Buprenorphine Suboxone,Subutex

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Buprenorphine(Suboxone,Subutex)

• Ken Roy, MD, FASAM
• Addiction Recovery Resources of New Orleans
• River Oaks Hospital
• Tulane Department of Psychiatry
• www.arrno.org
• kenroymd_at_bellsouth.net

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The Problem Opioid Abuse in US

• Data is available from different sources
• Drug Abuse Warning Network (DAWN)
• Treatment Episode Data Set (TEDS)
• National Survey on Drug Use and Health, formerly
  the National Household Survey on Drug Abuse
• Wealth of information
• Illicit drug abuse (heroin, cocaine)
• Prescription drug abuse (diazepam, oxycodone,
  hydrocodone)
• Patterns of drug abuse in different populations
• Compare rural and metropolitan areas

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Prescription Analgesics Non-Medical Use

• Use of a medication other than as prescribed
  taking it more often or a higher dose than
  prescribed, taking someone elses prescription,
  taking it for a purpose other pain relief
• Taking an opioid for euphoria or relief of
  depression
• Taking a higher dose escalating dose

SAMHSA NSDUH 2002
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Prescription Analgesics Non-Medical Use

• 30 million persons (13), used prescription
  analgesics non-medically at least once in their
  lifetime
• First time users Increased from 600,000 (1990)
  to 2 million (2002)
• 2002 1.5 million abuse or dependency
  prescription pain relievers

SAMHSA NSDUH 2002
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Rates of lifetime non-medical use of prescription
analgesics

• Rates of lifetime oxycodone abuse increased
  significantly from 2002 to 2003 while heroin
  rates are stable
• 1.9 million had used only heroin at least once in
  their lifetime
• 11 million had used oxycodone non medically at
  least once in their lifetime
• 1.7 million had used both in their lifetime at
  least once

SAMHSA NSDUH 2002, 2003
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TEDS Rural vs Urban

• Admissions for treatment of narcotic painkillers
• 155 increase from 1992-2002
• Greatest increase in rural areas (269), smallest
  in large central metro areas (58)
• 15 fall in admissions for injection users
• Increase in rural inhalant abuse from 2-12

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Medications in Opioid Dependence Treatment

• Detoxification
• Also rapid detoxification and initiation of
  Naltrexone
• Maintenance

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Buprenorphine is a Partial Agonist
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Detoxification

• Use a drug with a long half-life and low abuse
  potential
• Use a drug that is smoothly eliminated
• Replace the abused drug with the detox drug
• Initiate drug free treatment
• Taper the detox drug

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Maintenance Therapy

• Prevents withdrawal
• Diminishes drug craving
• Blocks or attenuates the effects of heroin and
  other abused opiates
• Increases retention rates in treatment
• NOT A CURE - enables participation in a
  comprehensive program of rehabilitation

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What Medications Are Available

• Methadone
• ORLAAM
• Naltrexone
• Buprenorphine

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Methadone Maintenance Treatment

• As part of a comprehensive rehabilitation program
  methadone maintenance has been shown to
• Decrease illicit opiate use
• Normalizes immune and endocrine systems
• Decrease criminal activities
• Increase pro-social activities

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Naltrexone

• Not very useful alone
• Useful adjunct to drug-free treatment
• Can provide a period of abstinence while
  treatment and recovery begin
• Can be part of supervised recovery
• Depot preparation eminent

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Clinical Trials of Buprenorphine

• Comparisons with Methadone
• Johnson et al. (1992) n162
• BUP 8 mg vs. METH 20 mg vs. METH 60 mg
  
• Strain et al. (1994) n164
• BUP 8 mg vs. METH 50 mg for 26 weeks
  
• Ling et al. (1996) n225
• BUP 8 mg vs. METH 30 mg vs. METH 80 mg for 52
  weeks,

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Buprenorphine, Methadone, LAAMOpioid Urine
Results
100
All Subjects
80
LAAM
49
60
Bup
40
Hi Meth
Mean Negative
40
39
Lo Meth
20
19
0
1
3
5
7
9
11
13
15
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Study Week
Adapted from Johnson, et al., 2000
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Full Agonist (Methadone) Partial
Agonist (Buprenorphine), Antagonist (Naloxone)
100 90 80 70 60 50 40 30 20 10 0
Full Agonist (Methadone)
Efficacy
Partial Agonist (Buprenorphine
Antagonist (Naloxone)
-10 -9 -8 -7
-6 -5 -4
Log Dose of Opioid
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Detoxification With Buprenorphine

• Now, rational detoxification is possible
• Some will tolerate rapid detoxification (one to
  two weeks)
• Some will require stabilization prior to
  detoxification
• Buprenorphine is a great detoxification medication

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Maintenance With Buprenorphine

• Partial agonist
• Binds to and activates receptor, but increasing
  dose only results in partial activation
• More competitively bound than almost all mu
  receptor drugs
• Blocks Heroin
• Induces detox in Heroin/Methadone patient unless
  they are already sick

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Maintenance With Buprenorphine

• Because of firm binding to receptor is literally
  metabolized from the site
• Detoxification symptoms are much more tolerable
• Patients may become involved in treatment, NA and
  Recovery and simply drop off into continued
  Recovery

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Buprenorphine Pharmacology

• High affinity for Mu opiate receptor
• Most competitive of opiates
• Blocks effects of other opiates
• Slow dissociation from Mu receptor
• Literally metabolized from the receptor
• Prolonged protection from craving
• Little detoxification from Buprenorphine

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Effects of Buprenorphine Dose on µ-Opioid
Receptor Availability in a Representative Subject
MRI
Bup 0 mg
Binding Potential (Bmax/Kd)
Bup 2 mg
4 -
Bup 16 mg
Bup 32 mg
0 -
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Buprenorphine Summary

• Partial Mu opiate agonist
• Antagonist properties
• Less risk of respiratory depression
• Lower innate risk of physical dependence
• Available compounded with Naloxone