MAT in the OTP Setting: Integrating theThree Approved Medications (Methadone,Buprenorphine, ER Naltrexone)Kelly J. Clark, MD, MBAChair, OTP WorkgroupAmerican Society of Addiction Medicine1

Kelly J. Clark, MD, MBA,DisclosuresCommercialDisclosersWhat Was ReceivedRoleGrünenthal USA, Inc.Honoraria and/or consultant feesConsultant2

ASAM CME Committee and Reviewers- Disclosure ListNature of Relevant Financial RelationshipNameCommercial InterestWhat was received?For what role?Daniel P. Alford, MD, MPH, FACP, FASAMNoneAdam J. Gordon, MD, MPH, FACP, FASAM, CMRO,Chair, Activity ReviewerNoneEdwin A. Salsitz, MD, FASAM,Reckitt-BenckiserHonorariumSpeakerJames L. Ferguson, DO, FASAMFirst LabSalaryMedical DirectorDawn Howell, ASAM StaffNoneNoel Ilogu, MD, MRCPNoneHebert L. Malinoff, MD, FACP, FASAM,Orex PharmaceuticalsHonorariumSpeakerHonorariumSpeaker and consult antActing Vice ChairActivity ReviewerMark P. Schwartz, MD, FASAM, FAAFPNoneJohn C. Tanner, DO, FASAMReckitt-BenckiserJeanette Tetrault, MD, FACPNone3

Accreditation Statement The American Society of Addiction Medicine(ASAM) is accredited by the Accreditation Councilfor Continuing Medical Education to providecontinuing medical education for physicians.4

Designation Statement The American Society of Addiction Medicine(ASAM) designates this enduring material for amaximum of 1 (one) AMA PRA Category 1 Credit .Physicians should only claim credit commensuratewith the extent of their participation in the activity. Date of Release: September 30, 2014 Date of Expiration: September 30, 20175

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Educational Objectives At the conclusion of this activity participants should beable to: Discuss the unique characteristics of OpioidTreatment Programs (OTPs) Identify OTPs as part of the continuum of care Understand the infrastructure available to supportmedication management in OTPs Understand challenges and opportunities inintegrating all three medications (methadone,buprenorphine and extended release naloxone) intothe OTP setting Discuss the clinical and operational issues related tomedication choice in the OTP setting.7

Target Audience The overarching goal of PCSS-MAT is to makeavailable the most effective medication-assistedtreatments to serve patients in a variety of settings,including primary care, psychiatric care, and painmanagement settings.8

What is an OTP? An Opioid Treatment Program (OTP) provides: multidisciplinary outpatient-based maintenance care of patients with opioid addiction, utilizing FDA approved medication (typicallymethadone), and operating under OTP regulations and licensesfrom the federal and state government9

Why are there OTPs? Under federal law, patients may be treated withscheduled narcotics for maintenance treatment of opioidaddiction only via medication ordered and dispensedfrom an “Opioid Treatment Program” (OTP) There is no “prescription” on a pad – medication isordered and dispensed from the OTP The DATA 2000 Act allows for physicians to obtainwaivers allowing limited prescribing of approvednarcotics less than Schedule II in other settings, such asOffice Based Opioid Treatment (OBOT)10

What is special about OTPs?Federal and State Requirements Full bio-psycho-social admission assessment, performed by nursing,counselling and physician staff, including physical examination, drugscreens and laboratory work Admission only under a physician’s order Open 6-7 days per week with nurses on site each day Patient’s methadone doses are dispensed and consumed undersupervision of nurse/pharmacist (state rules vary) Patients initially must come to clinic to dose daily Clinics licensed by state and feds, and accredited by either CARF or TheJoint Commission (prev. JCAHO)11

What is special about OTPs?Federal and State Requirements Required counselling for substance abuse (not synonymous withpsychotherapy for mental health issues) Documented full treatment planning Diversion control processes Drugs screens (urine, oral swabs). Drug testing for confirmations ifnecessary. Urine collections may be observed or unobserved. Call backs for both random urine drug screens (UDS) and to checkthat any take home meds are accounted for12

