Faculty/Presenter Disclosure

Provincial Guidelines for the Clinical Management of Opioid Use Disorder Leslie Lappalainen MD Family and Addiction Medicine Medical Lead for Addiction Medicine, Interior Health, Mental Health and Substance Use Clinical Instructor, UBC Provincial update: Officially Released Feb 7, 2017 Faculty/Presenter Disclosure Faculty: Leslie Lappalainen Relationships with commercial interests: Grants/Research Support: NIDA (previous) Speakers Bureau/Honoraria: None Consulting Fees: None Other: BC Centre on Substance Use (MoH), Interior Health 1

Disclosure of Commercial Support I have NOT received financial support or in kind support from any commercial interest. St Paul s Addiction Medicine Fellowship is funded in part by Goldcorp Corporation Potential for conflict(s) of interest: None Mitigating Potential Bias No sources of bias 2

Learning Objectives Opioid overdose emergency in the province and within the Interior Review new BC Centre on Substance Use and how this new centre plans to support IH Addition primer Review the role of detox as a standalone intervention for opioid use disorder Review the evidence for psychosocial treatments for opioid use disorder Learning Objectives Review evidence for pharmacotherapy options for opioid use disorder and potential advantages and disadvantages of each treatment option Review of specialist led treatments Review of harm reduction approaches (take home naloxone, supervised consumption sites) 3

Opioid Overdose Emergency 4

Number of deaths and mortality rate attributed to illicit drug use in B.C., 1990-2016 922 Source: Illicit Drug Overdose Deaths in BC, January 1, 2007 to January 30, 2017. Office of the Chief Coroner of BC. Released Feb 17, 2017. 5

Source: Illicit Drug Overdose Deaths in BC, January 1, 2007 to November 30, 2016. Office of the Chief Coroner of BC.. Source: Illicit Drug Overdose Deaths in BC, January 1, 2007 to November 30, 2016. Office of the Chief Coroner of BC. 6

2010 2012 7

2014 2016 8

9

Public Health Emergency Comparisons SARS (2003) 44 deaths; 400 ill; 25 000 quarantined (Canada) H1N1 (2009) 429 deaths, 15 000 ill (Canada) 56 deaths, 1059 ill (BC) EBOLA (2014) 0 deaths, 0 ill, 1000 at risk (Canada) 0 deaths, 0 ill, 100 at risk (BC) Opioid Overdose (2016) 916 deaths, 30 000 ill (BC) 154 deaths, 5000 ill (Interior Health) How do we stop this overdose trend? Requires a cultural shift to the way we treat opioid use and opioid addiction Application of evidence based practice Addressing gaps between evidence and practice More physicians trained to do addictions work within primary care settings 10

11

Core Functions Addiction Primer Addiction defined Review of reward pathways involved Opioid addiction why new guidelines? 12

What is addiction? Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. Source: American Society of Addiction Medicine (ASAM) What is addiction? Addiction is characterized by: Inability to abstain Impairment in behavioral control Craving Diminished recognition of significant problems Dysfunctional emotional response Cycles of relapse and remission Without treatment or engagement in recovery process can result in disability and premature death Source: American Society of Addiction Medicine (ASAM) 13

Piore et al. Resetting the Addictive Brain May 2015. Discover Magazine. 14

15

16

Science Inpatient/Outpatient Detox Withdrawal/Taper Psychosocial Treatment OAT Methadone Buprenorphine/Naloxone Mandatory Counselling? Tapers vs. Maintenance 17

Background The province has a guideline for the treatment of opioid use disorder with methadone Updated July 2016 to include buprenorphine Evidence-based guidance for when to use methadone versus other treatments lacking Background Released in 2015 18

