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

Medical issues about Methadone :What the counselor needs to know

Judith Martin, MD

Medical Director

The 14th Street Clinic,

Oakland, CA

www.14thstreetclinic.org

Counseling Staff

THE DOSING WINDOW

Epidemiology

Opioid dependence 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 1988-1995) $1.2 billion per year health care costs (NIDA

1992)

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+

1994- 2002, oxycodone 450% increase!

Bottom line: big street value!

Number of new non-medical users of therapeutics

(NSDUH, 2002)

Diacetylmorphine (Heroin)

Hydromorphone (Dilaudid)

Oxycodone (OxyContin, Percodan, Percocet, Tylox)

Meperidine (Demerol)

Hydrocodone (Lortab, Vicodin)

Commonly Abused Opioids

Morphine (MS Contin, Oramorph)

Fentanyl (Sublimaze)

Propoxyphene (Darvon)

Methadone (Dolophine)

Codeine

Opium

Commonly Abused Opioids (continued)

0%

25%

50%

75%

100%

1992 1993 1994 1995 1996 1997

Route of heroin administrationTreatment Entry Data System 1992-1997

Injection Inhalation Smoking Other

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?

Talking to patients about addiction treatment

models

Recovery

Psychodynamic Behavioral

Spiritual

Medical

ADDICTION AS A CHRONIC ILLNESS

Chronic relapsing condition which untreatedmay lead to severe complications and death.

ADDICTION AS CHRONIC DISEASE: IMPLICATIONSIt 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.

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?

How is methadone better than heroin?

Legal

Avoids needles

Known amount ingested

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.

IDU, pattern of heroin injection over 3 days

From Dole, Nyswander and Kreek, 1966

Do

se R

esp

on

se

Time

“Loaded” “High”

Normal Range“Comfort Zone”

“Sick”

Methadone Simulated 24 Hr. Dose/ResponseAt steady-state in tolerant patient

0 hrs.

24 hrs.

“Abnormal Normality”

Subjective w/d

Objective w/d

Opioid Agonist Treatment of Addiction - Payte - 1998

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

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?

Do

se R

esp

on

se

Time

“Loaded” “High”

Normal Range“Comfort Zone”

“Sick”

Methadone Simulated 24 Hr. Dose/ResponseAt steady-state in tolerant patient

0 hrs.

24 hrs.

“Abnormal Normality”

Subjective w/d

Objective w/d

Opioid Agonist Treatment of Addiction - Payte - 1998

trough

What is the right dose?

Eliminate physical withdrawal

Eliminate ‘craving’

Comfort/function: usually trough is 400-600 ng/ml, peak no more than twice the trough.

Not oversedated

Blocking dose

“How Much????

Enough!!!”Tom Payte, MD

Recent Heroin Use by Current Methadone Dose

0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90 100

Methadone Dose, in mg.

% H

eroi

n U

se

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

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?

Relapse to IV drug use after MMT105 male patients who left treatment

28.9

45.5

57.6

72.282.1

0

20

40

60

80

100

IN 1 to 3 4 to 6 7 to 9 10 to 12

Pe

rce

nt

IV U

se

rs

Treatment Months Since Stopping Treatment

Opioid Agonist Treatment of Addiction - Payte - 1998

Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991

“How Long???

Long Enough!!”Tom Payte, MD

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?

Side effects of methadone:

General opiate effects: Sedation/stimulation Maintained phys. dependence (stable) hypogonadism (not as severe as with heroin, may

be dose dependent)

ConstipationSlight QTc prolongation on ECG (Martell etal)SweatingMethadone treatment tied to regulated clinic

Treatment Outcome Data

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

Crime among 491 patients before and during MMT at 6 programs

0

50

100

150

200

250

300

A B C D E F

Before TX

During TX

Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991

Cri

me

Day

s P

er Y

ear

Opioid Agonist Treatment of Addiction - Payte - 1998

HIV CONVERSION IN TREATMENT

0%

5%

10%

15%

20%

25%

30%

35%

Base line 6 Month 12 Month 18 Month

ITOT

HIV infection rates by baseline treatment status. In treatment (IT) n=138, not in treatment (OT) n=88Source: Metzger, D. et. al. J of AIDS 6:1993. p.1052

Opioid Maintenance Pharmacotherapy - A Course for Clinicians - 1997

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

Partial vs Full Opiate Mu Agonist

Dose of Opiate

OpiateEffect

death

Full Agonist(e.g., methadone)

Partial Agonist(e.g. buprenorphine)

Credit: Don Wesson, MD

Buprenorphine, Methadone, LAAM:

Treatment Retention

Per

cent

Ret

aine

d

0

20

40

60

80

100

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

20% Lo Meth

58% Bup

73% Hi Meth

53% LAAM

Study WeekJohnson et al, 2000

Buprenorphine, Methadone, LAAM:Opioid Urine Results

Mea

n %

Neg

ativ

e

Study Week

All Subjects

Lo Meth

BupHi Meth

LAAM

1 3 5 7 9 11 13 15 170

20

40

60

80

100

19%

40%

39%

49%

Effect of counseling in buprenorphine treatment

(Fiellin, 2002)

0

0.2

0.4

0.6

0.8

1

Induction week 2-4 week 5-7 week 8-10

Op

ioid

po

sit

ive

uri

ne

s

MM

MM+DC

Retention in treatment

Treatment duration (days)

Remaining in treatment (nr)

0

5

10

15

20

0 50 100 150 200 250 300 350

Control, 6-day detox

Buprenorphine maintenance

Kakko et al, 2003,

Pharmacotherapy in context: correct glossaryAbstinence 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)

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.