pain management and addiction west coast symposium on addictive disorders la quinta, ca june 3, 2011...
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Pain Management and Addiction
West Coast Symposium on Addictive Disorders
La Quinta, CAJune 3, 2011
Stephen A. Wyatt, D.O.Middlesex Hospital
Middletown, CT
OutlineOutline
Case Presentation - PLCase Presentation - PL
• 57 M,C,♂57 M,C,♂• Alcohol related Alcohol related
injure at 25 injure at 25 resulting in a hip resulting in a hip replacement.replacement.
• Injury to his back Injury to his back at 32 resulting in at 32 resulting in disability. Onset of disability. Onset of prescribed opiatesprescribed opiates
• Remained on Remained on disabilitydisability
• Hospitalized 11-08 Hospitalized 11-08 d/t to Klonopin odd/t to Klonopin od
• Vicodin Vicodin (acetaminophen (acetaminophen 500mg, 500mg, Hydrocodone 5mg) Hydrocodone 5mg) #7 / 6 times a day.#7 / 6 times a day.
• Suggested long Suggested long acting opioidacting opioid
Case Presentation - PLCase Presentation - PL
• Came for consultation 3/09 Oxycontin 60mg #5
4 time a day
Prevalence of Recurrent and Persistent Pain in the US
• 1 in 4 Americans suffer from recurrent pain (day-long bout of pain/month)
• 1 in 10 Americans report having persistent pain of at least one year’s duration
• 1 in 5 individuals over the age of 65 report pain persisting for more than 24 hours in the preceding month
– 6 in 10 report pain persisting > 1 year
• 2 out of 3 US armed forces veterans report having persistent pain attributable to military service
– 1 in 10 take prescription medicine to manage pain
American Pain Foundation. http://www.painfoundation.org. Accessed March 2010.
The Problem of PainThe Problem of Pain Costs US economy Costs US economy
estimated estimated $100 billion/year$100 billion/year HealthcareHealthcare Welfare & disability Welfare & disability
paymentspayments Lost tax revenue Lost tax revenue Lost productivity Lost productivity
(work absence)(work absence) 40 million physician 40 million physician
visits annuallyvisits annually Most common reason Most common reason
for medical for medical appointmentsappointments
Push toward opioid Push toward opioid maintenance therapy in maintenance therapy in non malignant painnon malignant pain
National Institutes of Health. New Directions in Pain Research. Sept 1998. PA-98-102.
Pain StandardsPain Standards
• JCAHO – Installs a Quality Standard on JCAHO – Installs a Quality Standard on pain identification. (2001)pain identification. (2001)
• Strong encouragement to increase the Strong encouragement to increase the identification and treatment of pain.identification and treatment of pain.
• The development of new and very The development of new and very effective opiates for the treatment of effective opiates for the treatment of pain.pain.
• The tremendous rise in the prescription The tremendous rise in the prescription of opiates for non-cancer pain.of opiates for non-cancer pain.
Trend data: Distribution of Trend data: Distribution of prescription opioids, U.S., 2000–prescription opioids, U.S., 2000–
20072007Source: DEA, ARCOS system, 2007Source: DEA, ARCOS system, 2007
GR
AM
S P
ER
10
0K
PO
PU
LA
TIO
N
* Includes OTPs
Deaths per 100,000 related to Deaths per 100,000 related to unintentional overdose and annual unintentional overdose and annual
sales of sales of prescription opioids by year, 1990 - prescription opioids by year, 1990 -
2006 2006 Source: Paulozzi, CDC, Congressional testimony, 2007Source: Paulozzi, CDC, Congressional testimony, 2007
0
1
2
3
4
5
6
7
8
'90
'91
'92
'93
'94
'95
'96
'97
'98
'99
'00
'01
'02
'03
'04
'05
'06
Cru
de
ra
te p
er
10
0,0
00
0
100
200
300
400
500
600
Sa
les
in m
g/p
ers
on
Deaths per 100,000
Opioid sales (mg perperson)
Unintentional drug overdose deaths Unintentional drug overdose deaths are rising faster for prescription opioids are rising faster for prescription opioids
than for illicit drugsthan for illicit drugs Source: CDC, National Vital Statistics System, 2006Source: CDC, National Vital Statistics System, 2006
0
1000
2000
3000
4000
5000
6000
7000
8000
'99 '00 '01 '02 '03 '04
Year
Nu
mb
er o
f d
eath
s
Prescription opioid
Cocaine
Heroin
New Illicit Drug Use United States, 2006
PCP†Pain Relievers*
Tranquilizers
Cocaine
Ecstasy LSD†
Marijuana
Inhalants
Stimulants
Sedatives Heroin
6991264267
783845860977
1,112
2,0632,150
0
500
1,000
1,500
2,000
2,500
New
Use
rs (
thou
san
ds)
Substance Abuse and Mental Health Services Administration, Office of Applied Studies. 2006 National Survey on Drug Use and Health. Department of Health and Human Services Publication No. SMA 07-4293; 2007.
*533,000 new nonmedical users of oxycodone aged ≥ 12 years. Past year initiates for specific illicit drugs among people aged ≥ 12 years.†LSD, lysergic acid diethylamide; PCP, phencyclidine.
Medical Use
• Pain patients seeking more pain relief
• Pain patients escaping emotional pain
Who Misuses/Abuses Opioids and Why?
Nonmedical
Use• Recreational
abusers
• Patients with disease of addiction
Total Chronic Pain Population
Aberrant Medication Use Behaviors:
A spectrum of patient behaviors that may reflect misuse
40%
Prescription Drug Misuse20%
AddictionAbuse/Dependence
2-5%
Adapted from Passik. APS Resident Course, 2007
Where Pain Relievers Were Where Pain Relievers Were ObtainedObtained Most Recent Nonmedical Most Recent Nonmedical Use among Past Year Users Aged 12 or Use among Past Year Users Aged 12 or
Older: 2006Older: 2006
Note: Totals may not sum to 100% because of rounding or because suppressed estimates are not shown.1 The Other category includes the sources: “Wrote Fake Prescription,” “Stole from Doctor’s
Office/Clinic/Hospital/Pharmacy,” and “Some Other Way.”
