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transcript
Buprenorphine in the treatment of addiction
Matthew A. Torrington MDClinical Research Physician
UCLA: Integrated Substance Abuse ProgramsMatrix Institute on Addictions
Addiction Medicine ClinicNovember 4, 2004
Scope of this Talk
• What are we talking about? Addiction then buprenorphine….
• Buprenorphine: For the treatment of opioid dependence
• Buprenorphine: As an analgesic• Buprenorphine: On the horizon
AAPainMed,APainS, ASAMdefined ADDICTON in 2001
• Addiction is a primary, chronic, neurobiologic
disease, with genetic, psychosocial, and
environmental factors influencing its
development and manifestations. It is
characterized by behaviors that include one
or more of the following: impaired control
over drug use, compulsive use, continued use
despite harm, and craving
• Savage et al., 2001
DSM 4 criteria for opiate abuse
• Significant impairment or distress resulting
from use
• Failure to fulfill roles at work, home, or school
• Persistent use in physically hazardous
situations
• Recurrent legal problems related to use
• Continued use despite interpersonal problems
DSM 4 criteria for Opiate Depend.≥ 3 of the following occurring in the same 12- month period
1. Desire or unsuccessful efforts to cut down on opiate use
2. Large amount of time spent obtaining opiates, using opiates, or recovering from opiate effects
3. Social, occupational, or recreational activities reduced because of opiate use
4. Opiate use continued despite knowledge that a physical or psychological problem is being caused or exacerbated by use
5. Tolerance
• Need for increased amounts of opiates to achieve desired effect; or
• Diminished effect with continued use of the same amount of opiate– Tolerance develops normally with repeated
use– Tolerance to sedating effect develops quickly– Tolerance to respiratory depression can be
marked
6. Withdrawal
withdrawal syndrome with cessation of use, reduction of use, or use of opiate antagonist
Opiates or related
substance taken to relieve or avoid withdrawal symptoms
Pseudoaddiction
• operationally defined as aberrant drug-related behaviors that make patients with chronic pain look like addicts.
• these behaviors stop if opioid doses are increased and pain improves (Weissman and Haddox, 1989).
• This indicates that the aberrant drug-related behaviors were actually a search for relief
• Little data on the subject, but evidence in rats
Magnitude of the Problem
• There are ~ 1,110 licensed OTPs in the U.S.
• ~225,000 patients in methadone treatment• 800,000+ persons addicted to heroin• 4.7 million prescription opioid users• First time users are on the increase
Treatment Admissions
Schematic of Opiate Receptor
Source: Goodman and Gillman 9th ed, p. 526
Effect of Common Opiates at mu receptor
• Heroin, morphine,
methadone
• Buprenorphine
• Naltrexone (Revia, Vixo)
• Naloxone (Narcan)
• Nalmefene
Agonist
Partial Agonist
Antagonist
Receptor Binding at Mu receptor
Agonist:Opens door
Partial Agonist
Opens door with
safety chain
Antagonists
Dummy key
Morphine like effect
Weak morphine like effects with strong receptor affinity
• No effect in absence of an opiate or opiate dependence
Buprenorphine
Buprenorphine pharmacology contd.
• “Less bounce to the ounce”
• Ceiling effect on respiratory depression
• Less physical dependence capacity
• Blocks withdrawal in mildly dependent people
• Precipitates withdrawal in moderate to severely dependent people
Good Effect
0
20
40
60
80
100
p 0.5 2 8 16 32
Buprenorphine (mg)
Peak Score
3.75 15 60
Methadone (mg)
Respiration
02468
1012141618
p 1 2 4 8 16 32
Buprenorphine (mg)
Breaths/minute
Intensity of abstinence
60
50
40
30
20
10
0
Him
mel
sbac
h s
core
s
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Buprenorphine
Morphine
Days after drug withdrawal
Buprenorphine for Opiate Dependence:
• Suppresses withdrawal• Substitutes for street opiates• Blocks subsequently administered
opiates• Safety in long term use
Overview to theDrug Addiction Treatment Act
of 2000 – An Amendment
to the Controlled Substances Act
(October, 2000)
Narcotic drug:
Approved by the FDA for use in maintenance or detoxification treatment of opioid dependence
Schedule III, IV, or V
Drugs or combinations of drugs
Amended Controlled Substances Act
Practitioner requirements:“Qualifying physician”Has capacity to refer patients for
appropriate counseling and ancillary services
No more than 30 patients (individual or group practice)
Amended Controlled Substances Act
“Qualifying physician”:
A licensed physician who meets one or more of the following:
1. Board certified in Addiction Psychiatry
2. Certified in Addiction Medicine by ASAM
3. Certified in Addiction Medicine by AOA
4. Investigator in buprenorphine clinical trials
Amended Controlled Substances Act
“Qualifying physician” (continued):
Meets one or more of the following:
5. Has completed 8 hours training provided by ASAM, AAAP, AMA, AOA, APA (or other organizations which may be designated by HHS)
6. Training/experience as determined by state medical licensing board
7. Other criteria established through regulation by the Secretary of Health and Human Services
Amended Controlled Substances Act
Buprenorphine: Potent Analgesic
• 20-50 times potency of morphine• Available worldwide for pain treatment• Injectable formulation available in U.S.• Usual analgesic dose: .2-.4 mg sl• Higher dose for opiate dependence
Buprenorphine and Pain
• Animal data don’t predict human data• Good potent analgesic• No ceiling effect or inverted U curve• Mild CVS effect, mild G-I effect• Limited dependence, slow mild
withdrawal• Ceiling on respiratory depression • Analgesia not compromised by ceiling.• Effective for long term use mos. to yrs.
Buprenorphine: Analgesic Profile
Rapid onset of action
Long duration of peak effect (60-120 min)
Long half life (3.5 hrs)
Analgesic action up to 8 hrs.
Ceiling effect on respiratory depression
Low physical dependence profile
Buprenorphine – Clinical Analgesic Use
• Surgical pain– Intra-operative, peri-operative, post-
operative
• Labor pain• Back pain• Phantom pain• Post-herpetic neuralgia• Cancer pain
Buprenorphine for Pain
• Good for trans-dermal application– Lipophilic– High level analgesia– Low adverse effects
• Patch – Consistent delivery, desirable time course– Flexible dosing and compliance
Myths about buprenorphine and pain
• Partial agonist, limited clinical effects• Not reversible by naloxone• Can’t be given after other opioids.• Reality
• High affinity, mod intrinsic activity, slow dissociation from mu, highly lipophilic
Treating Acute pain in buprenorphine patients
• Keep on buprenorphine– Increase buprenorphine dose– Add high potency opioid—fentanyl– Add or switch to methadone (Caution)
• Regional analgesia• PCA• Non-opioids
Treating Chronic pain in buprenorphine patients
• Keep on sublingual buprenorphine• Consider buprenorphine patches (when
available) • Switch to morphine• Switch to methadone (CAUTION)• Use opioid rotation• High potency opioids for “break thru” pain• Non-opioid analgesics• Adjunct medications and local anesthetics• Non-pharmacological treatments
Issues on the horizon:
• Buprenorphine access: 30 pt rule, inability of NTPs to use buprenorphine, cost
• Buprenorphine abuse liability• Studies underway:
– Bup 3, CTN, outpatient detox schedules