Initiation of Medication in Treating Opioid Use Disorder.

Initiation of Medication in Treating Opioid Use Disorder. Colleen T. LaBelle MSN RN-BC CARN Program Director STATE OBAT B Nurse Manager Boston Medical Center OBAT Executive Director MA IntNSA *Images used for educational purposes only. All copyrights belong to image owners*

Objectives Identify the clinically relevant pharmacological characteristics of agonist and antagonist treatments Describe the induction process Identify the difference between short- vs. long-acting opioids and induction Describe how to induce opioid naive patient

Function at Receptors: Full Opioid Agonists Mu receptor Full agonist binding activates the mu receptor is highly reinforcing is the most misused opioid type includes heroin, codeine, & others Adapted from http://www.buppractice.com/node/1374 NIDA, Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition)

Function at Receptors: Partial Opioid Agonists Mu receptor Partial agonist binding elicits muted receptor activation is relatively less reinforcing is a less misused opioid type includes buprenorphine Adapted from http://www.buppractice.com/node/1374 NIDA, Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition)

Function at Receptors: Opioid Agonists Mu receptor Antagonist binding occupies without activating is not reinforcing blocks opioid agonist types includes naloxone and naltrexone Adapted from http://www.buppractice.com/node/1374 NIDA, Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition)

Opioid Effect https://www.naabt.org/education/technical_explanation_buprenorphine.cfm How Does Buprenorphine Work? (1) Full Agonist (Methadone) Partial Agonist (Buprenorphine) Log Dose Antagonist (Naloxone)

How Does Buprenorphine Work? (2) AFFINITY is the strength with which a drug physically binds to a receptor Buprenorphine has strong affinity; will displace full mu receptor agonists like heroin and methadone Synapse Receptor binding strength (strong or weak), is NOT the same as receptor activation H B B H Buprenorphine affinity is higher, therefore full agonist is displaced Mu receptor Adapted from https://www.drugabuse.gov/news-events/nidanotes/2017/03/impacts-drugs-neurotransmission

How Does Buprenorphine Work? (3) DISSOCIATION is the speed (slow or fast) of disengagement, or uncoupling, of a drug from the receptor Buprenorphine dissociates slowly Therefore buprenorphine stays on the receptor a long time and blocks heroin, methadone, and other opioids from binding to those receptors Synapse H B B H Buprenorphine dissociates slowly, so full agonist has reduced binding Mu receptor Adapted from https://www.drugabuse.gov/news-events/nidanotes/2017/03/impacts-drugs-neurotransmission

How Does Buprenorphine Work? (4) Ceiling effect on opioid effects High affinity for opioid receptor Slow dissociation from opioid receptor Formulated with naloxone Naloxone blocks opiate effect if injected Naloxone has low bioavailability if taking orally Gunderson, 2006

Formulations Generic sublingual (SL) buprenorphine tablets and generic SL bup/nlx Buprenorphine and buprenorphine/naloxone film Buccal film: cheek Buprenorphine patch: pain only New formula buprenorphine/naloxon: different dosage Implantable buprenorphine Buprenorphine sublingual film https://www.suboxone.com/medicaltreatment/how-to-take-suboxone ASAM, 2015

Planning for Induction Boston Medical Center 2016, P&P Build a Relationship. Build Trust: Early stages of withdrawal prior to induction Review with patient ahead of time: Usage history, withdrawal, last use Reinforcing the goal to improve symptoms Help them feel better Short-acting, long-acting What did they last use?

Buprenorphine Induction: Office Logistics (1) Boston Medical Center 2016, P&P Lee et al. (2009). Home Buprenorphine/Naloxone Induction in Primary Care

Collaborative care of opioid-addicted patients in primary care using buprenorphine: five-year experience. Daniel P. Alford, MD, MPH; Colleen T. LaBelle, RN; Natalie Kretsch, BA; Alexis Bergeron, MPH, LCSW; Michael Winter, MPH; Michael Botticelli, Med; Jeffrey H. Samet, MD, MA, MPH Collaborative care model at BMC utilizing nurse care managers working with physicians to deliver outpatient opioid treatment with buprenorphine More recently dubbed the Massachusetts Model Alford DP, LaBelle CT, Kretsch N, Bergeron A, Winter M, Botticelli M, Samet JH. Arch Intern Med. 2011;171:425-431.

