Opioids for Chronic NonCancer Pain

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Opioids for ChronicNon-Cancer Pain

• Bennet E. Davis, M.D.
• Integrative Pain Center of Arizona
• Adjunct Professor Colleges of Pharmacy and
  Education
• University of Arizona

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Definitions

• Chronic Pain Chronic pain is a state in which
  pain persists beyond the usual course of an acute
  disease or healing of an injury, or that may or
  may not be associated with an acute or chronic
  pathologic process that causes continuous or
  intermittent pain over months or years.

From AZ Medical Board Guidelines and FSMB Model
Guidelines
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Do Opioids Work on a chronic basis?

• YES
• Often enough

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But is toxicity or risk of addiction great enough
that the risk/benefit is too high?

• NO

5
Is the risk to the prescriber too great to
justify prescribing of Opioids on a chronic
basis?

• NO

• Provided
• The physician understands risk management and
• Regulatory agencies support use of opioids for
  legitimate medical purposes and
• Health plans support needed behavioral
  consultation
• Whats left to be done Medical board reform
  clarity on standard of care templates for
  documentation, consensus guidelines
  re-integration of behavioral health services into
  main stream primary care

6
Is chronic opioid management reimbursed
commensurate with the time it takes? (Relative to
other all undereimbursed EM services)

• NO!
• Documentation
• Monitoring
• Patient education
• Tracking down backup resources
• Additional training
• Whats left to be done Needs a unique CPT code

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Opioids and Chronic PainWhy do we struggle?

• Cultural attitudes toward pain No pain, no gain
  
• Cultural attitudes toward opioids Just say no
• The facts are not out
• Efficacy
• Addiction
• Side effects and toxicity
• Discomfort Provider fear of regulators play it
  safe
• Discomfort Pain is difficult to objectify How
  do I know when my patient is better
• Prescribing opioids is extra work, its a lost
  leader

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Opioids in Chronic Pain

• Efficacy

• Addiction, Drug tolerance, and drug dependence
• Regulation
• Adverse effects of treatment
• Common mistakes
• Specific drugs

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Opioids and Chronic PainEarly Views

• Not beneficial in reducing pain
• Increased disability
• Increased psychological distress
• Interfered with physical rehabilitation
• High incidence of substance abuse

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Opioids and Chronic PainThe Cancer Pain
Experience

• Large international body of literature
• Opioids used at high doses for long periods
• 80-85 of patients achieved adequate pain control
• Function improved with opioid treatment
• Side effects usually treatable
• Tolerance not a frequent problem
• Addiction disorders uncommon

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Opioids in ChronicNon-Cancer Pain

• Randomize double-blind, crossover, morphine
  versus active placebo
• 46 patients with musculoskeletal pain
• Patients had failed first-line medications and
  codeine
• Reduction of pain with morphine
• No cognitive deterioration with morphine
• No addictive behaviors
• Moulin, D.E., Lancet 1996 347143-47

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Opioids in ChronicNon-Cancer Pain

• Open label design
• 100 patients with variety of pain syndromes
• Failed first-time medication
• 51 good pain relief
• 28 partial pain relief
• Improvement in measures of function
• No severe side effects leading to discontinuation
  of therapy
• Zenz, Journal of Pain and Symptom Management,
  1992 767-77

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Opioids in ChronicNon-Cancer Pain

• 38 patients in a retrospective review
• Variety of pain syndromes
• 63 acceptable pain relief
• No tolerance
• 2 management problems - both had prior history of
  drug abuse
• Portenoy, R., Chronic Use of Opioid Analgesics in
• Non-Malignant Pain Report of 38 Cases, Pain,
  Vol. 25,
• Pgs. 171-86, 1986

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Efficacy of Opioidsfor Chronic Pain

• Outcome data for cancer pain (W.H.O.)
• Small sized prospective and other studies
• Responsiveness of different pain syndromes
• - Neuropathic pain, mixed syndromes Zenz 1992
• - 50 of patients with good pain relief
• Post-herpetic neuralgia Pappagallo 1994
• Rowbotham 1991
• - Phantom limb pain Urban 1986
• - Sustained release oxycodone in PHN Watson 1998
  Neurology
• - Sustained release opioids vs. TCA for PHN in
  elderly 2002 Opioids produced better pain relief
  and less side effects