Release date: Feb 7, 2017 19

Disclosures No member of guideline committee reported direct financial or indirect conflicts of interest Overview of treatment options a WITHDRAWAL MANAGEMENT 1 3 Tapered methadone, buprenorphine, or alpha 2 adrenergic agonists +/ psychosocial treatment 4 +/ residential treatment +/ oral naltrexone 5 LOW If opioid use continues, consider treatment intensifiction. >> AGONIST THERAPIES Buprenorphine/ naloxone 6 (preferred) Methadone 7,8 +/ psychosocial treatment +/ residential treatment TREATMENT INTENSITY SPECIALIST LED ALTERNATIVE APPROACHES* Slow release oral morphine 9,10 +/ psychosocial treatment +/ residential treatment HIGH Where possible, << simplify treatment. HARM REDUCTION 10 13 Across the treatment intensity spectrum, evidence based harm reduction should be offeed to al l, includi ng: Education re: safer use of sterile syringes/needles and other applicable substance use equipment Access to sterile syringes, needles, and other supplies Access to Supervised Injection Sites (SIS) Take Home Naloxone (THN) kits 20

Withdrawal management only Detox: Inpatient vs. Outpatient Intensive Psychosocial Treatment? Residential Treatment OAT Tapers, Clonidine? Outcomes? a r WITHDRAWAL MANAGEMENT 1 3 Tapered methadone, buprenorphine, or alpha 2 adrenergic agonists +/ psychosocial treatment 4 +/ residential treatment +/ oral naltrexone 5 LOW If opioid use continues, consider treatment intensifiction. >> AGONIST THERAPIES Buprenorphine/ naloxone 6 (preferred) Methadone 7,8 +/ psychosocial treatment +/ residential treatment TREATMENT INTENSITY SPECIALIST LED ALTERNATIVE APPROACHES* Slow release oral morphine 9,10 +/ psychosocial treatment +/ residential treatment HIGH Where possible, << simplify treatment. Across the treatment intensity spectrum, evidence based harm reduction should be offeed to al l, includi ng: Education re: safer use of sterile syringes/needles and other applicable substance use equipment HARM Access to sterile syringes, needles, and other supplies REDUCTION 10 13 Access to Supervised Injection Sites (SIS) Take Home Naloxone (THN) kits 21

22

Safety considerations - Withdrawal management alone Detox can potentially be an important first point of contact and a bridge to other treatment options However, detox as a stand alone intervention associated with: High rates of relapse (Strang et al., 2003) 90% relapse most within 7 days HIV-transmission (MacArthur et al., 2012) Morbidity and Mortality (Luty 2003, Simpson and Friend, 1988) THN Training Residential Treatment (without maintenance OAT) No systematic reviews or meta-analyses Signal to some clinical improvement, but much of the literature is outdated (Craddock 1997, Gossop 1999, Hubbard 1989, Simpson 1982) Relapse (Smyth et al., 2010) Without OAT 91% relapse, 59% within one week of D/C No OAT 2 times risk of death (Matthias Pierce 2016) 23

Withdrawal Options Buprenorphine/n aloxone taper Methadone taper Short-acting opioids Clonidine and ancillary meds Encourage: Long, slow taper Intensive psychosocial followup outpatient taper Ensure: take-home naloxone training Warn: risk of OD and death with inpatient taper Opioid Agonist (Maintenance) Therapy Methadone vs. buprenorphine First line? Safety profile of medications Mandatory counselling Take home dosing vs. methadone? How long; when and how to taper Other evidence-based options 24

a WITHDRAWAL MANAGEMENT 1 3 Tapered methadone, buprenorphine, or alpha 2 adrenergic agonists +/ psychosocial treatment 4 +/ residential treatment +/ oral naltrexone 5 LOW If opioid use continues, consider treatment intensifiction. >> AGONIST THERAPIES Buprenorphine/ naloxone 6 (preferred) Methadone 7,8 +/ psychosocial treatment +/ residential treatment TREATMENT INTENSITY SPECIALIST LED ALTERNATIVE APPROACHES* Slow release oral morphine 9,10 +/ psychosocial treatment +/ residential treatment HIGH Where possible, << simplify treatment. HARM REDUCTION 10 13 Across the treatment intensity spectrum, evidence based harm reduction should be offeed to al l, includi ng: Education re: safer use of sterile syringes/needles and other applicable substance use equipment Access to sterile syringes, needles, and other supplies Access to Supervised Injection Sites (SIS) Take Home Naloxone (THN) kits What does work for opioid addiction: Opioid Agonist Therapy Methadone Buprenorphine/naloxone (4:1 ratio) (Suboxone ) Treatment duration: usually at least 12 months and then a slow taper 25