How to Prevent Precipitated Withdrawal (1) http://americanaddictioncenters.org/withdrawal-timelines-treatments/opiate/

How to Prevent Precipitated Withdrawal (2) Withdrawal more likely when: Level of physical dependence is high Short time since last opioid use (shortvs long-acting opioids) Initial dose of buprenorphine too high Prevention: Administer 1st buprenorphine dose when objective signs of withdrawal are present ASAM, 2015; PCSS 2013

A Case Study in Induction Part 1

Buprenorphine Induction - Day 1 Instruct the patient to abstain from any opioid use prior to induction to avoid precipitated withdrawal: 8 12 hours for short-acting opioids 24 hours for sustained-release opioid medications 36 or > hours for methadone; assessment is critical Gunderson; PCSS; ASAM

Buprenorphine Induction - Day 2 If patient is not in opioid withdrawal at time of arrival in office: Assess last opioid use Consider returning another day, or wait and reassess for withdrawal. Ask specifically about last use (heroin, fentanyl, methadone, oxycodone) Short- vs long-term opioids Methadone requires more time Avoid precipitating withdrawal Boston Medical Center 2016 P&P

Case Study (1) John M., a 33-year-old tax accountant, presents to your office anxious to start buprenorphine and to be done with using. He has spent the last 4 years injecting 1 2 gms of heroin a day. His life has begun to spin out of control and his fiancé is onto him that something is not right, but she doesn t know he has an OUD.

Case Study (2) He has come to all his appointments, had urine screens and blood work done, and set up counseling. He is in the waiting room one hour before the clinic opens waiting to be seen. Presents to the visit anxious to get started, he is so excited that this day is finally here: Reports last use at 6 pm the night before, it is 9:30am. I am ready to put this life behind me.

Case Study (3) The nurse performs an assessment using the Clinical Opioid Withdrawal (COW) scale and rates him a 9, and he last used 15 ½ hours ago. During assessment, patient reports GI distress, joint pain, restlessness, sweating, and anxiety. On observation - pulse 120, patient shifting around in his seat, trouble sitting still.

Case Study: Questions to Consider Is this patient ready for induction? Should you do anything further prior to beginning induction? Is there any harm in starting the induction?

Return to Case Study: Induction (1) Presents to the visit anxious to get started, he is so excited that this day is finally here: I am ready to put this life behind me. Reports last use at 6 pm the night before, it is 9:30am. The nurse performs an assessment using the COW scale rates him a 9, and last used 15 ½ hours ago. During assessment, patient reports GI distress, joint pain, restlessness, sweating, and anxiety. On observation - pulse 120, patient shifting around in his seat, trouble sitting still.

Return to Case Study: Induction (2) Is John M. ready for induction? Presents to the visit anxious to get started, he is so excited that this day is finally here: I am ready to put this life behind me. Reports last use at 6 pm the night before, it is 9:30am. The nurse performs an assessment using the COW scale rates him a 9, and last used 15 ½ hours ago. During assessment, patient reports GI distress, joint pain, restlessness, sweating, and anxiety. On observation - pulse 120, patient shifting around in his seat, trouble sitting still.

Buprenorphine Induction - Day 1 First dose: 2 to 4 mg SL buprenorphine/naloxone Monitor in office for 1+ hours after first dose Opioid withdrawal symptoms should improve 30 45 minutes after the first dose Better, worse, or the same? If opioid withdrawal subsides but then reappears, re-dose every 2 3 hours Aim for a dose of 8 12 mg in the first 24 hours Boston Medical Center P&P 2016

Wesson, 2003

Buprenorphine Induction - Day 1 If opioid withdrawal appears: may have precipitated withdrawal Greatest severity precipitated withdrawal: First few hours (1 4) after a dose Decreasing symptoms over subsequent hours PCSS Guidelines

Buprenorphine Induction - Day 1 (Continued) If precipitate withdrawal: Continue dosing, provide agonist effect, suppress withdrawal OR Stop induction, provide symptomatic treatments, and have the patient return the next day Latter - risk losing the patient, the first option is often preferred

