List three different types of MAT (medication-assisted treatment) for opioid dependence Describe the mechanism of action and the proper dosing for three different types of MAT for opioid dependence Review common barriers to using MAT in a variety of treatment settings.

1. Medication-Assisted
Treatment (MAT) of
Opioid Dependence
Christina M. Delos Reyes, MD
Chief Clinical Officer, ADAMHS Board of Cuyahoga County
Medical Consultant, Center for Evidence-Based Practices at Case
SAMHSA/BJA Opiate Treatment Grant Training
Cleveland, Ohio January 26 & 27, 2012
1

2. Learning Objectives
 Following this presentation, participants will
be able to:
• List three different types of MAT (medication-
assisted treatment) for opioid dependence
• Describe the mechanism of action and the proper
dosing for three different types of MAT for opioid
dependence.
• Review common barriers to using MAT in a
variety of treatment settings.
2

3. Ritual of a Heroin
User
“A Fort Myers woman in her 30s prepares a heroin
fix at the home of a friend on a recent day. The
woman uses a hypodermic needle to inject heroin,
which she had heated in a spoonful of water, into a
vein in her hand. However, the increased purity of
the drug and a fear of contracting HIV from
contaminated needles, along with the social stigma
associated with needle use, has caused an upsurge in
users snorting and smoking heroin. "You first get an
adrenaline rush, then a sensation of mellow. You
lose sense of time and forget everything,'' the woman
said. "Heroin is easy to find...You can get a bag for
$10.”
3
SOURCE: Naples Daily News, 2001.

4. Opiate/Opioid : What’s the
Difference?
Opiate
 A term that refers to drugs or medications that are
derived from the opium poppy, such as heroin,
morphine, and codeine.
Opioid
 A more general term that includes opiates as well
as the synthetic drugs or medications, such as
buprenorphine, methadone, meperidine (Demerol®),
fentanyl—that produce analgesia and other effects
similar to morphine.
4

5. Basic Opioid Facts
Description: Opium-derived, or synthetics which
relieve pain, produce morphine-like addiction,
and relieve withdrawal from opioids
Medical Uses: Pain relief, cough suppression,
diarrhea
Methods of Use: Intravenously injected, smoked,
snorted, or orally administered
5

6. What’s What?
Agonists, Partial Agonists,
and Antagonists
Agonist Morphine-like effect (e.g., heroin)
Partial Agonist 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)
6

7. Opioid Agonists
 Natural derivatives of opium poppy
- Opium
- Morphine
- Codeine
7

8. Opium
8
SOURCE: www.streetdrugs.org

9. Morphine
9
SOURCE: www.streetdrugs.org

10. Opioid Agonists
 Semisynthetics: Derived from chemicals in
opium
- Diacetylmorphine – Heroin
- Hydromorphone – Dilaudid®
- Oxycodone – Percodan®, Percocet®
- Hydrocodone – Vicodin®
10

11. Heroin
11
SOURCE: www.streetdrugs.org

12. 12

13. Opioid
Agonists
13
SOURCE: www.pdrhealth.com

14. Opioid Agonists
 Synthetics
- Propoxyphene – Darvon®, Darvocet®
- Meperidine – Demerol®
- Fentanyl citrate – Fentanyl®
- Methadone – Dolophine®
- Levo-alpha-acetylmethadol – ORLAAM®
14

15. Methado
ne
Darvocet
15
SOURCE: www.methadoneaddiction.net

16. Opioid Partial Agonists
 Buprenorphine – Buprenex®, Suboxone®,
Subutex®
 Pentazocine – Talwin®
16

17. Buprenorphine/Naloxone combination
and Buprenorphine Alone
17

18. Opioid Antagonists
 Naloxone – Narcan®
 Naltrexone – ReVia®, Trexan®
18

19. Opioids and the Brain:
Pharmacology
and Half-Life
19

20. 20
SOURCE: National Institute on Drug Abuse, www.nida.nih.gov.

