Understanding Opioid Addiction and. Medication Assisted Treatment for. Families in the Child Welfare System

Transcription

1 Understanding Opioid Addiction and Medication Assisted Treatment for Families in the Child Welfare System Medicine Jason B. Fields, MD, FASAM Associate Medical Director, DACCO Behavioral Health, Inc. President of the Florida Society of Addiction Medicine Linda Mann, LCSW, CAP Director of Family Services DACCO Behavioral Health, Inc. 1

2 Scope of the Problem 90 Americans die of an opioid overdose daily In 2016, overdose deaths exceeded 59, the largest annual increase ever recorded in the United States Opioids thus have become the leading cause of death among Americans under age 50, and two-thirds of the deaths involve a prescription opioid

3 Overview of the Problem 2.1 million people in the U.S., ages 12 and older, had opioid use disorder (OUD) involving prescription opioids, heroin, or both in 2016 Opioid-related emergency department (ED) visits nearly doubled from 2005 to 2014 Opioid-related inpatient hospital stays increased 64% nationally from 2005 to 2014 Opioid addiction is linked with high rates of illegal activity and incarceration.

4 Current Treatment Gap Along Opioid Use Disorder Cascade of Care

5 Review of Medications

6 Introduction to TIP 63, Medications for OUD Reviews the three FDA-approved medications used to treat OUD methadone, naltrexone, and buprenorphine along with strategies and services to support recovery for people with OUD OUD medications are more effective than treatment with placebo or no medication in: Reducing illicit opioid use Retaining people in treatment OUD medication can be taken on a short- or long-term basis, including as part of medically supervised withdrawal or maintenance treatment

7 Purpose of TIP 63 Provides guidance for healthcare professionals and addiction treatment providers on: Appropriate prescribing practices for the three FDAapproved medications used to treat OUD. Effective strategies for supporting patients using medication for the treatment of OUD. Educates patients, families, and the general public about the benefits of OUD medications and how they work.

8 Purpose of TIP 63 The TIP series supports SAMHSA s mission by providing sciencebased best-practice guidance to the behavioral health field. This TIP reflects relevant clinical and health service research and addresses experience and implementation requirements for delivery of OUD medication Science demonstrates the effectiveness of medication treatment for OUD. Randomized control trials have shown that methadone, extended-release naltrexone (XR-NTX), and buprenorphine were more effective in reducing illicit opioid use than no medication Methadone and buprenorphine treatment also have been associated with reduced risk of overdose death

9 Introduction to Pharmacotherapy Overview of FDA-approved medications used to treat OUD. How they work Efficacy Expanding access to pharmacotherapy is an important clinical and public health strategy Specialty drug treatment programs should integrate pharmacotherapy. Requirements and regulations. Opioid treatment programs (OTPs) Waiver for buprenorphine Risk Evaluation and Mitigation Strategy (REMS) for buprenorphine implants and extended release buprenorphine

10 Introduction to Pharmacotherapy Medically supervised withdrawal: Often followed by relapse (Gruber et al., 2008; Weiss et al., 2011). Psychosocial strategies (e.g., contingency management) can reduce risk of relapse (Amato et al., 2011). Necessary prior to naltrexone treatment. Continue medication as long as benefits outweigh risks: Discontinuing medication is associated with relapse (Lee et al., 2016; Sees et al., 2000). Inform patients of risks of discontinuing medication.

11 Assessment of OUD Assess patients for OUD using DSM-5 criteria if they: spontaneously disclose opioid misuse. screen positive for opioid misuse. show signs or symptoms of opioid misuse. The extent of further assessment depends on the provider s ability to treat patients directly.

12 Providers Not Offering Pharmacotherapy Focus on medical assessment. Diagnose OUD. Discuss treatment options. Make a treatment referral. Provide overdose prevention information, naloxone prescription, and information on accessing sterile injection equipment. Make a follow-up appointment.

