copyright alcohol medical scholars program 1 opioid agonist treatment: “trading one substance for...

Copyright Alcohol Medical Scholars Program

1

Opioid Agonist Treatment:

“Trading one substance for another?”

Joseph Sakai, M.D.


2

Objectives:

• Opioids and opioid dependence

• Natural course

• Methadone

• Other agonist treatments


3

Opioids, Opioid Dependence:

• Define opioids– Opiates

– Semi-synthetic

– Synthetic


4


• Endogenous opioid system– Receptors

• Mu• Delta• Kappa

– Endorphins• Beta-endorphins• Enkephalins• Dynorphins


5


• Opioid dependence:ToleranceWithdrawalUse more than intendedUnable to cut downIncreased time usingGive up other activitiesUse despite consequences


6


• 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


7

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


8

Natural Course:

• Medical risks:– Abscesses– Sepsis– Osteomyelitis– Thrombophlebitis– Endocarditis


9

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%


10

Natural Course:

• Death– Overdose 1.5%/yr

– 24 yr study – 28% sample deceased

– Not in tx; 63x expected mortality rate

• Low employment:– 36.4% active users employed

– Heroin dosed Q 6 hours

– Need time to recover

– But need money to buy the drug


11

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


12

Natural Course: Summary

• Unlikely to remit with detox alone

• Medical risks

• High mortality

• Low employment

• Crime

• High cost to society


13

Treatment: Goals

• Complete abstinence

• Reduce use of heroin

• Reduce harm

• Increase employment

• Reduce crime

• Engage in treatment

• Be cost effective


14

Treatment: Modalities

• Rehabilitation– Engage patient– Support abstinence– Prevent relapse– Life management skills– Coping skills


15

Treatment:

• Rehabilitation– Individual– Groups– Urines– Psychosocial treatments– Medications


16

Treatment:

• Antagonists– Naltrexone

• Pure antagonist

• Absorbed orally

• 50-150 mg/dose

• Dosed daily or 3x/wk

• Retention poor


17

Treatment:

• Agonists– Theory

• Pre-existing dysphoria

• Pre-existing receptor dysfunction

• Induced receptor dysfunction


18

Treatment: Methadone

• Mu agonist

• Half life 22-48 hours

• Dosing (slowly ↑ to 80mg +)

• Needs specialized clinics


19


• ↓ Heroin use by 50%

• ↓ HIV 4 fold

• ↑ Employment 24%

• ↓ 50% criminal activity


20


• ↑ Retention in rehabilitation 28 times

• ↑ Retention in HCV treatment

• ↑ Health outcomes (HCV, HIV)


21


• ↓ Mortality 50%– Before and after methadone– In vs out of treatment

• Cost effective– <$13/day– 4:1 cost benefit ratio


22

Methadone: Summary

• Complete abstinence• Reduce use of heroin • Reduce harm • Increase employment• Reduce crime• Engage in treatment• Save lives• Be cost effective

Yes NoX

X

XX

X

X

X

X


23

Treatment: Barriers

• Out of medical mainstream

• Stigma of specialized clinics

• Location of clinics

• Daily dosing

• Federal regulations


24


• Barriers to use of methadone

• Misconceptions– Methadone dependence– Trading one substance for another?– Methadone must be taken for life


25

Treatment: LAAM (levo-alpha acetyl methadol)

• LAAM– Mu agonist– Orally dosed– Effects: 72 hours– Dose (20-100mg three times per week)– Licensed clinics


26

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


27

Treatment: Buprenorphine

• Buprenorphine– Agonist/antagonist– Half life 37 hrs– Dosing 8-32mg/d– Can precipitate withdrawal– Absorption (poor oral)


28


• 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


29


• 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)


30

Conclusions:

• Opioid dependence is destructive

• Methadone maintenance is effective

• Other agonist treatments are available

A challenge to you…

copyright alcohol medical scholars program 1 opioid agonist treatment: “trading one substance for...

Documents