Methadone Maintenance in the Treatment of Heroin Addiction Prop 36 CLAIM Meeting - Oct 2003 Joan E. Zweben, Ph.D. Executive Director: 14 th Street Clinic.

Methadone Maintenance in the Treatment of Heroin

Addiction

Methadone Maintenance in the Treatment of Heroin

Addiction

Prop 36 CLAIM Meeting - Oct 2003

Joan E. Zweben, Ph.D.Executive Director: 14th Street Clinic and EBCRP

Clinical Professor of Psychiatry; University of California, San Francisco

Prop 36 CLAIM Meeting - Oct 2003

Joan E. Zweben, Ph.D.Executive Director: 14th Street Clinic and EBCRP

Clinical Professor of Psychiatry; University of California, San Francisco

Questions & IssuesQuestions & Issues

How important is methadone in treating heroin addiction?

What is the rationale? What is the data? How do we decide when/if it can be

discontinued? What is included in the psychosocial

component of treatment?

Natural History of Heroin Addiction: A 33-Year Follow-up (1)

Natural History of Heroin Addiction: A 33-Year Follow-up (1)

581 male heroin addicts, admitted to Calif Civil Addicts Program, 1962-1964

CAP: compulsory drug tx for heroin-dependent criminal offenders

284 dead; 242 interviewed High rates of disability, hepatitis,

excessive drinking, cigarette smoking, marijuana use, other drug-related problems

(Hser et al, 2001)

Narcotics Addicts: A 33-Year Follow-up (2)

Narcotics Addicts: A 33-Year Follow-up (2)

Between 1985-1986 to 1996-1997: Dead: 49% Abstinent: 20%-22% Incarcerated: 4%-7% Methadone maintenance: 2%-6% Occasional use: 2%-3% Lost to follow-up: 12

(Hser et al, 2001)

Opiate Dependency:Hidden Populations

Opiate Dependency:Hidden Populations

Subscribers of Private Insurance Plan:

Empire Blue Cross/Blue Shield, NYC estimated from opiate dependency

diagnosis on admission & AIDS cases insured 141,000 opiate users between

1982-1992 85,000 among current subscribers

(1992)(Eisenhandler & Drucker, 1993)

Treatment Outcome Data: Methadone

Treatment Outcome Data: Methadone

8-10 fold reduction in death rate Reduction of drug use Reduction of criminal activity Engagement in socially productive roles;

improved family and social function Increased employment Improved physical and mental health Reduced spread of HIV Excellent retention

DEATH RATES IN TREATED AND UNTREATED HEROIN ADDICTS

MMT VOL DC TX INVOL DC TX UNTREATED0

1

2

3

4

5

6

7

8

MMT VOL DC TX INVOL DC TX UNTREATED

OBSERVED

EXPECTED

Slide data courtesy of Frank Vocci, MD, NIDA - Reference: Grondblah, L. et al. ACTA

PSCHIATR SCAND, P. 223-227, 1990

% A

nn

ua

l De

ath

Rat

es

Opioid Agonist Treatment of Addiction - Payte - 1998

Impact of MMT on IV Drug Use for 388 Male MMT Patients in 6 Programs

P

ER

CE

NT

IV

US

ER

S

0

100

LA

ST

AD

DIC

TIO

N P

ER

IOD

AD

MIS

SIO

N

100%

81.4%

Pre- | 1st Year | 2nd Year | 3rd Year | 4th Year Admission

*

*

63.3%

41.7%

28.9%

Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991Opioid Agonist Treatment of Addiction - Payte - 1998

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

28.9

45.5

57.6

72.2

82.1

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


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

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 Maintenance Pharmacotherapy - A Course for Clinicians - 1997

HIV DISEASE

• Role of MMTP

– Education, counseling, and testing -- prevention

– Decrease HIV transmission by decreasing needle sharing

– For HIV (+) patients, provide, refer, and coordinate treatment

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

OPIOID MAINTENANCE

THERAPY

OPIOID MAINTENANCE

THERAPY

The Addiction Process:Barriers to Understanding

INFLUENCE OF THE STIGMA: difficulty understanding the complexity of

the disorder treatment is denied treatment is diminished treatment is discouraged treatment is conditional

“I Don’t Believe in Methadone”

Methadone is a medication,

not a religionJ. Thomas Payte, MD

Founding Chair, Methadone Treatment Committee, ASAM

Overview:Opioid Maintenance

Therapy

Overview:Opioid Maintenance

Therapy

Methadone (MMT) & levoacetylmethadol (LAAM), buprenorphine (soon)

most highly regulated history rationale for replacement therapy political influences diversion

OMT, ContinuedOMT, Continued

Strong empirical support for safety and efficacy (30 years of data)

valuable tool in reducing spread of HIV makes the pt accessible to interventions

for other problems hidden populations of heroin users medical maintenance and office-based

practice

What is Abstinence?

