Transcript Opioid Substition Therapy - California Opioid Maintenance

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
Questions & 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)
581 male heroin addicts, admitted to
Calif Civil Addicts Program, 1962-1964
 CAP: compulsory drug tx for heroindependent 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)
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
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
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
8
7
6
5
OBSERVED
EXPECTED
4
3
2
1
0
MMT
VOL DC TX
INVOL DC TX
UNTREATED
Slide data courtesy of Frank Vocci, MD, NIDA - Reference: Grondblah, L. et al. ACTA
PSCHIATR SCAND, P. 223-227, 1990
Opioid Agonist Treatment of Addiction - Payte - 1998
Impact of MMT on IV Drug Use for 388 Male
MMT Patients in 6 Programs
ADMISSION
100
*
*
0
Pre| 1st Year
Admission
| 2nd Year
| 3rd Year
| 4th Year
Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991
Opioid Agonist Treatment of Addiction - Payte - 1998
Relapse to IV drug use after MMT
105 male patients who left treatment
Percent IV Users
100
82.1
80
72.2
60
57.6
45.5
40
28.9
20
0
IN
1 to 3
Treatment
4 to 6
7 to 9
10 to 12
Months Since Stopping Treatment
Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991
Opioid Agonist Treatment of Addiction - Payte - 1998
Crime among 491 patients before and during
MMT at 6 programs
Crime Days Per Year
300
250
200
Before TX
During TX
150
100
50
0
A
B
C
D
E
F
Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991
Opioid Agonist Treatment of Addiction - Payte - 1998
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
Opioid Maintenance Pharmacotherapy - A Course for Clinicians - 1997
HIV CONVERSION IN TREATMENT
35%
30%
25%
20%
IT
OT
15%
10%
5%
0%
Base line
6 Month
12 Month
18 Month
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 - 1997
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 religion
J. Thomas Payte, MD
Founding Chair, Methadone Treatment
Committee, ASAM
Overview:
Opioid Maintenance Therapy
Methadone (MMT) & levoacetylmethadol
(LAAM), buprenorphine (soon)
 most highly regulated
 history
 rationale for replacement therapy
 political influences
 diversion

OMT, 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)
PHARMACOTHERAPY
Methadone 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)
Long acting; prevents withdrawal for 2436 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)
Heroin Simulated 24 Hr. Dose/Response
Dose Response
With established heroin tolerance/dependence
“Loaded”
“High”
“Abnormal Normality”
Normal Range
“Comfort Zone”
Subjective w/d
0 hrs.
“Sick”
Objective w/d
Time
Opioid Agonist Treatment of Addiction - Payte - 1998
24 hrs.
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
Opioid Agonist Treatment of Addiction - Payte - 1998
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
Opioid Agonist Treatment of Addiction - Payte - 1998
Dose Response
Methadone Simulated 24 Hr. Dose/Response
At steady-state in tolerant patient
“Loaded”
“High”
“Abnormal Normality”
Normal Range
“Comfort Zone”
Subjective w/d
0 hrs.
“Sick”
Objective w/d
Time
Opioid Agonist Treatment of Addiction - Payte - 1998
24 hrs.
“Not Holding” Strategies
 Cognitive,
Behavioral Interventions
 Increased contact, counseling,
therapy
 Alter urinary pH?
 Is patient fixing? - Raise dose
 Split Dose?
Payte - Khuri
Opioid Agonist Treatment of Addiction - Payte - 1998
Rapid Metabolizer - High Single and
Split Dose Simulation
700
Single
600
High
High
Single
ng / ml
500
400
Split Dose
Normal
300
Minimum
200
Sick
'Normal'
Ceiling
100
0
0
4
8
12
16
20
Hours
Payte
Opioid Agonist Treatment of Addiction - Payte - 1998
24
TAPERING
how many remain abstinent?
 tapering readiness
 tapering strategies
 clonidine
 handling relapse

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

Buprenorphine (2)
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

Buprenorphine (3)
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
Buprenorphine (4)
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





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 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
Opioid Agonist Treatment of Addiction - Payte - 1998
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

Opioid Agonist Treatment of Addiction - Payte - 1998
PSYCHOSOCIAL
TREATMENT ISSUES
Population Characteristics
Heterogeneity
 Readiness for recovery; motivation
 Psychiatric comorbidity
 Medical comorbidity

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
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)
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 MODEL




Structure is essential: time scheduling, selfhelp 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 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
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/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
Some clients need higher level of care
 Issues for the methadone program
 Issues for the residential program
 Security issues
 Documentation issues
 Funding barriers
