroin-abuse/heroin-use-rare-in-prescription-drug-usershttps://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-abuse-heroin-use/rx-opioids-heroin-have-similar-effects-different-risk-factorshttps://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-abuse-heroin-use/subset-users-may-naturally-progress-rx-opioids-to-heroinhttps://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-abuse-heroin-use/increased-drug-availability-associated-increased-use-overdosehttps://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-abuse-heroin-use/heroin-use-driven-by-its-low-cost-high-availabilityhttps://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-abuse-heroin-use/emphasis-needed-both-prevention-treatmenthttp://wonder.cdc.gov/http://www.hhs.gov/news/press/2015pres/03/20150326a.html

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Prescriptionopioiduseisarisk

factorforheroinuse

Poolingdatafrom2002to2012,theincidenceofheroininitiationwas19times

higheramongthosewhoreportedpriornonmedicalpainrelieverusethan

amongthosewhodidnot(0.39vs.0.02percent) ).Astudyof

young,urbaninjectiondrugusersinterviewedin2008and2009foundthat86

percenthadusedopioidpainrelieversnonmedicallypriortousingheroin,and

theirinitiationintononmedicalusewascharacterizedbythreemainsourcesof

opioids:family,friends,orpersonalprescriptions .Thisrate

representsashiftfromhistoricaltrends.Ofpeopleenteringtreatmentforheroin

addictionwhobeganabusingopioidsinthe1960s,morethan80percent

startedwithheroin.Ofthosewhobeganabusingopioidsinthe2000s,75

percentreportedthattheirfirstopioidwasaprescriptiondrug .

Examiningnational-levelgeneralpopulationheroindata(includingthosein

andnotintreatment),nearly80percentofheroinusersreportedusing

prescriptionopioidspriortoheroin .

(Muhurietal.,2013

(Lankenauetal.,2012)

(Ciceroetal.,2014)

(Jones,2013;Muhurietal.,2013)

Percentageofthetotalheroin-dependentsamplethatusedheroinoraprescription

https://www.drugabuse.gov/sites/default/files/figure1prescripheroin.jpg

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References

CiceroTJ,EllisMS,SurrattHL,KurtzSP.Thechangingfaceofheroinusein

theUnitedStates:aretrospectiveanalysisofthepast50years.JAMA

Psychiatry.2014;71(7):821-826.

JonesCM.Heroinuseandheroinuseriskbehaviorsamongnonmedical

usersofprescriptionopioidpainrelievers–UnitedStates,2002-2004and

2008-2010.DrugAlcoholDepend.2013;132(1-2):95-100.

LankenauSE,TetiM,SilvaK,JacksonBloomJ,HarocoposA,TreeseM.

Initiationintoprescriptionopioidmisuseamongstyounginjectiondrug

users.IntJDrugPolicy.2012;23(1):37-44.

MuhuriPK,GfroererJC,DaviesMC;SubstanceAbuseandMentalHealth

ServicesAdministration.Associationsofnonmedicalpainrelieveruseand

initiationofheroinuseintheUnitedStates.CBHSQDataReview.

http://www.samhsa.gov/data/2k13/DataReview/DR006/nonmedical-pain-

reliever-use-2013.pdf.PublishedAugust2013.AccessedOctober8,2015.

opioidastheirfirstopioidofabuse.Dataareplottedasafunctionofthedecadein

whichrespondentsinitiatedtheiropioidabuse.Source:Ciceroetal.,2014

http://www.samhsa.gov/data/2k13/DataReview/DR006/nonmedical-pain-reliever-use-2013.pdf

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Heroinuseisrareinprescription

drugusers

Whileprescriptionopioidabuseisagrowingriskfactorforstartingheroinuse,

onlyasmallfractionofpeoplewhoabusepainrelieversswitchtoheroinuse.

AccordingtogeneralpopulationdatafromtheNationalSurveyonDrugUse

andHealth,lessthan4percentofpeoplewhohadabusedprescriptionopioids

startedusingheroinwithin5years .Thissuggeststhat

prescriptionopioidabuseisjustonefactorinthepathwaytoheroin.

Furthermore,analysessuggestthatthosewhotransitiontoheroinusetendto

befrequentusersofmultiplesubstances(polydrugusers) .

Additionalanalysesareneededtobettercharacterizethepopulationthat

abusesprescriptionopioidswhotransitiontoheroinuse,including

demographiccriteria,whatotherdrugstheyuse,andwhetherornottheyare

injectiondrugusers.

References:

JonesCM,LoganJ,GladdenRM,BohmMK.Vitalsigns:demographicand

substanceusetrendsamongheroinusers–UnitedStates,2002-2013.

MorbidityandMortalityWeeklyReport(MMWR).Atlanta,GA:Centersfor

DiseaseControlandPrevention;2015.






(Muhurietal.,2013)

(Jones,etal.,2015)


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Prescriptionopioidsandheroinhave

similareffects,differentriskfactors

Heroinandprescriptionopioidpainrelieversbothbelongtotheopioidclassof

drugs,andtheireuphoriceffectsareproducedbytheirbindingwithmuopioid

receptorsinthebrain.Differentopioiddrugshavedifferenteffectsthatare

determinedbythewaytheyaretakenandbythetiminganddurationoftheir

activityatmuopioidreceptors.

Peoplewhobeganusingheroininthe1960swerepredominantlyyoungmen

fromminoritygroupslivinginurbanareas(82.8percent;meanageatfirst

opioiduse,16.5years)whosefirstopioidofabusewasheroin(80percent).The

epidemicofprescriptionopioidabusehasbeenassociatedwithashiftingofthe

demographicofopioiduserstowardapopulationthatissomewhatolder(mean

ageatfirstopioiduse,22.9years),lessminority,morerural/suburban,withfew

genderdifferencesamongthosewhowereintroducedtoopioidsthrough

prescriptiondrugs.Whitesandnonwhiteswereequallyrepresentedinthose

initiatingusepriortothe1980s,butnearly90percentofrespondentswho

beganuseinthelastdecadewerewhite .(Ciceroetal.,2014)

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Becauseheroinisofteninjected,theupsurgeinusealsohasimplicationsfor

HIV,hepatitisC(HCV),andotherinjection-relatedillnesses.Recentstudies

suggestthathavingusedopioidpainrelieversbeforetransitioningtoheroin

injectionisacommontrajectoryforyounginjectiondruguserswithHCV

infection .AstudyofnewHCVinfectionsinMassachusetts

foundthat95percentofinterviewrespondentsusedprescriptionopioidsbefore

initiatingheroin .

References

ChurchD,BartonK,ElsonF,DeMariaA,etal.Notesfromthefield:risk

factorsforhepatitisCvirusinfectionsamongyoungadults–Massachusetts,

2010.MorbidityandMortalityWeeklyReport(MMWR).Atlanta,GA:Centers

forDiseaseControlandPrevention;2011.



Psychiatry.2014;71(7):821-826.

Racialdistributionofrespondentsexpressedaspercentageofthetotalsampleof

heroinusers.Dataareplottedasafunctionofdecadeinwhichrespondentsinitiated

theiropioidabuse.Source:Ciceroetal.2014.

(Klevensetal.,2012)

(Churchetal.,2010)

https://www.drugabuse.gov/sites/default/files/figure2prescripheroin.jpg

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KlevensRM,HuDJ,JilesR,HolmbergSD.Evolvingepidemiologyof

hepatitisCvirusintheUnitedStates.ClinInfectDis.2012;55(S1):S3-S9.

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Asubsetofpeoplewhoabuse

prescriptionopioidsmayprogressto

heroinuse

ArecentstudyofheroinusersintheChicagometropolitanareaidentifiedthree

mainpathstoheroinaddiction:Prescriptionopioidabusetoheroinuse,cocaine

usetoheroinuse(to"comedown"),andpolydruguse(i.e.,useofmultiple

substances)toheroinuse.Polydrugusetoheroinwasthemostcommonpath

inthisstudy .Theestimated4percentsubsetofpeoplewho

transitionfromprescriptionopioidabusetoheroinuse maybe

predisposedtopolydruguse,andthetransitionmayrepresentanatural

progressionforthem.ExaminationofnewHCVcasesinyoungadultslivingin

ruralareasidentifiedapopulationwhoreportedtransitionfromnon-injection

drugusetoinjectingopioidpainrelieversbeforeswitchingtoinjectingheroinor

methamphetamine .Astudylookingatalargersamplefound

thatprescriptionopioidabuseprecededheroinusebyanaverageof2years

.Frequentprescriptionopioidusersandthosediagnosed

withdependenceorabuseofprescriptionopioidsaremorelikelytoswitchto

heroin;dependenceonorabuseofprescriptionopioidshasbeenassociated

witha40-foldincreasedriskofdependenceonorabuseofheroin

.

(Kane-Willis,etal.,n.d.)

(Muhurietal.,2013)

(Stanleyetal.,2012)

(Suryaprasadetal.,2014)

(Jonesetal.,

2015)

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References

CDCWONDER.Atlanta,GA:CentersforDiseaseControlandPrevention;

2015.http://wonder.cdc.gov/.UpdatedSeptember17,2015.Accessed

September25,2015.

CenterforBehavioralHealthStatisticsandQuality,SubstanceAbuseand

MentalHealthServicesAdministration,TreatmentEpisodeDataSet(TEDS).

http://www.samhsa.gov/data/client-level-data-teds.UpdatedNovember19,

2014.AccessedSeptember25,2015.

JonesCM,LoganJ,GladdenRM,BohmMK.Vitalsigns:demographicand

substanceusetrendsamongheroinusers–UnitedStates,2002-2013.

