Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician...
-
Upload
joanna-flowers -
Category
Documents
-
view
221 -
download
2
Transcript of Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician...
![Page 1: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/1.jpg)
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
![Page 2: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/2.jpg)
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
![Page 3: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/3.jpg)
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
![Page 4: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/4.jpg)
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
![Page 5: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/5.jpg)
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
![Page 6: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/6.jpg)
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
![Page 7: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/7.jpg)
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
![Page 8: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/8.jpg)
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
![Page 9: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/9.jpg)
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
![Page 10: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/10.jpg)
Treatment Admissions
![Page 11: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/11.jpg)
Schematic of Opiate Receptor
Source: Goodman and Gillman 9th ed, p. 526
![Page 12: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/12.jpg)
Effect of Common Opiates at mu receptor
• Heroin, morphine,
methadone
• Buprenorphine
• Naltrexone (Revia, Vixo)
• Naloxone (Narcan)
• Nalmefene
Agonist
Partial Agonist
Antagonist
![Page 13: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/13.jpg)
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
![Page 14: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/14.jpg)
Buprenorphine
![Page 15: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/15.jpg)
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
![Page 16: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/16.jpg)
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)
![Page 17: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/17.jpg)
Respiration
02468
1012141618
p 1 2 4 8 16 32
Buprenorphine (mg)
Breaths/minute
![Page 18: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/18.jpg)
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
![Page 19: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/19.jpg)
Buprenorphine for Opiate Dependence:
• Suppresses withdrawal• Substitutes for street opiates• Blocks subsequently administered
opiates• Safety in long term use
![Page 20: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/20.jpg)
Overview to theDrug Addiction Treatment Act
of 2000 – An Amendment
to the Controlled Substances Act
(October, 2000)
![Page 21: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/21.jpg)
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
![Page 22: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/22.jpg)
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
![Page 23: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/23.jpg)
“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
![Page 24: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/24.jpg)
“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
![Page 25: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/25.jpg)
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
![Page 26: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/26.jpg)
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.
![Page 27: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/27.jpg)
![Page 28: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/28.jpg)
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
![Page 29: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/29.jpg)
Buprenorphine – Clinical Analgesic Use
• Surgical pain– Intra-operative, peri-operative, post-
operative
• Labor pain• Back pain• Phantom pain• Post-herpetic neuralgia• Cancer pain
![Page 30: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/30.jpg)
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
![Page 31: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/31.jpg)
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
![Page 32: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/32.jpg)
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
![Page 33: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/33.jpg)
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
![Page 34: Buprenorphine in the treatment of addiction Matthew A. Torrington MD Clinical Research Physician UCLA: Integrated Substance Abuse Programs Matrix Institute.](https://reader036.fdocuments.us/reader036/viewer/2022081513/56649e175503460f94b0345a/html5/thumbnails/34.jpg)
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