What is special about OTPs?Federal and State RequirementsGradual increase in take- home privilegesAfter several weeks / months (varies by state) of: Passed drug screens Perfect attendance Full adherence to treatment planThen patients may, under a physician’s order: Take home one fully labeled dose of methadone per week13

What is special about OTPs?Federal and State Requirements Earned number of days per week of take homemedications increase gradually by SAMHSA and statespecific guidelines The maximum a patient may have under federalguidelines is a 27 days supply per 28 days; may beearned after a minimum of 2 years in treatment14

Methadone and BuprenorphineSimilarities 1. Can cause withdrawal upon abrupt cessation 2. Have a range of dosing, which is titrated to theindividual patient’s needs 3. Relapse rates are high when treatment withmedication is discontinued 4. Patients can currently only be admitted to OTPs/prescribed buprenorphine by physicians15

What is special about OTPs? Around 1200 OTPs in the US Very few commercial health plans will contract with/ payfor OTP services Some urban areas have OTPs funded by block grants,other direct governmental funding, or Medicaid planscontracting with OTPs for services Meaning that typically OTPs operate on a patient selfpay model (daily or weekly payments) Around 70-130/week, all required services andmethadone medication included16

What is special about OTPs? Methadone is dispensed, not prescribed Liquid, 40 mg wafers and/or 5 mg pills 10 mg pills may not be provided to/used by OTPs 10 mg pills found on the street were therefore initiallyprescribed for pain, not dispensed by OTPs. This has allowed the CDC to state clearly that thevast majority of diverted methadone is not comingfrom OTPs Stored in unrefrigerated safes17

What is the “OTP Level of Care”? Outpatient care traditionally consists of such services as a 50 minute individualtherapy session, a 90 minute group therapy session, or a 15 minute medicationcheck by a prescriber. These typically occur 1-2 times per week, per month, or,for fully stable patients, per quarter. (ASAM Level I) Intensive outpatient services are approximately 3 hours of service, three times aweek and may not include prescribing (ASAM Level II.1) Partial Hospital Programs are 4 hours a day, 5 days a week (ASAM Level II.2) Inpatient services range from medically intensive hospitalizations torehabilitation programs with no medical services included (ASAM Level III-IV)18

What is the “OTP Level of Care”? “Opioid Maintenance Therapy” is a considered aspecific service that can be provided under any levelof care However, since most “OMT” is provided in “OTPs”, anoutpatient environment, criteria are provided in theoutpatient format The patient’s need for both high levels of structurestherapy and medication to prevent withdrawalseparate the OTP from outpatient levels of care19

Historically, OTPs providedmethadone maintenance therapy Methadone has been the “Gold Standard” of care for opioidaddiction for over 50 years Newer FDA approved medications, buprenorphine products(SL and buccal) and ER naltrexone, may be used outside ofthe OTP setting BUT - OTPs have a unique infrastructure which can beeffectively utilized to provide all these mediation modalities Specific operational and clinical issues must be considered tointegrate the full range of pharmacotherapies into the OTPsetting20

Methadone: Clinical issues Methadone is a full mu agonist with a long half life Once per day dosing for addiction, but 3-4 times daily dosingfor chronic pain management. OTPs can only dose a patientqd without state exception to split into 2 doses Prolongs QTc with risk of Torsades de Pointes Meaningful peak and trough blood levels No ceiling effect on respiratory depression Dangerous to titrate up quickly Dangerous mixed with “The 3 Bs” - benzos/barbs/booze21

Methadone: Clinical issues Uncomfortable and objectively obvious withdrawaloccurs after missing 1- 2 days of dose Requires daily dosing initially in the OTP Patient are not allowed to be in methadonetreatment and utilize a commercial driver’s license Patients who travel for work will need to either earntake homes or guest dose at other facilities22