MorbidityandMortalityWeeklyReport(MMWR).Atlanta,GA:Centersfor

DiseaseControlandPrevention;2015.

Kane-WillisK,SchmitzSJ,BazanM,Narloch,VF,WallaceCB.

Understandingsuburbanheroinuse.RooseveltUniversity.

https://www.robertcrown.org/files/Understanding_suburban_heroin_use.pdf.

Opioidsales,opioidtreatmentadmissions,andopioid-relateddeaths.Sources:CDC

Wonder,2015;DEAARCOS,2015;TEDS,2015

http://wonder.cdc.gov/http://www.samhsa.gov/data/client-level-data-tedshttps://www.robertcrown.org/files/Understanding_suburban_heroin_use.pdfhttps://www.drugabuse.gov/sites/default/files/fig3prescrheroin.jpg

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AccessedOctober8,2015.






StanleyMM,GuilfoyleS,VergerontJM,etal.Notesfromthefield:hepatitisC

virusinfectionsamongyoungadults–ruralWisconsin,2010.Morbidityand

MortalityWeeklyReport(MMWR).Atlanta,GA:CentersforDiseaseControl

andPrevention;2012.

SuryaprasadAG,WhiteJZ,XuF,etal.EmergingepidemicofhepatitisC

virusinfectionsamongyoungnonurbanpersonswhoinjectdrugsinthe

UnitedStates,2006-2012.ClinInfectDis.2014;59(10):1411-1419.

U.S.DrugEnforcementAdministration(DEA)ARCOS.Dataextracted

October8,2015.


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Increaseddrugavailabilityis

associatedwithincreaseduseand

overdose

From1991to2011,therewasaneartriplingofopioidprescriptionsdispensed

byU.S.pharmacies:from76millionto219millionprescriptions

.Inparallelwiththisincrease,therewasalsoaneartriplingof

opioid-relateddeathsoverthesametimeperiod.

Mexicanheroinproductionincreasedfromanestimated8metrictonsin2005to

50metrictonsin2009—morethanasix-foldincreaseinjust4years.

DominationoftheU.S.marketbyMexicanandColombianheroinsources,

alongwithtechnologytransferbetweenthesesuppliers,hasincreasedthe

availabilityofeasilyinjectable,whitepowderheroin

.Inarecentsurveyofpatientsreceivingtreatmentforopioidabuse,

accessibilitywasoneofthemainfactorsidentifiedinthedecisiontostartusing

heroin .

References



Psychiatry.2014;71(7):821-826.

IMSHealth,NationalPrescriptionAudit,Years1997-2013.Dataextracted

2014.

IMSHealth,VectorOne:National,Years1991-1996.Dataextracted2014.

NationalDrugIntelligenceCenter,U.S.DepartmentofJustice.National

DrugThreatAssessment2011.

http://www.justice.gov/archive/ndic/pubs44/44849/44849p.pdf.Published

August2011.AccessedOctober8,2015.

(IMSHealth,2014a;

IMSHealth,2014b)

(NationalDrugIntelligenceCenter,

2011)

(Ciceroetal.,2014)

http://www.justice.gov/archive/ndic/pubs44/44849/44849p.pdf

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Heroinuseisdrivenbyitslowcost

andhighavailability

Onemainfactorthatcontributestothepopularityofadrugisavailability.One

keytopreventionisreducingexposure.Whileeffortstoreducetheavailabilityof

prescriptionopioidanalgesicshavebeguntoshowsuccess,thesupplyof

heroinhasbeenincreasing(seeIncreaseddrugavailabilityisassociatedwith

increaseduseandoverdose).Prescriptionopioidsandheroinhavesimilar

chemicalpropertiesandphysiologicalimpacts;whenadministeredbythesame

method(i.e.,ingestedorinjected),thereisnorealdifferencefortheuser.

Itisnotclearwhethertheincreasedavailabilityofheroiniscausingtheupsurge

inuseoriftheincreasedaccessibilityofheroinhasbeencausedbyincreased

demand.Anumberofstudieshavesuggestedthatpeopletransitioningfrom

abuseofprescriptionopioidstoheroincitethatheroinischeaper,more

available,andprovidesabetterhigh.Notably,thestreetpriceofheroinhas

beenmuchlowerinrecentyearsthaninpastdecades .In

additiontothesemarketforces,somehavereportedthatthetransitionfrom

opioidpillstoheroinwaseasedbysniffingorsmokingheroinbefore

transitioningtoinjection .Inarecentsurveyofpeopleintreatment

foropioidaddiction,almostall—94percent—saidtheychosetouseheroin

becauseprescriptionopioidswere"farmoreexpensiveandhardertoobtain"

.

References



Psychiatry.2014;71(7):821-826.

MarsSG,BourgoisP,KarandinosG,MonteroF,CiccaroneD."Every'never'

Ieversaidcametrue":transitionsfromopioidpillstoheroininjecting.IntJ

DrugPolicy.2014;25(2)257-266.

UnickG,RosenblumD,MarsS,CiccaroneD.TherelationshipbetweenUS

heroinmarketdynamicsandheroin-relatedoverdose,1992-2008.

(Unicketal.,2014)

(Marsetal.,2014)

(Ciceroetal.,2014)

https://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-abuse-heroin-use/increased-drug-availability-associated-increased-use-overdose

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Addiction.2014;109(11):1889-1898.

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Emphasisisneededonboth

preventionandtreatment

Withtheincreasinguseofopioids,therehasbeenaconcomitantincreasein

thenumberoftreatmentadmissionsattributabletoprescriptionopioidsand

heroin.Thenumberofpersonsreceivingsubstanceusetreatmentfor

prescriptionopioidsrosefrom360,000in2002,representing10.3percentofthe

totaltreatmentpopulation,to772,000(18.6percent)in2014 .The

numberofpersonsreceivingtreatmentforheroinincreasedfrom277,000in

2002to618,000in2014 .Inaddition,thenumberofheroinusers

intheUnitedStatesjumpedfromabout404,000in2002to914,000in2014,

andthenumberofthosewithheroin"dependenceorabuse"morethandoubled

from2002to2014,increasingfromabout214,000to586,000 .

Inadditiontoeffortstopreventinitiationofabuseofprescriptionopioidsanduse

ofheroin,thereisasignificantneedtoidentifyandtreatpeoplewhohave

(CBHSQ,2015b)

(CBHSQ,2015b)

(CBHSQ,2015a)

Numberofpersons12yearsorolderwhoreceivedlastorcurrentsubstanceuse

treatmentforheroinorpainrelievers.Source:CBHSQ,2015b

https://www.drugabuse.gov/sites/default/files/fig4prescripheroin.jpg

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alreadydevelopedanaddictiontothesesubstances.Theprescriptiondrug

monitoringprogramsareonemeansbywhichstatesareidentifyingindividuals

whoaredoctorshopping.Inaddition,thereareongoingeffortstoencourage

healthcarepractitionerstoscreenpatientsforpotentialdrugabuseproblems.

However,identificationisonlythefirststep;itiscriticaltoprovideevidence-

basedtreatmentsfortheseindividuals.Treatmentshouldincludeaccesstothe

medication-assistedtreatment(MAT)optionsofmethadone,buprenorphine,or

extended-releasenaltrexone,whichareeffectiveforbothprescriptionopioid

andheroinaddiction.Infact,aNIDAstudyfoundthatoncetreatmentisinitiated,

bothabuprenorphine/naloxonecombinationandanextendedrelease

naltrexoneformulationaresimilarlyeffectiveintreatingopioidusedisorder.

Becausefulldetoxificationisnecessaryfortreatmentwithnaloxone,initiating

treatmentamongactiveuserswasdifficult,butoncedetoxificationwas

complete,bothmedicationshadsimilareffectiveness.Currently,farfewer

peoplereceiveMATthancouldpotentiallybenefitfromit.NearlyallU.S.states

havehigherratesofopioidabuseanddependencethantheirbuprenorphine

treatmentcapacity ,andfewerthan1millionofthe2.5million

Americanswhoabusedorweredependentonopioidsin2012receivedMAT

.RemovingbarrierstoMATaccessandutilizationisatop

priorityfortheU.S.DepartmentofHealthandHumanServicesandisakey

objectiveoftheSecretary’sOpioidInitiativetocombatopioiddrug-related

dependenceandoverdose.

References

CenterforBehavioralHealthStatisticsandQuality(CBHSQ).Table7.50A.

2014NationalSurveyonDrugUseandHealth:DetailedTables.Substance

AbuseandMentalHealthServicesAdministration,Rockville,MD;2015.

CenterforBehavioralHealthStatisticsandQuality(CBHSQ).Table7.62A.

2014NationalSurveyonDrugUseandHealth:DetailedTables.Substance

AbuseandMentalHealthServicesAdministration,Rockville,MD;2015.

JonesCM,CampopianoM,BaldwinG,McCance-KatzE.Nationalandstate

treatmentneedandcapacityforopioidagonistmedication-assisted

treatment.AmJPublicHealth.2015;105(8):e55-e63.

VolkowND,FriedenTR,HydePS,andChaSS.Medication-assisted

therapies—tacklingtheopioid-overdoseepidemic.NEnglJMed.

(Jonesetal.,2015)

(VolkowNDetal.,2014)

http://www.hhs.gov/news/press/2015pres/03/20150326a.html

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2014;370(22):2063-2066.

