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NationalInstituteonDrugAbuse(NIDA)
MedicationstoTreatOpioidUseDisorder
LastUpdatedJune2018https://www.drugabuse.gov
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TableofContents
MedicationstoTreatOpioidUseDisorder
Overview
Howdomedicationstotreatopioidusedisorderwork?
Howeffectivearemedicationstotreatopioidusedisorder?
Whataremisconceptionsaboutmaintenancetreatment?
Whatisthetreatmentneedversusthediversionriskforopioidusedisordertreatment?
WhatistheimpactofmedicationforopioidusedisordertreatmentonHIV/HCVoutcomes?
Howisopioidusedisordertreatedinthecriminaljusticesystem?
Ismedicationtotreatopioidusedisorderavailableinthemilitary?
Whattreatmentisavailableforpregnantmothersandtheirbabies?
HowMuchDoesOpioidTreatmentCost?
Isnaloxoneaccessible?
References
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Overview
Anestimated2.1millionpeopleintheUnitedStateshadasubstanceusedisorderrelatedtoprescriptionopioidpainmedicinesin2016. However,onlyafractionofpeoplewithprescriptionopioidusedisordersreceivespecialtytreatment(17.5percentin2016). Overdosedeathslinkedtothesemedicineswerefivetimeshigherin2016than1999. Thereisnowalsoariseinheroinuseandheroinusedisorderassomepeopleshiftfromprescriptionopioidstotheircheaperstreetrelative;626,000peoplehadaheroinusedisorderin2016,andmorethan15,000Americansdiedofaheroinoverdosein2016. Besidesoverdose,consequencesoftheopioidcrisisincludearisingincidenceofinfantsborndependentonopioidsbecausetheirmothersusedthesesubstancesduringpregnancy andincreasedspreadofinfectiousdiseases,includingHIVandhepatitisC(HCV),aswasseenin2015insouthernIndiana.
EffectivepreventionandtreatmentstrategiesexistforopioidmisuseandusedisorderbutarehighlyunderutilizedacrosstheUnitedStates.AninitiativeoftheSecretaryofHealthandHumanServices(HHS) beganin2015toaddressthecomplexproblemofprescriptionopioidandheroinuse.In2017,HHSannouncedfiveprioritiesforaddressingtheopioidcrisis:
1. improvingaccesstotreatmentandrecoveryservices
2. promotinguseofoverdose-reversingdrugs
3. strengtheningourunderstandingoftheepidemicthroughbetterpublichealthsurveillance
4. providingsupportforcutting-edgeresearchonpainandaddiction
5. advancingbetterpracticesforpainmanagement
Effectivemedicationsexisttotreatopioidusedisorder:methadone,buprenorphine,andnaltrexone.Thesemedicationscouldhelpmanypeoplerecoverfromopioidusedisorder,buttheyremainhighlyunderutilized.Fewerthanhalfofprivate-sectortreatmentprogramsoffermedicationsforopioidusedisorders,andofpatientsinthoseprogramswhomightbenefit,onlyathird
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actuallyreceiveit. OvercomingthemisunderstandingsandotherbarriersthatpreventwideradoptionofthesetreatmentsiscrucialfortacklingtheproblemofopioidusedisorderandtheepidemicofopioidoverdoseintheUnitedStates.
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Howdomedicationstotreatopioidusedisorderwork?
OpioidAgonistsandPartialAgonists(MaintenanceMedications)
Studiesshowthatpeoplewithopioidusedisorderwhofollowdetoxificationwithcompleteabstinenceareverylikelytorelapse,orreturntousingthedrug. Whilerelapseisanormalsteponthepathtorecovery,itcanalsobelifethreatening,raisingtheriskforafataloverdose.11Thus,animportantwaytosupportrecoveryfromheroinorprescriptionopioidusedisorderistomaintainabstinencefromthosedrugs.Someoneinrecoverycanalsousemedicationsthatreducethenegativeeffectsofwithdrawalandcravingswithoutproducingtheeuphoriathattheoriginaldrugofabusecaused.Forexample,theFDArecentlyapprovedlofexidine,anon-opioidmedicinedesignedtoreduceopioidwithdrawalsymptoms.Methadoneandbuprenorphineareothermedicationsapprovedforthispurpose.
Methadoneisasyntheticopioidagonistthateliminateswithdrawalsymptomsandrelievesdrugcravingsbyactingonopioidreceptorsinthebrain—thesamereceptorsthatotheropioidssuchasheroin,morphine,andopioidpainmedicationsactivate.Althoughitoccupiesandactivatestheseopioidreceptors,itdoessomoreslowlythanotheropioidsand,inanopioid-dependentperson,treatmentdosesdonotproduceeuphoria.Ithasbeenusedsuccessfullyformorethan40yearstotreatopioidusedisorderandmustbedispensedthroughspecializedopioidtreatmentprograms.