Threshold for Respiratory Depression 26

Partial Agonist (i.e. buprenorphine/naloxon e Suboxone) Partial activation 27

Full Agonist (i.e. heroin, methadone, morphine) Partial Agonist (i.e. buprenorphine) This relative difference between full activation of the receptor and partial activation of the receptor is called PRECIPITATED WITHDRAWAL Less Full activation Agonist Treatment Methadone MMT vs. no opioid replacement therapy (Mattick et al., Cochrane Review 2009) Methadone significantly more effective than nonpharmacological approaches in: o Treatment retention o Suppression of heroin use 28

Agonist treatment Buprenorphine/naloxone Buprenorphine vs. Methadone Maintenance Therapy (Mattick et al., Cochrane Review 2014) At medium/high doses bup/nlx ( 12-16 mg) is not markedly different from methadone in terms of treatment retention No difference between bup/nlx and MMT in reducing illicit opioid use Agonist treatment Buprenorphine/naloxone Buprenorphine vs. Methadone Maintenance Therapy (Mattick et al., Cochrane Review 2014) At medium/high doses bup/nlx is not markedly different from methadone in terms of treatment retention Safety profile? No difference between bup/nlx and MMT in reducing illicit opioid use 29

98 unintentional OD b/w June Oct 2013 2/98 cases tested positive for the bup metabolite Both tested + for 6-MAM, morphine (heroin OD) 30

31

mid 1990s MMT provided to only 20 30% of persons with OUD due to regulations and concerns re: safety 1995 all medical doctors allowed to prescribe buprenorphine without any special licensing Barriers minimized: physician compensation mechanisms in place, pharmacy services and insurance coverage Led to 65,000 patients per year getting on treatment (10 x more than with methadone) About 20% of all physicians in France use bup to treat OUD Reduction in overdose mortality with expanded access to buprenorphine (France) 2006 by the Infectious Diseases Society of America Carrieri et al., 2006 32

Advantages Potent opioid agonist Potentially better treatment retention, particularly for unstable opioiddependent individuals Disadvantages Higher risk of overdose, particularly during treatment initiation Generally requires daily witnessed ingestion (DWI) Methadone May be easier to initiate treatment Potentially better alternative if buprenorphine was unsuccessful at relieving withdrawal symptoms or associated with severe side effects Approved in Canada for primary purpose of pain control (split dose BID or TID dosing); Health Canada exemption required for prescribing More severe side effect profile More expensive if DWI required Longer time to achieve therapeutic dose (>35 days) Higher potential for adverse drug-drug interactions (e.g. Abx, ARVs) Increased risk of cardiac arrhythmias as a result of QTc prolongation Buprenorphine/Naloxone Advantages Risk of OD as partial agonist and ceiling effect for resp. depression Reduced risk of injection, diversion, and OD due to naloxone component Allows for safer take home schedules Milder side effect profile Easier to rotate from bup/nlx to methadone Flexible take home schedules many contribute to cost savings and patient autonomy Shorter time to achieve therapeutic dose (1-3 days) Disadvantages Potential risk of drop-out May cause precipitated withdrawal if induced inappropriately May block opioid analgesics used for concurrent pain treatment Not approved in Canada for the purposes of pain control 33

Opioid Use Disorder Bup/Nx 1 st line Primary Care = methadone 34

35

36

2011 review 35 studies, 4319 participants Psychosocial interventions + OAT vs. standard OAT No significant benefits retention or treatment outcomes Tapers? 37