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NationalInstituteonDrugAbuse(NIDA)

MedicationstoTreatOpioidAddiction

LastUpdatedJanuary2018

https://www.drugabuse.gov

https://www.drugabuse.gov/

2

TableofContents

MedicationstoTreatOpioidAddiction

Overview

HowDoMedicationstoTreatOpioidAddictionWork?

EfficacyofMedicationsforOpioidUseDisorder

MisconceptionsAboutMaintenanceTreatment

TreatmentNeedvs.DiversionRiskforOpioidAddictionTreatmentMedications

ImpactofMedicationforAddictionTreatmentonHIV/HCVOutcomes

TreatmentofOpioidUseDisorderintheCriminalJusticeSystem

OpioidAddictionMedicationintheMilitary

TreatmentforPregnantMothersandBabies

HowMuchDoesOpioidTreatmentCost?

AccesstoNaloxone

References

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Overview

Anestimated2millionpeopleintheUnitedStatessufferedfromsubstanceuse

disordersrelatedtoprescriptionopioidpainmedicinesin2015. Treatment

admissionslinkedtothesemedicationsmorethanquadrupledbetween2002

and2012,althoughonlyafractionofpeoplewithprescriptionopioiduse

disordersreceivespecialtytreatment(18percentin2015). Overdosedeaths

linkedtothesemedicinesnearlyquadrupled(from4,400tonearly19,000,or

1.5to5.9per100,000persons)from2000to2014. Thereisnowalsoarisein

heroinuseandheroinaddictionassomepeopleshiftfromprescriptionopioids

totheircheaperstreetrelative;591,000peoplehadaheroinusedisorderin

2015,andnearly13,000Americansdiedofaheroinoverdosein2015.

Besidesoverdose,consequencesoftheopioidcrisisincludearisingincidence

ofinfantsborndependentonopioidsbecausetheirmothersusedthese

substancesduringpregnancy andincreasedspreadofinfectiousdiseases,

includingHIVandhepatitisC(HCV),aswasseenin2015insouthernIndiana.

Effectivepreventionandtreatmentstrategiesexistforopioidmisuseand

addictionbutarehighlyunderutilizedacrosstheUnitedStates.Aninitiativeof

theSecretaryofHealthandHumanServices beganin2015toaddressthe

complexproblemofprescriptionopioidandheroinuse.Thisinitiative

emphasizesimprovededucationofhealthcareprovidersinmanagingpainand

prescribingopioidsappropriately;wideravailabilityandadoptionoftheeffective

overdose-reversingdrugnaloxone,whichresearchhasshowntobealifesaver

incommunitieswhereithasbeendistributedtopeoplewhouseopioids,their

families,andpotentialbystanders; andwiderimplementationofevidence-

basedtreatmentstrategies.

Effectivemedicationsexisttotreatopioidusedisorders:methadone,

buprenorphine,andnaltrexone.Thesemedicationscouldhelpmanypeople

recoverfromopioidaddiction,buttheyremainhighlyunderutilized.Fewerthan

halfofprivate-sectortreatmentprogramsoffermedicationsforopioiduse

disorders,andofpatientsinthoseprogramswhomightbenefit,onlyathird

actuallyreceiveit. Overcomingthemisunderstandingsandotherbarriersthat

preventwideradoptionofthesetreatmentsiscrucialfortacklingtheproblemof

opioidaddictionandtheepidemicofopioidoverdoseintheUnitedStates.

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4,5

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https://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/references

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HowDoMedicationstoTreatOpioid

AddictionWork?

OpioidAgonistsandPartialAgonists(Maintenance

Medications)

Studiesshowthatpeoplewithopioidaddictionwhofollowdetoxificationwith

completeabstinenceareverylikelytoreturntousingthedrug(relapse). While

relapseisanormalsteponthepathtorecovery,itcanalsobelifethreatening,

raisingtheriskforafataloverdose. Thus,animportantwaytosupport

recoveryfromheroinorprescriptionopioidaddictionistomaintainabstinence

fromthosedrugsusingmedicationsthatreducethenegativeeffectsof

withdrawalandcravingwithoutproducingtheeuphoriathattheoriginaldrugof

abusecaused.Methadoneandbuprenorphinearemedicationsapprovedfor

thispurpose.

Methadoneisasyntheticopioidagonistthateliminateswithdrawalsymptoms

andrelievesdrugcravingsbyactingonopioidreceptorsinthebrain—thesame

receptorsthatotheropioidssuchasheroin,morphine,andopioidpain

medicationsactivate.Althoughitoccupiesandactivatestheseopioidreceptors,

itdoessomoreslowlythanotheropioidsand,inanopioid-dependentperson,

treatmentdosesdonotproduceeuphoria.Ithasbeenusedsuccessfullyfor

morethan40yearstotreatopioidaddictionandmustbedispensedthrough

specializedopioidtreatmentprograms.

Buprenorphineisapartialopioidagonist,meaningthatitbindstothosesame

opioidreceptorsbutactivatesthemlessstronglythanfullagonistsdo.Like

methadone,itcanreducecravingsandwithdrawalsymptomsinapersonwith

anopioidusedisorderwithoutproducingeuphoria,andpatientstolerateitwell.

Researchhasfoundbuprenorphinetobesimilarlyeffectiveasmethadonefor

treatingopioidusedisorders,aslongasitisgivenatasufficientdoseandfor

sufficientduration. Unlikemethadone,buprenorphinecanbeprescribedby

certifiedphysiciansinanofficesetting.Ithasbeenavailablesince2002asa

tabletandsince2010asasublingualfilm, andtheU.S.FoodandDrug

Administration(FDA)approveda6-monthsubdermalbuprenorphineimplantin

10

11

12

13

14

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5

May2016andaonce-monthlybuprenorphineinjectioninNovember2017.

Bothformulationsareavailabletopatientsstabilizedonbuprenorphineandwill

eliminatethetreatmentbarrierofdailydosingforthesepatients.(Alsosee

"MisconceptionsAboutMaintenanceTreatment")

OpioidAntagonists

Naltrexoneisanopioidantagonist,whichmeansthatitworksbyblockingthe

activationofopioidreceptors.Insteadofcontrollingwithdrawalandcravings,it

treatsaddictionbypreventinganyopioiddrugfromproducingrewardingeffects

suchaseuphoria.Itsuseforongoingaddictiontreatmenthasbeensomewhat

limitedbecauseofpooradherenceandtolerabilitybypatients.However,in

2010aninjectable,long-actingformofnaltrexone(Vivitrol ),originally

approvedfortreatingalcoholusedisorder,wasFDA-approvedfortreating

opioidaddiction.Becauseitseffectslastforweeks,Vivitrol isagoodoptionfor

patientswhodonothavereadyaccesstohealthcareorwhostrugglewith

takingtheirmedicationsregularly.

Becauseeachmedicationworksdifferently,atreatmentprovidershoulddecide

ontheoptimalmedicationinconsultationwiththeindividualpatientandshould

considerthepatient’scaseuniquehistoryandcircumstances(see"Efficacyof

MedicationsforOpioidUseDisorder").

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6

EfficacyofMedicationsforOpioid

UseDisorder

Abundantevidenceshowsthatmethadone,buprenorphine,andnaltrexoneall

reduceopioiduseandopioidusedisorder-relatedsymptoms,andtheyreduce

theriskofinfectiousdiseasetransmissionaswellascriminalbehavior

associatedwithdruguse. Thesemedicationsalsoincreasethelikelihoodthat

apersonwillremainintreatment(treatmentretention),whichitselfisassociated

withlowerriskofoverdosemortality,reducedriskofHIVandHCVtransmission,

reducedcriminaljusticeinvolvement,andgreaterlikelihoodofemployment.

Methadone

Methadoneisthemedicationwiththelongesthistoryofuseforopioiduse

disordertreatment,havingbeenusedsince1947.Alargenumberofstudies

(someofwhicharesummarizedinthegraphbelow)supportmethadone's

effectivenessatreducingopioiduse.AcomprehensiveCochranereviewin

2009comparedmethadone-basedtreatment(methadonepluspsychosocial

treatment)toplacebowithpsychosocialtreatmentandfoundthatmethadone

treatmentwaseffectiveinreducingopioiduse,opioiduse–associated

transmissionofinfectiousdisease,andcrime. Patientsonmethadone

had33percentfeweropioid-positivedrugtestsandwere4.44timesmorelikely

tostayintreatmentcomparedtocontrols. Methadonetreatmentsignificantly

improvesoutcomes,evenwhenprovidedintheabsenceofregularcounseling

services; long-term(beyond6months)outcomesarebetteringroups

receivingmethadone,regardlessofthefrequencyofcounselingreceived.

15

15

12,16–20

12

18,19,21

22,23

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7

Buprenorphine

Buprenorphine,whichwasfirstapprovedin2002,iscurrentlyavailableintwo

forms:alone(Subutex )andincombinationwiththeopioidreceptorantagonist

naloxone(Suboxone ).Thelatterformulationisdesignedtodeterdiversion

andmisuse:thenaloxonehasnoeffectsolongasthedrugistakenorally,as

intended;ifitiscrushed,dissolved,andinjected,thenaloxoneblockstheeffect

ofthebuprenorphine.Bothformulationsofbuprenorphineareeffectiveforthe

treatmentofopioidusedisorders,thoughrecentstudieshaveshownhigh

recidivismratesamongpatientstaperedoffofbuprenorphinecomparedto

patientsmaintainedonthedrugforalongerperiodoftime.