Bought/Took from Friend/Relative
14.8%
Drug Dealer/Stranger
3.9%
Bought on Internet
0.1% Other 1
4.9%
Free from Friend/Relative
7.3%
Bought/Took fromFriend/Relative
4.9%
OneDoctor80.7%
Drug Dealer/Stranger
1.6%Other 1
2.2%
Source Where Respondent Obtained
Source Where Friend/Relative Obtained
One Doctor19.1%
More than One Doctor
1.6%
Free from Friend/Relative
55.7%
More than One Doctor3.3%
““Doctors are easy to find Doctors are easy to find and they don’t carry guns” and they don’t carry guns”
Medical EconomicsMedical Economics
““To stop Rx diversion, To stop Rx diversion, the agency (DEA) has the agency (DEA) has hired hundreds of hired hundreds of new investigators and new investigators and expanded it’s local expanded it’s local and state task forces”and state task forces”
““Quantity alone…may Quantity alone…may indicated diversion indicated diversion and trigger an and trigger an investigation”investigation”
In 1872, California passed the first anti-opium law. The administration of laudunum, an opium preparation, or any other narcotic constituted a felony. In 1881, the California was it a misdemeanor to maintain a place where opium was made available.
Private use was not covered by the legislation. Same year, California became the first state to establish a separate bureau to enforce narcotic laws, and one of the first states to treat addicts.
Connecticut, in 1874, established the narcotic addict was incompetent to attend to his personal affairs.
The law required that he be committed to a state insane asylum for "medical care and treatment.“
Nevada, in1877, first to make it illegal to sell or dispense opium without a physician's prescription.
Oregon, in 1887, first to pass a comprehensive anti-substance abuse law.
History
The federal Harrison Narcotic Act was passed in 1914.Official title of the Harrison bill had been "An Act to provide for the registration of, with collectors of internal revenuer and to impose a special tax upon all persons who produce, import, manufacture, compound, deal in, dispense, sell, distribute, or give away opium or coca Leaves,* their salts, derivatives or preparations, and for other purposes."
After passage of the law, this clause ["in the course of his professional practice only"] was interpreted by law-enforcement officers to mean that a doctor could not prescribe opiates to an addict to maintain his addiction.
History
Genesis in two statutes of the early Genesis in two statutes of the early 1970s1970s
Implemented by regulations from Implemented by regulations from HEW in 1975HEW in 1975
Revised by HHS in 1987 (42 CFR Part Revised by HHS in 1987 (42 CFR Part 2)2)
Congress reaffirmed and reorganized Congress reaffirmed and reorganized the two statutes into a single actthe two statutes into a single act
History
Model Policy for the Use of Controlled Substances for the Treatment of Pain
Federation of State Medical Boards House of Delegates, Federation of State Medical Boards House of Delegates, May 2004. http://fsmb.org. Accessed March 2010.May 2004. http://fsmb.org. Accessed March 2010.
Federation of State Medical Boardsof the United States, Inc
FSMB Model PolicyBasic Tenets
• Pain management is important and integral to the practice of medicine
• Use of opioids may be necessary for pain relief• Use of opioids for other than a legitimate medical
purpose poses a threat to the individual and society• Physicians have a responsibility to minimize the
potential for abuse and diversion• Physicians may deviate from the recommended
treatment steps based on good cause• Not meant to constrain or dictate medical decision-
making
FSMB, Federation of State Medical Boards
PainPain
The challenge is thatThe challenge is that
“treating pain is neither “treating pain is neither an absolute science nor an absolute science nor
risk-free”risk-free” Scott M. Fishman, MD - Anesthesia & Analgesia. 2007;105:8-9Scott M. Fishman, MD - Anesthesia & Analgesia. 2007;105:8-9
PainPain
• Acute PainAcute Pain• Trauma, injury, dental procedures, and Trauma, injury, dental procedures, and
labor and deliverylabor and delivery• Chronic Malignant PainChronic Malignant Pain
• CancerCancer• Chronic Nonmalignant PainChronic Nonmalignant Pain
• Arthritis, Disc DiseaseArthritis, Disc Disease• Withdrawal-related PainWithdrawal-related Pain
A. Nociceptive
B. Inflammatory
C. Neuropathic
D.Noninflammatory/ Nonneuropathic
Noxious Peripheral
Stimuli
Peripheral Nerve Damage
No Known Tissue or Nerve DamageAbnormal Central
Processing
Multiple Mechanisms
Inflammation
Multiple Types of Pain
Adapted from Woolf CJ. Ann Intern Med. 2004;140:441-451.1. Chong MS, Bajwa ZH. J Pain Symptom Manage. 2003;25:S4-S11.
• Patients may experience multiple pain states simultaneously1
Examples
• Strains and sprains
• Bone fractures
• Postoperative
• Osteoarthritis
• Rheumatoid arthritis
• Tendonitis
• Diabetic peripheral neuropathy
• Post-herpetic neuralgia
• HIV-related polyneuropathy
• Fibromyalgia
• Irritable bowel syndrome
PainPain• Perception of pain as a 4-step modelPerception of pain as a 4-step model
• TransductionTransduction: Acute stimulation in the form of noxious : Acute stimulation in the form of noxious thermal, mechanical, or chemical stimuli is detected by thermal, mechanical, or chemical stimuli is detected by nociceptive neurons.nociceptive neurons.
• TransmissionTransmission: Nerve impulses transferred via axons of : Nerve impulses transferred via axons of afferent neurons from the periphery to the spinal cord, afferent neurons from the periphery to the spinal cord, to the medial and ventrobasal thalamus, to the cerebral to the medial and ventrobasal thalamus, to the cerebral cortexcortex
• PerceptionPerception: Cortical and limbic structures in the brain : Cortical and limbic structures in the brain are involved in the awareness and interpretation of pain.are involved in the awareness and interpretation of pain.
• ModulationModulation: Pain can be inhibited or facilitated by : Pain can be inhibited or facilitated by mechanisms affecting ascending as well as descending mechanisms affecting ascending as well as descending pathways.pathways.