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Opioids in Chronic Pain

• Efficacy
• Addiction, Drug dependence and Tolerance
• Regulation
• Adverse effects of treatment
• Common mistakes
• Specific drugs

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Key issues surrounding addiction

• Learning to navigate the lack of clarity in the
  terminology
• Knowing how to make the diagnosis of addiction
• Knowing what to do when addiction is recognized

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Terminology

• Physical Dependence
• - The capacity to withdraw
• Addiction Psychological Dependence
• Tolerance
• -Increasing dose required to maintain clinical
  effect

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Addiction

• DSM IV - substance abuse and substance
  dependence
• Diagnostic criteria are convenient, but
• Not applicable to persons with chronic pain
• Influential in shaping beliefs and policy,
  nevertheless
• Addiction in Pain Patients - a behavioral
  diagnosis
• No universally accepted formal diagnostic
  criteria exist as yet
• There is poor support for primary care in
  obtaining help in this area

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Addiction making the diagnosis

• Look for a pattern of behavior that becomes
  obvious over time, and which is characterized by
• Compulsive use
• Loss of control
• Craving
• Use despite harm

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Addiction making the diagnosis - Behaviors

• Rapid dose escalation
• Drug hoarding
• Multiple sourcing
• Misrepresentation of dose
• Frequent losing/stolen of prescriptions
• Changing route of administration
• Drug preferences (especially for short acting
  drugs), multiple allergies
• Ill pay cash
• Altering prescriptions

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A Differential Diagnosis for Dose Escalation I
innocent causes

• Pharmacodynamic Tolerance - a right shift of the
  dose response curve
• Pharmacokinetic tolerance
• Psychological tolerance
• - Conditioned pain behavior
• - Increased distress
• - Altered pain perception
• Increased pain stimulus

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A Differential Diagnosis for Dose Escalation II

• Psychological dependence
• Diversion

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Differential Diagnosisfor other worrisome
behaviors

• Pseudoaddiction
• Confusion about drug regimen
• Co-existing psychopathology
• Psychological dependence
• Diversion

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Risk ofPsychological Dependence

• Early studies (high risk populations)
• Boston Collaborative Drug Surveillance Project
• - 4/11,8882
  Porter 1980
• Survey of headache centers
• - 3/2,369
  Medina 1977
• Survey of low back pain patients
• - family practice clinic
• - no increased incidence of substance abuse
• disorders
  Brown 1996

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Risk ofPsychological Dependence

• Survey of 12 primary care clinics in Wisconsin
  6 - Adams NJ 2001
• Pain clinics 3-20
• Aronoff GM. Opioids in chronic pain management
  is there a significant risk of addiction? Curr
  Rev Pain. 2000411221.

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Addiction in the patient with chronic
painIdentifying Risk Factors prospectively

• Prior history of psychological dependence
• Prescription drugs
• Street drugs
• Alcohol
• Chaotic social situation
• Importance of situational factors
• Family history
• Character pathology
• Misuse of health care system

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Addiction in the patient with chronic
painIdentifying Risk Factors prospectivelyOpioi
d Risk Tool ORT

• 5 questions that stratify patients into low,
  medium and high risk for aberrant behaviors
• Pain Med 2005 6(6)432-442.

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Monitoring for psychological dependence and
diversion

• Track average daily consumption of medication
• Compare to expected, intended dose
• Monitor for aberrant behaviors
• Urine screens
• Periodic calls to pharmacy or other physicians
• Pill counts
• Do not handle the medications
• Have a witness present, make this clinic policy
• Family members

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Urine screening

• Why?
• To make sure your patient is taking the
  prescribed drug
• To see if your patient is using illicit drugs
• Many labs will not give you oxycodone, fentanyl,
  and some others.
• Always specify what you are looking for!
• Be aware of the legitimate substances that cause
  positive results in amphetamine screens GCMS
• Is a heroic effort to prevent fraud necessary?
• Depends on your patient population.

