Buprenorphine Module Psychopharmacology of Addictions

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Buprenorphine ModulePsychopharmacology of
Addictions

• Kevin Kunz, M.D., M.P.H., FASAM
• Western Regional Conference of the Federation of
  State Physician Health Programs
• October 8, 2005

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Molecules Spirit

• Molecules
• we are a stack of matter interacting with
  other matter
• -- special software necessary
• Spirit Spirituality
• Relationship with self
• Relationship with others
• Relationship with the powers of universe
  whatever we conceive these to be

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Opioid Categories

• Agonist Relieve pain and alter mood
• Natural opium, morphine, codeine
• Semi-syn. hydrocodone, oxycodone, heroin
• Synthetic fentanyl, meperidine, methadone
• Antagonists Displace agonist/block receptor
• Naloxone, naltrexone
• Mixed Opioid Agonist and antagonist actions
• Butorphanol (Stadol), Pentazocine (Talwin),
  buprenorphine (Buprenex, Suboxone,Subutex)

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Opioid Agonists
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Increase in Poisoning Deaths Caused by
Non-Illicit Drugs --- Utah, 1991--2003MMWR,
1/21/05

• Figure 3

Figure 3
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Chronic Pain among Chemical Dependent
PatientsRosenblum et al., JAMA, May 14, 2003
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Opioid Withdrawal

• Acute
• Autonomic
• Rebound increased NE activity from locus
  coeruleus
• Increase BP, HR, peristalsis, diaphoresis, CNS
  irritability, etc.
• Affective
• Suppressed in the dopaminergic reward pathways
• Depression, anxiety, anhedonia, craving, anergia
• Protracted
• 3-6 months or longer, dopaminergic pathways
• Anxiety, insomnia, craving, cyclic changes in
  wgt, pupil size

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Acute Opioid Withdrawal

• 5-7 days in length
• Runny nose, sneezing,
• sweating, yawning,
• restless, insomnia
• Piloerection, twitching,
• myalgia, arthralgia,
• abdominal cramps
• Tachycardia,fever,
• hypertension,tachypnea,
• anorexia, diarrhea,
• vomiting, dehydration

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Protracted Opioid Withdrawal

• Anergia
• Ahedonia
• Sleep disturbance
• Emotional lability/dysphoria
• Stress incompetence
• Craving (for relief)
• Can persist for months

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Opioids Decrease D2 Receptors
Source Wang, G-J et al., Neuropsychopharmacology,
16(2), pp. 174-182, 1997.
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Opioid Withdrawal Options

• 1. Taper by 50 every several days
• Transition to longer acting analgesic
  (propoxyphene, methadone) and taper
• Symptomatic Rx
• Buprenorphine safe, easy, effective
• Rapid Opioid Detox, UROD

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Bup Diss curve
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Buprenorphine

• Analgesic with 20 years world wide use
• NIDA/Industry Orphan drug in US
• moderate to severe pain
• High activity bupmorphine 130 (IV/IM)
• Temgesic sublingual, IM/IV, transdermal
• Treatment for opioid dependence, addiction
• world wide use 10 years, 3 years in US
• Excellent safety profile

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Buprenorphine

• High affinity, low dissociation
• Displaces/blocks other opioids, long duration of
  action
• Partial agonist at mu receptor (MS is full
  agonist)
• Ceiling effect (increase dose effect peaks)
• Low abuse, diversion potential
• Pain dose .2 - .4 mg SL q 6 hours
• Addiction dose 2 8mg q.d.
• Off-label/controversial pain use in US
• NIDA study underway

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Bup US History

• Buprenex available for decades for pain
• FDA/CSAT/Legislative DATA 2000
• Can use schedule III drugs to Rx addiction
• FDA 2002 approves Bup and Bup combined with
  naloxone
• DEA 2002 moves Bup, Bup/Nlx to Schedule III,
  MDs will need DEA waiver
• 2005 4,500 physicians have waiver, 3,000Rxing
• Majority are psychiatrists, next Internists and
  FPs
• 106,000 patients induced on Bup for dependence

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Bup Drug Interactions

• P450 3A4 Inhibitors
• Azole antifungals, macrolides, protease
  inhibitors
• Such as.Biaxin, Nizoral, Ritonavir
• P450 3A4 Inducers
• Phenobarbital
• Carbemazepine, phentoin
• Rifampicin
• Sedatives
• Benzodiazepines
• For pain patients, eliminate or minimize stable
  pre-bup dose

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Office-Based Treatment for Opioid Addiction
Achieving GoalsJAMA, August 17, 2005 Vol 294,
No. 7, p784-786

• Safe
• Effective
• Minimal Diversion
• Hundreds of the physicians who have responded to
  our survey have said that the medication has been
  an absolute life-saver for many of their
  patients.
• Caroline McLeod, PhD
• Evaluation Project Manager, SAMHSA

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Bup Patient Series

• Practice setting Kona, Hawaii
• Practice Mix 30 addiction, 25 pain, 45
  primary care
• All pain or addiction patients referred
• Outpatient practice with immediately available
  access to hospitalization, counseling, drug
  rehab, medical specialists
• MD credentialed in addiction pain management

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108 Consecutive Bup Patients

• Addiction patients 64
• Pain patients 44
• Pain and Addiction 10
• Insurance Mix 75 commercial insurance
• The data on this series of pts. is preliminary

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64 Addiction Bup Patients

• M 46 F 18 Age 19-66
• Heroin 30 Prescription Rx 16 IDU 24
• Psychiatric Co-morbidity 50 initally
• Using other illicit drugs 50 initially
• Status
• 26 detoxed (70 still clean)
• 42 left care (16 relapse, 4 jail, 2 move, 2 ?,
  1 killed)
• 31 still on Bup, from 2 weeks to 2 ½ years
• None using controlled or illicit drugs
• All employed
• 25 with co-morbid psych Rx

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20 Current Pain/Bup Patients
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All Current Bup Patients

• Gender equal at about 50/50
• Psych Co-morbidity equal at 25
• Satisfaction equally high
• Adverse effects equally low
• Function equally improved
• Employment, family, spirit, life equally
  improved and acceptable to Pt and MD

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Bup Ideal patient

• Treatment seeking wants off mu opioids
• Opioid dependent, no other substance issues
• No acute medical conditions
• No untreated Axis II Disorders
• Transaminases less than 3X normal
• Willing to enter and persevere with substance
  abuse treatment ( addiction pts)
• PCP delegates/co-manages pain/addiction
• Must able to follow instructions
• Manageable environmental stressors

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Molecules Spirit

• Molecules
• we are a stack of matter interacting with
  other matter
• Spirit Spirituality
• Relationship with self
• Relationship with others
• Relationship with the powers of universe
  whatever we conceive these to be

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Buprenorphine Waiver/Training

• Waiver eligible
• Physicians Boarded in Addiction Psychiatry
• ASAM Certified physicians
• Physicians involved in Bup clinical trials
• Training
• 8 hours of CSAT approved CME
• www.ASAM.org, hhtp//buprenorphine.samsha.gov/
• Online courses available