Alternative Treatment Options a r WITHDRAWAL MANAGEMENT 1 3 Tapered methadone, buprenorphine, or alpha 2 adrenergic agonists +/ psychosocial treatment 4 +/ residential treatment +/ oral naltrexone 5 LOW If opioid use continues, consider treatment intensifiction. >> AGONIST THERAPIES Buprenorphine/ naloxone 6 (preferred) Methadone 7,8 +/ psychosocial treatment +/ residential treatment TREATMENT INTENSITY SPECIALIST LED ALTERNATIVE APPROACHES* Slow release oral morphine 9,10 +/ psychosocial treatment +/ residential treatment HIGH Where possible, << simplify treatment. Across the treatment intensity spectrum, evidence based harm reduction should be offeed to al l, includi ng: Education re: safer use of sterile syringes/needles and other applicable substance use equipment HARM Access to sterile syringes, needles, and other supplies REDUCTION 10 13 Access to Supervised Injection Sites (SIS) Take Home Naloxone (THN) kits 38

Emerging therapeutic options for severe OUD Slow release oral morphine (once daily witnessed ingestion) if failed 1 st line options off label use Prescribers must have methadone exemption and should consult with specialist experienced in prescribing SROM Injectable diacetylmorphine (heroin) and hydromorphone options in a supervised setting for treatment refractory opioid use disorder Included in Vancouver Coastal Health guidelines of OUD (but not in Provincial Guidelines), recommended injectable program expansion in Coroners Inquest (B. Jansen). Opioid Antagonist Naltrexone Full opioid blocker Reduced tolerance Low treatment retention rates Not superior to other forms of treatment Oral (Revia) vs. extended release (Vivitrol) (Naltrexone) 39

New Treatments (Not yet available in Canada) 40

Harm Reduction Approaches a r WITHDRAWAL MANAGEMENT 1 3 Tapered methadone, buprenorphine, or alpha 2 adrenergic agonists +/ psychosocial treatment 4 +/ residential treatment +/ oral naltrexone 5 LOW If opioid use continues, consider treatment intensifiction. > AGONIST THERAPIES Buprenorphine/ naloxone 6 (preferred) Methadone 7,8 +/ psychosocial treatment +/ residential treatment TREATMENT INTENSITY SPECIALIST LED ALTERNATIVE APPROACHES* Slow release oral morphine 9,10 +/ psychosocial treatment +/ residential treatment HIGH Where possible, << simplify treatment. Across the treatment intensity spectrum, evidence based harm reduction should be offeed to al l, includi ng: Education re: safer use of sterile syringes/needles and other applicable substance use equipment HARM Access to sterile syringes, needles, and other supplies REDUCTION 10 13 Access to Supervised Injection Sites (SIS) Take Home Naloxone (THN) kits 41

2012 2014 1318 trained 2012 2014 40 sites 42

Take Home Naloxone in BC Go to http://towardstheheart.com/ Find a harm reduction site in your area 43

Summary 44

Withdrawal Options Buprenorphine/n aloxone taper Methadone taper Short-acting opioids Clonidine and ancillary meds Encourage: Long, slow taper Intensive psychosocial followup outpatient taper Ensure: take-home naloxone training Warn: risk of OD and death with inpatient taper Treatment 1 st line: Buprenorphine/nalox one Relatively safer Take home doses Easier to transition from partial to full agonist Primary care settings Rural and remote settings Withdrawal Options Buprenorphine/nalox one taper Methadone taper Short-acting opioids Clonidine and ancillary meds 45

Treatment 1 st line: Buprenorphine/nalox one If contraindications: Methadone Withdrawal Options Buprenorphine/nalox one taper Methadone taper Short-acting opioids Clonidine and ancillary meds Treatment 1 st line: Buprenorphine/nalox one If contraindications: Methadone 2 nd line: Transition bup/nlx to methadone methadone to bup/nlx Withdrawal Options Buprenorphine/nalox one taper Methadone taper Short-acting opioids Clonidine and ancillary meds 46

a WITHDRAWAL MANAGEMENT 1 3 Tapered methadone, buprenorphine, or alpha 2 adrenergic agonists +/ psychosocial treatment 4 +/ residential treatment +/ oral naltrexone 5 LOW If opioid use continues, consider treatment intensifiction. >> AGONIST THERAPIES Buprenorphine/ naloxone 6 (preferred) Methadone 7,8 +/ psychosocial treatment +/ residential treatment TREATMENT INTENSITY SPECIALIST LED ALTERNATIVE APPROACHES* Slow release oral morphine 9,10 +/ psychosocial treatment +/ residential treatment HIGH Where possible, << simplify treatment. HARM REDUCTION 10 13 Across the treatment intensity spectrum, evidence based harm reduction should be offeed to al l, includi ng: Education re: safer use of sterile syringes/needles and other applicable substance use equipment Access to sterile syringes, needles, and other supplies Access to Supervised Injection Sites (SIS) Take Home Naloxone (THN) kits 47