®

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24

https://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/referenceshttps://www.drugabuse.gov/sites/default/files/methadone_treatment.gif

8

ASwedishstudycomparedpatientsmaintainedon16mgofbuprenorphine

dailytoacontrolgroupthatreceivedbuprenorphinefordetoxification(6days)

followedbyplacebo. Allpatientsreceivedpsychosocialsupports.Inthisstudy,

thetreatmentfailurerateforplacebowas100percentvs.25percentfor

buprenorphine—morethantwoopioid-positiveurinetestswithin3months

resultedincessationoftreatment,sotreatmentretentionwascloselyrelatedto

relapse.Ofpatientsnotretainedintreatment,therewasa20percentmortality

rate.

Meta-analysisdeterminedthatpatientsondosesofbuprenorphineof16mgper

dayormorewere1.82timesmorelikelytostayintreatmentthanplacebo-

treatedpatients,andbuprenorphinedecreasedthenumberofopioid-positive

drugtestsby14.2to25percent(thestandardizedmeandifferencewas

-1.17).

Tobeeffective,buprenorphinemustbegivenatasufficientlyhighdose

(generally,16mgperdayormore).Sometreatmentproviderswaryofusing

opioidshaveprescribedlowerdosesforshorttreatmentdurations,leadingto

failureofbuprenorphinetreatmentandthemistakenconclusionthatthe

medicationisineffective.

Source:Kakkoetal.,2003

25

13,25,26

13,27

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9

MethadoneandBuprenorphineCompared

Methadoneandbuprenorphineareequallyeffectiveatreducingopioiduse.A

comprehensiveCochranereviewcomparingbuprenorphine,methadone,and

placebofoundnodifferencesinopioid-positivedrugtestsorself-reported

heroinusewhentreatingwithmethadoneorbuprenorphineatmedium-to-high

doses.

Notably,flexibledoseregimensofbuprenorphineanddosesofbuprenorphine

of6mgorbelowarelesseffectivethanmethadoneatkeepingpatientsin

treatment,highlightingtheneedfordeliveryofevidence-baseddosing

regimensofthesemedications.

Naltrexone

Naltrexonewasinitiallyapprovedforthetreatmentofopioidusedisorderina

dailypillform.Itisanantagonistmedicationthatdoesnotproducetoleranceor

withdrawal.Poortreatmentadherencehasprimarilylimitedthereal-world

effectivenessofthisformulation. Asaresult,thereisinsufficientevidencethat

oralnaltrexoneisaneffectivetreatmentforopioidusedisorder. Extended-

releaseinjectablenaltrexone(XR-NTX)isadministeredoncemonthly,which

13

13

28

29

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10

removestheneedfordailydosing.Whilethisformulationisthenewestformof

medicationforopioidusedisorder,evidencetodatesuggeststhatitis

effective.

Thedouble-blind,placebo-controlledtrialthatwasmostinfluentialingetting

XR-NTXapprovedbytheFDAin2010foropioidusedisordertreatmentshowed

thatXR-NTXsignificantlyincreasedopioidabstinence;theXR-NTXgrouphad

90percentconfirmedabstinentweekscomparedto35percentintheplacebo

group.TreatmentretentionwasalsohigherintheXR-NTXgroup(58percentvs.

42percent),whilesubjectivedrugcravingandrelapse(0.8percentvs.13.7

percent)werebothdecreased. ImprovementintheXR-NTXgroupwas

sustainedthroughoutanopenlabelperiodoutto76weeks. Thesedatawere

collectedinRussia,andadditionalstudiesarerequiredtodetermineif

effectivenesswillbesimilarintheUnitedStates.

BuprenorphineandNaltrexoneCompared

ANIDAstudyshowsthatoncetreatmentisinitiated,abuprenorphine/naloxone

combinationandanextendedreleasenaltrexoneformulationaresimilarly

effectiveintreatingopioidusedisorder.Becausenaltrexonerequiresfull

detoxification,initiatingtreatmentamongactiveopioiduserswasmoredifficult

withthismedication.However,oncedetoxificationwascomplete,thenaltrexone

formulationhadasimilareffectivenessasthebuprenorphine/naloxone

combination.

28,30

31

32

33

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11

MisconceptionsAboutMaintenance

Treatment

Becausemaintenancemedications(methadoneandbuprenorphine)are

themselvesopioidsandareabletoproduceeuphoriainpeoplewhoarenot

dependentonopioids,manypeoplehaveassumedthatthisformoftreatment

justsubstitutesanewaddictionforanoldone.Thisbeliefhasunfortunately

hinderedtheadoptionoftheseeffectivetreatments.Inthepast,evensome

inpatienttreatmentprogramsthatwereotherwiseevidencebaseddidnotallow

patientstousethesemedications,infavorofan"abstinenceonly"philosophy.

Althoughitispossibleforindividualswhodonothaveanopioidaddictiontoget

highonbuprenorphineormethadone(see"TreatmentNeedvs.DiversionRisk

forOpioidAddictionTreatmentMedications"),thesemedicationsaffectpeople

whohavedevelopedahightolerance(see"OpioidTolerance")toopioids

differently.Atthedosesprescribed,andasaresultoftheirpharmacodynamic

andpharmacokineticproperties(thewaytheyactatopioidreceptorsitesand

theirslowermetabolisminthebody),thesemedicationsdonotproducea

euphoric"high"butinsteadminimizewithdrawalsymptomsandcravings(see

"MechanismsofOpioidDependence").Thismakesitpossibleforthepatientto

functionnormally,attendschoolorwork,andparticipateinotherformsof

treatmentorrecoverysupportservicestohelpthembecomefreeoftheir

addictionovertime.

Theultimateaimcanbetoweanoffthemaintenancemedication,butthe

treatmentprovidershouldmakethisdecisionjointlywiththepatient,and

taperingthemedicationmustbedonegradually.Itmaytakemonthsoryearsin

somecases.Justasbodytissuesrequireprolongedperiodstohealafterinjury

andmayrequireexternalsupports(e.g.,acastandcrutchesorawheelchairfor

abrokenleg),braincircuitsthathavebeenalteredbyprolongeddruguseand

addictiontaketimetorecoverandbenefitfromexternalsupportsintheformof

medication.Incasesofseriousandlong-termopioidaddiction,apatientmay

needthesesupportsindefinitely.

In2005,methadoneandbuprenorphinewereaddedtotheWorldHealth

https://www.drugabuse.gov/publications/research-reports/medications-to-treat-opioid-addiction/treatment-need-vs-diversion-risk-opioid-addiction-treatment-medicationsfile:////disk2/www/nida7/sites/default/files/node_pdf/21349-medications-to-treat-opioid-addiction.html#opioid%20tolerancefile:////disk2/www/nida7/sites/default/files/node_pdf/21349-medications-to-treat-opioid-addiction.html#opioid%20dependence

12

Organization'slistofessentialmedicines,definedasmedicinesthatare

"intendedtobeavailablewithinthecontextoffunctioninghealthcaresystemsat

alltimesinadequateamounts,intheappropriatedosageforms,withassured

quality,andatapricetheindividualandthecommunitycanafford."

OpioidTolerance

Peoplewhotakeopioidsforlongperiodsoftimetypicallydevelop

tolerance,astateinwhichmoreofthedrugisneededtoproducethesame

effect.Receptordesensitizationanddownregulationaremolecular

processesthatcausetolerance.Inpeoplewithopioidusedisorder,the

brainiscontinuallyexposedtohighlevelsofopioidsaswellasdopamine,

whichisreleasedintherewardcircuitfollowingopioidreceptoractivation.

Braincellsrespondtothisbyreducingtheirresponsetoreceptoractivation

andbyremovingopioidanddopaminereceptorsfromthecellmembrane,

resultinginfewerreceptorsthatcanbeactivatedbythedrug. These

mechanismsresultinalessenedresponsetothedrug,sohigherdoses

arerequiredtoelicitthesameeffect.Thisopioidtoleranceisthereason

thatpeoplewithopioidusedisorderdonotexperienceeuphoriceffects

fromtherapeuticdosesofbuprenorphineormethadone,whilepeople

withoutopioidusedisorderdo. Itisalsothereasonwhypeopleareat

increasedriskofoverdosewhenrelapsingtoopioiduseafteraperiodof

abstinence:Theylosetheirtolerancetothedrugwithoutrealizingit,so

theynolongerknowwhatdoseofthedrugtheycansafelytolerate.

34,35

36,37

38,39

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13

MechanismsofOpioidDependence

Thesustainedactivationofopioidreceptorsthatresultsfromopioiduse

disorderandcausestolerancealsocauseswithdrawalsymptomswhenthe

opioiddrugsleavethebody.Drugwithdrawalsymptomsareoppositeto

thesymptomscausedbydrugtaking.Inthecaseofopioids,theyinclude

anxiety,jitters,anddiarrhea. Avoidanceofthesenegativesymptomsis

onereasonthatpeoplekeeptakingopioids,andintheearlystagesof

treatment,medicationssuchasmethadoneandbuprenorphinereduce

withdrawalsymptoms.

40

Opioidreceptoractivity.Heroin(redline)activatesopioidreceptorsfullyand

quickly.Methadone(blue)isalsoafullagonist,buttheactivationismuchslower

andlongerlasting.Buprenorphine(green)activatesthereceptorspartially,with

asimilartimecoursetomethadone.Naltrexone(purple)isanopioidreceptor

antagonistandthereforepreventsreceptoractivation.