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Urine screening

• Diversion is likely, psychological dependence
  (substance abuse disorder) is certain, if the
  patient turns up GCMS positive for
• Methamphetamine
• Cocaine metabolite (benzoylecgonine)
• Treat the substance abuse disorder, meaning
  dont prescribe and try to get the patient to a
  treatment unit.

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Urine screening

• How often do urine screens turn up negative
  for the drug you are prescribing, or positive for
  illicit street drugs?
• 15 typical practice
• Higher in some areas

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Urine screening

• When a patient isnt responding to opioid as
  the dose is escalated
• CHECK TO SEE IF THE DRUG IS THERE!

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What to do when aberrantdrug-related behaviors
reach the critical point (your exit strategy)

• Document what, and document your plan
• Get the patients version in writing
• Consult pain specialist to help in their
  assessment (tell your consultant your concerns)
• Detox, start over
• DO NOT continue prescribing if you strongly
  suspect active substance abuse disorder
• Weekly or even Daily dosing alternative
  treatments

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What to do when aberrantdrug-related behaviors
reach the critical point 2

• If you must discontinue medication
• Taper off (if you do not feel there is active
  substance abuse). This may involve a
  prescription for a taper.
• Taper is not detox. Prescribing for a taper
  because you want to stop the medication is OK -
  as long as you are not detoxing the patient.
• Document the absence of substance
  abuse/dependence.
• Discontinue now if you feel there is active abuse

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What to do when aberrantdrug-related behaviors
reach the critical point 3

• If you must discontinue medication
  abruptly
• Document why and document communication
• Communicate to the patient
• The need for detox
• Where to go for detox
• Offer palliative treatment for withdrawl symptoms
• Antiemetics
• Beta blocker
• Clonidine
• Council to report to ER if cannot tolerate fluids
  for a long period of time

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Opioids in Chronic Pain

• Efficacy
• Addiction, Drug tolerance, and drug dependence
• Adverse effects of treatment
• Common mistakes
• Specific drugs

• Regulation

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Regulation of Prescribing Opioid Medications

• Federal law
• State law and regulation
• State regulatory agencies

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Regulation of Prescribing Opioid Medications for
PainThe fundamental conflict

• The Regulatory imperative
• Never prescribe when opioids are inappropriate
• The Therapeutic imperative
• Always prescribe when opioids are appropriate

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Regulation of Prescribing Opioid Medications for
Pain Federal

• Controlled Substances Act - 1914
• - Recognizes the use of opioids in chronic pain
  as legitimate medical practice
• - Provides that the Federal definition of
  addict does NOT apply to pain patients
• - Places no restriction on prescribing
• DEA monitoring of sales to vendors
• - Do not follow up on medical practice issues

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Regulation of Prescribing Opioid Medications for
PainFederal

• Require that medications be written for
  legitimate medical purposes
• Do not post-date prescriptions
• Avoid the word refill in your documentation for
  CII, its not legal to a refill CII.
• Methadone include the phrase for pain on
  prescriptions
• May write multiple fill on or after
  prescriptions for CII drugs after Dec 17, 2007
  for up to 3 30 day prescriptions, at one time.
• Title 21 CFR 1306.14

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Regulation of Prescribing Opioid Medications for
PainState

• Statute all states have statutory regs that
• Constitute State Controlled Substances Acts
• Govern practice of Medicine, Pharmacy, and
  Nursing
• Set up regulatory bodies Medical Boards,
  Pharmacy Boards
• And which MAY establish Prescription Monitoring
  Programs- Recently established by Statute in AZ,
  under Pharmacy Board
• Intractable pain acts none in AZ

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Regulation of Prescribing Opioid Medications for
PainState

• Statute
• CSA Title 36 Chapter 27 in AZ
  http//www.pharmacy.state.az.us/controlledsubstanc
  es.html
• These often contain vague, confusing language
  true of Title 36 in AZ

