1. 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

2. 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

3. Opioid Agonists

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

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

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

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

8. 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

9. 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.

10. 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

11. Methadone: A Full Agonist

12. 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

13. 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

14. 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

15. 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

16. Buprenorphine: A Partial Agonist

17. 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

18. 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

19. 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

20. 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

21. 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;

22. 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

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

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

25. 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

26. 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

27. 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

28. 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

29. 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