The Pain PathwayThe Pain Pathway
Transduction – Peripheral Sensory nociceptive
Transmission –Ascending spinal interpretation
Peripheral nerve stimulation in Peripheral nerve stimulation in PainPain
• Nociceptors quality of pain perceived dependent on: Nociceptors quality of pain perceived dependent on: • site of stimulation, site of stimulation, • nature of the fibres transmitting the sensation. nature of the fibres transmitting the sensation.
• sharp immediate pain ("first pain") transmitted by A delta sharp immediate pain ("first pain") transmitted by A delta fibres, fibres,
• prolonged unpleasant burning pain mediated through the prolonged unpleasant burning pain mediated through the smaller unmyelinated C fibres. smaller unmyelinated C fibres.
• Modulation receptors on their surfaces effect sensitivity to Modulation receptors on their surfaces effect sensitivity to stimulation. stimulation.
• GABA, GABA, • opiate, opiate, • bradykinin, bradykinin, • histamine, histamine, • Serotonin Serotonin • capsaicin receptorscapsaicin receptors
Mediation of transmission of Mediation of transmission of PainPain
•Neurotransmitters mediate transmission of pain in both brain and spinal cord.
•Excitatory neurotransmitters:•Glutamate and tachykinins, act at the various neurokinin receptors including as substance P ('P is for pain'), neurokinin A and neurokinin B, and on other substances that transmit pain impulses from incoming nerves in the dorsal horn.
•Inhibitory neurotransmitters:•gamma amino butyric acid (GABA) most prominent.
The Pain PathwayThe Pain Pathway
Modulation
- Midbrain- Thalamus, - Limbic system
Perception
- Cerebral Cortex
Modulation of PainModulation of Pain
•Descending Pain Regulation:• norepinephrine - alpha-2 stimulatory effects• serotonin• opiates relieve pain by stimulating mu and delta receptors at a host of sites.
Perceived Pain - Perceived Pain - SufferingSuffering
• At risk patientsAt risk patients• Past history of substance use disorderPast history of substance use disorder• Emotionally traumatized Emotionally traumatized • Dysfunctional / alcoholic familyDysfunctional / alcoholic family• Lacks effective coping skillsLacks effective coping skills• Dependent traitsDependent traits• Stimulus augmenters-deficit in hedonic Stimulus augmenters-deficit in hedonic
tonetonePaul Farnum, MD PHP, BC
Vicious Cycle of Uncontrolled Pain
Pain
Altered Functional
Status
Decreased Mobility
AvoidanceBehaviors
Social Limitations Diminished
Self-Efficacy
DoesDoesNotNot
NecessarilyNecessarilyEqualEqual
Chronic Chronic PainPain
SufferinSufferingg
Ed Salsizt
Fine PG, et al. J Support Oncol. 2004;2(suppl 4):5-22. Portenoy RK, et al. In: Lowinson JH, et al, eds. Substance Abuse: A Comprehensive Textbook. 4th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2005:863-903.
Multimodal Treatment
Lifestyle Change
Exercise, weight loss
Strategies for Pain and
Associated Disability
Pharmacotherapy
Opioids, nonopioids, adjuvant analgesics Interventional
ApproachesInjections,
neurostimulation
Physical Medicine and Rehabilitation
Assistive devices, electrotherapy
Psychological Support
Psychotherapy, group support
Complementary and
Alternative Medicine
Massage, supplements
Considerations
• What is conventional practice for this type of pain or What is conventional practice for this type of pain or pain patient?pain patient?
• Is there an alternative therapy that is likely to have an Is there an alternative therapy that is likely to have an equivalent or better therapeutic index for pain control, equivalent or better therapeutic index for pain control, functional restoration, and improvement in quality of functional restoration, and improvement in quality of life?life?
• Does the patient have medical problems that may Does the patient have medical problems that may increase the risk of opioid-related adverse effects?increase the risk of opioid-related adverse effects?
• Is the patient likely to manage the opioid therapy Is the patient likely to manage the opioid therapy responsibly?responsibly?
• Who can I treat without help?Who can I treat without help?• Who would I be able to treat with the assistance of a Who would I be able to treat with the assistance of a
specialist?specialist?• Who should I not treat, but rather refer, if opioid Who should I not treat, but rather refer, if opioid
therapy is a consideration?therapy is a consideration?Fine PG, Portenoy RK. Clinical Guide to Opioid Analgesia. Vendome Group, New York, 2007.
Non Pharmacologic InterventionsNon Pharmacologic Interventions
Behavioral Interventions-ie guided Behavioral Interventions-ie guided imagery, biofeedbackimagery, biofeedback
MeditationMeditation Osteopathic Manipulation, Chiropractic, Osteopathic Manipulation, Chiropractic,
Body workBody work Acupuncture with or without stimulationAcupuncture with or without stimulation Physical Therapy modalitiesPhysical Therapy modalities Tran-cutaneous Nerve StimulationTran-cutaneous Nerve Stimulation HypnosisHypnosis
Non-Opiate ApproachesNon-Opiate Approaches
• TransductionTransduction: nonsteroidal anti-inflammatory : nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 drugs (NSAIDs) and cyclooxygenase (COX)-2 inhibitors -- target the inflammatory processesinhibitors -- target the inflammatory processes
• TransmissionTransmission: Local anesthetics, gamma-: Local anesthetics, gamma-aminobutyric acid (GABA) agonists, non-N-aminobutyric acid (GABA) agonists, non-N-methylD-asparate (NMDA) antagonists, COX methylD-asparate (NMDA) antagonists, COX inhibitors, corticosteroids.inhibitors, corticosteroids.
• PerceptionPerception: Influenced by the situation as well as : Influenced by the situation as well as by the individual's experience and cultureby the individual's experience and culture
• ModulationModulation. Antidepressants are useful in treating . Antidepressants are useful in treating chronic pain because they increase the availability chronic pain because they increase the availability of serotonin or norepinephrine. in pain-modulating of serotonin or norepinephrine. in pain-modulating descending pathways. Recent studies identified descending pathways. Recent studies identified tapentadol, bicifadine, as effective.tapentadol, bicifadine, as effective.
