Transcript Opioid Agonist Treatment: “Trading one substance for another?”

Opioid Agonist Treatment:
“Trading one substance for another?”
Joseph Sakai, M.D.
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Objectives:
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Opioids and opioid dependence
Natural course
Methadone
Other agonist treatments
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Opioids, Opioid Dependence:
• Define opioids
– Opiates
– Semi-synthetic
– Synthetic
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Opioids, Opioid Dependence:
• Endogenous opioid system
– Receptors
• Mu
• Delta
• Kappa
– Endorphins
• Beta-endorphins
• Enkephalins
• Dynorphins
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Opioids, Opioid Dependence:
• Opioid dependence:
Tolerance
Withdrawal
Use more than intended
Unable to cut down
Increased time using
Give up other activities
Use despite consequences
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Opioids, Opioid Dependence:
• Epidemiology
– Lifetime use
• 1.8% of 10th graders used heroin (lifetime)
• 3.6 million Americans have used heroin
– Dependence
• 1:4 heroin users with lifetime dependence
• 1:1000 in US with opioid dependence in 2002
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Natural Course:
• Detox alone high relapse
• 20 yr after detox
– 10% stable abstinence at 5yrs
– 35% stable abstinence at 18 year
• 24 yr f/u
– ~20% no heroin use: last 10 yrs of the study
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Natural Course:
• Medical risks:
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Abscesses
Sepsis
Osteomyelitis
Thrombophlebitis
Endocarditis
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Natural Course:
• Medical risks:
– HCV
• 70% IV users
• 65% after 1 yr needle use; ~85% at 5 yrs
– HIV
• IV users ~75% of new HIV infections
• HIV ~20%
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Natural Course:
• Death
– Overdose 1.5%/yr
– 24 yr study – 28% sample deceased
– Not in tx; 63x expected mortality rate
• Low employment:
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36.4% active users employed
Heroin dosed Q 6 hours
Need time to recover
But need money to buy the drug
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Natural Course:
• Crime:
– Most commit crimes
– F/u 10 years ~18% incarcerated
– One study n=573 12 month period:
• >80,000 crimes reported
• Costs:
– Medical costs: $1.2 billion per yr
– Total cost estimate: $20 billion per yr
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Natural Course: Summary
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Unlikely to remit with detox alone
Medical risks
High mortality
Low employment
Crime
High cost to society
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Treatment: Goals
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Complete abstinence
Reduce use of heroin
Reduce harm
Increase employment
Reduce crime
Engage in treatment
Be cost effective
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Treatment: Modalities
• Rehabilitation
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Engage patient
Support abstinence
Prevent relapse
Life management skills
Coping skills
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Treatment:
• Rehabilitation
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Individual
Groups
Urines
Psychosocial treatments
Medications
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Treatment:
• Antagonists
– Naltrexone
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Pure antagonist
Absorbed orally
50-150 mg/dose
Dosed daily or 3x/wk
Retention poor
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Treatment:
• Agonists
– Theory
• Pre-existing dysphoria
• Pre-existing receptor dysfunction
• Induced receptor dysfunction
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Treatment: Methadone
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Mu agonist
Half life 22-48 hours
Dosing (slowly ↑ to 80mg +)
Needs specialized clinics
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Treatment: Methadone
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↓ Heroin use by 50%
↓ HIV 4 fold
↑ Employment 24%
↓ 50% criminal activity
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Treatment: Methadone
• ↑ Retention in rehabilitation 28 times
• ↑ Retention in HCV treatment
• ↑ Health outcomes (HCV, HIV)
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Treatment: Methadone
• ↓ Mortality 50%
– Before and after methadone
– In vs out of treatment
• Cost effective
– <$13/day
– 4:1 cost benefit ratio
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Methadone: Summary
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Complete abstinence
Reduce use of heroin
Reduce harm
Increase employment
Reduce crime
Engage in treatment
Save lives
Be cost effective
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No
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Treatment: Barriers
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Out of medical mainstream
Stigma of specialized clinics
Location of clinics
Daily dosing
Federal regulations
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Treatment: Methadone
• Barriers to use of methadone
• Misconceptions
– Methadone dependence
– Trading one substance for another?
– Methadone must be taken for life
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Treatment:
LAAM (levo-alpha acetyl methadol)
• LAAM
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Mu agonist
Orally dosed
Effects: 72 hours
Dose (20-100mg three times per week)
Licensed clinics
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Treatment: LAAM
• Retention ↓(39% vs. 60% LAAM vs.
methadone)
• Same reduction in heroin use (55% vs.
46% LAAM vs. methadone)
• Safety concerns
– Cardiac abnormalities (QT prolongation)
– LAAM (ORLAAM) sale and distribution
discontinued
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Treatment: Buprenorphine
• Buprenorphine
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Agonist/antagonist
Half life 37 hrs
Dosing 8-32mg/d
Can precipitate withdrawal
Absorption (poor oral)
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Treatment: Buprenorphine
• Office based
– Increased access
• 20% of heroin dependent persons can get methadone
• Methadone not available in some states
– Any physician can be trained
• Safer in overdose
• Risk for diversion
– Can combine with Naloxone to ↓injection
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Treatment: Buprenorphine
• Outcome
– Retention in treatment
• Slightly lower than methadone
• 50% vs. 59%(buprenorphine vs. methadone)
– Heroin use
• Slightly worse than methadone (low dose)
• 38% vs. 40.5% (buprenorphine vs. methadone)
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Conclusions:
• Opioid dependence is destructive
• Methadone maintenance is effective
• Other agonist treatments are available
A challenge to you…
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