21. Terminology
Receptor:
specific cell binding site or molecule: a molecule,
group, or site that is in a cell or on a cell surface
and binds with a specific molecule, antigen,
hormone, or antibody
21

22. Opioid Agonists:
Pharmacology
 Stimulate opioid receptors in central
nervous system & gastrointestinal tract
 Analgesia – pain relief (somatic &
psychological)
 Antitussive action – cough suppression
 Euphoria, stuperousness, “nodding”
 Respiratory depression
22

23. Opioid Agonists:
Pharmacology
 Pupillary constriction (miosis)
 Constipation
 Histamine release (itching, bronchial
constriction)
 Reduced gonadotropin secretion
 Tolerance, cross-tolerance
 Withdrawal: acute & protracted
23

24. What is the Definition of
“Half-Life?”
The time it takes for half a given amount of a
substance such as a drug to be removed from living
tissue through natural biological activity
24

25. Duration of Action
Two factors determine the duration of action of
the medication:
• Half-life - time it takes to metabolize half the
drug. In general, the longer the half-life, the
longer the duration of action.
• Receptor affinity or strength of the bond
between the substance and the receptor -
medications that bind strongly to the receptor
may have very long action even though the
half-life may be quite short. 25

26. Opioid Antagonist Half-
Lives
 Naloxone – 15-30 minutes
 Naltrexone – 24-72 hours
26

27. Opioid Agonist Half-Lives
 Heroin, codeine, morphine – 2-4 hours
 Methadone – 24 hours
 LAAM – 48-72 hours
27

28. Opioid Partial Agonist
Half-Lives
 Buprenorphine – 4-6 hours (however, duration of
action very long due to high receptor affinity)
 Pentazocine – 2-4 hours
28

29. Opioid Addiction
and the Brain
Opioids attach to receptors in brain Pleasure
Repeated opioid use Tolerance
Absence of opioids after prolonged use Withdrawal
29

30. What Happens When
You Use Opioids?
 Acute Effects: Sedation, euphoria, pupil
constriction, constipation, itching, and lowered
pulse, respiration and blood pressure
 Results of Chronic Use: Tolerance, addiction,
medical complications
 Withdrawal Symptoms: Sweating, gooseflesh,
yawning, chills, runny nose, tearing, nausea,
vomiting, diarrhea, and muscle and joint aches
30

31. Possible Acute Effects
of Opioid Use
 Surge of pleasurable sensation = “rush”
 Warm flushing of skin
 Dry mouth
 Heavy feeling in extremities
 Drowsiness
 Clouding of mental function
 Slowing of heart rate and breathing
 Nausea, vomiting, and severe itching
31

32. Consequences of Opioid Use
 Addiction
 Overdose
 Death
 Use related (e.g., HIV infection, malnutrition)
 Negative consequences from injection:
• Infectious diseases (e.g., HIV/AIDS, Hepatitis B and C)
• Collapsed veins
• Bacterial infections
• Abscesses
• Infection of heart lining and valves
• Arthritis and other rheumatologic problems
32

33. Heroin Withdrawal Syndrome
 Intensity varies with level & chronicity of use
 Cessation of opioids causes a rebound in function
altered by chronic use
 First signs occur shortly before next scheduled dose
 Duration of withdrawal is dependent upon the half-
life of the drug used:
• Peak of withdrawal occurs 36 to 72 hours after last dose
• Acute symptoms subside over 3 to 7 days
• Protracted symptoms may linger for weeks or months
33

34. Opioid Withdrawal
Syndrome
Acute Symptoms
 Pupillary dilation
 Lacrimation (watery eyes)
 Rhinorrhea (runny nose)
 Muscle spasms (“kicking”)
 Yawning, sweating, chills, gooseflesh
 Stomach cramps, diarrhea, vomiting
 Restlessness, anxiety, irritability
34

35. Opioid Withdrawal
Syndrome
Protracted Symptoms
 Deep muscle aches and pains
 Insomnia, disturbed sleep
 Poor appetite
 Reduced libido, impotence, anorgasmia
 Depressed mood, anhedonia
 Drug craving and obsession
35

36. Treatment Options
for
Opioid-Addicted
 Individuals
Behavioral treatments educate patients about the
conditioning process and teach relapse prevention
strategies.
 Medications such as methadone and
buprenorphine operate on the opioid receptors to
relieve craving.
 Combining the two types of treatment
enables patients to stop using opioids
and return to more stable and
productive lives.
36

37. Treatment Options
for
Opioid-Addicted
Individuals
 Medically-assisted withdrawal
 Long-term residential treatment
 Outpatient psychosocial treatment
 Behavioral therapies
 Medication-Assisted Treatment (MAT)
37

