Medication-Assisted Treatment and Recovery with Methadone or Buprenorphine: What Really Are They?

1. Medication-Assisted Treatment and Recovery with Methadone or Buprenorphine: What Really Are They? Yngvild Olsen, MD, MPH Maryland Addictions Directors Council Conference May 1, 2014

2. Objectives • Understand the science behind medications used to help treat opioid use disorder • Review two currently available medications • Identify indications for specific medications • Address myths about methadone and buprenorphine

3. Case 38 year old female who has been using heroin and cocaine intravenously for 20 years, has never been in treatment, has had two prior arrests for possession, serving sentences for both. She has hepatitis C, depression, hypertension, and diabetes but no regular health care. She is seen in the Emergency Department for headache with a blood pressure of 190/110 and a finger stick of 380. The ED physician mentions substance use disorder treatment including a medication, perhaps methadone or buprenorphine.

4. Her questions • Isn’t being on one of those medications (methadone or buprenorphine) just substituting one addiction for another? • How long would I need to take it? • What would happen to me while I was taking methadone or buprenorphine? • Will I go through withdrawal when I want to come off?

5. BACKGROUND INFORMATION

6. Basic Definitions Addiction • 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.* • A chronic, relapsing disease characterized by compulsive drug seeking and use despite harmful consequences as well as neurochemical and molecular changes in the brain.** • A brain disease that affects behaviour. *American Society of AddictionMedicine **National Institute on Drug Abuse (NIDA)

7. Basic Definitions Physical Dependence • An adaptation of the body to a specific substance so that in the absence of that substance a withdrawal syndrome develops. The withdrawal syndrome may be relieved in total or in part by readministration of the substance.

8. Basic Definitions Tolerance • A state in which an increased dose of a substance is needed to produce a desired effect

9. Why do some people develop addiction?

10. Genetic Variants of the Human Mu Opioid Receptor:Single Nucleotide Polymorphisms in the Coding Region Including the Functional A118G (N40D) Variant HYPOTHESIS Gene variants: • Alter physiology “PHYSIOGENETICS” • Alter response to medications “PHARMACOGENETICS” • Are associated with specific addictions Slide Source: Dr. Kreek Bond, LaForge… Kreek, Yu, PNAS, 95:9608, 1998; Kreek, Yuferov and LaForge, 2000

11. Lifetime Prevalence and Odds Ratios of Mental Disorders by Substance Use Disorder: ECA Alcohol Drug Comorbid Disorder % O.R. % O.R. Any mental 36.6 2.3 53.1 4.5 Schizophrenia 3.8 3.3 6.8 6.2 Affective 13.4 1.9 26.4 4.7 Anxiety 19.4 1.5 28.3 2.5 Antisocial 14.3 21.0 17.8 13.8 (Regier et al., JAMA 264:2511-2518, 1990)

12. Route of Administration • The faster a drug gets to the brain, the more addictive it is • Injecting • Smoking • Snorting • Oral • Across the skin

13. Duration of Action • The shorter acting a drug is, the more addictive potential it has • Heroin • Cocaine • Xanax

14. Potency • More potent drugs have higher addictive potential • Takes less of drug to achieve effect • Potent drugs: • Heroin • Crack • Fentanyl • Less potent: • Marijuana • Codeine

15. How does opioid addiction develop?

16. The Human Brain The limbic system contains the reward or pleasure center of the brain

17. The Human Brain Source: NIDA. www.drugabuse.gov

18. The Reward Pathway

19. 1. Neurotransmitter binds to receptor on second cell 2. This binding excites the second cell into action 3. The reward center in the limbic system contains thousands of nerves and many different neurotransmitters

20. Dopamine

21. Dopamine

22. Innate Opioid Receptor System • Purpose • Regulate pleasure • Regulate pain

23. The Reward Center and Endorphins dopamine receptor opioid receptor dopamine endorphin Reward center activation

24. But…… • All substances of abuse target the reward center and hijack it

25. Cocaine

26. Heroin

27. The Reward Center and Opioids dopamine receptor opioid receptor dopamine Heroin Euphoria!

28. Why is euphoria from drugs a bad thing? • Overwhelms natural process for feeling pleasure • The brain remembers the intense pleasure brought about by drugs. These memories drive continued use and implicated in relapse