13 Providers Offering Pharmacotherapy Check Prescription Drug Monitoring Program (PDMP) Medical, mental health and substance use history Current medications Physical exam Assess opioid withdrawal, intoxication, & injection sites Drug testing Laboratory tests (e.g., pregnancy, liver function, HIV, hepatitis) Make diagnosis (DSM-5)

14 Treatment Planning Share the OUD diagnose and obtain patient feedback Use shared decision-making strategies Medication: Yes or No Which medication? Where to receive medication? Primary care. Specialty drug treatment program. Outpatient, OTP, residential. Which additional services are needed and wanted? Behavioral health. Self-help meetings.

15 Patients Not Ready to Engage in Treatment Provide information on: Reducing injection drug risk. Overdose prevention. Provide naloxone prescription. Make a follow-up appointment to mental health, medical, addiction treatment, & recovery support services as needed. Provide resource list

16 Methadone Methadone treatment is the most studied OUD treatment. World Health Organization considers methadone an essential medication (WHO, 2015). Clinical trials and meta-analyses show that methadone treatment is superior to treatment with placebo and to no treatment (e.g., waiting list or supervised withdrawal with methadone) in reducing illicit opioid use (Mattick et al., 2009).

17 Regulatory Issues In the US, methadone treatment must be delivered through licensed and accredited Opioid Treatment Programs (OTPs). Federal regulations stipulate admission criteria & services that must be provided (42 CFR 8.12). Admission criteria: >1 year of opioid addiction prior to admission. Can be waived for pregnant women; patients within 6 months of release from incarceration; former patients within 2 years of discharge. Youth < 18 years of age must have: parental consent. >2 unsuccessful prior treatments.

18 Pharmacology Review methadone s pharmacology: Full mu-opioid agonist. Wide individual variability in half-life (8 to 59 hours). 5 half-lives to reach steady state (average is about 5 days). metabolized largely by CYP450 3A4 enzymes. Clinical implications: Dosing must be individualized. Start at low dose and increase slowly. Adequate dose: No withdrawal symptoms for 24 hours. Reduces or eliminates craving. Blunts or blocks euphoria from illicit opioids.

19 Review of Medication Managment Precautions: Including QTc prolongation Respiratory depression Drug interactions, especially benzodiazepines and alcohol Side effects Assessment Dosing considerations Patient education

20 Comparative Effectiveness Cochrane Review of RCTs comparing methadone v. buprenorphine (Mattick et al., 2014): Methadone patients retained longer in treatment Methadone and buprenorphine equally effective in reducing illicit opioid use No RCTs comparing methadone with long-acting buprenorphine formulations No RCTs comparing methadone with XR-NTX

21 Methadone Dose Induction Considerations First methadone dose: Opioid tolerant patients: between 10 and 30 mg Use lower dose range (10-20 mg) for patients: >60 years old with lower levels of opioid tolerance based on recent history of use treated with medications that: are sedating increase methadone serum levels (or stop taking ones that decrease levels) Disorders that cause: hypoxia hypercapnia cardiac arrhythmia

22 Methadone Dosing Considerations Weeks 1-2: Avoid sedation at peak serum levels (2-4 hours after dose). Gradually extend the time without opioid withdrawal and craving Individualize dosing based on careful assessment of patient response ASAM panel recommended: 5 mg increase about every 5 days (Baxter et al., 2013) American Pain Society/CPDD panel recommended: 5-10 mg increase about every 3-4 days (Chou et al., 2014) Weeks 3-4: Suppress opioid withdrawal Reach a dose that will blunt the euphoric effect of illicit opioids Dose can be increased by 5 mg every 3-4 days

23 Special Dosing Considerations First dose for patients without current opioid tolerance: An alternative for patients not wanting XR-NTX (or buprenorphine). Former OTP patients fearing relapse Incarcerated patients with history of OUD: prior to release or upon returning to treatment begin with 5 mg per day. increase slowly by 5 mg increments every 5 7 days (Kinlock et al., 2008)

24 Duration of Methadone Treatment Longer stays are associated with better outcomes (Timko et al., 2016): Leaving methadone treatment is associated with increased risk of overdose death (Sordo et al., 2017) Patients should continue in treatment as long as they wish to and as long as the benefits outweigh the risks Dose tapering request should prompt a risk benefit discussion Plan for dose tapering should be gradual and individualized: Offer increased psychosocial and recovery supports. Stop taper if indicated and desired by patient

