Transcript Treatment options for the Opioid Dependent Patient

Buprenorphine in the
treatment of addiction
Matthew A. Torrington MD
Clinical Research Physician
UCLA: Integrated Substance Abuse Programs
Matrix Institute on Addictions
Addiction Medicine Clinic
November 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, ASAM
defined 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
Pseudoaddiction
• operationally defined as aberrant drugrelated 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.
Effect of Common Opiates at mu receptor
• Heroin, morphine,
Agonist
methadone
• Buprenorphine
Partial Agonist
• Naltrexone (Revia, Vixo)
• Naloxone (Narcan)
• Nalmefene
Antagonist
Receptor Binding at Mu receptor
Agonist:Opens door
Morphine like effect
Partial Agonist
Opens door with
safety chain
Antagonists
Dummy key
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
100
Peak Score
80
60
40
20
0
p
0.5
2
8
16
Buprenorphine (mg)
32
3.75
15
Methadone (mg)
60
Breaths/minute
Respiration
18
16
14
12
10
8
6
4
2
0
p
1
2
4
Buprenorphine (mg)
8
16
32
Intensity of abstinence
Buprenorphine
Himmelsbach scores
60
Morphine
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
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 the
Drug Addiction Treatment Act
of 2000 –
An Amendment
to the Controlled Substances
Act
(October, 2000)
Amended Controlled Substances Act
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
Buprenorphine: Potent Analgesic
•
•
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•
•
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, postoperative
•
•
•
•
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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