Sources:Cruciani&Knotkova,2013;Goodmanetal.,2006

41,42

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14

TreatmentNeedvs.DiversionRiskfor

OpioidAddictionTreatment

Medications

Likeotheropioidmedications,buprenorphineandmethadonearesometimes

divertedandmisused.However,mostdatasuggestthatthemajorityof

buprenorphineandmethadonemisuse(usewithoutaprescription)isforthe

purposeofcontrollingwithdrawalandcravingsforotheropioidsandnottoget

high.Amongallopioidagonistmedications,methadoneandbuprenorphine

togethermakeup15percentofdiversionreports,whileoxycodoneand

hydrocodoneareresponsiblefor67percent. Naltrexone,thethirdmedication

usedtotreatopioidaddiction,isanopioidantagonist,whichmeansitdoesnot

causeeuphoriceffectsandisnotadiversionrisk.

Bothbuprenorphineandbuprenorphine/naloxoneformulationscaninterfere

withtheeffectsoffullopioidagonistssuchasheroinandcanprecipitate

withdrawalinindividualswithopioiddependence.TwoU.S.surveysofpeople

withopioidusedisordersfoundthatamajorityofthosewhousedillicit

buprenorphinereportedthattheyuseditfortherapeuticpurposes(i.e.,to

reducewithdrawalsymptoms,reduceheroinuse,etc.). Ninety-seven

percentreportedusingtopreventcravings,90percenttopreventwithdrawal,

and29percenttosavemoney. Illicituseofbuprenorphinedecreasedas

individualshadaccesstotreatment. Theminorityproportionofpeoplewho

usebuprenorphineillicitlytogethigh(rangingfrom8to25percent) has

beenshowntodecreaseovertime,whichcouldsuggestthatpeopleabandon

thisgoalaftertheyexperiencethedrug’sbluntedrewardingeffects. Indeed,

patientsintreatmentforopioidusedisorderrarelyendorsebuprenorphineas

theprimarydrugofabuse.

Methadonediversionisprimarilyassociatedwithmethadoneprescribedforthe

treatmentofpain,andnotforthetreatmentofopioidusedisorders.Opioid

treatmentprogramsarerequiredtomaintainandimplementadiversioncontrol

plan;theytypicallyrequirepatientstocomeindailytoreceivetheirmedication

andstrictlymonitortake-homedoses.Inaddition,evidencesuggeststhatthe

43

44,45

45

45

45,46

46

47

48

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15

diversionthatdoesoccurisassociatedwithalackofaccesstomedication. In

onesurvey,givingmethadoneawaywasidentifiedasthemostcommonformof

methadonediversion, whichalignswithotherfindingsthat80percentof

peoplewhoreportdivertingmethadonedidsotohelpotherswhomisused

substances. Amongthoseusingillicitmethadone,themostcommonreason

wasamissedmedicationpick-up.

Whilethereissomeriskassociatedwithmisuseofbuprenorphine,theriskof

harms,suchasfataloverdose,aresignificantlylowerthanthoseoffullagonist

opioids(oxycodone,hydrocodone,heroin). Overdosesandrelateddeaths

dooccurbutareusuallytheresultofcombinationwithotherrespiratory

depressantdrugssuchasbenzodiazepinesoralcohol.Emergencydepartment

(ED)visitsinvolvingbuprenorphineincreasedfrom3,161in2005to30,135

visitsin2010asavailabilityofthedrugincreased(buprenorphinewasfirst

approvedin2002);butEDvisitsforbuprenorphineremainsignificantlyless

commonthanthoseforotheropioids. Fifty-twopercent,or15,778visits(see

leftbarchartbelow),wererelatedtononmedicalusein2010;59percentof

thesevisitsinvolvedadditionaldrugs(seerightbarchartbelow).

Methadone,asafullopioidagonistthatismetabolizedslowly,posesagreater

riskofoverdosethanbuprenorphine.In2010,65,945EDvisitsinvolved

nonmedicaluseofmethadone. However,methadonethatisdispensedfor

useasapainreliever,notasanaddictionmedication,isthemainsourceofthe

methadoneinvolvedinoverdosedeaths.

48

49

48,50

50

39,51

52

53,54

53

55

Emergencydepartment(ED)visitsinvolvingbuprenorphineincreasedasdrug

availabilityincreased,butEDvisitsforbuprenorphinearefarlesscommonthanthose

forotheropioids.


16

Source:CBHSQ,2011

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17

ImpactofMedicationforAddiction

TreatmentonHIV/HCVOutcomes

InjectiondruguseisstillaprimarydriveroftheHIV/AIDSepidemicacrossthe

world. ArecentexampleisthesmallcommunityofAustin,Indiana,where170

newHIVinfectionsoccurredinthe8monthsbetweenNovember2014and

June2015amongpeoplemisusingtheprescriptionopioidpainreliever

oxymorphone(Opana )viainjection. Peoplewhoinjectdrugsfrequentlyshare

theirneedlesandotherinjectionequipment,enablingvirusessuchasHIVand

hepatitisC(HCV)tospreadbetweenpeople.

MedicationsforaddictiontreatmentcanreducetransmissionofHIVandHCVby

reducingriskbehaviorsinpeoplewhoinjectdrugsandcanimproveHIV-and

HCV-relatedoutcomesbytreatingthosenotengagedininjectionopioiduse

whomightotherwisetransitiontoinjection,linkingthosewithHIV/HCVinfection

toappropriatetreatment andimprovingadherencetoHIV/HCV

treatment. Theseimprovementsdependonaccessibilityofmedicationsfor

opioidusedisorderstopeoplewhoneeditandcoordinatingmedication

deliverywithHCV/HIVscreeningandtreatment.

Treatmentwithmethadoneorbuprenorphineisassociatedwithreduced

injectiondruguseriskbehaviors.Meta-analyseshaveshownareductioninrisk

behaviorsincludinga32to69percentreductioninillicitopioiduse,a20to60

percentreductionininjectiondruguse,anda25to86percentreductionin

sharingofinjectionequipment. Treatmentwithextended-release

naltrexonealsoreducedHIVriskbehaviorscomparedtoplacebo.

MethadoneandbuprenorphinetreatmentarealsoassociatedwithlowerHCV

infectionratesinyoungadultswhoinjectsdrugs,whileothertreatmentsand

detoxificationalonearenot. Methadonetreatmentisassociatedwithlowrates

ofcontractingHCVoverall, withmathematicalmodelingsuggestingthatitcan

prevent22.6newHCVinfectionsper100treatedpeoplewhoengagedin

injectiondruguse,peryear. MethadonetreatmentalsoreducesbothHIV

riskbehaviorsandHIVinfection,withbetteroutcomesforpeoplewhoinject

drugswhoareintreatment(3.5percentcontractingHIVvs.22percent),and

56

® 6

57,58

59,60

61,62

31

63

64

65,66

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18

betteroutcomesforlongertreatmentdurationandforcontinuous(vs.

interrupted)treatment.

Astudycomparingtheeffectsofmethadoneandbuprenorphinetreatmenton

HIVriskfrominjectionbehaviorsandHIVriskfromsexualbehaviorsshowed

equalandsignificantreductionsinriskyinjectionbehaviors.Riskysexual

behaviorswerereducedinbothmaleandfemalemethadonepatientsbutwere

higherinmalepatientsonbuprenorphine.

MitigatingFactors

ThereareseveralknowninteractionsbetweenmedicationsusedtotreatHIVor

HCVandbothmethadoneandbuprenorphine. Thesecouldrequirean

adjustmentofdosageorrevisionofthetreatmentplan,andhighlighttheneed

forintegratedcare.Forexample,somepatientsarereluctanttobeginhighly

activeantiretroviraltherapy(HAART)becauseofworriesthatitwillinterferewith

theirmethadonetreatment,sotreatmentprovidersshouldconsiderrevised

methadonedosesforthesepatients.

ContractingHCVwhileonmethadoneisassociatedwithcontinuedinjection

druguse. Somestudieshaveshownmethadonedetoxificationalonetobe

associatedwithincreasedratesofcontractingHIV,soongoingtreatmentwith

thismedicationiskeytoreducingtransmissionofviralinfection.

PossibilityofDualTherapeuticPotential

Onerecentreportdemonstratesthepotentialofbuprenorphinetocounteracta

neuroinflammatoryprocessthatisinvolvedinHIV-associatedneurocognitive

disorders,suggestingthatbuprenorphinecouldpotentiallybesimultaneously

therapeuticforopioidaddictionandHIV. Opioidusedisordermedications

arealsoassociatedwithincreasedadherencetoHAARTforthetreatmentof

HIV. SomeprovidershesitatetotreatHCVinpeoplewhoinjectdrugs,buta

naltrexoneimplantationclinicshowedratesofsustainedvirologicresponsein

theirpatientsthatwerecomparabletoclinicstreatingnon-injectiondrug-using

patients.

67–69

70

71,72

72

73

74

75,76

59,60

77


19

TreatmentofOpioidUseDisorderin

theCriminalJusticeSystem

Opioidusedisordersarehighlyprevalentamongcriminaljusticepopulations.

AccordingtodatafromtheU.S.DepartmentofJustice,approximatelyhalfof

stateandfederalprisonersmeetcriteriaforsubstanceusedisorder. Evenso,

therehasbeenreticenceincriminaljusticesettingstousingmedications

(methadone,buprenorphine,naltrexone)totreatopioidusedisorders.In

nationalsurveys,utilizationofthesemedicationsisverylowincriminaljustice

settings,includingdrugcourts, jails, andprisons. Thus,opioiduse

disordergoeslargelyuntreatedduringperiodsofincarceration,andopioiduse

oftenresumesafterrelease.