Case (Part I)Johnny is a 34 yo male; hurt back working in the coalmines and was rxed opioids; use escalated and hebegan using multiple oxycodone with APAP 30/500 mgtabs through IV route daily. Meets criteria for OpioidDependence, LFTs less than 3x normal.Tried buprenorphine from a clinic where he saw adoctor and received a prescription: “It didn’t work forme. I just stopped taking it and used, and took it somemore and then stopped and used. It was too easy togame it. I need more. I don’t want that medicine”.23

What patients may do well withmethadone treatment? Long hx of opioid addiction IV route of illicit drug administration Require diversion control procedures Respond to high levels of external daily structure Benefit from contingency management techniquesof the take home / phase system24

Methadone and BuprenorphineSimilarities1. Are daily dosed medication taken via the oral cavity2. Can be stored in an unrefrigerated safe3. Act to cover the mu receptor in order to:i. Decrease or eliminate cravingsii. Control physiological withdrawaliii. Prevent euphoria from use of other mu agonists25

Methadone and BuprenorphineSimilarities1. Can cause withdrawal upon abrupt cessation2. Have a range of dosing, which is titrated to theindividual patient’s needs3. The endpoint of an episode of care consists ofgradual tapering to medication discontinuation4. Patients can currently only be admitted to OTPs/prescribed buprenorphine by physicians26

Methadone and BuprenorphineSimilarities1.Are mu receptor agonists (full and partial, respectively), and therefore can beused by people not dosing daily with them to get high2.Have significant street value when diverted3.Can be lethal in overdose (low threshold for unintentional overdose seen inadults due to long half-life and no respiratory depression ceiling;buprenorphine fatalities have occurred in children or in other people withouttolerance)4.Are seen as “using” by many 12 step groups; patients are often advised not totell others at meetings they are taking these medications5.Stigma by some people in 12 step groups, criminal justice system, otherhealth care providers that these are “just substituting one drug for another’27

Buprenorphine Issues in the OTP 1.Buprenorphine may be obtained in 2 ways:Prescribed by an OTP physician under their Data 2000 waver using OBOTrestrictions ( 30/100 pt limit)Or2.Ordered and dispensed under methadone rules (full admission work up, dailysupervised dosing, medication ordered and dispensed from the OTP,required counselling, drug screens, call backs, etc) EXCEPT: the time in treatment requirement to earn take homephases is not applicable under federal regs (states vary) As with methadone, there is no limit on the number of patients aphysician may have on buprenorphine in an OTP ( states vary)28

Buprenorphine Issues in the OTP OTP vs. OBOT in the clinic: It is either/or but notboth for a single patient during an episode of care. Patients being prescribed buprenorphine by theirwavered physician may not be dosed at the OTPunless they are first admitted and maintainedunder OTP rules.29

Buprenorphine Issues in the OTP:Available InfrastructureAlthough not required for OBOT, the OTPs have the abilityto perform a variety of useful services for buprenorphinepatients who require additional structure: CounselingPhysical examinationsNursing services including observed dosingDiversion control processes Drug screens/tests Random call backs Pill/film counts30

Buprenorphine Issues in the OTP1. Buprenorphine does not require as an careful inductionbecause of ceiling effect on respiratory depression2. Patients must have their mu receptors adequately“uncovered” by full mu agonist in order to begin dosingthe partial agonist of buprenorphine, or they will bethrown into withdrawal3. Because of the slow to absorb time SL vs. oral injestionof methadone, dosing SL buprenorphine can takesignificantly more staff time to monitor and ensure nodiversion.31

Case (Part II) Johnny did extremely well with methadone at amaximum dose of 85 mg per day and began a gradualdose reduction. At 3 years he on 70 mg and has beeneligible for 27 take homes per 28 days, but opts to get 13in 14 days (“I don’t trust myself with more. I need tocome here to keep myself honest”) He has an opportunity to change jobs from undergroundmining to hauling coal locally, which requires acommercial driver’s license. He is willing to change tobuprenorphine, recognizing he is now doing wellpresenting 2 weeks to clinic.32