25 Buprenorphine On WHO s list of essential medications DATA 2000 applies only to buprenorphine formulations FDA approved for OUD treatment Physicians, nurse practitioners and physician assistants 6-month implant (Probuphine ): additional training required per FDA REMS for ordering and inserting/removing, not dispensed directly to patient Monthly injection (Sublocade ): special certification required persuant to FDA-approved REMS, not dispensed directly to patient

26 Duration of Treatment Continued medication treatment associated with better outcomes compared to medically supervised withdrawal Expert TIP panel:...supports maintaining patients on medication for years, decades and even a lifetime if patients are benefiting. Does not recommend medically supervised short-term withdrawal alone because of high rates of return to illicit opioid use Recommends discontinuing dose reductions and allowing for dose increases if patient destabilizing, prompt re-entry to treatment, encouraging psychosocial adjuncts

27 Pharmacology Review of buprenorphine pharmacology High affinity, partial opioid agonist, improved safety profile vs. full agonists Wide individual variability in pharmacokinetics: Peak plasma concentrations after a first dose of transmucosal (TM) product occur between 40 min-3.5 hours after dosing (Elkader et al., 2005) Long and variable elimination half-life from hours (Kuhlman et al., 1998) TM products: long half-life and partial agonist properties allow for less than daily dosing (e.g., doubling the daily dose once stable and giving on alternate days, 12 mg daily = 24 mg every other day; Marsh et al., 2005)

28 New Transmucosal Formulations New transmucosal (TM) formulations with improved bioavailability Ex: Zubsolv 5.7/1.4, Bunavail 4.2/0.7, Suboxone film 8/2, generic 8/2 Suboxone tablets all with bioequivalent buprenorphine exposures compared to 8/2 mg Suboxone tablet (that is no longer available) Goals of dosing of all TM formulations: Eliminate withdrawal Reduce or eliminate opioid craving. Provide effective blockade when there is illicit opioids use (patient reports diminished positive effects from the use of illicit opioid) Be well-tolerated

29 Review of Transmucosal Dosing Induction: In-office or at home. Home induction can be safe and effective (Gunderson et al, 2010; Lee et al., 2014) Individualize dosing several factors to consider including level of physical dependence For those with current physical dependence, initiate when in withdrawal with an initial 2-4 mg dose of bup/nx. FDA label recommends a maximum dose of 8 mg on day 1 and 16 mg on Day 2. Remember some patients stabilize on lower doses. Scant data to support more than 24 mg daily For those not currently physically dependent, initiate at lower doses (e.g., 1 mg with slow incremental increases, holding for sedation; Vocci et al. 2015)

30 New Long-Acting Formulations 6-month implant: approved in 2016 for clinically stable patients on buprenorphine(bup)/naloxone (nx) <8 mg / day for at least 90 days Monthly injection: recently approved for moderatesevere OUD after initiation with TM bup/nx with at least 7 days of dose adjustment

31 New Long Acting Formulations: Implant 6 month subdermal implants: Dose is 4 implants (each containing 80 mg buprenorphine), inserted in upper arm Peak plasma concentration 12 hours after insertion Removed & replaced after 6 months, wound care check within 1 week of implant and removal, office visits at least monthly to assess continued stability Consider TM supplementation if destabilize 17.9% required in Phase 3 RCT but low dose (2/0.5) and for short periods (Rosenthal et al. 2016) In a non-inferiority trial, improved abstinence rates compared to SL bup/nx (Rosenthal et al., 2016) Approved for two rounds of implants Serious adverse events: uncommon but possible including migration and nerve damage, potential for extraction and misuse. USE ONLY IN STABLE PATIENTS Limited data in pregnancy