Buprenorphineisapartialopioidagonist,meaningthatitbindstothosesameopioidreceptorsbutactivatesthemlessstronglythanfullagonistsdo.Likemethadone,itcanreducecravingsandwithdrawalsymptomsinapersonwithanopioidusedisorderwithoutproducingeuphoria,andpatientstendtotolerateitwell.Researchhasfoundbuprenorphinetobesimilarlyeffectiveasmethadonefortreatingopioidusedisorders,aslongasitisgivenatasufficientdoseandforsufficientduration. TheU.S.FoodandDrugAdministration(FDA)approvedbuprenorphinein2002,makingitthefirstmedicationeligibletobe
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prescribedbycertifiedphysiciansthroughtheDrugAddictionTreatmentAct.Thisapprovaleliminatestheneedtovisitspecializedtreatmentclinics,therebyexpandingaccesstotreatmentformanywhoneedit.Additionally,theComprehensiveAddictionandRecoveryAct(CARA),whichwassignedintolawinJuly2016,temporarilyexpandseligibilitytoprescribebuprenorphine-baseddrugsformedication-assistedtreatment(MAT)toqualifyingnursepractitionersandphysicianassistantsthroughOctober1,2021.Buprenorphinehasbeenavailableforopioidusedisorderssince2002asatabletandsince2010asasublingualfilm. TheFDAapproveda6-monthsubdermalbuprenorphineimplantinMay2016andaonce-monthlybuprenorphineinjectioninNovember2017.Theseformulationsareavailabletopatientsstabilizedonbuprenorphineandwilleliminatethetreatmentbarrierofdailydosingforthesepatients.(Alsosee"Whataremisconceptionsaboutmaintenancetreatment?")
OpioidAntagonists
Naltrexoneisanopioidantagonist,whichmeansthatitworksbyblockingtheactivationofopioidreceptors.Insteadofcontrollingwithdrawalandcravings,ittreatsopioidusedisorderbypreventinganyopioiddrugfromproducingrewardingeffectssuchaseuphoria.Itsuseforongoingopioidusedisordertreatmenthasbeensomewhatlimitedbecauseofpooradherenceandtolerabilitybypatients.However,in2010,aninjectable,long-actingformofnaltrexone(Vivitrol ),originallyapprovedfortreatingalcoholusedisorder,wasFDA-approvedfortreatingopioidusedisorder.Becauseitseffectslastforweeks,Vivitrol isagoodoptionforpatientswhodonothavereadyaccesstohealthcareorwhostrugglewithtakingtheirmedicationsregularly.
Becauseeachmedicationworksdifferently,atreatmentprovidershoulddecideontheoptimalmedicationinconsultationwiththeindividualpatientandshouldconsiderthepatient’suniquehistoryandcircumstances.
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Howeffectivearemedicationstotreatopioidusedisorder?
Abundantevidenceshowsthatmethadone,buprenorphine,andnaltrexoneallreduceopioiduseandopioidusedisorder-relatedsymptoms,andtheyreducetheriskofinfectiousdiseasetransmissionaswellascriminalbehaviorassociatedwithdruguse. Thesemedicationsalsoincreasethelikelihoodthatapersonwillremainintreatment,whichitselfisassociatedwithlowerriskofoverdosemortality,reducedriskofHIVandHCVtransmission,reducedcriminaljusticeinvolvement,andgreaterlikelihoodofemployment.
Methadone
Methadoneisthemedicationwiththelongesthistoryofuseforopioidusedisordertreatment,havingbeenusedsince1947.Alargenumberofstudies(someofwhicharesummarizedinthegraphbelow)supportmethadone'seffectivenessatreducingopioiduse.AcomprehensiveCochranereviewin2009comparedmethadone-basedtreatment(methadonepluspsychosocialtreatment)toplacebowithpsychosocialtreatmentandfoundthatmethadonetreatmentwaseffectiveinreducingopioiduse,opioiduse-associatedtransmissionofinfectiousdisease,andcrime. Patientsonmethadonehad33percentfeweropioid-positivedrugtestsandwere4.44timesmorelikelytostayintreatmentcomparedtocontrols. Methadonetreatmentsignificantlyimprovesoutcomes,evenwhenprovidedintheabsenceofregularcounselingservices; long-term(beyond6months)outcomesarebetteringroupsreceivingmethadone,regardlessofthefrequencyofcounselingreceived.
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Buprenorphine
Buprenorphine,whichwasfirstapprovedin2002,iscurrentlyavailableintwoforms:alone(Probuphine ,Sublocade™,Bunavail )andincombinationwiththeopioidreceptorantagonistnaloxone(Suboxone ,Zubsolv ).Bothformulationsofbuprenorphineareeffectiveforthetreatmentofopioidusedisorders,thoughsomestudieshaveshownhighrelapseratesamongpatientstaperedoffofbuprenorphinecomparedtopatientsmaintainedonthedrugforalongerperiodoftime.
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Source:Kakkoetal.,2003
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ASwedishstudycomparedpatientsmaintainedon16mgofbuprenorphinedailytoacontrolgroupthatreceivedbuprenorphinefordetoxification(6days)followedbyplacebo. Allpatientsreceivedpsychosocialsupports.Inthisstudy,thetreatmentfailurerateforplacebowas100percentvs.25percentforbuprenorphine.Morethantwoopioid-positiveurinetestswithin3monthsresultedincessationoftreatment,sotreatmentretentionwascloselyrelatedtorelapse.Ofpatientsnotretainedintreatment,therewasa20percentmortalityrate.
Meta-analysisdeterminedthatpatientsondosesofbuprenorphineof16mgperdayormorewere1.82timesmorelikelytostayintreatmentthanplacebo-treatedpatients,andbuprenorphinedecreasedthenumberofopioid-positivedrugtestsby14.2percent(thestandardizedmeandifferencewas-1.17).
Tobeeffective,buprenorphinemustbegivenatasufficientlyhighdose(generally,16mgperdayormore).Sometreatmentproviderswaryofusingopioidshaveprescribedlowerdosesforshorttreatmentdurations,leadingtofailureofbuprenorphinetreatmentandthemistakenconclusionthatthemedicationisineffective.