38. Medication-Assisted
Treatment
 Naltrexone—antagonist
 Methadone—agonist
 Buprenorphine—partial agonist
38

39. Naltrexone
 Opiate antagonist to treat opiate dependence
 All effects of opiates are blocked
• Must be detoxed and opiate-free or else will cause
opiate withdrawal syndrome
 Blocks opioid receptors that are involved in
the rewarding effects of opiates (& alcohol!)
 Risk for hepatotoxicity
• Monitor for liver enzymes
39

40. Naltrexone
 Brand name: Revia (oral tablets)
 Usual dose: 50mg daily
 Efficacy highest in patients who can abstain
for 4 to 7 days before initiating treatment
 No negative effect with use
 Some clients notice anxiolytic effect
40

41. Long- Acting Naltrexone
 Brand name is Vivitrol
 Approved for alcoholism in 2006
 Approved for opiate dependence Oct 2010
 Given monthly, 380 mg appears to have
increased efficacy versus 190 mg
 May have increased efficacy for men vs.
women, and those abstinent when medication
is initiated vs. those still drinking
41

42. Long- Acting Naltrexone
 Discontinuation rate- 14% in patients on 380
mg a month, 7% in patients on 190 mg a
month and placebo. Most common side
effects: nausea, injection site reaction,
headache.
 LFTs remained stable throughout the
medication trial
42

43. Naltrexone:
Recent Research
 2005: Cuts the relapse risk during first 90 days
by 36% (28% relapse rate on oral naltrexone
vs. 43% relapse rate on placebo)
 2005: injectable naltrexone resulted in a 25%
reduction in proportion of heavy drinking days
vs. placebo
 Overall: helps to curb consumption in patients
with multiple “slips” but less effective in
maintaining abstinence
43

44. Naltrexone
 Non-compliance is the main barrier to success
 Most useful for highly motivated patients w/
external circumstances
• Impaired professionals, parolees, probationers, etc
44

45. Methadone
 Opiate agonist to treat opiate dependence
 Well-studied and effective treatment
• Normalizes function/return to work, decreases
crime/violence, reduces HIV exposure
 Doses > 70mg/day generally better than low doses
 Enhanced services = improved outcomes
• Counseling, medical, social/vocational services,etc
 No contraindication in SMI, though not well studied
45

46. Methadone
 Usually taken once a day to suppress
withdrawal for 24 to 36 hours
 Usually given in liquid form by Opiate
Treatment Programs
 Induction phase—no more than 30 to 40 mg
on the first day of treatment
 Dosage changes usually occur once a week
• More rapid dosage increases can cause overdose
 Maintenance phase—usually 80-120mg daily
46

47. Methadone
 Common side effects
• Sweating, constipation, abnormal libido, sleep
abnormalities, mild anorexia, weight gain, water
retention
 Adverse effects
• Prologation of QTc (usually seen with very high
doses, mean of 350mg daily)
47

48. Buprenorphine
 Opioid partial agonist
 ↓ risk of overdose and ↓ abuse potential
 May precipitate opiate withdrawal in dependent
individuals
 Approved for treatment of opiate dependence
• Maintenance dose in the range of 8-16 mg daily
 Sublingual route of administration
 Subutex= Bup only; Suboxone= Bup + Naloxone
48

49. Buprenorphine
 Approved in U.S. (2002) as office-based
treatment vs. ‘methadone clinics’
 Individual doctors may treat up to 30 patients
at a time, using an special DEA #
• After 1 year, may increase to 100 patients
 Must be addiction medicine/addiction
psychiatry certified OR complete 8-hr training
49

50. Direct Buprenorphine
Induction from Short-
Acting Opioids
 Ask patient to abstain from short-acting opioid (e.g.,
heroin) for at least 6 hrs. and be in mild withdrawal
before administering buprenorphine/naloxone.
 When transferring from a short-acting opioid, be sure
the patient provides a methadone-negative urine screen
before 1st buprenorphine dose.
SOURCE: Amass, et al., 2004, Johnson, et al. 2003.

