Buprenorphine in the treatment of addiction

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Treatment Admissions
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Schematic of Opiate Receptor
Source Goodman and Gillman 9th ed, p. 526
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Effect of Common Opiates at mu receptor

• Heroin, morphine, methadone
• Buprenorphine
• Naltrexone (Revia, Vixo)
• Naloxone (Narcan)
• Nalmefene

• Agonist
• Partial Agonist
• Antagonist

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Receptor Binding at Mu receptor

• Morphine like effect
• Weak morphine like effects with strong receptor
  affinity
• No effect in absence of an opiate or opiate
  dependence

• AgonistOpens door
• Partial Agonist
• Opens door with safety chain
• Antagonists
• Dummy key

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Buprenorphine
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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

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Good Effect
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Respiration
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Intensity of abstinence
Buprenorphine Morphine
60 50 40 30 20 10 0
Himmelsbach scores
Days after drug withdrawal
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Buprenorphine for Opiate Dependence

• Suppresses withdrawal
• Substitutes for street opiates
• Blocks subsequently administered opiates
• Safety in long term use

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Overview to theDrug Addiction Treatment Act of
2000 An Amendmentto the Controlled Substances
Act(October, 2000)
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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

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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)

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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

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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

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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

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Buprenorphine and Pain

• Animal data dont 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.

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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

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Buprenorphine Clinical Analgesic Use

• Surgical pain
• Intra-operative, peri-operative, post-operative
• Labor pain
• Back pain
• Phantom pain
• Post-herpetic neuralgia
• Cancer pain

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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

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Myths about buprenorphine and pain

• Partial agonist, limited clinical effects
• Not reversible by naloxone
• Cant be given after other opioids.
• Reality
• High affinity, mod intrinsic activity, slow
  dissociation from mu, highly lipophilic

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Treating Acute pain in buprenorphine patients

• Keep on buprenorphine
• Increase buprenorphine dose
• Add high potency opioidfentanyl
• Add or switch to methadone (Caution)
• Regional analgesia
• PCA
• Non-opioids

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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

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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