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MethadoneandBuprenorphineCompared
Methadoneandbuprenorphineareequallyeffectiveatreducingopioiduse.AcomprehensiveCochranereviewcomparingbuprenorphine,methadone,andplacebofoundnodifferencesinopioid-positivedrugtestsorself-reportedheroinusewhentreatingwithmethadoneorbuprenorphineatmedium-to-highdoses.
Notably,flexibledoseregimensofbuprenorphineanddosesofbuprenorphineof6mgorbelowarelesseffectivethanmethadoneatkeepingpatientsintreatment,highlightingtheneedfordeliveryofevidence-baseddosingregimensofthesemedications.
Naltrexone
Naltrexonewasinitiallyapprovedforthetreatmentofopioidusedisorderinadailypillform.Itdoesnotproducetoleranceorwithdrawal.Poortreatmentadherencehasprimarilylimitedthereal-worldeffectivenessofthisformulation. Asaresult,thereisinsufficientevidencethatoralnaltrexoneisaneffectivetreatmentforopioidusedisorder. Extended-releaseinjectablenaltrexone(XR-NTX)isadministeredoncemonthly,whichremovestheneedfordailydosing.Whilethisformulationisthenewestformofmedicationforopioidusedisorder,evidencetodatesuggeststhatitiseffective.
Thedouble-blind,placebo-controlledtrialthatwasmostinfluentialingettingXR-NTXapprovedbytheFDAin2010foropioidusedisordertreatmentshowedthatXR-NTXsignificantlyincreasedopioidabstinence.TheXR-NTXgrouphad90percentconfirmedabstinentweekscomparedto35percentintheplacebogroup.TreatmentretentionwasalsohigherintheXR-NTXgroup(58percentvs.42percent),whilesubjectivedrugcravingandrelapsewerebothdecreased(0.8percentvs.13.7percent). ImprovementintheXR-NTXgroupwassustainedthroughoutanopenlabelperiodoutto76weeks. ThesedatawerecollectedinRussia,andadditionalstudiesarerequiredtodetermineifeffectivenesswillbesimilarintheUnitedStates.
BuprenorphineandNaltrexoneCompared
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ANIDAstudyshowedthatoncetreatmentisinitiated,abuprenorphine/naloxonecombinationandanextendedreleasenaltrexoneformulationaresimilarlyeffectiveintreatingopioidusedisorder.Becausenaltrexonerequiresfulldetoxification,initiatingtreatmentamongactiveopioiduserswasmoredifficultwiththismedication.However,oncedetoxificationwascomplete,thenaltrexoneformulationhadasimilareffectivenessasthebuprenorphine/naloxonecombination.
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Whataremisconceptionsaboutmaintenancetreatment?
Becausemaintenancemedications(methadoneandbuprenorphine)arethemselvesopioidsandareabletoproduceeuphoriainpeoplewhoarenotdependentonopioids,manypeoplehaveassumedthatthisformoftreatmentjustsubstitutesanewsubstanceusedisorderforanoldone.Thisbeliefhasunfortunatelyhinderedtheadoptionoftheseeffectivetreatments.Inthepast,evensomeinpatienttreatmentprogramsthatwereotherwiseevidence-baseddidnotallowpatientstousethesemedications,infavorofan"abstinenceonly"philosophy.
Althoughitispossibleforindividualswhodonothaveanopioidusedisordertogethighonbuprenorphineormethadone(see"Whatisthetreatmentneedversusthediversionriskforopioidusedisordertreatment?"),thesemedicationsaffectpeoplewhohavedevelopedahightolerance(see"OpioidTolerance")toopioidsdifferently.Atthedosesprescribed,andasaresultoftheirpharmacodynamicandpharmacokineticproperties(thewaytheyactatopioidreceptorsitesandtheirslowermetabolisminthebody),thesemedicationsdonotproduceaeuphorichighbutinsteadminimizewithdrawalsymptomsandcravings(see"MechanismsofOpioidDependence").Thismakesitpossibleforthepatienttofunctionnormally,attendschoolorwork,andparticipateinotherformsoftreatmentorrecoverysupportservicestohelpthembecomefreeoftheirsubstanceusedisorderovertime.
Theultimateaimcanbetoweanoffthemaintenancemedication,butthetreatmentprovidershouldmakethisdecisionjointlywiththepatientandtaperingthemedicationmustbedonegradually.Itmaytakemonthsoryearsinsomecases.Justasbodytissuesrequireprolongedperiodstohealafterinjuryandmayrequireexternalsupports(e.g.,acastandcrutchesorawheelchairforabrokenleg),braincircuitsthathavebeenalteredbyprolongeddruguseandsubstanceusedisordertaketimetorecoverandbenefitfromexternalsupportsintheformofmedication.Incasesofseriousandlong-termopioidusedisorder,apatientmayneedthesesupportsindefinitely.
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In2005,methadoneandbuprenorphinewereaddedtotheWorldHealthOrganization'slistofessentialmedicines,definedasmedicinesthatare"intendedtobeavailablewithinthecontextoffunctioninghealthcaresystemsatalltimesinadequateamounts,intheappropriatedosageforms,withassuredquality,andatapricetheindividualandthecommunitycanafford."
