1. Medical issues about Methadone : What the counselor needs to know
Judith Martin, MD
Medical Director
The 14th Street Clinic,
Oakland, CA

2. Counseling Staff

3. THE DOSING WINDOW

4. Epidemiology Opioid dependence Cost
Office of National Drug Control Policy (1999)
810,000 persons
Only 170,000 receiving medication treatment
Cost
$20 billion per year total costs (NIDA 1992)
$9.6 billion spent on heroin (ONDCP )
$1.2 billion per year health care costs (NIDA 1992)

5. Prescription opioid abuse epidemiology
Prescription opioid use (2001), ED reports: 90,000+ (DAWN)
Reports of oxycodone abuse:18,000+
Reports hydrocodone abuse: 21,000+
Reports methadone abuse: 10,000+
, oxycodone 450% increase!
Bottom line: big street value!

6. Number of new non-medical users of therapeutics
1. This figure is taken from the NSDUH, and shows the annual number of persons who have non-medical use of different substances. As can be seen in the figure, during the 1970s and most of the 1980s there was a relative stable number of new users for each class, and this did not really differ between drug classes. However, starting in the 1990s, the number of new users of pain relievers (opioids) has increased dramatically, and is markedly higher than the other classes of substances.
(NSDUH, 2002)

7. Diacetylmorphine (Heroin) Hydromorphone (Dilaudid)
Commonly Abused Opioids
Diacetylmorphine (Heroin)
Hydromorphone (Dilaudid)
Oxycodone (OxyContin, Percodan, Percocet, Tylox)
Meperidine (Demerol)
Hydrocodone (Lortab, Vicodin)
1. While most patients abuse heroin, there are several other opioids that can be abused. This list is continued on the next slide, and it is not meant to be exhaustive. Note that all of these opioids exert a mu agonist effect.

8. Morphine (MS Contin, Oramorph) Fentanyl (Sublimaze)
Commonly Abused Opioids (continued)
Morphine (MS Contin, Oramorph)
Fentanyl (Sublimaze)
Propoxyphene (Darvon)
Methadone (Dolophine)
Codeine
Opium 1.

10. Four questions patients ask:
How is methadone better for me than heroin?
What is the right dose of methadone for me?
How long should I stay on methadone?
What are the side effects of methadone?

11. Talking to patients about addiction treatment models
Medical
Recovery
Spiritual
Psychodynamic
Behavioral

12. ADDICTION AS A CHRONIC ILLNESS
Chronic relapsing condition
which untreated
may lead to severe complications
and death.

13. ADDICTION AS CHRONIC DISEASE: IMPLICATIONS
It is treatable but not curable.
Adjustment to diagnosis is part of patient’s task.
There is a wide spectrum of severity.
Retention in treatment is key.
Best treatment is integrated.

14. Four questions patients ask:
How is methadone better for me than heroin?
What is the right dose of methadone for me?
How long should I stay on methadone?
What are the side effects of methadone?

15. How is methadone better than heroin?
Legal
Avoids needles
Known amount ingested

16. Opiate effects, physical
Predictable physical effects of administering opiates:
Tolerance: the body becomes efficient in processing the drug and requires ever higher doses to produce the desired effect.
Dependence: when the drug is discontinued there are typical withdrawal signs and symptoms.

17. IDU, pattern of heroin injection over 3 days
From Dole, Nyswander and Kreek, 1966

18. Normal Range “Comfort Zone” Dose Response
Methadone Simulated 24 Hr. Dose/Response At steady-state in tolerant patient
“Loaded”
“High”
“Abnormal Normality”
Normal Range “Comfort Zone”
Dose Response
Subjective w/d
“Sick”
Objective w/d
Time
0 hrs.
24 hrs.
Opioid Agonist Treatment of Addiction - Payte

19. How is methadone better than heroin?
Legal
Avoids needles
Known amount ingested
Slow onset: no “rush”
Long acting: can maintain “comfort” or normal brain function
Stabilized physiology, hormones, tolerance

20. Four questions patients ask:
How is methadone better for me than heroin?
What is the right dose of methadone for me?
How long should I stay on methadone?
What are the side effects of methadone?