There is more to treating pain than Opiates….
but opiates remain important!
OpiatesOpiates
Opiates & Opiates & OpioidsOpioids
OpiatesOpiates = naturally present = naturally present in opiumin opium e.g. thebaine, codeine, e.g. thebaine, codeine,
morphine morphine
OpioidsOpioids = manufactured = manufactured Semisynthetics are derived Semisynthetics are derived
from an opiatefrom an opiate heroin from morphineheroin from morphine buprenorphine from thebainebuprenorphine from thebaine
Synthetics are completely Synthetics are completely man-made to work like opiatesman-made to work like opiates
methadonemethadone
Function at Receptors: Function at Receptors: Full AgonistsFull Agonists
MuMureceptorreceptor
Full agonist binding …Full agonist binding …
activates the mu receptor
is highly reinforcing
is the most abused opioid type
includes heroin, methadone, & others
Formulation Points to Consider
• Dose-limiting issues and toxicity with co-analgesicsDose-limiting issues and toxicity with co-analgesics• 4 g/day acetaminophen limit4 g/day acetaminophen limit
• Importance of titrationImportance of titration• Risk of overdose, challenges of dose conversion during Risk of overdose, challenges of dose conversion during
rotationrotation• Pharmacokinetics versus temporal patterns of painPharmacokinetics versus temporal patterns of pain• AdherenceAdherence• CostCost• ConvenienceConvenience• Caregiving issuesCaregiving issues
Medical issues in opioid Medical issues in opioid prescribingprescribing
• Potential Potential benefitsbenefits• AnalgesiaAnalgesia• FunctionFunction• Quality of lifeQuality of life
• Potential risksPotential risks • ToxicityToxicity• Functional impairmentFunctional impairment• Physical dependencePhysical dependence• AddictionAddiction• Hyperalgesia Hyperalgesia
Are opioids effective for Are opioids effective for CNMP?CNMP?
• What do we know?What do we know?• What don’t we know?What don’t we know?
• What don’t we know What don’t we know about:about:• AddictionAddiction• Chronic painChronic pain• Effects of long term opioid analgesiaEffects of long term opioid analgesia
46
Review of opioid efficacyReview of opioid efficacy
• In short-term studies:In short-term studies:• Single IV studySingle IV study• Oral studies ≤ 32 wksOral studies ≤ 32 wks• Both demonstrate that CNMP Both demonstrate that CNMP can can
bebe opioid responsive opioid responsive
47
Review of opioid efficacy Review of opioid efficacy (cont.)(cont.)
• In long-term studiesIn long-term studies::• Usually observational – non randomized / poorly Usually observational – non randomized / poorly
controlledcontrolled• Treatment durations ≤ 6 years. Treatment durations ≤ 6 years. • Patients usually attain satisfactory analgesia with Patients usually attain satisfactory analgesia with
moderatemoderate non-escalatingnon-escalating doses (≤ 195 mg doses (≤ 195 mg morphine/d), often accompanied by an improvement morphine/d), often accompanied by an improvement in function, with minimal risk of addiction. in function, with minimal risk of addiction.
• The question of whether benefits can be The question of whether benefits can be maintained over years rather than months maintained over years rather than months remains unanswered.remains unanswered.
Ballantyne JC: Southern Med J 2006; 99(11):1245-1255Ballantyne JC: Southern Med J 2006; 99(11):1245-1255
Back PainBack Pain• There has been 423% increase in the There has been 423% increase in the
expenditure for spine-related expenditure for spine-related narcotic analgesics from 1997 to narcotic analgesics from 1997 to 2004*2004*
• Yet in assessment of health status Yet in assessment of health status there has been no significant there has been no significant improvement. improvement.
* JAMA February 13,2008 Vol. 299, No. 6
Opioid HyperalgesiaOpioid Hyperalgesia
• Cellular responses to chronic opioid intake:Cellular responses to chronic opioid intake:• an increase in neuropeptides such as an increase in neuropeptides such as
dynorphindynorphin1111, cholecystokinin,, cholecystokinin,1212 and substance P and substance P1313
• all of which have been demonstrated to enhance pain all of which have been demonstrated to enhance pain sensitivitysensitivity
• the activation of glial cells, producing the activation of glial cells, producing inflammatory cytokines and resulting in inflammatory cytokines and resulting in amplified pain.amplified pain.1414
11. Vanderah TW, Suenaga NM, Ossipov MH, Malan TP Jr. Lai J. Porreca F. 11. Vanderah TW, Suenaga NM, Ossipov MH, Malan TP Jr. Lai J. Porreca F. J Neuwsci. J Neuwsci. 2001 ;21:279-286.2001 ;21:279-286.
12. Xie JY. Herman DS, Stiller CO. el al. 12. Xie JY. Herman DS, Stiller CO. el al. JNeurosci. JNeurosci. 2005;25:409-416.2005;25:409-416.
13. King T, Gardel) LR. Wang R. et al. 13. King T, Gardel) LR. Wang R. et al. Pain. Pain. 2005;! 16:276-288.2005;! 16:276-288.
14. Watkins LR. Hutchinson 14. Watkins LR. Hutchinson MR, MR, Ledeboer A. Wieseler-Frank J, MilliganLedeboer A. Wieseler-Frank J, MilliganED, Maier SF. ED, Maier SF. Brain Behav linrmin. Brain Behav linrmin. 2007;2];J31-146.2007;2];J31-146.
Opioid HyperalgesiaOpioid Hyperalgesia
• Methadone maintenance patients have Methadone maintenance patients have a reduction in their pain tolerance.a reduction in their pain tolerance.11
• Ballantyne NEJM report 2003, review Ballantyne NEJM report 2003, review of opioid therapy for chronic pain- of opioid therapy for chronic pain- “neither safe nor effective”“neither safe nor effective”22
1. Doverty M, White JM. Somogyi AA, Bochner F. Ali R. Ling W. 1. Doverty M, White JM. Somogyi AA, Bochner F. Ali R. Ling W. Pain. Pain. 2001:90:91-2001:90:91-96.96.
