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  • 1.  
  • 2. “We must all die. But that I can spare a person from days of torture, that is what I feel is my great and ever new privilege. Pain is a more terrible lord over mankind than even death itself.” Albert Schweitzer 1953
  • 3. Pain and Addiction: Common Etiologies, Co-Morbidities and Treatment Kevin Kunz, M.D., FASAM Kona Community Hospital November 7, 2005
  • 4. 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
  • 5. Overview of Today’s Talk
    • Definitions - Morphing
    • Shared Bio-Psycho-Social Features
    • Epidemic of Prescription Drug Abuse
    • Shared Treatment Approaches
    • Opioids, Buprenorphine
    • Treatment Strategies
      • - Molecules and Spirit
  • 6. Webster Defines Pain
    • “ a sensation of hurting or a strong discomfort caused by injury or disease or dysfunctional disorder and transmitted through the nervous system.”
    • Webster’s New World Dictionary
  • 7. IASP Defines Pain
    • “ an unpleasant sensory and emotional experience associated with actual or threatened tissue damage, or described in terms of such.”
    • International Association for the Study of Pain
  • 8. Hospice Defines Pain
    • “ Pain can be timeless, endless, meaningless, (and) bring a sense of isolation and despair.”
    • Cicely Saunders, M.D. Founder of Hospice
  • 9. Addiction
    • A primary, chronic, neurobiologic disease, with genetic, psychosocial and environmental factors influencing its development and manifestations. Characterized by behaviors that include one or more of the following: impaired control over drug use; compulsive use; continued use despite harm; and craving. APS, ASAM, AAPM
    • Addiction is a brain disease, expressed as behaviors. NIDA
  • 10. Chronic Pain or Addiction?
    • Primary, chronic neuobiologic disease
    • Genetic, psychosocial, environmental factors influencing its development, physical and behavioral manifestations
    • Caused by an actual or perceived injury, disease or dysfunctional disorder
    • Leading to unpleasant, uncomfortable, hurting, emotions and sensations
    • It is often timeless, endless and meaningless, engendering isolation and despair.
    • Core issues of control, pre-occupation, consequences, craving/relief
  • 11. More Definitions
    • Misuse Use leads to impairment/distress
    • Abuse A maladaptive pattern of substance use
    • Therapeutic Dependence
      • Physically dependence but pt. not seeking psychic effects as misusers, abusers, addict
    • Pseudo-addiction
    • Pre-occupation with obtaining meds reflects need to control pain or withdrawal
    • Tolerance
    • increased dosage to maintain effect
  • 12. Definition: Dependence
    • DSM IV criteria (need 3 in one year)
      • Tolerance
      • Withdrawal (“within minutes to several days”)
      • Larger amounts/longer period… than intended
      • Inability to/persistent desire to cut down, control
      • Social, occupational, recreation reduced, given up
      • Continued desire to use opioids despite adverse consequences
    • Using to avoid unpleasant feelings caused by stopping
    • Profound and enduring changes in neurocircuitry
  • 13.
    • Dependence is a chronic relapsing medical condition.
    • And for the record…
    • Addiction is a chronic
    • relapsing medical condition.
  • 14. Dependence or Addiction?
    • Physical dependence is a normal physiologic response to the medical use of opioids
    • Addiction involves the non-medical use of opioids (and other molecules), and a constellation of abnormal behaviors.
