# Presentation: 235027

## Buprenorphine{Suboxone®, Subutex®}

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

## Available Medications for Treatment of Heroin Addiction

**Agonists****	****	****	****Opiate Analgesics****	****	****	****	****Methadone **
**	****	****	****	****	****LAAM**
**Partial Agonists ****	****Buprenorphine**
**Antagonists****	****	****Naloxone (short-acting)****	****	****	****	****Naltrexone  (long-acting****)**

## 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

## 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

**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

## 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

## 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)

## Opiate Potency of Methadone, LAAM, and Buprenorphine

**100**
**90**
**80**
**70**
**60**
**50**
**40**
**30**
**20**
**10**
**0**

**-10             -9             -8             -7             -6             -5             -4**

**%**
**Efficacy**

**Log Dose of Opioid**

**Full Agonist**
**(Methadone)**

**Partial Agonist**
**(Buprenorphine**

**Antagonist**
**(Naloxone)**

**Opiate Potency of Methadone, LAAM, and Buprenorphine**
*Slide courtesy of Laura McNicholas, MD, PhD, Univ of Penn.*

## How good is buprenorphine as a 

- treatment for opiate addiction??

## 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

## 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,

## Buprenorphine, Methadone, LAAM:Urine Testing for Opioids

- Mean % Negative

- Study Week

**All Subjects**

**Lo Methadone**

**Buprenorphine**

**Hi Methadone**

**LAAM**

**1**

**3**

**5**

**7**

**9**

**11**

**13**

**15**

**17**

**0**

**20**

**40**

**60**

**80**

- 100

- 19%

- 40%

- 39%

**49%**

*Adapted from Johnson, et al., 2000*

## Opioid Agonist Medications

- Rolley Johnson et al., NEJM, 343(18):1290-1297, 2000

**90% Reduction in Heroin Use**

## Buprenorphine Blockade of Hydromorphone Opiate Effects

**Buprenorphine Dose (mg/day)**

**Change in**
**Total Score**
**(post-HYD**
***minus***
**Post-BUP****)**

*Slide Courtesy of Laura MacNicholas, MD, PhD*

## 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**

## Buprenorphine Summary

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