2. Ballantyne JC. Mao J. 2. Ballantyne JC. Mao J. N Engl J Med. N Engl J Med. 2003:349:1943-1953.2003:349:1943-1953.
Conclusions as to opioid Conclusions as to opioid efficacyefficacy
• Opioids are an essential treatment for Opioids are an essential treatment for some patients with CNMP.some patients with CNMP.• They are rarely sufficientThey are rarely sufficient• They almost never provide total lasting They almost never provide total lasting
reliefrelief• They ultimately fail for manyThey ultimately fail for many• They pose some hazards to patients and They pose some hazards to patients and
societysociety• It is not possible to accurately predict It is not possible to accurately predict
who will be helped – but those with who will be helped – but those with contraindications are at high riskcontraindications are at high risk
Use of Opiates in Use of Opiates in Pain Pain
ManagementManagement
Positioning Opioid Therapy
for Chronic Pain• Chronic non-cancer pain: evolving Chronic non-cancer pain: evolving perspectiveperspective• Consider for all patients with severe chronic pain, Consider for all patients with severe chronic pain,
but weigh the influencesbut weigh the influences• What is conventional practice?What is conventional practice?• Are there reasonable alternatives?Are there reasonable alternatives?• What is the risk of adverse events?What is the risk of adverse events?• Is the patient likely to be a responsible drug-Is the patient likely to be a responsible drug-
taker? taker?
Fine PG, Portenoy RK. Clinical Guide to Opioid Analgesia, 2nd edition, 2007.Jovey RD, et al. Pain Res Manag. 2003;8(Suppl A):3A-28A.Eisenberg E, et al. JAMA. 2005;293:3043-3052.Gilron I, et al. N Engl J Med. 2005;352:1324-1334.
Treatment goals in managing CNMP:
Improve patient functioningImprove patient functioning Identify and eliminate positive reinforcersIdentify and eliminate positive reinforcers Increase physical activityIncrease physical activity Avoid opioid misuse and other drug useAvoid opioid misuse and other drug use
The goal is NOT pain eradication!The goal is NOT pain eradication!
Chronic Opioid Therapy Guidelines and Treatment Principles
Patient Selection
Patient Selection and Risk Stratification (1.1-1.3)
Initial Patient Assessment
Informed Consent and Opioid Management Plans (2.1-2.2)
High-Risk Patients (6.1-6.2)
Alternatives to Opioid Therapy
Use of Psycho-
therapeutic Cointerventio
ns (9.1)Comprehensive Pain Management Plan
Driving and Work Safety (10.1)
Identifying a Medical Home* and When to Obtain Consultation (11.1-11.2)
Chou R, et al. J Pain. 2009;10:113-130. *Clinician accepting primary responsibility for a patient’s overall medical care.
Chronic Opioid Therapy Guidelines and Treatment Principles (cont)
Trial of Opioid Therapy
Initiation and Titration of Chronic Opioid Therapy (3.1-
3.2)
Methadone (4.1)
Opioids and Pregnancy (13.1)
Patient Reassessment
Monitoring (5.1-5.3)
Dose Escalations, High-Dose Opioid Therapy, Opioid Rotation, Indications for Discontinuation of Therapy
(7.1-7.4)
Opioid Policies (14.1)
Implement Exit Strategy
Opioid-Related Adverse Effects (8.1)
Continue Opioid Therapy
Monitoring (5.1-5.3)
Breakthrough Pain (12.1)Chou R, et al. J Pain. 2009;10:113-130. *Clinician accepting primary responsibility for a patient’s overall medical care.
Initial Visits
• Initial comprehensive evaluation• Risk assessment• Prescription monitoring assessment• Urine drug test
• Opioid treatment agreement• Opioid consent form• Patient education
Principles of Responsible Opioid Prescribing
• Patient EvaluationPatient Evaluation• Pain assessment and history Pain assessment and history • Directed physical examDirected physical exam• Review of diagnostic studiesReview of diagnostic studies• Analgesic and other medication historyAnalgesic and other medication history• Personal history of illicit drug use or substance Personal history of illicit drug use or substance
abuseabuse• Personal history of psychiatric issuesPersonal history of psychiatric issues• Family history of substance abuse/psychiatric Family history of substance abuse/psychiatric
problemsproblems• Assessment of comorbiditiesAssessment of comorbidities• Accurate record keepingAccurate record keeping
Fine PG, Portenoy RK. Clinical Guide to Opioid Analgesia, 2nd edition, 2007.
A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:
1. Tolerance, as defined by either of the following:
a) a need for markedly increased amounts of the substance to achieve intoxication or the desired effect, or
b) markedly diminished effect with continued use of the same amount of the substance
2. Withdrawal, as manifested by either of the following:
a) the characteristic withdrawal syndrome for the substance, or
b) the same (or closely related) substance is taken to relieve or avoid withdrawal symptoms
DSM-IV Criteria for Opioid Dependence
3. The substance is often taken in larger amounts or over a longer period than was intended
4. There is a persistent desire or unsuccessful efforts to cut down or control substance use
5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects
6. Important social, occupational, or recreational activities are given up or reduced because of substance use
7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance
DSM-IV Criteria for Opioid Dependence
Control Control (loss of)(loss of) Compulsion to use Compulsion to use Consequences Consequences (continued use (continued use
despite negative consequences – despite negative consequences – family, occupational/educational, family, occupational/educational, legal, psychological, medicallegal, psychological, medical) )
CravingCraving
Characteristics of Addiction: The 4 “Cs”
Nomenclature in Pain Treatment
ToleranceTolerance Decreased effect over timeDecreased effect over time
Physical Dependence Physical Dependence Withdrawal symptoms upon Withdrawal symptoms upon
discontinuationdiscontinuation Addiction Addiction
Impaired control, compulsive use, Impaired control, compulsive use, continued use in spite of negative continued use in spite of negative consequencesconsequences
Pseudo AddictionPseudo Addiction Behavior surrounding obtaining adequate Behavior surrounding obtaining adequate
pain medspain meds Pseudo TolerancePseudo Tolerance
Worsening of underlying conditionWorsening of underlying condition
Identifying Who Is at Risk for Opioid Abuse and Diversion
• Predictive tools Predictive tools • Aberrant behaviorsAberrant behaviors• Urine drug testingUrine drug testing• Prescription monitoring Prescription monitoring • programsprograms• Severity and duration of painSeverity and duration of pain• Pharmacist communicationPharmacist communication• Family and friendsFamily and friends• PatientsPatients
Risk Assessment Tools
• Addiction Severity Index (ASI)• Assess current and lifetime substance-
use problems and prior treatment• Drug Abuse Screening Test (DAST-10)
• Screen for probably drug abuse or dependence
• Addiction Behaviors Checklist (ABC) • Evaluate and monitor behaviors
indicative ofaddiction related to prescription
opioids in patients with chronic pain
Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14.
