Methadone Maintenance in the Treatment of Heroin Addiction

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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

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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?

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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)

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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)

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Opiate DependencyHidden 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)

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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

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DEATH RATES IN TREATED AND UNTREATED HEROIN
ADDICTS
Annual Death Rates
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
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Impact of MMT on IV Drug Use for 388 Male MMT
Patients in 6 Programs
100
100
81.4
63.3
41.7
LAST ADDICTION PERIOD
PERCENT IV USERS
ADMISSION
28.9


0
Pre- 1st Year 2nd Year
3rd Year 4th Year Admission
Adapted from Ball Ross - The Effectiveness of
Methadone Maintenance Treatment, 1991
Opioid Agonist Treatment of Addiction - Payte -
1998
9
Relapse to IV drug use after MMT105 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 -
1998
10
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 -
1998
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• 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
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HIV CONVERSION IN TREATMENT
HIV infection rates by baseline treatment status.
In treatment (IT) n138, not in treatment (OT)
n88Source Metzger, D. et. al. J of AIDS
61993. p.1052
Opioid Maintenance Pharmacotherapy - A Course for
Clinicians - 1997
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OPIOID MAINTENANCETHERAPY
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The Addiction ProcessBarriers 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

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I Dont Believe in Methadone
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Methadone is a medication,not a religion

• J. Thomas Payte, MD
• Founding Chair, Methadone Treatment Committee,
  ASAM

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OverviewOpioid Maintenance Therapy

• Methadone (MMT) levoacetylmethadol (LAAM),
  buprenorphine (soon)
• most highly regulated
• history
• rationale for replacement therapy
• political influences
• diversion

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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

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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
• Its just another medication. Meds are a tool,
  not a solution

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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)

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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

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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)

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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)

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PHARMACOTHERAPY
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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

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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)
• (Physicians Guide Opioid Agonist Medical
  Maintenance Treatment CSAT 2000)

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Heroin Simulated 24 Hr. Dose/ResponseWith
established heroin tolerance/dependence
Loaded High
Abnormal Normality
Normal RangeComfort Zone
Dose Response
Subjective w/d
Sick
Objective w/d
Time
0 hrs.
24 hrs.
Opioid Agonist Treatment of Addiction - Payte -
1998
28

• 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
29
PROFILE FOR POTENTIAL PSYCHOTHERAPEUTIC AGENT

• Effective after oral administration
• Long biological half-life (gt24 hours)
• Minimal side effects during chronic
  administration
• Safe, no true toxic or serious adverse effects
• Efficacious for a substantial of persons with
  the disorder (gt 15-20)

Source MJ Kreek, Rationale for Maintenance
Pharmacotherapy of Opiate Dependence, 1992
Opioid Agonist Treatment of Addiction - Payte -
1998
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Methadone Simulated 24 Hr. Dose/ResponseAt
steady-state in tolerant patient
Loaded High
Abnormal Normality
Normal RangeComfort Zone
Dose Response
Subjective w/d
Sick
Objective w/d
Time
0 hrs.
24 hrs.
Opioid Agonist Treatment of Addiction - Payte -
1998
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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
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Rapid Metabolizer - High Single and Split Dose
Simulation
High
ng / ml
Normal
Sick
Hours
Payte
Opioid Agonist Treatment of Addiction - Payte -
1998
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TAPERING

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

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Buprenorphine (1)

• 1970s - partial opioid agonist useful in opioid
  dependence treatment
• 1990s - clinical trials
• long duration of action smooth onset
• low physical dependence
• mild withdrawal syndrome
• good name on the street

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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

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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

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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?

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Naltrexone

• antagonist how it works
• who does it work for?
• accelerated withdrawal protocols
• Doles critique
• utility with alcoholics

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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

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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

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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
42
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
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PSYCHOSOCIAL TREATMENT ISSUES
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Population Characteristics

• Heterogeneity
• Readiness for recovery motivation
• Psychiatric comorbidity
• Medical comorbidity

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Program Characteristics

• Medical component assessment, dosing, client
  interactions
• Individual counseling
• Group counseling
• Case management
• Staff training (ongoing)

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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
• Its just another medication. Meds are a tool,
  not a solution

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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

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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

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CBT 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)

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Clinical Issues
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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

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Dual Diagnosis Issues

• depression
• trauma history PTSD
• schizophrenia
• medication strategies

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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)

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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

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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

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Womens Issues

• remove practical barriers transportation, child
  care
• intimate relationships as primary hazard
• sexual issues
• contraceptive practices

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Family/Couples Work

• engaging family, significant others
• education about addiction and MMT
• develop existing and new support structures
• couples issues
• parenting classes

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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

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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

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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