Aformerinmate’sriskofdeathwithinthefirst2weeksofreleaseismorethan

12timesthatofotherindividuals,withtheleadingcauseofdeathbeingafatal

overdose. Overdosesaremorecommonwhenapersonrelapsestodruguse

afteraperiodofabstinenceduetolossoftolerancetothedrug.Untreated

opioidusedisordersalsocontributetoareturntocriminalactivity,

reincarceration,andriskybehaviorcontributingtothespreadofHIVand

hepatitisBandCinfections(see"ImpactofMedicationforAddictionTreatment

onHIV/HCVoutcomes").

TheWorldHealthOrganization’sGuidelinesforthePsychosociallyAssisted

PharmacologicalTreatmentofOpioidDependencestates:"Prisonersshould

notbedeniedadequatehealthcarebecauseoftheirimprisonment...Opioid

withdrawal,agonistmaintenanceandnaltrexonetreatmentshouldallbe

availableinprisonsettings,andprisonersshouldnotbeforcedtoacceptany

particulartreatment."

Manystatescurrentlydonotofferappropriateaccesstoorutilizemedicationsto

treatopioidusedisordersamongarresteesorinmates, eventhough

researchhasshownmanybenefitsofincorporatingmedication-assisted

treatmentintocriminaljusticetreatmentprograms.Inmateswhoreceive

buprenorphinetreatmentpriortoreleasearemorelikelytoengageintreatment

aftertheirreleasethaninmateswhoonlyparticipateincounseling.

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79 80 81

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86

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20

Participantswhoengageinmethadonetreatmentandcounselinginprisonare

morelikelytoentercommunity-basedmethadonetreatmentcentersaftertheir

release(68.6percent)thanthosereceivingonlycounseling(7.8percent)or

thoseincounselingandreferredtoatreatmentcenter(50percent).

Inonestudy,inmateswhobeganbuprenorphinetreatmentwhileincarcerated

engagedinpost-releasetreatmentsooner,averaging3.9daysafterrelease,

comparedto9.2daysforparticipantsreferredtotreatmentpost-release. They

werealsolikelytostayintreatmentlongeriftheywereinitiatedintreatment

priortorelease(20.3weeksonaverage)thaniftheybegantreatmentaftertheir

release(13.2weeks).

Inmateswhoparticipateinmethadonetreatmentandcounselingwhileinprison

arelesslikelytotestpositiveforillicitopioidsatonemonthfollowingtheir

release(27.6percent)comparedtothosewhoonlyreceivecounseling(62.9

percent)andthosewhoreceivecounselingandareferraltoatreatmentcenter

(41percent).

Arandomizedcontrolledtrialwaspublishedin2016,comparingprison-initiated

extended-releasenaltrexone(XR-NTX)treatmenttostandardcounseling

protocolsforpreventionofopioidrelapse.Duringthetreatmentphase,relapse

wassignificantlylowerinthegroupreceivingXR-NTX(43percentvs.64

percent).TheXR-NTXgroupalsoexperiencednooverdoseevents,whilethere

weresevenoverdoseeventsinthecontrolgroup.

Asurveyofcommunitycorrectionagents’viewsonusingmedicationstotreat

opioidaddictionshowedthatmorefavorableattitudestowardmedicationuse

areassociatedwithgreaterknowledgeabouttheevidencebaseforthese

medicationsandgreaterunderstandingofaddictionasamedicaldisorder.

Organizationallinkagebetweencorrectionalstakeholdersandcommunity

treatmentproviders,alongwithtrainingsessions,canbeaneffectivewayto

changeperceptionsandincreaseknowledgeabouttheefficacyofthese

medicationsandcanincreasetheintentwithincorrectionalfacilitiestorefer

individualswithopioidusedisordertotreatmentthatincorporates

medications.

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21

Amechanismtoreducerecidivismanddivertnonviolentoffendersfrom

traditionaljailandprisonsettingsisthedrugtreatmentcourtmodel,which

providestreatmentservicesincombinationwithjudicialsupervision. Still,

resistancetomedicationspersistseveninthisareaofthecriminaljustice

system;asurveypublishedin2013reportedthat50percentofdrugcourtsdid

notallowagonisttreatmentforopioidusedisorderunderanycircumstances.

In2015,theOfficeofNationalDrugControlPolicyannouncedthatstatedrug

courtsreceivingfederalgrantsmustnot:1)denyanyappropriateandeligible

clientforthetreatmentdrugcourtaccesstotheprogrambecauseoftheiruseof

FDA-approvedmedications(methadone,injectablenaltrexone,non-injectable

naltrexone,disulfiram,acamprosatecalcium,buprenorphine,etc.)thatisin

accordancewithanappropriatelyauthorized[physician'sprescription];or2)

mandatethatadrugcourtclientnolongerusemedicationsaspartofthe

conditionsofthedrugcourtifsuchamandateisinconsistentwithaphysician’s

recommendationorprescription.

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OpioidAddictionMedicationinthe

Military

Ratesofprescriptionopioidmisusearehigheramongservicemembersthan

amongcivilians. Surveyresultssuggestdruguseamongreturningsoldiersis

oftenacopingstrategytotreatarousalsymptomsofpost-traumaticstress

disorder. Returningmilitarypersonnelalsoexperiencehigherratesofchronic

painandrelatedmedicaluseofopioidpainrelieverscomparedtothecivilian

population.Thesedatacollectivelysuggestanunmetneedfortheassessment,

management,andtreatmentofbothchronicpainandopioidusedisordersin

thispopulation.

TheVeteransHealthAdministration(VHA)acknowledgesthattreatmentwith

opioidagonists(methadoneorbuprenorphine)isthefirst-linetreatmentfor

opioidaddictionandrecommendsitforallopioid-dependentpatients.Notably,

a2015revisionoftreatmentguidelinesfortheU.S.DepartmentofVeteran

AffairsandU.S.DepartmentofDefenseshiftedtowardallowingthese

medicationsasatreatmentoptionforactivedutymilitarymembers. Still,only

aboutaquarterofpatientswithanopioidaddictiontreatedatVHAfacilities

receivemedication. BarrierstoopioidagonistmedicationamongVHA

providersinclude:lackofperceivedpatientinterest,stigmatowardthepatient

population,andlackofeducationaboutopioidagonisttreatment.

Inthepast,lackofinsurancecoverageforopioidagonistmedicationswasa

barrierforuseamongactivedutymilitary;however,asof2013,TRICARE

includedcoverageforthesemedications,anda2016modificationofTRICARE

regulationincludedprovisionsforexpandedcoverageofopioidusedisorder

treatment. Thisexpandedcoverageremovedannualandlifetimelimitations

onsubstanceusedisordertreatment,allowedforoffice-basedopioidtreatment

andestablishedopioidtreatmentprogramsasanewlyrecognizedcategoryof

institutionalproviderunderTRICARE.

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TreatmentforPregnantMothersand

Babies

Parallelingthelargerecentincreasesinopioiduse,usedisorders,and

overdose,theincidenceofbabiesborndependentonopioids(neonatal

abstinencesyndrome,orNAS)asaresultofthemother’sopioiduseduring

pregnancyhasalsogreatlyincreased. IncidenceofNASrosenearlyfivefold

between2000and2012; thisincreasewasassociatedwithincreasesinthe

prescriptionofopioidstopregnantwomenforpain,whichdoubledbetween

1995and2009.

Untreatedopioidaddictionduringpregnancycanhavedevastatingeffectson

thefetus.Thefluctuatinglevelsofopioidsinthebloodofmothersmisusing

opioidsexposethefetustorepeatedperiodsofwithdrawal, whichcanalso

harmthefunctionoftheplacentaandincreasetheriskof:

fetalgrowthrestriction

placentalabruption

pretermlabor

fetalconvulsions

fetaldeath

Source:Toliaetal.,2015

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4

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100

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intrauterinepassageofmeconium

Inadditiontothesedirectphysicaleffects,otherriskstothefetusinclude:

untreatedmaternalinfectionssuchasHIV

malnutritionandpoorprenatalcare

dangersconferredbydrug-seekinglifestyle,includingviolenceand

incarceration

MethadoneandBuprenorphineAstheStandardofCarefor

OpioidUseDisorderinPregnancy

Tolessenthenegativeeffectsofopioiddependenceonthefetus,treatmentwith

methadonehasbeenusedforpregnantwomenwithopioidusedisordersince

the1970sandhasbeenrecognizedasthestandardofcaresince1998.

Recentevidence,however,suggeststhatbuprenorphinemaybeanevenbetter

treatmentoption.

Bothmethadoneandbuprenorphinetreatmentduringpregnancy:

stabilizefetallevelsofopioids,reducingrepeatedprenatalwithdrawal

improveneonataloutcomes

increasematernalHIVtreatmenttoreducethelikelihoodoftransmittingthe

virustothefetus

linkmotherstobetterprenatalcare

Ameta-analysisshowedthat,comparedtosingle-dosemethadonetreatment,

buprenorphineresultedin:

10percentlowerincidenceofNAS

shorterneonataltreatmenttime(anaverageof8.4daysshorter)

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103

101,103

101,102

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100,105

101–103

101,103

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25

loweramountofmorphineusedforNAStreatment(anaverageof3.6mg

lower)

highergestationalage,weight,andheadcircumferenceatbirth

DatafromtheNIDA-fundedMaternalOpioidTreatment:HumanExperimental

Researchstudyshowsimilarbenefitsofbuprenorphine. Still,methadoneis

associatedwithhighertreatmentretentionthanbuprenorphine. Divided

dosingwithmethadonehasbeenexploredasawaytoreducefetalexposureto

withdrawalperiods,andrecentdatashowlowlevelsofNASinbabiesbornto

motherstreatedwithdivideddosesofmethadone. Largercomparison

studiesareneededtodetermineifsplitmethadonedosingforopioiduse

disordersinpregnancyisassociatedwithbetteroutcomes.