Medication is compatible with 12-step participation if appropriately prescribed by physician knowledgeable about addiction

Pt on methadone is abstinent if not using illicit drugs and using legal ones as prescribed

It’s just another medication. Meds are a tool, not a solution

Dole: Receptor System Dysfunction

Endogenous ligand-narcotic receptor system is defective; hence high relapse rate

Stabilize blood level at 150-600 ng/mL This normalizes neurological and endocrine

functioning This treatment is corrective but not curative Future research: identify the specific defect and

repair it(Dole, JAMA 1988)

Genetic Factors

Recent studies show distinct genetic vulnerability to heroin and other opiates:

heroin had larger genetic influences unique to itself than marijuana, sedatives, stimulants, psychedelics (Tsuang et all; Merikangas et al; ARCHIVES 1998)

Alcoholism and drug disorders appear to be independent

Genetic factors impact the transition from drug use to abuse/dependence, not use itself

Diversion of Medication

political hot button key issue in formulating original regs IOM report: cannot document significant

public health or safety problem confusion about DAWN data difficulty of determining cause of death

(Rettig 1995)

Reasons for Diversion

selling take-homes to buy illicit drugs need to supplement income share with or sell to addicted friend/mate unwilling or unable to enter treatment low dose policies of some programs

IOM conclusion: risks of diverted methadone do not outweigh benefits of making MMT more available

(Rettig 1995)

PHARMACOTHERAPYPHARMACOTHERAPY

Methadone vs HeroinMethadone vs Heroin

Can be taken by mouth Slow onset of action No continuing increase in tolerance levels

after optimal dose is reached; relatively constant dose over time

Pt on stable dose rarely experiences euphoric or sedating effects; is able to perceive pain and have emotional reactions; can perform; can perform daily tasks normally and safely

Methadone vs Heroin (2)Methadone vs Heroin (2)

Long acting; prevents withdrawal for 24-36 hours (4x-6x as long as heroin), permitting once-a day-dosing

At sufficient dosage, blocks euphoric effect of normal street doses of heroin

Medically safe when used on long-term basis (10 years or more)

(Physician’s Guide: Opioid Agonist Medical Maintenance Treatment; CSAT 2000)

Do

se R

esp

on

se

Time

“Loaded” “High”

Normal Range“Comfort Zone”

“Sick”

Heroin Simulated 24 Hr. Dose/ResponseWith established heroin tolerance/dependence

0 hrs. 24 hrs.

“Abnormal Normality”

Subjective w/d

Objective w/d



GOALS FOR PHARMACOTHERAPY

• Prevention or reduction of withdrawal symptoms

• Prevention or reduction of drug craving

• Prevention of relapse to use of addictive drug

• Restoration to or toward normalcy of any physiological function disrupted by drug abuse

Source: MJ Kreek, Rationale for Maintenance Pharmacotherapy of Opiate Dependence, 1992

PROFILE FOR POTENTIAL PSYCHOTHERAPEUTIC AGENT

Effective after oral administration

Long biological half-life (>24 hours)

Minimal side effects during chronic administration

Safe, no true toxic or serious adverse effects

Efficacious for a substantial % of persons with the disorder (> 15-20%)


Source: MJ Kreek, Rationale for Maintenance Pharmacotherapy of Opiate Dependence, 1992

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


“Not Holding” Strategies

Cognitive, Behavioral Interventions Increased contact, counseling,

therapyAlter urinary pH? Is patient fixing? - Raise doseSplit Dose?


Payte - Khuri

Rapid Metabolizer - High Single and Split Dose Simulation

0

100

200

300

400

500

600

700

0 4 8 12 16 20 24

Single

HighSingle

Split Dose

Minimum

'Normal'Ceiling

High

Normal

Sick


Payte

ng

/ m

l

Hours

TAPERING

how many remain abstinent? tapering readiness tapering strategies clonidine handling relapse

Buprenorphine (1)Buprenorphine (1)

1970’s - partial opioid agonist useful in opioid dependence treatment

1990’s - clinical trials long duration of action; smooth onset low physical dependence mild withdrawal syndrome good name on the street


DATA 2000 permitted use in MD office FDA approved Subutex and Suboxone in

2002 Physicians must meet training

requirements: certified in addiction medicine, participated in clinical trials, or took 8 hour course by specified organizations


SUBUTEX & SUBOXONE Sublingual tablets Suboxone has naloxone added to

discourage needle use Partial agonist: ceiling effect Expensive: $300/month at average dose Not interchangeable with methadone


Poor oral bioavailability Sublingual administration requires

longer observation Abuse documented in Europe, Australia,

and New Zealand How much training should be required

for physicians to use it?