    • Addiction is psychological dependence
    • Addiction does not equal dependence
    • DSM IV: no such thing as addiction
    • “ you can be dependent without being addicted and you can be addicted without being dependent”
  • 15. Term Merge
    • Non-medical use
    • Misuse
    • Inadvertent use
    • Abuse
    • Therapeutic Dependence
    • Current use
    • Lifetime use
    • “ Habit”
    • Problem Use
    • Illicit use
    • Licit use
    • Addiction
    • Pseudo-addiction
    • Comfort use
    • Innocent use
    • “ Doesn’t meet criteria”
    • Medical use
    • Dependence
  • 16. Common Etiologies
    • Environmental, trauma
    • Psychological
    • Genetic
    • Social
    • Neurophysiologic
  • 17. Host, agent. Environment
  • 18. Set genetics, age,sex, expectations, motivations, medical status, past history Setting Drug and/orPain An idiosyncratic response will occur when a susceptible person is drug or pain exposed
  • 19. Commonalities: Spectrum of Disease
    • Pain
    • mild, intermittent…….severe, intractable
    • Dependence
    • mild, intermittent…….severe, intractable
  • 20. Common Components
    • PAIN
    • Sensory
    • Emotional
    • Cognitive
    • ADDICTION/
    • DEPENDENCE
    • Sensory
    • Emotional
    • Cognitive
  • 21. Common Vulnerability
    • Genetically vulnerable
          • Drug addiction 60/40
          • Pain ?
    • Vulnerable by history
          • Past problems/consequences with any drugs,chronic pain
          • Present problems with any drug (even nicotine), pain
          • Family history of substance abuse, chronic pain
          • Family history of mental health issues?
    • Mental Health Co-morbidity
          • Untreated mood disorders (i.e.anxiety, depression, PTSD) PDs
          • Psychosocial, Environmental Problems (Axis IV)
          • GAF: Global Assessment of Functioning (Axis V)
  • 22.  
  • 23. C ommon Maladaptive Behaviors
    • Loss of c ontrol (over drug use, or pain)
            • Toxic at important family events, external locus of control
            • Unable to take pain medications as directed
    • C ontinuing preoccupation (with drug use, or pain)
            • Works side job to pay for marijuana, cocaine
            • Seeks new cures, hopeful of cure, seeks extra meds, victim script
    • Adverse c onsequences (of drug use, or pain)
          • Declining function despite “stable” drug use
          • Declining function despite analgesia
          • All spheres of life decaying, patient can’t discern
    • C raving
          • For relief
  • 24. Common Biology
    • Neurophysiologic
    • common brain pathways
    • common neurotransmitter systems
    • common perturbations in neural circuitry and neurohormones
  • 25. Mesolimbic Dopamine System
    • Circuit #1
      • Relief/Like
        • Pleasure/Pain circuit
          • Meso-accumbens
    • Circuit #2
      • Repeat/Want
        • Desire and urge circuit
          • Basolateral n. of amygdala
    • Circuit #3
      • Need
        • Pathologic desire & demand circuit
          • Periaqueducal gray of brain stem
  • 26. Mesolimbic Dopamine System Modulates:
    • Tolerance
    • Withdrawal
    • Craving
    • Self-administration
  • 27. Pain Reinforcement
    • Opioids stimulate dopamine release
    • Produce euphoria, and a sense of comfort in most people
    • Opioid use thus reinforcing, opioids are freely self-administered by most animal species
    • Learned association between opioid taking and pain relief, which could perpetuate pain in the absence of opioid administration
    • The experience of chronic pain is complex, shaped by a variety of cognitive, behavioral, psychological and other variables, all of which can be modulated with opioids neurophysiologically
  • 28. More Commonalities
    • Both are diseases, not volitional states
    • Patients can become powerless to eliminate their pain or their drug problem
    • Both groups must eventually relinquish the quest for a cure
    • Both must accept responsibility and be empowered to do what is necessary to recover
  • 29. Common Co-Morbidities
    • Anxiety Disorder ( 3 of 6)
        • Restless/on edge
        • Fatigue
        • Difficulty concentrating
        • Irritable
        • Muscle tension
        • Sleep disturbance
    • Depression (5 of 9)
        • Depressed mood
        • Diminished interest or pleasure
        • Insomnia or hypersomnia
        • Psychomotor agitation or retardation
        • Fatigue /loss of energy
        • Diminished ability to think/concentrate / indecisiveness
        • Thoughts of death
    • Insomnia
    • PTSD, Functional Disability, Medical Illnesses, Relationships, Occupation, Recreation, Self-identity, SA, Pain
  • 30. Common Treatments
    • Non-pharmacologic
      • Education, relaxation, individual & family therapy, biofeedback, cognitive behavioral therapy, Rx mood disorder, distraction, accupuncture, active movement, CAM, etc.