21. Normal Range “Comfort Zone” Dose Response
Methadone Simulated 24 Hr. Dose/Response At steady-state in tolerant patient
“Loaded”
“High”
“Abnormal Normality”
Normal Range “Comfort Zone”
Dose Response
Subjective w/d
trough
“Sick”
Objective w/d
Time
0 hrs.
24 hrs.
Opioid Agonist Treatment of Addiction - Payte

22. What is the right dose? Eliminate physical withdrawal
Eliminate ‘craving’
Comfort/function: usually trough is ng/ml, peak no more than twice the trough.
Not oversedated
Blocking dose

23. “How Much????
Enough!!!”
Tom Payte, MD

24. Ref: J. C. Ball, November 18, 1988
Slide adapted from Tom Payte

25. Four questions patients ask:
How is methadone better for me than heroin?
What is the right dose of methadone for me?
How long should I stay on methadone?
What are the side effects of methadone?

26. Relapse to IV drug use after MMT 105 male patients who left treatment
Percent IV Users
Treatment Months Since Stopping Treatment
Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991
Opioid Agonist Treatment of Addiction - Payte

27. “How Long???
Long Enough!!”
Tom Payte, MD

28. Four questions patients ask:
How is methadone better for me than heroin?
What is the right dose of methadone for me?
How long should I stay on methadone?
What are the side effects of methadone?

29. Side effects of methadone:
General opiate effects:
Sedation/stimulation
Maintained phys. dependence (stable)
hypogonadism (not as severe as with heroin, may be dose dependent)
Constipation
Slight QTc prolongation on ECG (Martell etal)
Sweating
Methadone treatment tied to regulated clinic

30. Treatment Outcome Data
8-10 fold reduction in death rate
reduction of drug use
reduction of criminal activity
engagement in socially productive roles
reduced spread of HIV
excellent retention

31. Crime among 491 patients before and during MMT at 6 programs
Crime Days Per Year
Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991
Opioid Agonist Treatment of Addiction - Payte

32. HIV CONVERSION IN TREATMENT
HIV infection rates by baseline treatment status. In treatment (IT) n=138, not in treatment (OT) n=88 Source: Metzger, D. et. al. J of AIDS 6:1993. p.1052
Opioid Maintenance Pharmacotherapy - A Course for Clinicians

33. A FEW WORDS ABOUT BUPRENORPHINE
“Ceiling effect” and safety
Displaced other opiates: withdrawal on induction
Less agonist strength
Schedule 3(methadone is 2)
One form combined with naloxone
Office – based use available

34. Credit: Don Wesson, MD

36. Buprenorphine, Methadone, LAAM: Treatment Retention
100 80
73% Hi Meth 60
58% Bup
Percent Retained
53% LAAM 40 20
20% Lo Meth 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Study Week
Johnson et al, 2000

37. Buprenorphine, Methadone, LAAM: Opioid Urine Results
100
All Subjects 80
LAAM
49% 60
Bup
40%
Hi Meth
Mean % Negative 40
39%
Lo Meth 20
19% 1 3 5 7 9 11 13 15 17
Study Week

38. Effect of counseling in buprenorphine treatment (Fiellin, 2002)

39. Retention in treatment
Kakko et al, 2003, 20 15
Remaining in treatment (nr) 10 5
Control, 6-day detox
Buprenorphine maintenance 50
100
150
200
250
300
350
Treatment duration (days)

40. Pharmacotherapy in context: correct glossary
Abstinence includes pharmacotherapy
Maintenance, not substituion or replacement (new term also: MAT)
Tapering from maintenance, not detoxification, (also ‘medically supervised withdrawal’, or MSW)
Discontinuation, not discharge
Toxicology screens: pos/neg, not clean/dirty)

41. Opioid pharmacotherapy, summary:
Methadone, buprenorphine and LAAM all approved by the FDA for treatment of opiate dependence. (LAAM not currently available from any drug company)
Best evidence so far supports maintenance.
Detoxification attempts should have maintenance as a back up in case of relapse.