Risk Assessment Tools (cont)
• Screening Instrument for Substance Abuse Potential (SISAP)
• Identify individuals with possible substance-abuse history
• Opioid Risk Tool (ORT)• Predict which patients might develop
aberrant behavior when prescribed opioids for chronic pain
• Diagnosis, Intractability, Risk, Efficacy (DIRE)• Predict the analgesic efficacy of, and patient
compliance to, long-term opioid treatment in the primary care settingg
Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14.
Risk Assessment Tools (cont)
• Screener and Opioid Assessment for Patients with Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R)Pain-Revised (SOAPP-R)
• Predict aberrant medication-related behaviors in Predict aberrant medication-related behaviors in patients with chronic pain considered for long-term patients with chronic pain considered for long-term opioid therapyopioid therapy
• Empirically-derived, 24-item self-report Empirically-derived, 24-item self-report questionnairequestionnaire
• Reliable and validReliable and valid• Less susceptible to overt deception than past Less susceptible to overt deception than past
versionversion• Scoring: Scoring: 18 identifies 90% of high-risk 18 identifies 90% of high-risk
patientspatients
Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14. Butler SF, et al. J Pain. 2008;9:360-372.
Opioid Risk ToolOpioid Risk Tool
5-item initial risk assessment5-item initial risk assessment Stratifies risk into low (6%), Stratifies risk into low (6%),
moderate (28%) and high (91%)moderate (28%) and high (91%) Family HistoryFamily History Personal HistoryPersonal History AgeAge Preadolescent sexual abusePreadolescent sexual abuse Past or current psychological diseasePast or current psychological disease
www.emergingsolutionsinpain.comwww.emergingsolutionsinpain.com
Webster, Webster. Pain Med. 2005
Mark each box that applies Female Male
1. Family history of substance abuse
– Alcohol
– Illegal drugs
– Prescription drugs
1
2
4
3
3
4
2. Personal history of substance abuse
– Alcohol
– Illegal drugs
– Prescription drugs
3
4
5
3
4
5
3. Age (mark box if 16-45 years) 1 1
4. History of preadolescent sexual abuse 3 0
5. Psychological disease
– ADD, OCD, bipolar, schizophrenia
– Depression
2
1
2
1
ORT Validation
•Exhibits high degree of sensitivity and specificity
•94% of low-risk patients did not display an aberrant behavior
•91% of high-risk patients did display an aberrant behavior
N = 185ADD, attention deficit disorder; OCD, obsessive-compulsive disorder.Webster LR, Webster RM. Pain Med. 2005;6:432-442.
Source: Journal of Pain, The 2009; 10:113-130.e22 (DOI:10.1016/j.jpain.2008.10.008 )
Copyright © 2009 American Pain Society Terms and Conditions
SOAPP
Mr. Jackson’s Score = 3
To score the SOAPP, add ratings of all questions.
A score of 4 or higher is
considered positive
Sum of Questions
SOAPP Indication
4 +
< 4 -
Name:_________________ Date:___________
The following survey is given to all patients who are on or being considered for opioids for their pain. Please answer each question as honestly as possible. This information is for our records and will remain confidential. Your answers will not determine your treatment. Thank you.
Please answer the questions below using the following scale:
0 = Never, 1 = Seldom, 2 = Sometimes, 3 = Often, 4 = Very Often
1. How often do you have mood swings?
2. How often do you smoke a cigarette within an hour after you wake up?
3. How often have you taken medication other than the way that it was prescribed?
4. How often have you used illegal drugs (for example, marijuana, cocaine, etc.) in the past five years?
5. How often in your lifetime have you had legal problems or been arrested?
Please include any additional information you wish about the above answers. Thank you
0 1 2 3 4
0 1 2 3 4
0 1 2 3 4
0 1 2 3 4
0 1 2 3 4
Chris Jackson 9/16/09
О
О
Risk Assessment Tools (cont)
• Pain Medication Questionnaire (PMQ)• Assess risk for opioid medication misuse
in patients with chronic pain• Current Opioid Misuse Measure (COMM)
• Periodically monitor aberrant medication-related behaviors in patients with chronic pain currently on opioid therapy
Principles of Responsible Opioid Prescribing
• Drug selection, route of administration, dosing/dose titration
• Managing adverse effects of opioid therapy
• Assessing outcomes
• Written agreements in place outlining patient expectations/responsibilities
• Consultation as needed
• Periodic review of treatment efficacy, side effects, aberrant drug-taking behaviors
74
Initiation of opioid therapyInitiation of opioid therapy
• Is there a Is there a clear diagnosisclear diagnosis??• Is there Is there documentationdocumentation of an adequate of an adequate
work-up?work-up?• Is there Is there impairment of functionimpairment of function??• Has Has non-opioid multimodal therapynon-opioid multimodal therapy
failedfailed??• Have Have contraindicationscontraindications been ruled out? been ruled out?
