Buprenorphine {Suboxone

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BuprenorphineSuboxone, Subutex

• Herbert D. Kleber, M.D.
• Professor of Psychiatry, Columbia University
  College of Physicians Surgeons
• Director, Division on Substance Abuse, NYSPI

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Available Medications for Treatment of Heroin
Addiction

• Agonists Opiate Analgesics Methadone
• LAAM
• Partial Agonists Buprenorphine
• Antagonists Naloxone (short-acting) Naltrexon
  e (long-acting)

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How Does Buprenorphine Work?

• High Affinity for Mu Opioid Receptor
• Competes with other opioids and blocks their
  effects
• Displaces heroin or other opiates from
  receptors(This can produce withdrawal if patient
  has opiates in system)
• Slow Dissociation from Mu Opioid Receptor
• Prolonged therapeutic effect
• gt 24 hours
• Ceiling Effect on Opiate Effects
• Poor drug for intoxication purposes
• Safer in an overdose
• Formulated with Naloxone
• Naloxone is poorly absorbed if taken orally
• Naloxone blocks opiate effects if injected

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• Agonist
• Heroin, Morphine, Codeine, Methadone, LAAM
• Mild-moderate binding to mu receptors
• Short-acting Powerful opiate high
• Long-acting Weak opiate high
• Partial Agonist
• Buprenorphine
• Strong and long binding to mu receptors
• But Relatively weak opiate effect
• Antagonist
• Naloxone, Naltrexone
• Strong binding to mu receptors but does not
  activate them
• Thus, blocks all opiates with no opiate effects

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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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Why Not Use Blockers?

• Naltrexone
• High non-compliance rates
• Early gastrointestinal discomfort
• Possible dysphoric effects
• No opiate effect benefits
• Useful only in highly selected, highly
  leveraged, patient populations (i.e., doctors
  nurses)

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Opiate Potency of Methadone, LAAM, and
Buprenorphine Slide courtesy of Laura McNicholas,
MD, PhD, Univ of Penn.
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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How good is buprenorphine as a treatment for
opiate addiction??
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Clinical Uses of Buprenorphine

• Withdrawal Detoxification
• Maintenance
• Prevents withdrawal
• Diminishes craving
• Does not produce a high
• Blocks (or reduces effect of) heroin
• Increases treatment retention

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Comparison TrialsBUP vs. 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, LAAMUrine Testing for
Opioids
100
All Subjects
80
LAAM
Buprenorphine
60
49
40
Hi Methadone
Mean Negative
40
39
Lo Methadone
20
19
0
1
3
5
7
9
11
13
15
17
Study Week
Adapted from Johnson, et al., 2000
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Opioid Agonist Medications
Rolley Johnson et al., NEJM, 343(18)1290-1297,
2000
90 Reduction in Heroin Use
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Buprenorphine Blockade of Hydromorphone Opiate
Effects
Change in Total Score (post-HYD minus Post-BUP)
Buprenorphine Dose (mg/day)
Slide Courtesy of Laura MacNicholas, MD, PhD
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Buprenorphine Summary

• A Partial Mu-Opioid Agonist
• As effective as Methadone or LAAM
• Lower level of physical dependence
• Lower risk of respiratory depression
• Abusable, but the combination with naloxone
  (opiate blocker) reduces diversion to street

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Buprenorphine Summary

• WELL ACCEPTED MAINTENANCE THERAPY
• MILD WITHDRAWAL
• DECREASES OPIOID USE
• GREATER SAFETY
• LOWER DIVERSION POTENTIAL