Intensive specialized Addiction care IM Psychiatry Primary Care Addiction Care Hospital Detox Health Care System Integrated with BCCSU Practical Tips: Continuing patients on Bup/Nx Collateral from initiating doctor Pharmanet! Improved retention: 12 16 mg/d Know how medication is taken (SL) Course: suboxonecme.ca IH will cover 3.5 hours at sessional rate for doing this! Lower barriers: how long and who to DWI? Benzos, AUD, youth, working, school, psych, homeless Random pill counts Random UDS RACE line support 48

Practical tips billing T00039 fee code for methadone or buprenorphine/naloxone $22.98/week (payable once per patient per week, regardless of visits per week) P15039 fee code for point of care urine testing for individuals on methadone or bup/nal $12.42/per test (up to 26 per year) Revisions to fee codes are underway Coverage for bup/nlx recent update Income Assistance and PWD fully covered As of Feb 1, 2017 buprenorphine/naloxone is covered through Plan G (coverage for psychiatric medication) Available if family adjusted net income below $42,000 (plus $3000 per dependent) 49

Additional Guideline Supports New guidelines Online on BCCSU website Point of care summary tools Patient information sheets Addiction teams and services (e.g. detox for challenging buprenorphine induction) RACE Line: 604-696- 2131 http://www.raceconnect.ca bweitzel@providencehealth.bc.ca 50

3 streams: Clinical, Nursing, and Social Work Timeline for 2018-2019 Clinical Fellowship: August 28, 2017 Application process opens October 2, 2017 Application deadline Nov 6, 2016 Interview period to Dec 4, 2017 December 11, 2017 Acceptance notification December 18, 2017 Deadline for acceptance July 3, 2018 Fellowship begins Questions? Please email Carmen Rock at crock@cfenet.ubc.ca 3 streams: Clinical, Nursing, and Social Work Timeline for 2017-2018 Nursing Fellowship: September 30, 2016 Application process opens October 31, 2016 Application deadline Nov 15, 2016 to Interview period Jan 16, 2017 January 30, 2017 Acceptance notification February 10, 2017 Deadline for acceptance July 3, 2017 Fellowship begins Questions? Please email Carmen Rock at crock@cfenet.ubc.ca 51

3 streams: Clinical, Nursing, and Social Work Timeline for 2017-2018 Social Work Fellowship: December 5, 2016 Application process opens January 16, 2017 Application deadline Feb 6 to Mar 3, 2017 Interview period March 13, 2017 Acceptance notification March 20, 2017 Deadline for acceptance July 3, 2017 Fellowship begins Questions? Please email Carmen Rock at crock@cfenet.ubc.ca Timeline for 2017-2018 Research Fellowship: October 31, 2016 Application process opens December 5, 2016 Application deadline December 12, 2016 Interview period January 23, 2017 Acceptance notification January 30, 2017 Deadline for acceptance July 3, 2017 Fellowship begins Questions? Please email Carmen Rock at crock@cfenet.ubc.ca 52

Training Opportunities UBC Enhanced Skills 3-6 months Questions? Please email Carmen Rock at crock@cfenet.ubc.ca Treatment Guideline Committee 53

Acknowledgements Dr. Rolando Barrios Ms. Laura Case Ms. Anne McNabb Mr. Andrew McFarlane The BC Centre for Excellence in HIV AIDS Ms. Pauline Voon Ms. Deborah Graham Ms. Emily Wagner Mr. James Nakagawa Ms. Lianlian Ti Ms. Cheyenne Johnson Ms. Jessica Jun Ms. Maryam Babaei Ms. Josey Ross Mr. Peter Vann 54