Dailymed.nlm.nih.gov Buprenorphine Induction - Patient Education Sublingual tablets/film held under tongue until dissolved Start with a moist mouth Avoid acidic drinks (coffee or fruit juice) No smoking immediately before or after No talking during administration Keep tablet or film under tongue or buccal mucosa Do not swallow until entire tablet or film dissolves PCSS, 2006

A Case Study in Induction Part 2

Clinical Opioid Withdrawal Scale (COWS) Recovery.org Total Score: 5 12 Mild 13 24 Moderate 25 36 Moderately Severe >36 Severe Aim for Score: 8 10 Wesson, 2003

Return to Case Study: Induction (1) Is John M. ready for induction? Presents to the visit anxious to get started, he is so excited that this day is finally here: I am ready to put this life behind me. Reports last use at 6 pm the night before, it is 9:30am. The nurse performs an assessment using the COW scale rates him a 9, and last used 15 ½ hours ago. During assessment, patient reports GI distress, joint pain, restlessness, sweating, and anxiety. On observation - pulse 120, patient shifting around in his seat, trouble sitting still.

Return to Case Study: Induction (2) Is John M. ready for induction? Should you do anything further prior to beginning induction? Is there any harm in starting the induction?

Wesson, 2003 Opioid Withdrawal Assessment Hours after use 4-6 6-8 8-12 12-72 Grade 0 1 2 3 4 Symptoms / Signs Anxiety, Drug Craving What symptoms do you see? Yawning, Sweating, Runny nose, Tearing eyes, Restlessness Insomnia Dilated pupils, Gooseflesh, Muscle twitching & shaking, Muscle & Joint aches, Loss of appetite Nausea, extreme restlessness, elevated blood pressure, Heart rate > 100, Fever Vomiting / dehydration, Diarrhea, Abdominal cramps, Curled-up body position Clinical Opiate Withdrawal Scale (COWS): pulse, sweating, restlessness & anxiety, pupil size, aches, runny nose & tearing, GI sx, tremor, yawning, gooseflesh (score 5-12 mild, 13-24 mod, 25-36 mod sev, 36-48 severe)

Timing of Induction: Short-Acting Opioids Abstain 8 12 hours (mild withdrawal) If not in documented withdrawal: Review/assess history Assess, support, and wait What did you use in the last 24 hours? Ask specifically: methadone, oxycontin, heroin, fentanyl? Urine testing prior to induction if possible PCSS, 2006

Return to Case: Induction (1) John M., a 33-year-old tax accountant, presents to your office anxious to start buprenorphine and to be done with using. He has spent the last 4 years injecting 1 2 gms of heroin a day. His life has begun to spin out of control and his fiancé is onto him that something is not right, but she doesn t know he has a OUD.

Return to Case Study: Induction (3) Is John M. ready for induction? Should you do anything further prior to beginning induction? Is there any harm in starting the induction??

Wesson, 2003 Opioid Withdrawal Assessment Hours after use 4-6 6-8 8-12 Grade 0 1 2 3 John, what did 12-72 you use in the last 24 hours? 4 Symptoms / Signs Anxiety, Drug Craving What symptoms do you see? Yawning, Sweating, Runny nose, Tearing eyes, Restlessness Insomnia Dilated pupils, Gooseflesh, Muscle twitching & shaking, Muscle & Joint aches, Loss of appetite Nausea, extreme restlessness, elevated blood pressure, Heart rate > 100, Fever Vomiting / dehydration, Diarrhea, Abdominal cramps, Curled-up body position Clinical Opiate Withdrawal Scale (COWS): pulse, sweating, restlessness & anxiety, pupil size, aches, runny nose & tearing, GI sx, tremor, yawning, gooseflesh (score 5-12 mild, 13-24 mod, 25-36 mod sev, 36-48 severe)

Return to Case Study: Induction (1) John reports: I wanted to be safe and to be done with everything so I bought some methadone and got rid of my works and contacts. Should you do anything further prior to beginning induction? Is there any harm in starting the induction?

