Best Practices in Medication Assisted Treatment for Opioid Use Disorder Gregory S. Brigham, Ph.D., CEO Adapt|Compass Behavioral Health | SouthRiver Community Health Center Douglas County Pain Summit, March 21, 2017

Objectives Provide overview of opioid use disorder Review 3 types of FDA-approved medications for opioid use disorder Review best practices for integrated MAT and behavioral interventions

Opioid Agonists

Mu (μ) receptors stimulated by opioids causing the full range of opioid effects. Adapted from slides at vivitrol.com

Opioids Progressive CNS Depression Death Coma Nod Action Euphoria Relax Pain Progressive CNS Depression Dose

Dependence vs. Addiction Increased tolerance Withdrawal Addiction Craving Loss of control Impairment & distress in important life areas

Differing Strengths & Durations of Action Opioid Agonist Half-Lives Heroin, codeine, morphine – 2-4 hours Methadone – 24 hours Buprenorphine – 24-60 hours Adapted from NIDA/ATTC Blending Product

Acute Opioid Withdrawal Symptoms Pupillary dilation Watery eyes Runny nose Muscle spasms (“kicking”) Yawning, sweating, chills, gooseflesh Stomach cramps, diarrhea, vomiting Restlessness, anxiety, irritability Usually result in further use to quiet symptoms

Three Types of Medication for Opioid Use Disorder Agonist Morphine-like effect (e.g., heroin, methadone) Partial Maximum effect is less than a full agonist (e.g., buprenorphine) Antagonist No effect in absence of an opiate or opiate dependence (e.g., naloxone) Affinity: The strength with which a drug binds to a receptor. Affinity for a receptor and activation of the receptor are two different qualities of drugs. A drug can have a high affinity for a receptor but not activate the receptor (I.e., an antagonist). Drugs also vary in their rate of dissociation from receptors, which is a measure of the disengagement or uncoupling of the drug from the receptor. Full agonist: increasing doses of full agonists produce increasing effects until a maximum effect is reached that the receptor is fully activated. Partial agonist: share some characteristics of full agonists. At low doses, full and partial agonists produce effects that are essentially indistinguishable. However, increasing the dose of a partial agonist does not produce as great an effect as that which results when increasing the dose of a full agonist. There is a ceiling to the agonist effects. Antagonist: Also bind to receptors, but rather than activating receptors they block receptors by preventing them from being activated by an agonist compound. It is as if an antagonist is a key that fits in a lock but does not open it. It also prevents another key from opening the lock. When people take an antagonist and an agonist they do not feel the agonist effects. Patients who take naltrexone, for example, do not feel the effects of heroin or other agonists.

Methadone Progressive CNS Depression Death Coma Nod Action Euphoria Relax Buprenorphine’s low intrinsic activity at the opioid (mu) receptor results in a “ceiling” effect such that higher doses of buprenorphine do not increase its agonist activity but lengthen its duration of action. Pain Progressive CNS Depression Dose

Methadone: A Full Agonist www.methadoneaddiction.net/m-pictures.htm

Conclusion methadone is superior to placebo in: Authoritative review of 11 randomized clinical trials with 1,969 patients Conclusion methadone is superior to placebo in: Retaining patients in treatment Reducing illicit opioid use

Advantages of Methadone 70% or more treatment retention at 1 year Treats craving Blocks illicit opioid use Over 40 years of research and treatment experience demonstrating effectiveness Significantly reduces risk for addiction related death and health problems Medication cost is minimal

Limitations of Methadone Full agonist with abuse potential Potential for dangerous interactions with other drugs when misused Highly regulated resulting in limited access to care Strong physical dependence results in difficult withdrawal Significant stigma in the community Heavy burden on patients for compliance

Buprenorphine Opioid Effect Partial Agonist Dose Buprenorphine’s low intrinsic activity at the opioid (mu) receptor results in a “ceiling” effect such that higher doses of buprenorphine do not increase its agonist activity but lengthen its duration of action. Dose

Buprenorphine: A Partial Agonist

Review of 24 randomized clinical trials with 4,497 patients Conclusion buprenorphine is superior to placebo and to moderate dose methadone: Retaining patients in treatment Reducing illicit opioid use

BUP/NX Office-Based Practice DATA 2000 physicians office-based prescription BUP for opioid use disorder CARA 2016 (7/22/16): increase patient # limits; NP & PA to prescribe Retention rates ≈48% at 6 months. Requires ability to refer for behavioral treatment Diversion and other problems are common and require close monitoring & intervention

Advantages of Buprenorphine DATA 2000 greatly increases access Less severe dependency allows for easier transitions between recovery with and without medication Partial agonist is safer with less overdose potential Lower abuse potential People live a normal life free from craving and withdrawal SAVES LIVES

Limitations of Buprenorphine Not a full agonist and does not retain people in treatment as well as full agonist Has diversion potential and may be misused Medication is expensive and access is limited Stigma in the recovery community

About 4% 12-month mortality risk positively correlated with longer abstinence. Strang, J., McCambridge, J., Best, D., Beswick, T. Bearn, J., Rees, S., & Gossop, M. (2003). Loss of tolerance and overdose mortality after inpatient opiate detoxification. British Medical Journal. May 2003; 959-960.

Opioid Antagonist Opioid Effect Antagonist, e.g., naloxone Dose Buprenorphine’s low intrinsic activity at the opioid (mu) receptor results in a “ceiling” effect such that higher doses of buprenorphine do not increase its agonist activity but lengthen its duration of action. Dose

Receptor blocked by antagonist Opioid Antagonist Receptor blocked by antagonist Adapted from slides at vivitrol.com

Gluteal Intramuscular Injection of Vivitrol Adapted from slides at vivitrol.com

Advantages of Vivitrol Safe to use, no abuse potential Blocks the effects of opioids Reduces danger of accidental overdose No physical dependence Little or no stigma in the recovery community

Limitations of Vivitrol Less research and clinical experience No reinforcing effects to support retention in treatment No withdrawal symptoms to prevent treatment drop-out High cost limits access May not control cravings Must be opioid free for induction, indication is for relapse prevention

No One Treatment is Right for Everyone 3 FDA-approved medications to support recovery Numerous ways to integrate pharmacotherapies & behavioral interventions 3 MAT approaches available in Douglas County

MAT for Opioid Use Disorder Available in Douglas County BUP Taper followed by Vivitrol for Relapse Prevention Office-based Buprenorphine at SRCHC and URMC BUP + Motivational Stepped Care Opioid Treatment Program (eff. 3/15/17) Methadone or Buprenorphine Motivational Stepped Care

Acknowledgements Umpqua Health for grant support to develop the OTP, as well as ongoing support for ongoing services OHA & SAMHSA for grant support to establish the Opioid Treatment Program