OpioidTolerance
Peoplewhotakeopioidsforlongperiodsoftimetypicallydeveloptolerance,astateinwhichmoreofthedrugisneededtoproducethesameeffect.Receptordesensitizationanddownregulationaremolecularprocessesthatcausetolerance.Inpeoplewithopioidusedisorder,thebrainiscontinuallyexposedtohighlevelsofopioidsaswellasdopamine,whichisreleasedintherewardcircuitfollowingopioidreceptoractivation.Braincellsrespondtothisbyreducingtheirresponsetoreceptoractivationandbyremovingopioidanddopaminereceptorsfromthecellmembrane,resultinginfewerreceptorsthatcanbeactivatedbythedrug. Thesemechanismsresultinalessenedresponsetothedrug,sohigherdosesarerequiredtoelicitthesameeffect.Thisopioidtoleranceisthereasonthatpeoplewithopioidusedisorderdonotexperienceeuphoriceffectsfromtherapeuticdosesofbuprenorphineormethadone,whilepeoplewithoutopioidusedisorderdo. Itisalsothereasonwhypeopleareatincreasedriskofoverdosewhenrelapsingtoopioiduseafteraperiodofabstinence:Theylosetheirtolerancetothedrugwithoutrealizingit,sotheynolongerknowwhatdoseofthedrugtheycansafelytolerate.
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MechanismsofOpioidDependence
Thesustainedactivationofopioidreceptorsthatresultsfromopioidusedisorderandcausestolerancealsocauseswithdrawalsymptomswhentheopioiddrugsleavethebody.Drugwithdrawalsymptomsareoppositetothesymptomscausedbydrugtaking.Inthecaseofopioids,theyincludeanxiety,jitters,anddiarrhea. Avoidanceofthesenegativesymptomsisonereasonthatpeoplekeeptakingopioids,andintheearlystagesoftreatment,medicationssuchasmethadoneandbuprenorphinereducewithdrawalsymptoms.
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Opioidreceptoractivity.Heroin(redline)activatesopioidreceptorsfullyandquickly.Methadone(blue)isalsoafullagonist,buttheactivationismuchslowerandlongerlasting.Buprenorphine(green)activatesthereceptorspartially,withasimilartimecoursetomethadone.Naltrexone(purple)isanopioidreceptorantagonistandthereforepreventsreceptoractivation.Sources:Cruciani&Knotkova,2013;Goodmanetal.,2006
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Whatisthetreatmentneedversusthediversionriskforopioidusedisordertreatment?
Likeotheropioidmedications,buprenorphineandmethadonearesometimesdivertedandmisused.However,mostdatasuggestthatthemajorityofbuprenorphineandmethadonemisuse(usewithoutaprescription)isforthepurposeofcontrollingwithdrawalandcravingsforotheropioidsandnottogethigh.Amongallopioidagonistmedications,methadoneandbuprenorphinetogethermakeup15percentofdiversionreports,whileoxycodoneandhydrocodoneareresponsiblefor67percent. Naltrexone,anopioidantagonistusedtotreatopioidaddiction,doesnotcauseeuphoriceffectsandisnotadiversionrisk.
DiversionRiskofBuprenorphine
Bothbuprenorphineandbuprenorphine/naloxoneformulationscaninterferewiththeeffectsoffullopioidagonists,suchasheroin,andcanprecipitatewithdrawalinindividualswithopioiddependence.TwoU.S.surveysofpeoplewithopioidusedisorderfoundthatamajorityofthosewhousedillicitbuprenorphinereportedthattheyuseditfortherapeuticpurposes(i.e.,toreducewithdrawalsymptoms,reduceheroinuse,etc.). Ninety-sevenpercentreportedusingittopreventcravings,90percenttopreventwithdrawal,and29percenttosavemoney. Illicituseofbuprenorphinedecreasedasindividualshadaccesstotreatment. Theminorityproportionofpeoplewhousebuprenorphineillicitlytogethigh(rangingfrom8to25percent) hasbeenshowntodecreaseovertime,whichcouldsuggestthatpeopleabandonthisgoalaftertheyexperiencethedrug’sbluntedrewardingeffects. Indeed,patientsintreatmentforopioidusedisorderrarelyendorsebuprenorphineastheprimarydrugofmisuse.
Whilethereissomeriskassociatedwithmisuseofbuprenorphine,theriskofharms,suchasfataloverdose,aresignificantlylowerthanthoseoffullagonistopioids(oxycodone,hydrocodone,heroin). Overdosesandrelateddeaths
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dooccurbutareusuallytheresultofcombinationwithotherrespiratorydepressantdrugssuchasbenzodiazepinesoralcohol.Emergencydepartment(ED)visitsinvolvingbuprenorphineincreasedfrom3,161in2005to30,135visitsin2010asavailabilityofthedrugincreased(buprenorphinewasfirstapprovedin2002);butEDvisitsforbuprenorphineremainsignificantlylesscommonthanthoseforotheropioids. Fifty-twopercent,or15,778visits(seeleftbarchartbelow),wererelatedtononmedicalusein2010;59percentofthesevisitsinvolvedadditionaldrugs(seerightbarchartbelow).
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Emergencydepartment(ED)visitsinvolvingbuprenorphineincreasedasdrugavailabilityincreased,butEDvisitsforbuprenorphinearefarlesscommonthanthoseforotheropioids.
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DiversionRiskofMethadone
Methadonediversionisprimarilyassociatedwithmethadoneprescribedforthetreatmentofpainandnotforthetreatmentofopioidusedisorders.Opioidtreatmentprogramsarerequiredtomaintainandimplementadiversioncontrolplan;theytypicallyrequirepatientstocomeindailytoreceivetheirmedicationandstrictlymonitortake-homedoses.Inaddition,evidencesuggeststhatthediversionthatdoesoccurisassociatedwithalackofaccesstomedication. Inonesurvey,givingmethadoneawaywasidentifiedasthemostcommonformofmethadonediversion, whichalignswithotherfindingsthat80percentofpeoplewhoreportdivertingmethadonedidsotohelpotherswhomisusedsubstances. Amongthoseusingillicitmethadone,themostcommonreasonwasamissedmedicationpick-up.