Short-Acting Opioids 8 to 12 hours Oxycodone (Percocet, crushed Oxycontin ) Hydrocodone (Vicodin ) Heroin Morphine

Theaddictionhotline.org Long-Acting Opioids: Oxycontin P.O.: 24+ hours Methadone: 48+ hours Much harder and longer process Patient and provider need to be engaged PCSS Gunderson

Timing of Induction: Long-Acting Opioids: PCSS

Timing of Induction: Long Acting Opioids Abstain for at least 48+ hours Assess for withdrawal Timing is often not a good indicator Need to assess symptoms Slow and steady PCSS

First Dose of Buprenorphine Patient in clinical opioid withdrawal Objective signs are key to making diagnosis (can be challenging) COWS > 8 12 Start with 2 4 mg sl Assess: 40 60 minutes after dosing Ask: better, worse, or the same? ASAM, PCSS

Induction Continue to titrate until symptoms resolve Re-assess patient 40 60 minutes after first dose Dose with 2 4 mg sl Reassess over the next few hours Stabilize day one around 8 mg or per your protocol and clinical assessment PCSS

Induction days 2 3 Assess symptoms Adjust dose accordingly: withdrawal symptoms decrease over-medicated Continue adjusting by 2 4 mg increments target dose of 12 16 mg Resolution of craving and withdrawal

Determining the Best Dose Remember goals of treatment Relieve withdrawal symptoms Reduce craving Opioid blockade Achieving these should result in improved function Gunderson, ASAM

Methadone to Buprenorphine (1) Challenging transition Objective withdrawal: most important May take much longer than 36 hours Support, communication, support Back-up plan: can they return to methadone?

Buprenorphine/Naloxone Toxicity, Medscape Methadone to Buprenorphine (2) PCSS; ASAM Practice guidelines

Methadone to Buprenorphine (3) Primary Goal: Minimize risk of precipitated withdrawal, manage withdrawal Knowledgeable provider Communication: MMT and BUP provider Taper methadone 30 mg/d or <, hold for 1 2 weeks (ideal) Stop methadone for 2 3 days, COWS score > 12 Ensure patient supports, comfort meds, emergency numbers

Methadone to Buprenorphine (4) Day 3 off methadone, observed induction with bup/nlx 2/0.5 mg, up to 8 mg on day as symptoms dictate. Treat symptoms Seamless return to methadone, if needed Utilize inpatient detox, if possible, allows added supports

What is the Optimal Dose? Like most medications, the optimal dose is the lowest dose that maximizes function and minimizes side effect Most patients stabilize on 8 24 mg/day Narcotic blockade Rarely 32 mg with the highly tolerant patient

Buprenorphine Induction: Procedure Patients not physically dependent on opioids For example: high risk for relapse i.e., released from prison First dose: Start low, go slow (2 mg buprenorphine) Monitor and reassess Gradually increase dose over days/weeks Support

Buprenorphine Induction: Goals Dose of buprenorphine at which the patient: Has no opioid withdrawal symptoms Discontinues use of opioids No cravings Has narcotic blockade Has minimal or no side effects

Induction: Not Physically Dependent on Opioids Examples: High risk for relapse to opioid use: Pre/post incarceration Environmental Life stressor Cravings

Induction: Not Physically Dependent on Opioids First dose: 2 mg SL buprenorphine Monitor after first dose Gradually increase dose ( +2 mg/day) over several days/week as needed Stabilize dose that eliminates craving; dose range 2 mg to 16 mg Go slow and low. Avoid relapse. Gunderson, ASAM, PCSS

Induction Summary Put systems in place prior to starting Provide ongoing education and support Do not assume anything: ask questions Good clinical assessment: trust your gut No harm in waiting it out Objective assessment vs subjective reports Go slow and low Ask for help Use mentors AHRQ, Gunderson

Additional Resources: Buprenorphine Methadone and Buprenorphine: Opioid Agonist Substitution Tapers http://pcssmat.org/opioid-resources/medication-assisted-treatmentfor-opioid-addiction/ Models of Buprenorphine Induction http://pcssmat.org/wpcontent/uploads/2015/07/models-of-buprenorphine-induction.pdf How-To Guide: How to Conduct Buprenorphine Induction http://www.buppractice.com/node/12086 - This resource covers several procedures and is printer-friendly, so the clinician can print out the sections of the process that are most useful. Boston Medical Center. (2016). OBAT Policy and Procedure Manual: Policies and Procedure manual of the Office Based Addiction Treatment Program for the Use of Buprenorphine and Naltrexone Formulations in the Treatment of Substance Use Disorders (available in the course s Additional Resources tab).