    • Interventional
      • “ Intervention” – procedures/surgery
    • Medications
  • 31. Common Molecules
    • Opioids
    • Sedative-Hypnotics
    • Stimulants
    • Anti-depressants, anti-anxiety agents
    • Anti-seizure medications
    • Adjunctives
    • OTC, Current Fad Drug, Hot Rx Drug
  • 32. Commonalities: Licit and Illicit Drugs
    • Psychoactive potential
    • Reinforcement potential
        • Decrease negative symptoms
      • Increase positive symptoms
    • Tolerance and withdrawal potential
  • 33. Impending Disasters?
    • Opioids
    • Benzodiazepines
      • including Ambien, Sonata, Lunesta
    • Barbiturates
      • Including Soma, Fioricet
    • Stimulants
      • Including Adderal, Ritalin, etc.
  • 34. How significant a problem is prescription drug abuse today? A Major Problem!
  • 35. How Many Americans Have a Drug “Problem”?
    • Nicotine 20-30 %
    • Marijuana 14 %
    • Alcohol 6-12 %
    • Opioids ?
    • Any illicit drug 8 %
    • Prescription drugs 3 %
    • Perspective: 45% take a RX qd; there are >150,000 OTCs;
    • 1965: 300 Rx drugs 2005: 9,000 Rx drugs (RxList.com)
  • 36. Generation Rx
    • 18% of teens have abused Vicodin
    • 20% tried Ritalin or Adderall without Rx
    • 9% abused OTC cough syrup to get high
    • Equal or greater abuse of OTC/Rx than cocaine, Ecstasy, LSD, ketamine, heroin, GHB, ice
    • Rx Meds safer (50%), less addictive (33%)
    • Ease of access: medicine cabinets
    • “ Drugs are fun” vs “Drugs help kids when they are having a hard time”
    • Rx/OTC med abuse has penetrated teen culture
    • April 21, 2005. Partnership for a Drug Free America. 17 th annual study of teen drug abuse. N= 7,300, error margin +/- 1.5%
  • 37. Why Has the Abuse of Prescription Drugs Been Increasing?
    • Pain and DSM relief
    • Production and availability increased
    • Marketing and media attention
    • Molecular factors
    • User characteristics
    • Physician factors
  • 38. Increased Production DEA Quotas, 1990-2000
    • Morphine + 300%
    • Hydrocodone + 500%
    • Hydromorphone + 600%
    • Oxycodone + 1200%
    • Fentanyl + 1700%
  • 39.
    • Hydrocodone 84M
    • Lipitor 69M $6.7B
    • Synthroid 49M
    • Norvasc 36M
    • Zoloft 33M $2.9B
    • (Others in the top 130: Xanax, Ambien, Ativan, Klonipin, Soma
    • Valium, oxycodone, Oxycontin , Darvocet, Ultracet, Concerta, Adderal)
    Drug 2003 # Rx Revenue
  • 40. Rx Opioids In Hawaii (Source: K. Kamita, Chief, NED, State of Hawaii. 11/7/03)
    • Drug
    • APAP/hydrocodone
    • Tussionex
    • Endocet
    • OxyContin
    • Morphine sulfate
    • Methadone
    • Prescriptions
    • 2,310,398
    • 564,258
    • 561,658
    • 506,408
    • 335,502
    • 326,446
  • 41. Physician Factors
    • Dated
    • Duped
    • Disabled
    • Dishonest
    • Medication Mania
  • 42. Confused Physicians…
    • “ The use of narcotics in terminal cases is to be condemned…undesirable side effects. Dominant on the list of these unfortunate effects is addiction.”