Methadone,asafullopioidagonistthatismetabolizedslowly,posesagreaterriskofoverdosethanbuprenorphine.In2010,65,945EDvisitsinvolvednonmedicaluseofmethadone. However,methadonethatisdispensedforuseasapainreliever,notasansubstanceusedisordermedication,isthemain
Source:CBHSQ,2011
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sourceofthemethadoneinvolvedinoverdosedeaths.55
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WhatistheimpactofmedicationforopioidusedisordertreatmentonHIV/HCVoutcomes?
InjectiondruguseisstillaprimarydriveroftheHIV/AIDSepidemicacrosstheworld. ArecentexampleisthesmallcommunityofAustin,Indiana,where170newHIVinfectionsoccurredinthe8monthsbetweenNovember2014andJune2015amongpeoplemisusingtheprescriptionopioidpainrelieveroxymorphone(Opana )viainjection. Peoplewhoinjectdrugsfrequentlysharetheirneedlesandotherinjectionequipment,enablingvirusessuchasHIVandhepatitisC(HCV)tospreadbetweenpeople.
MedicationsforopioidusedisordertreatmentcanreducetransmissionofHIVandHCVbyreducingriskbehaviorsinpeoplewhoinjectdrugsandcanimproveHIV-andHCV-relatedoutcomesbytreatingthosenotengagedininjectionopioidusewhomightotherwisetransitiontoinjection,linkingthosewithHIV/HCVinfectiontoappropriatetreatment, andimprovingadherencetoHIV/HCVtreatment. TheseimprovementsdependonaccessibilityofmedicationsforopioidusedisordertopeoplewhoneeditandcoordinatingmedicationdeliverywithHCV/HIVscreeningandtreatment.
Treatmentwithmethadoneorbuprenorphineisassociatedwithreducedinjectiondruguseriskbehaviors.Meta-analyseshaveshownareductioninriskbehaviorsincludinga32to69percentreductioninillicitopioiduse,a20to60percentreductionininjectiondruguse,anda25to86percentreductioninsharingofinjectionequipment. Treatmentwithextended-releasenaltrexonealsoreducedHIVriskbehaviorscomparedtoplacebo.
MethadoneandbuprenorphinetreatmentarealsoassociatedwithlowerHCVinfectionratesinyoungadultswhoinjectdrugs,whileothertreatmentsanddetoxificationalonearenot. MethadonetreatmentisassociatedwithlowratesofcontractingHCVoverall, withmathematicalmodelingsuggestingthatitcanprevent22.6newHCVinfectionsper100treatedpeoplewhoengagedininjectiondruguse,peryear. MethadonetreatmentalsoreducesbothHIV
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riskbehaviorsandHIVinfection,withbetteroutcomesforpeoplewhoinjectdrugswhoareintreatment(3.5percentcontractingHIVvs.22percent),andbetteroutcomesforlongertreatmentdurationandforcontinuous(versusinterrupted)treatment.
AstudycomparingtheeffectsofmethadoneandbuprenorphinetreatmentonHIVriskfrominjectionbehaviorsandHIVriskfromsexualbehaviorsshowedequalandsignificantreductionsinriskyinjectionbehaviors.Riskysexualbehaviorswerereducedinbothmaleandfemalemethadonepatientsbutwerehigherinmalepatientsonbuprenorphine.
MitigatingFactors
ThereareseveralknowninteractionsbetweenmedicationsusedtotreatHIVorHCVandbothmethadoneandbuprenorphine. Thesecouldrequireanadjustmentofdosageorrevisionofthetreatmentplan,andhighlighttheneedforintegratedcare.Forexample,somepatientsarereluctanttobeginhighlyactiveantiretroviraltherapy(HAART)becauseofworriesthatitwillinterferewiththeirmethadonetreatment,sotreatmentprovidersshouldconsiderrevisedmethadonedosesforthesepatients.
ContractingHCVwhileonmethadoneisassociatedwithcontinuedinjectiondruguse. SomestudieshaveshownmethadonedetoxificationalonetobeassociatedwithincreasedratesofcontractingHIV,soongoingtreatmentwiththismedicationiskeytoreducingtransmissionofviralinfection.
PossibilityofDualTherapeuticPotential
OnerecentreportdemonstratesthepotentialofbuprenorphinetocounteractaneuroinflammatoryprocessthatisinvolvedinHIV-associatedneurocognitivedisorders,suggestingthatbuprenorphinecouldpotentiallybesimultaneouslytherapeuticforopioidusedisorderandHIV. OpioidusedisordermedicationsarealsoassociatedwithincreasedadherencetoHAARTforthetreatmentofHIV. SomeprovidershesitatetotreatHCVinpeoplewhoinjectdrugs,butanaltrexoneimplantationclinicshowedratesofsustainedvirologicresponseintheirpatientsthatwerecomparabletoclinicstreatingnon-injection-
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drug-usingpatients.
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Howisopioidusedisordertreatedinthecriminaljusticesystem?