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AZ Statute confusion of terminology Drug
dependence (this confusion is not reflected in
AMB guidelines)
ARS 36-2501 5. drug dependent person means a
person who is using a controlled substance and
who is in a state of psychic or physical
dependence, or both, arising from the use of that
substance on a continuous basis. Drug dependence
is characterized by behavior and other responses
which include a strong compulsion to take the
substance on a continuing basis in order to
experience its psychic effects or to avoid the
discomfort caused by its absence.
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Regulation of Prescribing Opioid Medications for
PainState

• Statute Prescription Monitoring
  Programs-Recently established by Statute in AZ,
  under Pharmacy Board Title 36 Chapter 28
• Directs the AZ Board of Pharmacy to establishes a
  computerized data base to track Schedule 2, 3,
  and 4 prescriptions
• Will require those possessing a Federal license
  to write prescriptions for controlled substances
  to acquire (but not pay for pay for) a state
  registration.
• Will Provide information to patients, medical
  practitioners and pharmacists to help avoid the
  inappropriate use of schedule II, III and IV
  controlled substances.

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Regulation ofOpioid MedicationsState

• Medical Board
• Defines appropriate prescribing practice
• Public health mission
• Arizona guidelines disseminated 1998, revised
  2004 http//www.azmd.gov/pain_management/Guideline
  s.pdf

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Regulation ofOpioid MedicationsAZ med Board
guidelines

• Assessment
• History
• Corroboration of history
• Psychosocial assessment
• Patient education 4 elements
• Patient understands diagnosis, therapy, risks,
  and goals
• Physical exam of painful area
• Urine drug screens used where appropriate
• Use consultation where appropriate

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Regulation ofOpioid MedicationsAZ Medical Board

• Opioid therapy not an end in itself - Document
  that alternatives have been considered
• Document discussion of treatment goals and risks
  with patient
• Document history and exam and rationale for
  opioid use
• Document benefit and presence or absence of
  adverse effects and aberrant behavior

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Regulation ofOpioid MedicationsAZ Medical
Board FAQ http//www.azmd.gov/Pain_Management/FA
Qs20Pain20Management.pdf

• Do the Guidelines for Treatment of Chronic Pain
  mandate frequent office visits, opioid
  agreements, specialist consultation and/or urine
  drug screens when prescribing opioids for chronic
  non-malignant pain? No. Although a clinician may
  choose to use one or more of these tools at
  his/her discretion, none of these are mandated in
  the Guidelines for routine use when prescribing
  opioids for chronic pain.
• Are there cases in which frequent office visits,
  opioid agreements, specialist consultation and/or
  urine drug screens are strongly indicated when
  prescribing opioids for chronic pain? Yes. As
  with many medical problems in addition to chronic
  pain (for example diabetes, coronary artery
  disease, seizure disorder, etc), a patient with
  poorly controlled symptoms, history of
  non-compliance with medications, and/or at high
  risk for medication-related complications may
  require closer monitoring, more frequent office
  visits, specialist consultations

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Opioids in Chronic Pain

• Efficacy
• Addiction, Drug tolerance, and drug dependence
• Regulation
• Common mistakes
• Specific drugs

• Adverse effects

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Side Effects

• Tolerance to side effects much greater than
• to analgesia - nausea, pruritis, sedation,
  urinary
• retention
• Constipation - routine motility agent plus
• stool softener
• Side effect profile varies - change medications
• Increase in small increments

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Neuropsychological Impairment

• Early studies
• - Patients on multiple medications
• - Studies of addict population
• Studies in cancer pain population

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Neuropsychological Impairment

• 24 non-cancer pain patients on a stable dose of
  long-acting oral morphine (average 209 mg/day)
• Multiple tests of vigilance, reaction time,
• division of attention and concentration
• No difference from a matched cohort not
• taking opioid medications
• Vanio A. Lancet 1995 346, 667-70

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Neuropsychological Impairment

• Compared non-cancer pain patients receiving
  stable intermittent short-acting dose of opioid
  to those who underwent dose increase
• Found increased somnolence and
• deterioration in cognitive and fine motor
• testing in dose increase group- resolved in 2
  weeks
• 
  Bruera Pain, 1989 3913-16

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Neuropsychological Impairment

• 18 patients on 40-140 mg/d morphine
• 10 controls with non-cancer pain
• Neuropsychological testing done at 3, 6, 12
  months
• No difference between groups except
• Improved memory in morphine treated patients
• Tassain V Pain 2003 104 386-400

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Side Effectsfinal comment

• Opioids are non-toxic, so
• Does the WHO analgesic ladder make sense for
  chronic non-cancer pain?
• NSAIDs over opioids?