What patients may do well withBuprenorphine?1. Able to maintain treatment plan without dailysupportive contacts/ structure of clinici. Structure (employed, other)ii. Strong sober support systemiii. Adequate stress management skillsOr OTP can order and dispense buprenorphineunder methadone rules33

Overview of Issue Direct cost of methadone 1 a day Direct Cost of buprenorphine (SL) 4 - 30 a day Direct Cost of ER naltrexone 700-1000 perinjection ( monthly)34

Buprenorphine Issues in the OTP:Payment for Medication Buprenorphine retails 7-10 for 8 mg (with or without naloxone). Health plans might/ might not cover buprenorphine Buprenorphine costs to OTP through a distributer might be retail But not 1 per day as with methadone OTPs dispensing buprenorphine instead of methadone will need tocover the increased costs by: increasing daily/weekly charges to the patientbilling medication costs directly to plans (such as byobtaining a pharmacy license)35

Extended Release Naltrexone Full mu antagonist Blocks the high of using mu agonists Will precipitate withdrawal if agonists (full or partial)are occupying mu receptors 7-10 days without other opioid use beforenaltrexone Monthly dosing improves adherence36

How ER naltrexone differs frommethadone and buprenorphine IM injection into buttocksDoses once monthlyNo abuse potential; not a scheduled narcoticCan be prescribed by advanced practicenurses/physician assistants (varies by state) Specialty pharma product Medication must be refrigerated and mixed shortlybefore administration Substantially less stigma37

ER naltrexone OD risks Fatal overdoses have been reported in patientstaking ER naltrexone, especially when: Trying to overcome opioid blockade Using opioids at or near end of 1 month dosinginterval Using opioids after missing dosePatients may not understand their loss of tolerancewhen taking ER naltrexone is a danger when theylapse.38

Case (Part III) Johnny made the change from methadone to buprenorphine,stabilized at 12 mg qd for a year and gradually tapered to 4 mgqd. Attempts to lower the dose have failed. Continues to choose present q 2 weeks to clinic, althougheligible for monthly visits and has been encouraged to findsupport outside of clinic Local mines have closed, and he has the option for work inanother state. Plans to come home once monthly. Will haveinsurance with new job, and has saved substantial moneysince he stopped using street opioids and began treatment 6years ago.39

Which patients may do well with ERnaltrexone? High motivation for abstinence Patients needing treatment where drug courtjudges, professional boards, others may not allowagonist tx Short/less severe hx of opioid addictionFailed agonist treatmentDo not wish to use agonist txSucceeded in agonist tx and want to change to lessintensive medication treatment regimen40

How to Choose Medications? No evidence-informed guidelines on choosing thethree options currently Guidelines are being built by ASAM with date ofrelease mid-2015 In lieu of formal guidelines, physicians must useclinical judgment considering multiple issues41

Choosing Medications Patient history of tx response/failureFamily history of tx response/failurePatient’s / family’s beliefs about specific medicationsPatient’s financial ability to obtain Medication itself all services necessary to support amedication treatment42

Choosing Medications Restrictions due to professional boards/ employers/family services or court representatives Potential for abuse/diversion Potential for drug interactions medical contraindication (relative or absolute ) Patient’s access to OTP: geographically time constraints transportation availability and cost43

Operational ChallengesIntegrating all three medications into OTP setting Expanding safe storage for medications Refrigeration for ER naltrexone “patient flow” - different times of day for differentmedications? Recall slower buprenorphine SLdosing flow Pricing new services Establish protocols for induction, maintenance, andtherapeutic discontinuation with buprenorphine andER naltrexone44

Operational ChallengesIntegrating all three medications into OTP setting Relationships with payers and medicationdistributers New patient and family education materials New patient informed consent materials Education of all staff on all three modalities Education of community on availability of all threemodalities Obtaining physician resources to lead clinical carein all modalities Probable availability of new buprenorphineformulations in near future45