References (1) Alford DP, LaBelle CT, Richardson JM, O'Connell JJ, Hohl CA, Cheng DM, Samet JH. 2007. Treating homeless opioid dependent patients with buprenorphine in an office-based setting. J Gen Intern Med. Feb;22(2):171-6. Casadonte PP, Sullivan MA. 2013. American Society of Addiction Medicine. (2015). Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. http://www.asam.org/docs/default-source/practice-support/guidelines-andconsensus-docs/asam-national-practice-guidelinepocketguide.pdf?sfvrsn=0 Buprenorphine induction. Providers clinical support system for medication assisted treatment, PCSS guidance. August 9, 2006 (Updated November 27, 2013). Available at http://pcssmat.org/wp-content/uploads/2014/02/ Boston Medical Center. (2016). OBAT Policy and Procedure Manual: Policies and Procedure manual of the Office Based Addiction Treatment Program for the Use of Buprenorphine and Naltrexone Formulations in the Treatment of Substance Use Disorders

References (2) Chou R, Korthuis PT, Weimer M, Bougatsos C, Blazina I, Zakher B, Grusing S, Devine B, McCarty D. Medication-Assisted Treatment Models of Care for Opioid Use Disorder in Primary Care Settings. Technical Brief No. 28. (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2015-00009-I.) AHRQ Publication No. 16(17)-EHC039-EF. Rockville, MD: Agency for Healthcare Research and Quality. December 2016. www.effectivehealthcare.ahrq.gov/reports/final.cfm. Gunderson EW, Fiellin DA, Levin FR, et al. 2006. Evaluation of a combined online and in person training in the use of buprenorphine. Subst Abuse.27:39 45. Gunderson EW, Fiellin DA. 2008. Office-Based Maintenance Treatment of Opioid Dependence: How Does it Compare with Traditional Approaches? CNS Drugs.22(2):99-11

References (3) LaBelle CT, Choongheon h, Bergeron A, Samet JA.. Office Based Opioid Treatment with Buprenorphine (OBOT): Statewide Implementation of Massachusetts Collaborative Care Model in Community Health Centers. J Subst Abuse Treat. 2016; 60: 6-13. Mintzer IL, Eisenberg M, Terra M, et al. 2007. Treating opioid addiction with buprenorphine-naloxone in community-based primary care settings. Ann Fam Med.5:146 150. Netherland J, Botsko M, Egan J, et al. 2009. Factors affecting willingness to provide buprenorphine treatment. J Subst Abuse Treat.36:244 251 Walley AY, Alperen JK, Cheng DM, et al. 2008. Office-based management of opioid dependence with buprenorphine: clinical practices and barriers. J Gen Intern Med.23:1393 1398. Wesson D, Ling W. 2003. The Clinical Opiate Withdrawal Scale (COWS) J Psychoactive Drugs. 35:253

Unit Resources Bup.Practice - Opioid Classification: Agonists, Partial Agonists, and Antagonists NIDA - Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition) The National Alliance of Advocates for Buprenorphine Treatment (naabt.org) - Thorough Technical Explanation of Burprenorphine NIDA Notes - Impacts of Drugs on Neurotransmission How to take SUBOXONE Film Boston Medical Center - Office Based Addiction Treatment Policy and Procedure Manual - Office Based Addiction Treatment Program for the Use of Buprenorphine and Naltrexone Formulations in the Treatment of Substance Use Disorders American Society of Addiction Medicine (ASAM) - National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use

Collaborative care of opioid-addicted patients in primary care using buprenorphine: five-year experience American Addiction Centers - Opiate Withdrawal Timelines, Symptoms and Treatment Clinical Opiate Withdrawal Scale (COWS) (pdf) Providers Clinical Support System for Medication Assisted Treatment, (PCSS-MAT) - Buprenorphine induction (pdf) Providers Clinical Support System for Medication Assisted Treatment, (PCSS-MAT) - Buprenorphine induction (pdf) American Society of Addiction Medicine (ASAM) - National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use Providers Clinical Support System for Medication Assisted Treatment, (PCSS-MAT) - Buprenorphine induction (pdf) Agency for Healthcare Research and Quality (AHRQ) Providers Clinical Support System (PCSS-MAT) - Mentoring