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Opioids in Chronic PainCommon mistakes

• No exit strategy
• Expectations for success not managed
• Dose escalated too quickly
• Opioids used to treat anxiety or depression
• Absence of clear endpoint for titration
• Inadequate patient education
• Inadequate documentation

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Analgesic effect
Overall analgesia
Algesic effect
1-8 weeks?
Dose increase
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Titration to functional improvement

• Initially it is ok to increase the dose
  frequently
• Later, wait at least 1 month in between dose
  increases
• Consider using the Brief Pain Inventory or
  similar tool
• Look for lack of sustained improvement in
  function from last dose increase, over at least 1
  month this means you are at max effective dose.
  Dont increase further!!!
• Do not increase the dose unless improvement has
  been sustained, or clear-cut progression of the
  patient's disease

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Patient Education

• Treatment goals
• 50 decrease in pain would be great, all you can
  ask of an opioid
• A discussion of functional goals
• Physical vs. psychological dependence
• Tolerance
• Side effect management
• Constipation
• Sedation, nausea are likely to be temporary
• Patient responsibilities
• Discuss the exit strategy Conditions under which
  the doctor will stop opioids

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36 y.o. secretary with back pain following
fusion, surgeon says no further treatment needed.
Unremarkable history otherwise. Non-focal neuro
exam.Sleep quality is poor, missing 4-10 days
of work a month, collapses on the couch after
work and needs to rest most of her days
off.Meds vicodin 5/500 90/month (helps, no
side effects), nabumetone 750 BID
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You decide to offer ATC Opioid as part of the
pain treatment plan Getting started

• Assessment Screen for risk factors, esp
  psychosocial factors (ORT)
• Goals
• It will NOT take all the pain away.
• Arrive at specific goals for treatment, or when
  will we stop increasing the dose? (function
  function function)
• Discuss the exit strategy, or This is a 2-way
  street of trust, and there are circumstances
  under which I would stop prescribingthey are
  outlined in your opioid agreement.
• Educate side effect management, driving,
  physical dependence
• Have the patient sign your opioid agreement /
  informed consent
• Treat any coexisting depression and anxiety

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Follow up

• Start low and give the patient an initial range
  if they can handle this
• Ex MS Contin 15 at bedtime, may increase to 30,
  HS, and may add 15 mg in the am before I see you
  next.
• Reassess function each visit, use patient
  specific treatment goals.
• Assess side effects each visit (use a check list)
• Wait until after the honeymoon period to assess
  results of a dose increase.
• STOP titration when no further improvement in
  function occurs with an increase.
• Spot urine screen 2 x yr
• How often to see in clinic?

See info point
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36 y.o. secretary with back pain following
fusion, surgeon says no further treatment needed.
Unremarkable history otherwise except she
endorses depressive symptoms and many affective
pain descriptors. Non-focal neuro exam. Mildly
distressed.Protected movement, lots of
grimacing, jumps with light palpation of back.
Sleep quality is poor, missing 4-10 days of work
a month, collapses on the couch after work and
needs to rest most of her days off.Meds 180 mg
Oxycodone SR t.i.d., Percocet 5/325 2 every 4
hrs, neurontin 300 t.i.d.
OR Your departed partners patient, first visit
with you
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• Treat depression and anxiety first
• Set specific functional goals, orient treatment
  to these. You may find this is very difficult!
• Educate Opioids will NOT take all the pain
  away, and it looks like you may have reached the
  maximal effective dose (long ago). Increases
  from your current daily dose will not help in the
  long run!
• Get a urine screen at the first visit

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Three options for the medication management

• Taper opioid to the point where function
  deteriorates
• Switch to an alternate opioid at lower dose
  (better acceptance, maybe)
• Wean off (consider inpatient program)
• start over with a different opioid or not.