1. Buprenorphine {Suboxone®, Subutex®}
Herbert D. Kleber, M.D.
Professor of Psychiatry, Columbia University College of Physicians & Surgeons
Director, Division on Substance Abuse, NYSPI

2. Available Medications for Treatment of Heroin Addiction
Agonists Opiate Analgesics Methadone
LAAM
Partial Agonists Buprenorphine
Antagonists Naloxone (short-acting) Naltrexone (long-acting)

3. 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
> 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

4. Agonist Partial Agonist Antagonist
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

5. 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

6. 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)

7. 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
Full Agonist
(Methadone) %
Efficacy
Partial Agonist
(Buprenorphine
Antagonist
(Naloxone)
Log Dose of Opioid

8. How good is buprenorphine as a treatment for opiate addiction??

9. 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

10. Comparison Trials: BUP vs. Methadone
Johnson et al. (1992) n=162
BUP 8 mg vs. METH 20 mg vs. METH 60 mg
Strain et al. (1994) n=164
BUP 8 mg vs. METH 50 mg for 26 weeks
Ling et al. (1996) n=225
BUP 8 mg vs. METH 30 mg vs. METH 80 mg for 52 weeks,

11. Buprenorphine, Methadone, LAAM: Urine Testing for Opioids
100
All Subjects 80
LAAM 60
Buprenorphine
49%
40%
Hi Methadone
Mean % Negative 40
39%
Lo Methadone 20
19% 1 3 5 7 9 11 13 15 17
Study Week
Adapted from Johnson, et al., 2000

12. Opioid Agonist Medications
Rolley Johnson et al., NEJM, 343(18): , 2000
90% Reduction in Heroin Use

13. Buprenorphine Blockade of Hydromorphone Opiate Effects32 16 2 4 6 8 10 12 14 18
Change in
Total Score
(post-HYD
minus
Post-BUP)
Buprenorphine Dose (mg/day)
Slide Courtesy of Laura MacNicholas, MD, PhD

14. 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

15. Buprenorphine Summary
WELL ACCEPTED MAINTENANCE THERAPY
MILD WITHDRAWAL
DECREASES OPIOID USE
GREATER SAFETY
LOWER DIVERSION POTENTIAL