32 New Long Acting Formulations: Injection Monthly subcutaneous abdominal injection: Refrigerate, keep at room temperature for at least 15 minutes prior to injection Dose: Months one and two 300 mg, month 3 and thereafter 100 mg (may increase if clinically indicated) Do NOT rub or massage or let belts/waistbands rub against Obtain baseline liver function tests(lfts) and monitor monthly, particularly with 300 mg dose Most common side effects were: nausea, vomiting, headache, constipation, increased LFTs, tiredness, injection site itching and pain. Uncommon: need for surgical removal of injection Limited data in pregnancy. Contains excipient, N-Methyl- 2pyrrolindone, that has reported adverse fetal effects in animal studies

33 Regulatory Considerations Waiver for physicians: 30, 100, 275 patients. Additional proactive reporting requirements for medical doctors (MDs) with approval to treat 275 patients. Requires on-call service and documented diversion control plan. Waiver for nurse practitioners (NPs) and physician assistants (PAs): 30 and 100 patients. 24 hours of training. Unique requirements for new long-acting formulations.

34 Sample Forms Buprenorphine treatment agreement Patient urine drug screen and medication count monitoring form: to assist with conduct of random urine and medication counts Pharmacy medication count form: sample of how to collaborate with pharmacies, particularly when patients may live closer to pharmacy than clinic. Sample goal-setting and coping strategy forms Checklist for induction and maintenance when using TM buprenorphine

35 Naltrexone Oral naltrexone not widely used: low acceptance and poor adherence Extended release naltrexone (XR-NTX, Vivitrol ): efficacy for preventing return to illicit opioid use after period of illicit opioid abstinence (Krupitskyet al., 2011; Lee et al., 2016): Prior to release from incarceration or residential treatment Following medically supervised withdrawal No special regulatory requirements.

36 Pharmacology Oral: peak concentrations within 1-2 hrs, half-life ~4 hrs XR-NTX: transient peak concentration 2 hrs after injection & then another at 2-3 days after injection. Concentrations gradually diminish after 14 days Elimination half-life is 5-10 days Can precipitate opioid withdrawal: Typically patients must wait ~7-10 days after a short-acting or days after a long-acting opioid to initiate XR-NTX Active area of research to effectively and expeditiously facilitate initiation of naltrexone

37 Comparative Effectiveness None comparing XR-NTX to methadone or to new longacting buprenorphine formulations Compared to sublingual buprenorphine/naloxone: Among inpatients undergoing medically supervised withdrawal in USA (n=580) XR-NTX had higher return to illicit opioid use over 24 weeks outpatient study due to difficulty initiating XR-NTX (Lee et al., 2018) Among the groups that were able to start the two medications, there were no significant differences in relapse 12-week outpatient non-inferiority trial in Norway (n=159), XRNTX non-inferior to buprenorphine/naloxone (Tanum et al., 2018)

38 XR-NTX Must have no signs of opioid withdrawal before administration, negative opioid test, consider naloxone challenge prior to initiating naltrexone Dose: intramuscular 380 mg monthly (or every 4 weeks) injection into upper outer quadrant of buttock. Alternate sides every month. Proper technique critical to avoid serious injection site reactions. Follow package insert/visual aids provided Refrigerated, keep at room temp for ~45 min before administration Assess baseline LFTs and periodically (e.g., 6 and 12 months intervals)

39 Sample Forms & Further Discussions Patient counseling tool for XR-NTX. Sample treatment agreement for XR-NTX. Goal setting and coping strategies forms also applicable. Discontinuation discussion question and points for patient and provider.

40 Efficacy of MAT and Relapse Rates

41 Bottom Line! In both controlled and retrospective studies, the success rate for most medications is between 40 and 60 % (one or two years, Connery 2015) When patients come off the medications, they relapse (Weiss 2011, Fiellin 2014) Relapse may be associated with an increased chance of overdose and death (Kakko 2003)

42 Ball 1988: Reduction in IVDU with Methadone

43 Ball 1988: Reduction in IVDU with Methadone

44 Buprenorphine Long-Term Follow Up: Fiellin, 2008

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46 No XRNTX: Abstinence 40%

47 XRNTX: Abstinence 50%

48 Ball 1988: Resumption of IVDU After Tapering Off Methadone

49 Ball 1988: Resumption of IVDU After Tapering Off Methadone

50 Buprenorphine Taper VS. Maintenance 40 heroin addicts were started on buprenorphine/naloxone. 20 were detoxed off and offered counseling. 20 were kept on buprenorphine/naloxone and offered counseling. A year later.