Begin opioid therapy:Begin opioid therapy: DocumentDocument MonitorMonitor Avoid poly-pharmacyAvoid poly-pharmacy
Medical Records
• Maintain accurate, complete, and Maintain accurate, complete, and current recordscurrent records• Medical Hx & PEMedical Hx & PE• Diagnostic, therapeutic, lab resultsDiagnostic, therapeutic, lab results• Evaluations/consultationsEvaluations/consultations• Treatment objectivesTreatment objectives• Discussion of risks/benefitsDiscussion of risks/benefits• Tx and medicationsTx and medications• Instructions/agreementsInstructions/agreements• Periodic reviewsPeriodic reviews• Discussions with and about patientsDiscussions with and about patients
Fishman SM. Pain Med. 2006;7:360-362. Federation of State Medical Boards of the United States, Inc. Model Policy for the Use of Controlled Substances for the Treatment of Pain. 2004.
Marcus DA. Am Fam Physician. 2000;61(5):1331-1338.
Initiation of Initiation of Therapy for Therapy for
Chronic PainChronic Pain
Monitoring Chronic Pain
Review of Efficacy of Therapy
Marcus DA. Am Fam Physician. 2000;61(5):1331-1338.
Opioid Treatment Agreement
http://www.lni.wa.gov/ClaimsIns/Files/OMD/agreement.pdf. Accessed March 2010.
79
Opiate management of painOpiate management of pain
• A trial (6 mo±) generally is safeA trial (6 mo±) generally is safe
((IFIF contraindications are ruled contraindications are ruled out)out)
• Opiate use and decreased activity Opiate use and decreased activity results in a worsened condition.results in a worsened condition.• Push functional restoration, exercises Push functional restoration, exercises • Make increased drugs contingent on Make increased drugs contingent on
increased activity increased activity
Monitoring:Monitoring:
Regularly assess the 5 A’s:Regularly assess the 5 A’s: • AnalgesiaAnalgesia• Adverse effectsAdverse effects• Activity / functionActivity / function• Aberrant behaviorsAberrant behaviors• AffectAffect
Treating the Addicted Treating the Addicted Patient Patient
in in PainPain
These patients suffer thrice:These patients suffer thrice: from the painful diseasefrom the painful disease from the addiction, which makes from the addiction, which makes
pain management difficultpain management difficult from the health care provider’s from the health care provider’s
ignoranceignorance
Pain TreatmentPain Treatmentin Patients with an Addictionin Patients with an Addiction
Pain Treatment in Patients with an Addiction
Must consider:Must consider: High tolerance to medicationsHigh tolerance to medications Low pain thresholdLow pain threshold High risk for relapseHigh risk for relapse
Pain treatmentPain treatment Inadequate pain treatmentInadequate pain treatment Psychological statusPsychological status
Search for physical causesSearch for physical causes Identify and address possible non-Identify and address possible non-
pain sustaining factorspain sustaining factors Address and improve functional Address and improve functional
statusstatus Treat associated symptoms, if Treat associated symptoms, if
indicatedindicated Case managementCase management
Pain Treatment in Patients with an Addiction
Pain Treatment in Patients with an Addiction Address addictionAddress addiction Use non-pharmacologic approaches, if Use non-pharmacologic approaches, if
effectiveeffective Use non-opioid analgesics, if effectiveUse non-opioid analgesics, if effective Provide effective opioid doses, if neededProvide effective opioid doses, if needed Treat associated symptoms, if indicatedTreat associated symptoms, if indicated Address addictionAddress addiction
Identifying and Managing Abuse and Diversion
• Assessing risk and aberrant behaviorsAssessing risk and aberrant behaviors• Performing scheduled and random UDTsPerforming scheduled and random UDTs• Utilization of PMPsUtilization of PMPs• Assessing stress and adequacy of pain controlAssessing stress and adequacy of pain control• Developing good communication with pharmacistsDeveloping good communication with pharmacists• Receiving input from family, friends, and other Receiving input from family, friends, and other
patientspatients
Differential Diagnosis of Aberrant Drug-Taking Attitudes and Behavior
• Addiction (out-of-control, compulsive drug Addiction (out-of-control, compulsive drug use)use)
• Pseudoaddiction (inadequate analgesia)Pseudoaddiction (inadequate analgesia)• Other psychiatric diagnosisOther psychiatric diagnosis
• Organic mental syndrome Organic mental syndrome (confused, stereotyped drug-taking)(confused, stereotyped drug-taking)
• Personality disorder (impulsive, entitled, chemical-coping Personality disorder (impulsive, entitled, chemical-coping behavior)behavior)
• Chemical coping (drug overly central)Chemical coping (drug overly central)• Depression/anxiety/situational stressors Depression/anxiety/situational stressors
(self-medication)(self-medication)
• Criminal intent (diversion)Criminal intent (diversion)
Passik SD, Kirsh KL. Curr Pain Headache Rep. 2004;8:289-294.
Signs of Potential Abuse and Diversion
• Request appointment toward end-of-office hours• Arrive without appointment• Telephone/arrive after office hours when staff are
anxious to leave• Reluctant to have thorough physical exam,
diagnostic tests, or referrals• Fail to keep appointments• Unwilling to provide past medical records or
names of HCPs• Unusual stories
However, emergencies happen: not every person in a hurry is an
abuser/diverter
Drug Enforcement Administration. Don't be Scammed by a Drug Abuser. 1999. Cole BE. Fam Pract Manage. 2001;8:37-41.
Urine Drug Testing
• When to test?When to test?• Randomly, annually, PRNRandomly, annually, PRN
• What type of testing?What type of testing?• POC, GS/MSPOC, GS/MS
• How to interpretHow to interpret• Metabolism of opioidsMetabolism of opioids• False positive and negative resultsFalse positive and negative results
• What to do about the resultsWhat to do about the results• Consult, refer, change therapy, dischargeConsult, refer, change therapy, discharge
• Positive forensic Positive forensic testingtesting• Legally prescribed Legally prescribed
medicationsmedications• Over-the-counter Over-the-counter
medicationsmedications• Illicit drugs or Illicit drugs or
unprescribed medicationsunprescribed medications• Substances that produce Substances that produce
the same metabolite as that the same metabolite as that of a prescribed or illegal of a prescribed or illegal substancesubstance
• Errors in laboratory Errors in laboratory analysisanalysis
• Negative Negative compliance testingcompliance testing• Medication bingeingMedication bingeing• DiversionDiversion• Insufficient test sensitivityInsufficient test sensitivity• Failure of laboratory to Failure of laboratory to
test for desired substancestest for desired substances
Heit HA, Gourlay DL. J Pain Symptom Manage. 2004;27:260-267.