Opioidusedisordersarehighlyprevalentamongcriminaljusticepopulations.AccordingtodatafromtheU.S.DepartmentofJustice,approximatelyhalfofstateandfederalprisonersmeetcriteriaforsubstanceusedisorder. Evenso,therehasbeenreticenceincriminaljusticesettingstousingmethadone,buprenorphine,andnaltrexonetotreatopioidusedisorder.Innationalsurveys,utilizationofthesemedicationsisverylowincriminaljusticesettings,includingdrugcourts, jails, andprisons. Thus,opioidusedisordergoeslargelyuntreatedduringperiodsofincarceration,andopioiduseoftenresumesafterrelease.
Aformerinmate’sriskofdeathwithinthefirst2weeksofreleaseismorethan12timesthatofotherindividuals,withtheleadingcauseofdeathbeingafataloverdose. Overdosesaremorecommonwhenapersonrelapsestodruguseafteraperiodofabstinenceduetolossoftolerancetothedrug.Onestudyfoundareductioninpost-incarcerationdeathsfromoverdoseamongindividualswhohadreceivedmedicationforopioidusedisorderincorrectionalfacilities. Untreatedopioidusedisordersalsocontributetoareturntocriminalactivity,reincarceration,andriskybehaviorcontributingtothespreadofHIVandhepatitisBandCinfections(see"WhatistheimpactofmedicationforopioidusedisordertreatmentonHIV/HCVoutcomes?").
TheWorldHealthOrganization’sGuidelinesforthePsychosociallyAssistedPharmacologicalTreatmentofOpioidDependencerecommendsthatincarceratedindividualsshouldreceiveadequatehealthcareandthatopioidwithdrawal,agonistmaintenanceandnaltrexonetreatmentshouldallbeavailableinprisonsettings,andprisonersshouldnotbeforcedtoacceptanyparticulartreatment."
Manystatescurrentlydonotofferappropriateaccesstoorutilizemedicationstotreatopioidusedisorderamongarresteesorinmateseventhoughresearchhasshownmanybenefitsofincorporatingmedication-assistedtreatmentintocriminaljusticetreatmentprograms.Inmateswhoreceivebuprenorphine
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treatmentpriortoreleasearemorelikelytoengageintreatmentaftertheirreleasethaninmateswhoonlyparticipateincounseling. Participantswhoengageinmethadonetreatmentandcounselinginprisonaremorelikelytoentercommunity-basedmethadonetreatmentcentersaftertheirrelease(68.6percent)thanthosereceivingonlycounseling(7.8percent)orthoseincounselingandreferredtoatreatmentcenter(50percent).
Inonestudy,inmateswhobeganbuprenorphinetreatmentwhileincarceratedengagedinpost-releasetreatmentsooner,averaging3.9daysafterrelease,comparedto9.2daysforparticipantsreferredtotreatmentpost-release. Theywerealsolikelytostayintreatmentlongeriftheywereinitiatedintreatmentpriortorelease(20.3weeksonaverage)thaniftheybegantreatmentaftertheirrelease(13.2weeks).
Inmateswhoparticipateinmethadonetreatmentandcounselingwhileinprisonarelesslikelytotestpositiveforillicitopioidsatonemonthfollowingtheirrelease(27.6percent)comparedtothosewhoonlyreceivecounseling(62.9percent)andthosewhoreceivecounselingandareferraltoatreatmentcenter(41percent).
Arandomizedcontrolledtrialwaspublishedin2016,comparingprison-initiatedextended-releasenaltrexone(XR-NTX)treatmenttostandardcounselingprotocolsforpreventionofopioidrelapse.Duringthetreatmentphase,relapsewassignificantlylowerinthegroupreceivingXR-NTX(43percentvs.64percent).TheXR-NTXgroupalsoexperiencednooverdoseevents,whilethereweresevenoverdoseeventsinthecontrolgroup.
Asurveyofcommunitycorrectionagents’viewsonusingmedicationstotreatopioidusedisordershowedthatmorefavorableattitudestowardmedicationuseareassociatedwithgreaterknowledgeabouttheevidencebaseforthesemedicationsandgreaterunderstandingofopioidusedisorderasamedicaldisorder. Organizationallinkagebetweencorrectionalstakeholdersandcommunitytreatmentproviders,alongwithtrainingsessions,canbeaneffectivewaytochangeperceptionsandincreaseknowledgeabouttheefficacyofthesemedications,andcanincreasetheintentwithincorrectionalfacilitiestoreferindividualswithopioidusedisordertotreatmentthatincorporates
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medications.
Amechanismtoreducerecidivismanddivertnonviolentoffendersfromtraditionaljailandprisonsettingsisthedrugtreatmentcourtmodel,whichprovidestreatmentservicesincombinationwithjudicialsupervision. Still,resistancetomedicationspersistseveninthisareaofthecriminaljusticesystem;asurveypublishedin2013reportedthat50percentofdrugcourtsdidnotallowagonisttreatmentforopioidusedisorderunderanycircumstances.In2015,theOfficeofNationalDrugControlPolicyannouncedthatstatedrugcourtsreceivingfederalgrantsmustnot:1)denyanyappropriateandeligibleclientforthetreatmentdrugcourtaccesstotheprogrambecauseoftheiruseofFDA-approvedmedicationsthatisinaccordancewithanappropriatelyauthorizedprescription;or2)mandatethatadrugcourtclientnolongerusemedicationsaspartoftheconditionsofthedrugcourtifsuchamandateisinconsistentwithamedicalpractitioner’srecommendationorprescription.
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Ismedicationtotreatopioidusedisorderavailableinthemilitary?