NASstilloccursinbabieswhosemothershavereceivedbuprenorphineor

methadone,butitislessseverethanitwouldbeintheabsenceoftreatment.

ResearchdoesnotsupportreducingmaternalmethadonedosetoavoidNAS,

asthismaypromoteincreasedillicitdruguse,resultinginincreasedrisktothe

fetus.

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Source:Jonesetal.,2010

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HowMuchDoesOpioidTreatment

Cost?

Althoughthepriceforopioidtreatmentmayvarybasedonanumberoffactors,

recentpreliminarycostestimatesfromtheU.S.DepartmentofDefensefor

treatmentinacertifiedopioidtreatmentprogram(OTP)provideareasonable

basisforcomparison:

methadonetreatment,includingmedication,andintegratedpsychosocial

andmedicalsupportservices(assumesdailyvisits):$126.00perweekor

$6,552.00peryear

buprenorphineforastablepatientprovidedinacertifiedOTPincluding

medicationandtwice-weeklyvisits:$115.00perweekor$5,980.00peryear

naltrexoneprovidedinanOTP,includingdrug,drugadministration,and

relatedservices:$1,176.50permonthor$14,112.00peryear

Toputthesecostsintocontext,itisusefultocomparethemwiththecostsof

otherconditions.AccordingtotheAgencyforHealthcareResearchandQuality,

annualexpendituresforindividualswhoreceivedhealthcareare$3,560.00for

thosewithdiabetesmellitusand$5,624.00forkidneydisease.

Itisalsoimportanttorememberthecostsassociatedwithuntreatedopioiduse

disorders,includingcostsassociatedwith:

criminaljustice

treatingbabiesborndependentonopioids

greatertransmissionofinfectiousdiseases

treatingoverdoses

injuriesassociatedwithintoxication(e.g.,druggeddriving)

lostproductivity

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27

Theamountpaidfortreatmentofsubstanceusedisordersisonlyasmall

portionofthecoststhesedisordersimposeonsociety.Arecentanalysis

suggestedthatthetotalcostsofprescriptionopioidusedisordersand

overdosesintheUnitedStateswas$78billionin2013.Ofthat,only3.6percent,

orabout$2.8billion,wasfortreatment. 110

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28

AccesstoNaloxone

Naloxoneisanopioidantagonistthatcanreverseanopioidoverdose.

Naloxoneaccessincreasedbetween2010and2014,with:

morethanthreetimesthenumberoflocalsitesprovidingnaloxone(from

188to644)

nearlythreetimesthenumberoflaypersonsprovidednaloxonekits(from

53,032to152,283)

a94percentincreaseinstates(from16to30),includingWashington,DC,

withatleastoneorganizationprovidingnaloxone

morethan2.5timesthenumberofoverdosereversalsreported(from

10,171to26,463)

Naloxoneprescriptionsdispensedfromretailpharmaciesincreasednearly

twelvefoldbetweenthefourthquarterof2013andthesecondquarterof

2015.

Manystateshavepassedlawstowidentheavailabilitytonaloxoneforfamily,

friends,andotherpotentialbystandersofoverdose.

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Naloxonehasbecomewidelyusedbyemergencymedicalproviders,withall50

statesandtheDistrictofColumbia,Guam,andPuertoRicocertifyingand

approvingemergencymedicalservicepersonnelattheparamediclevelto

administernaloxone.Onestepfurther,emergencymedicaltechnicians(EMTs)

wereexplicitlypermittedtoadministernaloxonein12ofthese53jurisdictions

(23percent—California,Colorado,DistrictofColumbia,Massachusetts,

Maryland,NewMexico,NorthCarolina,Ohio,Oklahoma,RhodeIsland,

Virginia,andVermont)asofNovember2013.BecausenonparamedicEMTs

aretypicallythefirstandsometimesonlysourceofemergencycare,providing

authorizationandtrainingforthemtoadministernaloxoneisapromising

strategytoreduceoverdosedeaths.

Afteranaloxonetrainingsession,amajorityofpoliceofficersreportedthatit

wouldnotbedifficulttousenaloxoneatthesceneofanoverdose(89.7

percent)andthatitwasimportantthatotherofficersbetrainedtousenaloxone

(82.9percent).

EffectsofNaloxoneDistribution

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Overdoseeducationandnaloxonedistribution(OEND)hasbeenshownto

increasethereversalofpotentiallyfataloverdoses;onestudyshowedopioid

overdosedeathratestobe27to46percentlowerincommunitieswhereOEND

wasimplemented. Among4,926peoplewhousedsubstancesand

participatedinOENDinMassachusetts,373(7.6percent)reported

administeringnaloxoneduringanoverdoserescue,withfewdifferencesin

behaviorbetweentrainedanduntrainedoverdoserescuers. Analoxone

distributionstudyinSanFranciscoreportedthat11percentofparticipantsused

naloxoneduringanoverdose;of399overdoseeventswherenaloxonewas

used,89percentwerereversed. Briefeducationissufficienttoimprove

comfortandcompetenceinrecognizingandmanagingoverdose.

Prospectivestudiesareneededtodeterminetheoptimalleveloftrainingand

whethernaloxonerescuekitscanmeetthestandardforbecomingavailable

overthecounter.

Inaprobabilisticanalysis,naloxonedistributionprogramswereshownto

preventoverdosedeaths,increasequality-adjustedlifeyears(QALYs)andbe

highlycost-effective.Naloxonedistributionwaspredictedtoprevent6percentof

overdosedeaths,1forevery227naloxonekitsdistributed.Costeffectiveness,

undermarkedlyconservativepredictions,wasmeasuredtobe$14,000.00per

QALY,wellwithinthestandardfavorablerangeofcost-benefitratios(under

$50,000.00perQALY).

Criticsofnaloxonedistributionhaveclaimedthatitcouldleadtoanincreasein

riskyopioiduse,butastudyinMassachusettsshowedratesofopioid-related

visitstoanemergencydepartmentandhospitaladmissionwerenotsignificantly

differentincommunitieswithloworhighimplementationofOENDprograms.

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References

1. SubstanceAbuseCenterforBehavioralHealthStatisticsandQuality.

Resultsfromthe2015NationalSurveyonDrugUseandHealth:Detailed

Tables.SAMHSA.https://www.samhsa.gov/data/sites/default/files/NSDUH-

DetTabs-2015/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015.pdf.

PublishedSeptember8,2016.AccessedJanuary18,2017.

2. RuddRA,AleshireN,ZibbellJE,GladdenRM.IncreasesinDrugand

OpioidOverdoseDeaths--UnitedStates,2000-2014.MMWRMorbMortal

WklyRep.2016;64(50-51):1378-1382.doi:10.15585/mmwr.mm6450a3.

3. RuddRA,SethP,DavidF,SchollL.IncreasesinDrugandOpioid-Involved

OverdoseDeaths-UnitedStates,2010-2015.MMWRMorbMortalWkly

Rep.2016;65(5051):1445-1452.doi:10.15585/mmwr.mm655051e1.

4. PatrickSW,DavisMM,LehmannCU,LehmanCU,CooperWO.Increasing

incidenceandgeographicdistributionofneonatalabstinencesyndrome:

UnitedStates2009to2012.JPerinatolOffJCalifPerinatAssoc.

2015;35(8):650-655.doi:10.1038/jp.2015.36.

5. ToliaVN,PatrickSW,BennettMM,etal.Increasingincidenceofthe

neonatalabstinencesyndromeinU.S.neonatalICUs.NEnglJMed.

2015;372(22):2118-2126.doi:10.1056/NEJMsa1500439.

6. ConradC,BradleyHM,BrozD,etal.CommunityOutbreakofHIVInfection

LinkedtoInjectionDrugUseofOxymorphone--Indiana,2015.MMWRMorb

MortalWklyRep.2015;64(16):443-444.

7. U.S.DepartmentofHealthandHumanServices,OfficeoftheAssistant

SecretaryforPlanningandEvaluation.OpioidAbuseintheU.S.andHHS

ActionstoAddressOpioid-DrugRelatedOverdosesandDeaths.ASPE.

https://aspe.hhs.gov/pdf-report/opioid-abuse-us-and-hhs-actions-address-

opioid-drug-related-overdoses-and-deaths.PublishedNovember23,2015.

AccessedMay11,2017.

8. WheelerE,JonesTS,GilbertMK,DavidsonPJ,CentersforDiseaseControl

andPrevention(CDC).OpioidOverdosePreventionProgramsProviding

NaloxonetoLaypersons-UnitedStates,2014.MMWRMorbMortalWkly

Rep.2015;64(23):631-635.

https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015/NSDUH-DetTabs-2015.pdfhttps://aspe.hhs.gov/pdf-report/opioid-abuse-us-and-hhs-actions-address-opioid-drug-related-overdoses-and-deaths

32

9. KnudsenHK,AbrahamAJ,RomanPM.Adoptionandimplementationof

medicationsinaddictiontreatmentprograms.JAddictMed.2011;5(1):21-

27.doi:10.1097/ADM.0b013e3181d41ddb.

10. BartG.Maintenancemedicationforopiateaddiction:thefoundationof

recovery.JAddictDis.2012;31(3):207-225.

doi:10.1080/10550887.2012.694598.