      • AMA Consensus Paper, 1940
    • Physicians told not to fear discipline for pain treatment
    • amednews.com 6/16/03
  • 43. Medication Mania
    • Societal phenomenon, perception of safety
    • High efficacy of certain meds
    • Patient expectation, pressure to prescribe
    • Difficult access, payment for non-pharm Rx
  • 44. Who’s Fault?
    • Physicians?
    • Pharmaceutical Industry?
    • Society & Culture?
    • Consumer/Patient?
  • 45. Molecular Factors
    • .
  • 46.  
  • 47. .morphine molecule
    • .
  • 48. Buprenorphine
  • 49. Opioids can increase pain!
    • 30+%, of patients feel better after withdrawal from chronic opioids
    • Can cause hyperalgesia, allodynia
    • Prolonged use increases expression of dynorphin, associated with increased pain sensitivity
  • 50.
      • “ Recent studies have shown that continuous opioid exposure produces exaggerated pain and, importantly, such pain occurs while the opioid is continuously present in the system”
    • Vanderah, et al., Pain 92:5-9, 2001
  • 51.
    • Strong Opioid consensus
      • Use aggressively for severe acute pain
      • Use aggressively for terminal pain (cancer, AIDS)
      • Trial for severe CNMP
    • Weak or no Opioid consensus
      • Use in less well-defined syndromes (CRPS, PPS,)
      • Use in pain syndromes with moderate pain and complex psychosocial components ( FM, LBP)
  • 52. 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
        • Anxiety, insomnia, craving, cyclic changes in wgt, pupil size
  • 53. Acute Opioid Withdrawal
    • 5-7 days in length
    • R unny nose, sneezing,
      • sweating, yawning,
      • restless, insomnia
      • Piloerection, twitching,
      • myalgia, arthralgia,
      • abdominal cramps
      • Tachycardia,fever,
      • hypertension,tachypnea,
      • anorexia, diarrhea,
      • vomiting, dehydration
  • 54. Protracted Opioid Withdrawal (and/or Chronic Pain?)
    • Anergia
    • Anhedonia
    • Sleep disturbance
    • Emotional lability/dysphoria
    • Stress incompetence
    • Craving (for relief)
    • Can persist for months
  • 55. Source: Wang, G-J et al., Neuropsychopharmacology, 16(2), pp. 174-182, 1997. Opioids Decrease D2 Receptors
  • 56. Detox vs. Medical Withdrawal
    • Detoxification:
      • A term referring to the return of alcoholics and addicts to a drug free state with or without medical supervision
    • Medical Withdrawal:
      • Is the medically supervised process of safely and comfortably taking a dependant person off controlled medications
  • 57. 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
  • 58. Opioid Categories
    • Agonist: Relieve pain and alter mood
        • Natural: opium, morphine, codeine
        • Semi-syn.: hydrocodone, oxycodone, heroin
        • Synthetic: fentanyl, meperidine, methadone
    • Antagonist: Displace agonist/block receptor
        • Naloxone, naltrexone
    • Mixed/Partial: Agonist and antagonist actions
        • Butorphanol (Stadol), Pentazocine (Talwin), buprenorphine (Buprenex, Suboxone,Subutex)
  • 59. Bup Diss curve
  • 60. Buprenorphine
    • Analgesic with 20 years world wide use
      • NIDA/Industry Orphan drug in US
      • Moderate to severe pain
      • High activity; bup:morphine 1:30/40 (IV/IM)
      • Temgesic sublingual, IM/IV, transdermal
    • Rx for opioid withdrawal/maintenance
      • First evidence of efficacy in dependence: 1978
      • world wide use 10 years, 3 years in US
    • Excellent safety profile
  • 61. 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
  • 62. “ Office-Based Treatment for Opioid Addiction Achieving Goals” JAMA, 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