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53 Luty 2003: Opioid Detox During Pregnancy 101 women underwent detox during pregnancy 40 successfully detoxed. No adverse fetal effects documented BUT:

54 Luty 2003: Opioid Detox During Pregnancy 101 women underwent detox during pregnancy 40 successfully detoxed. No adverse fetal effects documented BUT: only 1 of 101 abstinent at delivery!

55 Can You Taper of Buprenorphine Without Relapse?

56 Can You Taper of Buprenorphine Without Relapse? 654 patients enroll on buprenorphine for 2 weeks. 50%stay abstinent. They are tapered off and over 90% relapse. 360 remain, they go back on buprenorphine for 12 weeks, 50% stay abstinent. They taper off and 90+% relapse. Moral of the story: medications work as long as you take them. Weiss, 2011

57 42 Months Later.

58 Outcomes? About half were reached by phone No urine drug screens were done; interviews only 32% were abstinent without M.A.T. 29% were abstinent WITH M.A.T. 8% were using while on M.A.T. 31% were using without M.A.T. Conclusion: M.A.T. was twice as successful

59 Other Concerns about Buprenorphine It can be abused (mostly for withdrawal; Kenney 2017) It is unsafe when combined with sedatives & alcohol. Adding naloxone (Suboxone/Zubsolv) doesn t help (Cohier2014) It is an opioid. Relapse rates after detox exceed 90%. (Weiss, 2011)

60 Opioid use prevention effects weaned after treatment discontinuation : Lee 2017 NEJM

61 Conclusions MAT is effective-at decreasing opioid use. Stopping MAT will usually (?) result in relapse & potentially increased chance of death. (Sordo, 2017) Why would you expect otherwise? Methadone is better at keeping you in treatment. Buprenorphine has a superior safety profile. (Mattick2014) Vivitrol (injectable naltrexone) is effective at reducing opioid use. (Kruptisky2011); it doesn t work when you don t take it (Lee 2016)

62 Successful Efforts!

63 Successful Rhode Island Project!

64 CDC Recommends Use of MAT for Patients with OUD

65 Science = Solutions: Improving Addiction Treatment

66 CDC s New Study Enrolling Through January 2019

67 Frequently Heard MAT Myths in the Child Welfare System

68 Frequently Heard MAT Myth # 1 MAT patients are still using (continuing drug use) and not really in recovery. They re just substituting one drug for another. MAT is a medical intervention used to treat symptoms of opioid addiction, similar to a SSRI treating depression, also a brain disorder. Buprenorphine and methadone are not street heroin/opioid substitutes patients withdrawal symptoms and cravings are ameliorated and no euphoria/ high is produced.

69 Frequently Heard MAT Myth # 2 The lower dose of Methadone or Buprenorphine, the better. An effective dose is determined by the patient's presenting needs. If the maintenance dosage is too low the patient will continue to experience withdrawal symptoms and may then use opioids. Dosing is an individualized medical decision.

70 Frequently Heard MAT Myth # 3 Parents in the child welfare system should only be on MAT a max of 12 months. Accepted practice that 12 months is necessary for methadone maintenance to be effective, 9 months for buprenorphine and 5 months for naltrexone. Longer treatment usually recommended. A detrimental consequences of leaving MAT are illustrated by greatly increased death rates following discharge.

71 Frequently Heard MAT Myth # 4 Parents should to be off all drugs, including Methadone, in order to be reunified. Discontinuing methadone treatment places the parent at elevated risk for relapse to illicit opiate use and associated high-risk factors, including unsafe injection practices and illegal behavior to support using. These factors can significantly increase the risk of abuse or neglect to children in the custody of these parents. The decision to require methadone detoxification should be measured carefully and based upon sound clinical principles rather than the stigma associated with methadone treatment.