Conclusion OTPs offer a unique characteristics which can beused to provide care with methadone,buprenorphine, and ER naltrexone There are multiple clinical and operationalchallenges in integrating all modalities All three FDA approved medications have uniqueprofiles which provide real treatment options forpatients46

References ASAM Ppc-2R: ASAM Patient Placement Criteria for the Treatment of Substance-RelatedDisorders. Editor David Mee-Lei . American Society of Addiction Medicine, 2001 Substance Abuse and Mental Health Services Administration. (2012). An Introduction toExtended-Release Injectable Naltrexone for the Treatment of People With OpioidDependence. Advisory, Volume 11, Issue 1. Center for Substance Abuse Treatment. (2009). Emerging Issues in the Use ofMethadone. HHS Publication No. (SMA) 09-4368. Substance Abuse Treatment Advisory,Volume 8, Issue 1. Center for Substance Abuse Treatment. (2004). Clinical guidelines for the use ofbuprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP)Series 40. HHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and MentalHealth Services Administration. Center for Substance Abuse Treatment. (2008). Medication-assisted treatment for opioidaddiction in opioid treatment programs. Treatment Improvement Protocol (TIP) Series 43. HHSPublication No. (SMA) 08-4214. Rockville, MD: Substance Abuse and Mental Health ServicesAdministration. Mattick, R. P., Breen C., Kimber J., & Davoli, M. (2009). Methadone maintenance therapyversus no opioid replacement therapy for opioid dependence. Cochrane Database ofSystematic Reviews, Issue 3, Art. No.: CD002209. doi: 0.1002/14651858.CD002209.47

PCSS-MAT Mentoring Program PCSS-MAT Mentor Program is designed to offer general information toclinicians about evidence-based clinical practices in prescribingmedications for opioid addiction. PCSS-MAT Mentors comprise a national network of trained providers withexpertise in medication-assisted treatment, addictions and clinicaleducation. Our 3-tiered mentoring approach allows every mentor/mentee relationshipto be unique and catered to the specific needs of both parties. The mentoring program is available, at no cost to providers.For more information on requesting or becoming a mentor

PCSSMAT is a collaborative effort led by American Academyof Addiction Psychiatry (AAAP) in partnership with: AmericanOsteopathic Academy of Addiction Medicine (AOAAM),American Psychiatric Association (APA) and American Societyof Addiction Medicine (ASAM).For More Information: www.pcssmat.orgTwitter: @PCSSProjectsFunding for this initiative was made possible (in part) by Providers’ Clinical Support System forMedication Assisted Treatment (5U79TI024697) from SAMHSA. The views expressed in writtenconference materials or publications and by speakers and moderators do not necessarily reflect theofficial policies of the Department of Health and Human Services; nor does mention of trade names,commercial practices, or organizations imply endorsement by the U.S. Government. 49

Please Click the Link Below to Accessthe Post Test for the Online ModuleClick Here to Take the Post TestUpon completion of the Post Test: If you pass the Post Test with a grade of 80% or higher, you will be instructed to click a linkwhich will bring you to the Online Module Evaluation Survey. Upon completion of theOnline Module Evaluation Survey, you will receive a CME Credit Certificate or Certificate ofCompletion via email. If you received a of 79% or lower on the Post Test, you will be instructed to review theOnline Module once more and retake the Post Test. You will then be instructed to click alink which will bring you to the Online Module Evaluation Survey. Upon completion of theOnline Module Evaluation Survey, you will receive a CME Credit Certificate or Certificate ofCompletion via email. After successfully passing, you will receive an email detailing correct answers,explanations and references for each question of the Post Test.50

Methadone: Clinical issues Methadone is a full mu agonist with a long half life Once per day dosing for addiction, but 3-4 times daily dosing for chronic pain management. OTPs can only dose a patient qd without state exception to split into 2 doses Prolongs QTc with risk of Torsades de Pointes Meaningful peak and trough blood levels