  • 63. 0 10 20 30 40 50 60 70 80 90 100 2 mg 16 mg 32 mg Dose % Receptor Occupancy Source: Greenwald, MK et al, Neuropsychopharmacology 28, 2000-2009, 2003. 27 to 47% 85 to 92% 94 to 98% μ Effects of Buprenorphine Dose on - Opioid Receptor Availability
  • 64. 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
  • 65. 108 Consecutive Bup Patients
    • Addiction patients: 64
    • Pain patients: 44
    • Pain and Addiction: 10
    • Current patients 20 addiction, 25 pain
      • Induced, but not all currently in KK practice
    • Insurance Mix: 75% commercial insurance
    • The data on this series of pts. is preliminary
  • 66. 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
  • 67. 44 Pain Bup Patients
    • Detoxed: 10
          • Were taking no other illicit/controlled drugs
          • Length of detox: 4-8 weeks
          • Return to opiates: 1
          • Co-occurring psych disorder: 4
    • Terminated Bup Induction: 4
          • All taking other controlled drugs (Ambien, Soma, Ritalin)
          • All had unstable medical conditions
          • All returned to mu opioid agonists
    • Co-Morbid Pain and Addiction: 10
          • Detoxed 3, 2 returned to mu opioids, 5 current
    • Pain Only, Current: 20
    • Overall rotation/succesful detox: 76%
  • 68. 20 Current Pain Bup Patients (Pain and Addiction Pts. Omitted)
    • F 11, M 9 Age 32 –88
    • Length on mu opioids: 3-25 years
    • Length on Bup: 2 weeks – 2 ½ years
    • Procedures for pain 17/20
    • Surgery for pain 12/20
    • Criteria for Bup: dependence, request transfer from mu opioid secondary to insurance, adverse effects, inadequate pain relief, unable or unwilling to detox off all opioids
    • Buprenorphine dose range: 2–32 mg/d, 10mg ave
  • 69. 20 Current Pain/Bup Patients 25% 40% Psych Co-Morbid 25% (Ambien 2, Soma 1, BNZ 2) 70% Controlled Rx (non-opioid) 5% 70% Adverse Effects (moderate to significant) 90% 50% Function (acceptable) 90% 50% Pain Control (adequate) After Bup Before Bup Measure
  • 70. The French Patient n= 749
    • Means
        • age: 33; duration on Bup: 11 months
        • Mean dose: 11mg/day
    • Daily dose – 56%; split dose 43%
    • AE: 4% IV Bup: 8%
    • Improvements
      • Relationships: 95%
      • Physical activity: 77%
      • Life habits: 94%
      • Employment: 74%
      • The French Experience. European Addiction Research. 4 S1 98, Oct. 1998, pp. 19-23
  • 71. 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
  • 72. 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
  • 73. OPIOID THERAPY FOR CHRONIC PAIN ?
    • “… evidence now suggests that prolonged, high-dose opioid therapy may be neither safe nor effective.It is therefore important that physician’s make every effort to control indiscriminate prescribing, even when they are under pressure by patients to increase the dose of opioids.”
    • BALLANTYNE & MAO, NEJM, 349:1943-53, 2003
  • 74. New Paradigm
    • “ I just minimized or dismissed the issues …of abuse, addiction and diversion…
    • … ten years later, and we recognize that was a big error..we need to talk about the use of opioids and other prescription drugs from the perspective of two skill sets…how to prescribe, but at the same time, (doctors) have to have a skill set in addiction medicine, how to assess the risk of abuse and diversion and addiction…or they shouldn’t use them.”
    • Dr. Russell Portenoy, ABC National Radio 12/5/04
  • 75. Bup: Downside
    • 30 patient limit
    • High acuity patients, office must gear-up
    • Drug interactions (3A4)
    • Patients will also need non-pharmacologic treatments
    • Insurance coverage not yet universal
    • Diversion?
    • Still new “Use it while it works”
  • 76. 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