11. DavoliM,BargagliAM,PerucciCA,etal.Riskoffataloverdoseduringand

afterspecialistdrugtreatment:theVEdeTTEstudy,anationalmulti-site

prospectivecohortstudy.AddictAbingdonEngl.2007;102(12):1954-1959.

doi:10.1111/j.1360-0443.2007.02025.x.

12. MattickRP,BreenC,KimberJ,DavoliM.Methadonemaintenancetherapy

versusnoopioidreplacementtherapyforopioiddependence.Cochrane

DatabaseSystRev.2009;(3):CD002209.

doi:10.1002/14651858.CD002209.pub2.

13. MattickRP,BreenC,KimberJ,DavoliM.Buprenorphinemaintenance

versusplaceboormethadonemaintenanceforopioiddependence.

CochraneDatabaseSystRev.2014;(2):CD002207.

doi:10.1002/14651858.CD002207.pub4.

14. SubstanceAbuseandMentalHealthServicesAdministration.Clinical

GuidelinesfortheUseofBuprenorphineintheTreatmentofOpioid

Addiction:ATreatmentImprovementProtocolTIP40.SubstanceAbuseand

MentalHealthServicesAdministration;2004.

https://www.ncbi.nlm.nih.gov/books/NBK64245/pdf/Bookshelf_NBK64245.pdf.

AccessedMay11,2017.

15. TheAmericanSocietyofAddictionMedicine.AdvancingAccesstoAddiction

Medications.http://www.asam.org/docs/default-

source/advocacy/aaam_implications-for-opioid-addiction-treatment_final.

AccessedMay11,2017.

16. YancovitzSR,DesJarlaisDC,PeyserNP,etal.Arandomizedtrialofan

interimmethadonemaintenanceclinic.AmJPublicHealth.

1991;81(9):1185-1191.

17. VanichseniS,WongsuwanB,ChoopanyaK,WongpanichK.Acontrolled

trialofmethadonemaintenanceinapopulationofintravenousdrugusersin

Bangkok:implicationsforpreventionofHIV.IntJAddict.1991;26(12):1313-

http://www.asam.org/docs/default-source/advocacy/aaam_implications-for-opioid-addiction-treatment_final

33

1320.

18. SchwartzRP,HighfieldDA,JaffeJH,etal.Arandomizedcontrolledtrialof

interimmethadonemaintenance.ArchGenPsychiatry.2006;63(1):102-109.

doi:10.1001/archpsyc.63.1.102.

19. KinlockTW,GordonMS,SchwartzRP,O’GradyK,FitzgeraldTT,WilsonM.

Arandomizedclinicaltrialofmethadonemaintenanceforprisoners:results

at1-monthpost-release.DrugAlcoholDepend.2007;91(2-3):220-227.

doi:10.1016/j.drugalcdep.2007.05.022.

20. DolanKA,ShearerJ,MacDonaldM,MattickRP,HallW,WodakAD.A

randomisedcontrolledtrialofmethadonemaintenancetreatmentversus

waitlistcontrolinanAustralianprisonsystem.DrugAlcoholDepend.

2003;72(1):59-65.

21. SchwartzRP,KellySM,O’GradyKE,GandhiD,JaffeJH.Randomizedtrial

ofstandardmethadonetreatmentcomparedtoinitiatingmethadonewithout

counseling:12-monthfindings.AddictAbingdonEngl.2012;107(5):943-

952.doi:10.1111/j.1360-0443.2011.03700.x.

22. SeesKL,DelucchiKL,MassonC,etal.Methadonemaintenancevs180-

daypsychosociallyenricheddetoxificationfortreatmentofopioid

dependence:arandomizedcontrolledtrial.JAMA.2000;283(10):1303-

1310.

23. GruberVA,DelucchiKL,KielsteinA,BatkiSL.Arandomizedtrialof6-month

methadonemaintenancewithstandardorminimalcounselingversus21-

daymethadonedetoxification.DrugAlcoholDepend.2008;94(1-3):199-

206.doi:10.1016/j.drugalcdep.2007.11.021.

24. FiellinDA,SchottenfeldRS,CutterCJ,MooreBA,BarryDT,O’ConnorPG.

Primarycare-basedbuprenorphinetapervsmaintenancetherapyfor

prescriptionopioiddependence:arandomizedclinicaltrial.JAMAIntern

Med.2014;174(12):1947-1954.doi:10.1001/jamainternmed.2014.5302.

25. KakkoJ,SvanborgKD,KreekMJ,HeiligM.1-yearretentionandsocial

functionafterbuprenorphine-assistedrelapsepreventiontreatmentfor

heroindependenceinSweden:arandomised,placebo-controlledtrial.

LancetLondEngl.2003;361(9358):662-668.doi:10.1016/S0140-

6736(03)12600-1.

34

26. FudalaPJ,BridgeTP,HerbertS,etal.Office-basedtreatmentofopiate

addictionwithasublingual-tabletformulationofbuprenorphineand

naloxone.NEnglJMed.2003;349(10):949-958.

doi:10.1056/NEJMoa022164.

27. MacDonaldK,LambK,ThomasML,KhentiganW.Buprenorphine

MaintenanceTreatmentofOpiateDependence:CorrelationsBetween

PrescriberBeliefsandPractices.SubstUseMisuse.2016;51(1):85-90.

doi:10.3109/10826084.2015.1089905.

28. NunesEV,KrupitskyE,LingW,etal.TreatingOpioidDependenceWith

InjectableExtended-ReleaseNaltrexone(XR-NTX):WhoWillRespond?J

AddictMed.2015;9(3):238-243.doi:10.1097/ADM.0000000000000125.

29. MinozziS,AmatoL,VecchiS,DavoliM,KirchmayerU,VersterA.Oral

naltrexonemaintenancetreatmentforopioiddependence.Cochrane

DatabaseSystRev.2011;(4):CD001333.

doi:10.1002/14651858.CD001333.pub4.

30. KrupitskyE,NunesEV,LingW,GastfriendDR,MemisogluA,SilvermanBL.

Injectableextended-releasenaltrexone(XR-NTX)foropioiddependence:

long-termsafetyandeffectiveness.AddictAbingdonEngl.

2013;108(9):1628-1637.doi:10.1111/add.12208.

31. KrupitskyE,NunesEV,LingW,IlleperumaA,GastfriendDR,SilvermanBL.

Injectableextended-releasenaltrexoneforopioiddependence:adouble-

blind,placebo-controlled,multicentrerandomisedtrial.LancetLondEngl.

2011;377(9776):1506-1513.doi:10.1016/S0140-6736(11)60358-9.

32. SyedYY,KeatingGM.Extended-releaseintramuscularnaltrexone

(VIVITROL®):areviewofitsuseinthepreventionofrelapsetoopioid

dependenceindetoxifiedpatients.CNSDrugs.2013;27(10):851-861.

doi:10.1007/s40263-013-0110-x.

33. JacksonH,MandellK,JohnsonK,ChatterjeeD,VannessDJ.Cost-

EffectivenessofInjectableExtended-ReleaseNaltrexoneComparedWith

MethadoneMaintenanceandBuprenorphineMaintenanceTreatmentfor

OpioidDependence.SubstAbuse.2015;36(2):226-231.

doi:10.1080/08897077.2015.1010031.

34. WorldHealthOrganization.ProposalfortheInclusionofBuprenorphinein

theWHOModelListofEssentialMedicines.;2004.

35

http://www.who.int/substance_abuse/activities/buprenorphine_essential_medicines.pdf

AccessedMay11,2017.

35. WorldHealthOrganization.ProposalfortheInclusionofMethadoneinthe

WHOModelListofEssentialMedicines.WorldHealthOrganization;2004.

http://www.who.int/substance_abuse/activities/methadone_essential_medicines.pdf.

AccessedMay11,2017.

36. WilliamsJT,IngramSL,HendersonG,etal.Regulationofµ-opioid

receptors:desensitization,phosphorylation,internalization,andtolerance.

PharmacolRev.2013;65(1):223-254.doi:10.1124/pr.112.005942.

37. AlloucheS,NobleF,MarieN.Opioidreceptordesensitization:mechanisms

anditslinktotolerance.FrontPharmacol.2014;5:280.

doi:10.3389/fphar.2014.00280.

38. WalshSL,JuneHL,SchuhKJ,PrestonKL,BigelowGE,StitzerML.Effects

ofbuprenorphineandmethadoneinmethadone-maintainedsubjects.

Psychopharmacology(Berl).1995;119(3):268-276.

39. HighlightsofPrescribingInformation:SUBOXONE®.February2017.

https://www.suboxone.com/content/pdfs/prescribing-information.pdf.

AccessedMay11,2017.

40. KostenTR,GeorgeTP.Theneurobiologyofopioiddependence:

implicationsfortreatment.SciPractPerspect.2002;1(1):13-20.

41. CrucianiRA,KnotkovaH,eds.HandbookofMethadonePrescribingand

BuprenorphineTherapy.NewYork:Springer-Verlag;2013.

42. BruntonLL,LazoJS,ParkerKL,eds.Goodman&Gilman’sThe

PharmacologicalBasisofTherapeutics.11thed.

43. U.S.DepartmentofJusticeDrugEnforcementAdministration,Officeof

DiversionControl.NationalForensicLaboratoryInformationSystem(NFLIS)

2013AnnualReport.

https://www.nflis.deadiversion.usdoj.gov/DesktopModules/ReportDownloads/Reports/NFLIS2013AR.pdf

AccessedMay11,2017.

44. BazaziAR,YokellM,FuJJ,RichJD,Zall

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