29. Over time……..

30. Receptor Changes • Changes happen in the shape of opioid receptors with chronic, prolonged exposure • These changes alter the way nerve cells in the brain act • These changes may be irreversible (or at least long-term)‏ • May be why so many people relapse after detox or after years of not using

32. Opioid Withdrawal Syndrome • With chronic exposure to opioids, the receptors and the cells get used to being activated by the opioid • This means it takes more opioids to get the same feeling (tolerance)‏ • When suddenly the receptor is empty, the cells can’t act and withdrawal occurs (physical dependence)‏

33. Addiction Vs. Physical Dependence Source: NIDA. www.drugabuse.gov

34. Symptoms of Opioid Withdrawal • Dysphoria: anxiety, irritability, restlessness • Hot and cold flashes • Goose bumps • Yawning • Runny nose • Watery eyes • Diarrhea • Abdominal cramps • Joint and body pains and aches • Headache • Dilated pupils • Nausea, vomiting • Insomnia • Fever

35. Summary • All born with endorphin opioid system that helps us feel pleasure and regulate pain • Too much opioids taken into body overstimulate the reward center • With repeated exposure to opioids, the body adapts so that long-term changes happen to the receptors and cells in the brain • These changes are manifested by tolerance, withdrawal, and memory of overstimulation, all of which drive continued drug use

36. Why are methadone or buprenorphine then different from opioids of abuse?

37. Pharmacologic Mechanism of Heroin • Binds to opioid receptors in the reward center of the brain • Produces intense euphoria • Route of administration: • Snort • Injection • Short-acting • Causes physical dependence

38. Heroin Dose-Response

39. Pharmacologic Mechanism of Heroin High Normal Withdrawal Time

40. Pharmacologic Mechanism of Methadone and Buprenorphine • Binds to opioid receptors in the reward center of the brain • Route of administration: oral (methadone), sublingual (buprenorphine) • Long-acting • Causes physical dependence • In people with opioid addiction, at the correct dose, does not overstimulate the reward center

41. Methadone/Suboxone Dose-Response

42. Mu Receptor Activation Full agonist methadone mu receptor site Partialagonist buprenorphine mu receptor site Antagonist naloxone mu receptor site

43. (e.g. heroin) 100 Full Agonist 90 80 70 (e.g. buprenorphine) Partial Agonist But due to its “ceiling” maximum opioid agonist effect is never achieved 60 % Mu ReceptorIntrinsic Activity 50 40 30 Like full agonists, partial agonist drugs produce increasing mu opioid receptor specific activity at lower doses 20 no drug low dose high dose DRUG DOSE 10 0 Partial Agonist Activity Levels

44. Treatment Effectiveness • Goal of treatment is to return to productive functioning • Reduces drug use by 40-60% • Drug treatment is as successful as treatment of diabetes, asthma, and hypertension • Strongest predictor of recovery is retention in treatment

45. Benefits Of Treatment Including Methadone • Reduces risk of HIV infection • Reduces risk of infection with hepatitis C and B • Increases rates of employment among patients as a group • Decreases crime • Increases length of life

46. Maintenance Treatment Using Buprenorphine • Numerous outpatient clinical trials comparing efficacy of daily buprenorphine to placebo, and to methadone • Consistently find: • Buprenorphine more effective than placebo • Buprenorphine equally effective as moderate doses of methadone

47. Example: Buprenorphine and HAART Adherence • Roux et al demonstrated improved adherence to HAART among IV heroin users treated with buprenorphine in outpatient medical clinic* • Sullivan et al found significant reduction in HIV RNA levels among 13 IV heroin users treated with buprenorphine in HIV clinic** *Roux et al, Addiction, 2008 ** Sullivan et al, CID, 2006

48. Effect of Medications on Opioid Use Opioid Positive Urine Specimens From: Johnson et al., 2000

49. Treatment Outcomes For Tapering off Medication In methadone studies, 50-80% relapse within one year after taper 91% of patients receiving buprenorphine for 4 months had relapsed to prescription opioids within 2 months of taper* Opioid overdose fatality rates are 3 to 20 times higher in the month after tapering off than during treatment *Weiss R. et al. NIDA CTN Prescription Opioid Treatment Study. http://www.medscape.com/viewarticle/722342

50. Source: Dennis M et al, Evaluation Review, 2009