Ratesofprescriptionopioidmisusearehigheramongservicemembersthanamongcivilians. Surveyresultssuggestdruguseamongreturningsoldiersisoftenacopingstrategytotreatarousalsymptomsofpost-traumaticstressdisorder. Returningmilitarypersonnelalsoexperiencehigherratesofchronicpainandrelatedmedicaluseofopioidpainrelieverscomparedtothecivilianpopulation.Thesedatacollectivelysuggestanunmetneedfortheassessment,management,andtreatmentofbothchronicpainandopioidusedisorderinthispopulation.
TheVeteransHealthAdministration(VHA)acknowledgesthattreatmentwithopioidagonists(methadoneorbuprenorphine)isthefirst-linetreatmentforopioidusedisorderandrecommendsitforallopioid-dependentpatients.Notably,a2015revisionoftreatmentguidelinesfortheU.S.DepartmentofVeteranAffairsandU.S.DepartmentofDefenseshiftedtowardallowingthesemedicationsasatreatmentoptionforactivedutymilitarymembers. Still,onlyaboutaquarterofpatientswithanopioidusedisordertreatedatVHAfacilitiesreceivemedication. BarrierstoopioidagonistmedicationamongVHAprovidersincludelackofperceivedpatientinterest,stigmatowardthepatientpopulation,andlackofeducationaboutopioidagonisttreatment.
Inthepast,lackofinsurancecoverageforopioidagonistmedicationswasabarrierforuseamongactivedutymilitary;however,asof2013,TRICAREincludedcoverageforthesemedications,anda2016modificationofTRICAREregulationincludedprovisionsforexpandedcoverageofopioidusedisordertreatment. Thisexpandedcoverageremovedannualandlifetimelimitationsonsubstanceusedisordertreatmentallowedforoffice-basedopioidtreatment,andestablishedopioidtreatmentprogramsasanewlyrecognizedcategoryofinstitutionalproviderunderTRICARE.
92
93
94
95
96
97
98
26
Whattreatmentisavailableforpregnantmothersandtheirbabies?
Parallelingthelargerecentincreasesinopioiduse,usedisorder,andoverdose,theincidenceofbabiesborndependentonopioids(neonatalabstinencesyndrome,orNAS)asaresultofthemother’sopioiduseduringpregnancyhasalsogreatlyincreased. IncidenceofNASrosenearlyfivefoldbetween2000and2012; thisincreasewasassociatedwithincreasesintheprescriptionofopioidstopregnantwomenforpain,whichdoubledbetween1995and2009.
Untreatedopioidusedisorderduringpregnancycanhavedevastatingeffectsonthefetus.Thefluctuatinglevelsofopioidsinthebloodofmothersmisusingopioidsexposethefetustorepeatedperiodsofwithdrawal, whichcanalsoharmthefunctionoftheplacentaandincreasetheriskof:
fetalgrowthrestriction
placentalabruption
pretermlabor
fetalconvulsions
intrauterinepassageofmeconium
Source:Toliaetal.,2015
5
4
99,100
101
101
101
101
101
101
102
27
fetaldeath
Inadditiontothesedirectphysicaleffects,otherriskstothefetusinclude:
untreatedmaternalinfectionssuchasHIV
malnutritionandpoorprenatalcare
dangersconferredbydrug-seekinglifestyle,includingviolenceandincarceration
MethadoneandBuprenorphineastheStandardofCareforOpioidUseDisorderinPregnancy
Tolessenthenegativeeffectsofopioiddependenceonthefetus,treatmentwithmethadonehasbeenusedforpregnantwomenwithopioidusedisordersincethe1970sandhasbeenrecognizedasthestandardofcaresince1998.Recentevidence,however,suggeststhatbuprenorphinemaybeanevenbettertreatmentoption.
Bothmethadoneandbuprenorphinetreatmentduringpregnancy:
stabilizefetallevelsofopioids,reducingrepeatedprenatalwithdrawal
improveneonataloutcomes
increasematernalHIVtreatmenttoreducethelikelihoodoftransmittingthevirustothefetus
linkmotherstobetterprenatalcare
Ameta-analysisshowedthat,comparedtosingle-dosemethadonetreatment,buprenorphineresultedin:
10percentlowerincidenceofNAS
shorterneonataltreatmenttime(anaverageof8.4daysshorter)
102
103
104
102,104
102,103
105
101,106
104
102–104
102,104
28
loweramountofmorphineusedforNAStreatment(anaverageof3.6mglower)
highergestationalage,weight,andheadcircumferenceatbirth
DatafromtheNIDA-fundedMaternalOpioidTreatment:HumanExperimentalResearchstudyshowsimilarbenefitsofbuprenorphine. Still,methadoneisassociatedwithhighertreatmentretentionthanbuprenorphine. Divideddosingwithmethadonehasbeenexploredasawaytoreducefetalexposuretowithdrawalperiods,andrecentdatashowlowlevelsofNASinbabiesborntomotherstreatedwithdivideddosesofmethadone. Largercomparisonstudiesareneededtodetermineifsplitmethadonedosingforopioidusedisordersinpregnancyisassociatedwithbetteroutcomes.
NASstilloccursinbabieswhosemothershavereceivedbuprenorphineormethadone,butitislessseverethanitwouldbeintheabsenceoftreatment.ResearchdoesnotsupportreducingmaternalmethadonedosetoavoidNAS,asthismaypromoteincreasedillicitdruguse,resultinginincreasedrisktothefetus.
105
107
105
108
109
101
Source:Jonesetal.,2010
29
HowMuchDoesOpioidTreatmentCost?