Naltrexone

antagonist; how it works who does it work for? accelerated withdrawal protocols Dole’s critique utility with alcoholics

Methadone in Pregnancy

Methadone in Pregnancy

Comprehensive MMT treatment with prenatal care improves neonatal outcome

Withdrawal is rarely appropriate during pregnancy

Methadone is not teratogenic; children have been followed into adulthood

Appropriate dosing is very important Breast feeding OK if no other drug use

Opioids and Chronic PainOpioids and Chronic Pain

Opioid tolerance & physical dependence DO NOT equal opioid addiction

Loss of Control Indices:

» Continued use despite adverse consequences

» Illicit or inappropriate drug seeking behavior

– In response to craving or drug hunger

– In the absence of pain or withdrawal

Pseudo Addiction- in chronic pain patient

Inadequate Treatment of Pain

“Apparent” Drug Seeking Behavior

» Effort to achieve adequate analgesia

» Early refill, doctor shopping, etc.

–Manipulation seen as “addictive behavior”

–May be seen as non-compliance

“Cured” by adequate treatment of pain


Chronic Pain Disorder

Opioid Tolerance Opioid Physical Dependence Absence of illicit or inappropriate drug

seeking behavior» No drug hunger in absence of pain» No loss of control

No “doctor shopping” Little tendency to escalate dose over time


PSYCHOSOCIAL TREATMENT ISSUES

PSYCHOSOCIAL TREATMENT ISSUES

Population Characteristics

Heterogeneity Readiness for recovery; motivation Psychiatric comorbidity Medical comorbidity

Program Characteristics

Program Characteristics

Medical component: assessment, dosing, client interactions

Individual counseling Group counseling Case management Staff training (ongoing)

What is Abstinence?

Medication is compatible with 12-step participation if appropriately prescribed by physician knowledgeable about addiction

Pt on methadone is abstinent if not using illicit drugs and using legal ones as prescribed

It’s just another medication. Meds are a tool, not a solution

Cognitive-Behavioral Therapy

Cognitive-Behavioral Therapy

Lends itself to controlled studies; strong support for its effectiveness

Especially useful to help establish abstinence, teach early recovery and relapse prevention skills

Emphasizes changing behavior and managing symptoms

Cognitive Behavioral Strategies (CBT)

Cognitive Behavioral Strategies (CBT)

MATRIX MODEL - Organizing Principles Create explicit structure and expectations Establish positive, collaborative relationship Teach information and CBT concepts Positively reinforce behavior change Provide corrective feedback when necessary Encourage self-help participation

CBT: MATRIX MODELCBT: MATRIX MODEL

Structure is essential: time scheduling, self-help meetings, exercise, work, treatment activities

Identify external and internal triggers and make a plan

Tools for managing cravings: thought stopping, visual imagery, change environment/behavior

TIP #33 has description, patient worksheets(Rawson 1999)

Clinical IssuesClinical Issues

Is Psychotherapy Useful?

Philadelphia group study, begun 1977 global psychiatric status ratings elements of drug counseling models of psychotherapy utilized benefits to low severity patients benefits to high severity patients

Dual Diagnosis Issues

depression trauma history; PTSD schizophrenia medication strategies

PTSD Influence in Early Tx

PTSD Influence in Early Tx

Aim: determine tx adherence relative to frequency of violence and PTSD in MMT pts, male & female

96 pts; over 2/3 exposed to one or more violent traumatic events

Trauma or PTSD did not predict dropout rates Those with current PTSD had significantly more

ongoing drug use at 3 months, especially cocaine

(Hein et al, 2000)

Continued heroin, alcohol, and other drug use

patient and provider expectations enhancing motivation cocaine use alcohol use medical comorbidity; AIDS, chronic pain controversies about discharge

Psychological Issues

AOD use in family of origin high frequency of childhood physical

and sexual abuse recognition and appropriate expression

of feelings issues of self-care, self-soothing

Women’s Issues

remove practical barriers: transportation, child care

intimate relationships as primary hazard sexual issues contraceptive practices

Family/Couples Work

engaging family, significant others education about addiction and MMT develop existing and new support

structures couples issues parenting classes

HIV/AIDSHIV/AIDS

impact on MMT staff; providing support regular assessment of staff attitudes and

knowledge integrating primary care promoting medication compliance impact of dementia on treatment

MMT and 12-Step Programs

benefits and hazards simulated meetings as a launching

strategy meetings in the community Vincent Dole and Bill W. other types of self-help advocacy groups

Making Residential Treatment Available to Methadone

Patients

Making Residential Treatment Available to Methadone

Patients

Some clients need higher level of care Issues for the methadone program Issues for the residential program Security issues Documentation issues Funding barriers

Methadone Maintenance in the Treatment of Heroin Addiction Prop 36 CLAIM Meeting - Oct 2003 Joan E. Zweben, Ph.D. Executive Director: 14 th Street Clinic.

Documents