51. Buprenorphine
 Suboxone= buprenorphine + naloxone in a 4:1
mixture
• Available doses: 8/2mg and 2/0.5mg
• 2 sublingual forms: tablet and Film
 Induction phase Day 1: usual dose is 2 mg
given every 2-3 hours, up to 8 mg
 Induction phase Day 2: start with 8mg, can go
up to 16mg depending on patient symptoms
51

52. Buprenorphine
 Maintenance phase: usually 8 to 16 mg daily
 This may vary in clinical practice, but realize
that 16mg dose covers ~95% of opiate
receptors
 Adverse side effects: Increased LFTs, cytolytic
hepatitis
 Common side effects: generally mild
• Constipation; dizziness; drowsiness; headache;
nausea; sweating; vomiting;
52

53. Buprenorphine:
Recent Research
 The SAMHSA Evaluation of the Impact of the DATA Waiver
Program
• FINAL REPORT in March 2006
 Buprenorphine clinically effective and well accepted by
patients.
 Waiver Program has ↑ the availability of medication-assisted
treatment for opioid addiction.
 Adverse effects, whether involving diversion or adverse
clinical events or public health consequences, have been
minimal.
 The 30-patient limit on individual physician practices and cost
/ reimbursement issues may be decreasing potential access to
treatment.
 For more information, see www.buprenorphine.samhsa.gov 53

54. Partial vs. Full Opioid
Agonist
death
Opiate Full Agonist
(e.g., methadone)
Effect
Partial Agonist
(e.g. buprenorphine)
Antagonist
(e.g. Naloxone)
Dose of Opiate 54

55. Possible Barriers
to using MAT
Potential Fear # 1:  Rationale # 1:
Medication will  Medication may be a
eventually replace useful adjunct to
rehabilitation as the treatment
treatment of choice for  “Another tool in your
addiction “a pill for toolbox”
every ill”
55

56. Possible Barriers
to using MAT
Potential Fear # 2:  Rationale # 2:
Medication will distract  Medication makes detox
from the difficult work safer and more humane
of recovery from  Medication may allow
addiction the process of recovery
to begin and continue
 Medication may make
recovery possible for
those with severe
mental illness
56

57. Possible Barriers
to using MAT
Potential Fear # 3:  Rationale # 3:
Medication will perpetuate  Physical dependence to
an existing addiction medication may occur,
but addictive behavior
should decrease
Potential Fear # 4:
 Rationale # 4:
Medication will cause new
 New addictions to
addictions medications are a risk,
but the actual incidence
is quite low
57

58. Other Barriers to MAT?
 Financial
• MAT may be very expensive and many still do not
have insurance
 Regulatory
 Until very recently, doctor visits for MAT were not
covered by ODADAS
 Logistical
• Usual treatment settings may not be set up to
provide MAT
 Others? 58

59. Medications only work if…
 …they are getting “from the bottle to the
bloodstream”
 How to help clients with the idea of starting
meds?
• “that will mean I am really sick…” OR “I don’t
need a crutch…”
 How to help clients with the idea of staying on
meds?
• “I feel fine, I don’t need it anymore” OR “if I take
meds, then I am not really sober”

60. Some Lessons from
Motivational Interviewing
 What are the client’s goals?
 How does medication fit (or not fit) with those
goals?
 What are the pros and cons of the
medications?
 Use of reflective listening
 What is the patient willing to do right now?
 What are the patient’s fears about medication?

61. Hope for Recovery
 People with addictive disorders often lack
experiences of success and have lost hope
 Medications in conjunction with other
interventions can increase hope for a better life
• Reduced symptoms of withdrawal
• Reduced symptoms of craving
• Support for long-term sobriety
61

62. Resources
 “BUPRENORPHINE TREATMENT:
A TRAINING FOR MULTIDISCIPLINARY
ADDICTION PROFESSIONALS”
• http://www.nida.nih.gov/blending/buptreatment.htm
 NIDA Methadone Research Web Guide
http://international.drugabuse.gov/collaboration/PDFs/Me
 Mid-America Addiction Technology Transfer Center.
Psychotherapeutic Medications 2011: What Every
Counselor Should Know. http://www.mattc.org
62

63. Contact
Information
Christina M. Delos Reyes, MD
Chief Clinical Officer
ADAMHS Board of Cuyahoga County
Phone: 216-241-3400 x 728
Fax: 216-241-0805
delosreyes@adamhscc.org
Center for Evidence-Based Practices at Case
www.centerforebp.case.edu