72 The Yin & Yang of MAT Some patients will divert and misuse, even sell the medications on the street. Unfortunately, these medications do not prevent the concurrent use of other drugs including illegal opiates, cannabis and benzodiazepines. Crushing, snorting and injecting the medications occurs. The benefits of MAT greatly outweigh the drawbacks.

73 Strategies to Overcome Resistance to MAT

74 Approaches to Educating Child Welfare Professionals Dissemination of MAT current research & practice information on multiple system levels. Whenever and wherever opioid misuse is discussed MAT as an option. Share case information in SA/CW cross-system, reciprocal staffings. Cross-system trainings with case managers and supervisors.

75 Approaches to Educating Child Welfare Workers and Administrators Presentations to key community stakeholders for example, DACCO provides MAT training to various community agencies and county child welfare committees. Tours of medically monitored, licensed Methadone programs to dispel myths to Judges, court administration, CBC s and CPI leaders, case managers, etc..

76 Responding to Dependency Judges & Court Administrators Accurate program, research & practice information distributed to judges & court administrators. 1:1 meetings with judges to facilitate communication & strengthen collaboration. MAT trainings with court staff. Develop MAT progress reports to courts, as needed, to assist and indirectly educate court staff. SA case managers in courts to communicate accurate client & program information.

77 Suggestions for Enhancing Services for MAT Patients

78 Family Dependency Treatment Court MAT Case Review Form This client is medically monitored by Medical staff. The following treatment was provided to the above client and meets medical protocol: NO YES Current Medication and Dose: Methadone at mg. Suboxone at mg. Admission: New Methadone client admitted on with initial dose of 30 mg. Up to four 5 mg. increases as needed for withdrawal ordered. (Please note that blockade actually doesn t start until 60 mg.) A new Suboxone client admitted on with initial dose of 4 mg. and additional 4 mg. dose after one hour if needed. Up to three 2 mg. doses as needed for withdrawal ordered. Client transferred from another clinic and receiving their established dose of Methadone/Suboxone as prescribed at their previous clinic.

79 Family Dependency Treatment Court MAT Case Review Form Dose increased because of: Nausea Headache Cramps Craving Doctor approval of counselor request / treatment plan Other: Dose decreased because of: Sleepiness Physical illness Medical problems High methadone levels Other: Client missed 3 days in a row, and their dose is more than 30 mg., so his/her dose was automatically cut by 1/3 to. Client missed 4 days in a row and their dose is more than 30 mg., so his/her dose was automatically cut by 2/3 to. Client missed 5 days in a row and was required to meet with the Physician to resume dosing. They have not met OR met with the Physician.

80 Family Dependency Treatment Court MAT Case Review Form Client is currently a candidate for detox: NO YES Nurse Signature/date required Physician Signature/date required Form faxed to court and program case manager present to answer questions.

81 Treatment Status Reports Includes: Compliance Medical compliance Attendance & participation Positive changes, accomplishments and /or challenges in treatment Scheduled visitation Drug screen compliance (missed?) & results (abnormal or rejected?) Current prognosis Provider Recommendations

82 Suggestions for Child Welfare Case Management of Parents Enrolled in MAT Learn the basics of MAT to more effectively manage case. Remain non-judgmental, open minded and supportive. Have patient sign Release of Information for MAT provider so as to facilitate open communication. Tour a MAT program and ask for an explanation of their dosing & drug screening practices.

83 And the work continues

84 Continuing MAT Challenges Cost - Medicaid pays for Methadone and Buprenorphine, otherwise client must self-pay. Medicaid currently pays for Methadone but not Suboxone or Vivitrol Appropriate MAT training to child welfare and court staff due to time, cost restraints and turn-over. Coordination of services that client is concurrently engaged in. Other SA TX providers not embracing MAT.

85 RESOURCES Florida Alcohol & Drug Abuse Association Hazelden National Center on Substance Abuse & Child Welfare National Institute on Drug Abuse (NIDA) Treatment Improvement Exchange www. treatment.org US Dept. of Health and Human Services, Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment csat.samsha.gov US Dept. of Health and Human Services, Substance Abuse and Mental Health Services Administration

86 QUESTIONS???