Althoughthepriceforopioidtreatmentmayvarybasedonanumberoffactors,recentpreliminarycostestimatesfromtheU.S.DepartmentofDefensefortreatmentinacertifiedopioidtreatmentprogram(OTP)provideareasonablebasisforcomparison:
methadonetreatment,includingmedicationandintegratedpsychosocialandmedicalsupportservices(assumesdailyvisits):$126.00perweekor$6,552.00peryear
buprenorphineforastablepatientprovidedinacertifiedOTP,includingmedicationandtwice-weeklyvisits:$115.00perweekor$5,980.00peryear
naltrexoneprovidedinanOTP,includingdrug,drugadministration,andrelatedservices:$1,176.50permonthor$14,112.00peryear
Toputthesecostsintocontext,itisusefultocomparethemwiththecostsofotherconditions.AccordingtotheAgencyforHealthcareResearchandQuality,annualexpendituresforindividualswhoreceivedhealthcareare$3,560.00forthosewithdiabetesmellitusand$5,624.00forkidneydisease.
Itisalsoimportanttorememberthecostsassociatedwithuntreatedopioidusedisorders,includingcostsassociatedwith:
criminaljustice
treatingbabiesborndependentonopioids
greatertransmissionofinfectiousdiseases
treatingoverdoses
injuriesassociatedwithintoxication(e.g.,druggeddriving)
lostproductivity
98
110
30
Theamountpaidfortreatmentofsubstanceusedisordersisonlyasmallportionofthecoststhesedisordersimposeonsociety.AnanalysissuggestedthatthetotalcostsofprescriptionopioidusedisordersandoverdosesintheUnitedStateswas$78billionin2013.Ofthat,only3.6percent,orabout$2.8billion,wasfortreatment.111
31
Isnaloxoneaccessible?
Naloxoneisanopioidantagonistthatcanreverseanopioidoverdose.Naloxoneaccessincreasedbetween2010and2014,with:
morethanthreetimesthenumberoflocalsitesprovidingnaloxone(from188to644)
nearlythreetimesthenumberoflaypersonsprovidednaloxonekits(from53,032to152,283)
a94percentincreaseinstates(from16to30),includingWashington,DC,withatleastoneorganizationprovidingnaloxone
morethan2.5timesthenumberofoverdosereversalsreported(from10,171to26,463)
Naloxoneprescriptionsdispensedfromretailpharmaciesincreasednearlytwelvefoldbetweenthefourthquarterof2013andthesecondquarterof2015.
Moststateshavepassedlawstowidentheavailabilitytonaloxoneforfamily,friends,andotherpotentialbystandersofoverdose.
8
112
32
Naloxonehasbecomewidelyusedbyemergencymedicalproviders,withall50statesandtheDistrictofColumbia,Guam,andPuertoRicocertifyingandapprovingemergencymedicalservicepersonnelattheparamedicleveltoadministernaloxone.Onestepfurther,emergencymedicaltechnicians(EMTs)wereexplicitlypermittedtoadministernaloxonein12ofthese53jurisdictions(23percent—California,Colorado,DistrictofColumbia,Massachusetts,Maryland,NewMexico,NorthCarolina,Ohio,Oklahoma,RhodeIsland,Virginia,andVermont)asofNovember2013.Becausenon-paramedicEMTsaretypicallythefirstandsometimesonlysourceofemergencycare,providingauthorizationandtrainingforthemtoadministernaloxoneisapromisingstrategytoreduceoverdosedeaths.
Afteranaloxonetrainingsession,amajorityofpoliceofficersreportedthatitwouldnotbedifficulttousenaloxoneatthesceneofanoverdose(89.7percent)andthatitwasimportantthatotherofficersbetrainedtousenaloxone(82.9percent).
EffectsofNaloxoneDistribution
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114
33
Overdoseeducationandnaloxonedistribution(OEND)hasbeenshowntoincreasethereversalofpotentiallyfataloverdoses;onestudyshowedopioidoverdosedeathratestobe27to46percentlowerincommunitieswhereOENDwasimplemented. Among4,926peoplewhousedsubstancesandparticipatedinOENDinMassachusetts,373(7.6percent)reportedadministeringnaloxoneduringanoverdoserescue,withfewdifferencesinbehaviorbetweentrainedanduntrainedoverdoserescuers. AnaloxonedistributionstudyinSanFranciscoreportedthat11percentofparticipantsusednaloxoneduringanoverdose;of399overdoseeventswherenaloxonewasused,89percentwerereversed. Briefeducationissufficienttoimprovecomfortandcompetenceinrecognizingandmanagingoverdose.Prospectivestudiesareneededtodeterminetheoptimalleveloftrainingandwhethernaloxonerescuekitscanmeetthestandardforbecomingavailableoverthecounter.
Inaprobabilisticanalysis,naloxonedistributionprogramswereshowntopreventoverdosedeaths,increasequality-adjustedlifeyears(QALYs)andbehighlycost-effective.Naloxonedistributionwaspredictedtoprevent6percentofoverdosedeaths,1forevery227naloxonekitsdistributed.Costeffectiveness,undermarkedlyconservativepredictions,wasmeasuredtobe$14,000.00perQALY,wellwithinthestandardfavorablerangeofcost-benefitratios(under$50,000.00perQALY).
Criticsofnaloxonedistributionhaveclaimedthatitcouldleadtoanincreaseinriskyopioiduse,butastudyinMassachusettsshowedratesofopioid-relatedemergencydepartmentvisitsandhospitaladmissionswerenotsignificantlydifferentincommunitieswithloworhighimplementationofOENDprograms.
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116
119
115
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