Positive and Negative Urine Toxicology Results
Urine Drug Testing
• Initial testing done with class-specific Initial testing done with class-specific immunoassay drug panelsimmunoassay drug panels• Typically do not identify individual drugs within a class Typically do not identify individual drugs within a class
Heit HA, Gourlay D. J Pain Sympt Manage. 2004:27:260-267.
• Followed by a technique such as GC/MS• To identify or confirm
the presence or absence of a specific drug and/or its metabolites
Detection of Opioids
• Opiate immunoassays detect morphine Opiate immunoassays detect morphine and codeineand codeine• Do not detect synthetic opioidsDo not detect synthetic opioids
• Methadone Methadone • FentanylFentanyl
• Do not reliably detect semisynthetic opioidsDo not reliably detect semisynthetic opioids• OxycodoneOxycodone• HydrocodoneHydrocodone• HydromorphoneHydromorphone
• GC/MS will identify these medicationsGC/MS will identify these medications
Heit HA, Gourlay D. J Pain Sympt Manage. 2004:27:260-267.
UDT Laboratory-Based Tests
• GC/MS, LC/ GC/MS, LC/ MS, ELISAMS, ELISA• High sensitivity, High sensitivity,
high specificityhigh specificity• ExpensiveExpensive• QuantitativeQuantitative• 1-3 days for 1-3 days for
resultsresults
ELISA, enzyme-linked immunosorbent assay; GC, gas chromatography; LC, liquid chromatography; MS, mass spectrometry.
Hammett-Stabler CA, Webster LR. A Clinical Guide to Urine Drug Testing. Stamford, CT: PharmaCom Group Inc; 2008.
RESULTS OF CONTROLLED
SUBSTANCE UDT: WORKPLACE
Donor Name: Jack Donor ID #: 1897221 Specimen ID #: 1897221-112
Accession #: None assigned Reason for test: RandomDate collected: 04/11/2008 Time collected: 1648Date received: 04/15/2008 Date reported: 04/15/2008
Class or Analyte Result Screen Cut-OffAMPHETAMINES NEGATIVE 1,000 ng/mlBARBITUATES NEGATIVE 200 ng/mlBENZODIAZEPINES NEGATIVE 200 ng/mlCANNABINOIDS NEGATIVE 50 ng/mlCOCAINE NEGATIVE 300 ng/mlMETHADONE NEGATIVE 150 ng/mlOPIATES POSITIVE 100 ng/ml
Validity Test Result Normal RangeCREATININE NORMAL at 33.4 mg/dL ≥ 20 mg/dLSPECIFIC GRAVITY NORMAL ≥ 1.003pH NORMAL 4.6-8.0
Risk Evaluation and Mitigation Strategies
• Position of the FDAPosition of the FDA• The current strategies for intervening with [the The current strategies for intervening with [the
problem of prescription opioid addiction, misuse, problem of prescription opioid addiction, misuse, abuse, overdose and death] are inadequateabuse, overdose and death] are inadequate
• New authorities granted under FDAAA: [FDA] will New authorities granted under FDAAA: [FDA] will now be implementing Risk Evaluation and Mitigation now be implementing Risk Evaluation and Mitigation Strategies (REMS) for a number of opioid productsStrategies (REMS) for a number of opioid products
• [FDA expects] all companies marketing these [FDA expects] all companies marketing these products to [cooperate] to get this done expeditiouslyproducts to [cooperate] to get this done expeditiously
• If not, [FDA] cannot guarantee that these products If not, [FDA] cannot guarantee that these products will remain on the marketwill remain on the market
Rappaport BA. REMS for Opioid Analgesics: How Did We Get Here? Where are We Going? FDA meeting of manufacturers of ER opioids, FDA White Oak Campus, Silver Spring, MD. March 3, 2009.
NASPERNASPERNational All Schedules Prescription Electronic National All Schedules Prescription Electronic
Reporting ActReporting Act Signed into law by Signed into law by
President Bush August President Bush August 20052005
Point of care reference Point of care reference to all controlled to all controlled substances prescribed substances prescribed to a given patientto a given patient
Each state will Each state will implement it’s own implement it’s own programprogram
Treatment tool vs. Law Treatment tool vs. Law enforcement tool?enforcement tool?Source: 2002 National Survey on Drug Use and Health (NSDUH). Results from the 2002 National Survey on Drug Use and Health: National Findings. Department of Health and Human Services
73.3%
117.1%
402.9% 410.8%
0%
50%
100%
150%
200%
250%
300%
350%
400%
450%
Morphine Hydrocodone Oxycodone Methadone
Sale of Opioids 1997-2002
States with Pharmacy Monitoring Programs
Operational PMP:32
Start-up phase: 6 In legislative process: 11
No action: 1
Office of Diversion Control. http://www.deadiversion.usdoj.gov/faq/rx_monitor.htm#1. Accessed March 2010.
Case Study: Opioid Renewal Clinic What is the impact of a structured opioid renewal program?
• Primary goal: reduce oxycodone SA use to 3% of opioids Primary goal: reduce oxycodone SA use to 3% of opioids • SettingSetting
• Primary care Primary care • Managed by nurse practitioner and clinical pharmacist Managed by nurse practitioner and clinical pharmacist • Philadelphia VA pain clinicPhiladelphia VA pain clinic
• Structured programStructured program• Electronic referral by PCPElectronic referral by PCP
• Signed Opioid Treatment AgreementSigned Opioid Treatment Agreement• UDTUDT
• Support from multidisciplinary pain team: addiction psychiatrist, Support from multidisciplinary pain team: addiction psychiatrist, rheumatologist, orthopedist, neurologist, and physiatristrheumatologist, orthopedist, neurologist, and physiatrist
• Multimodal management Multimodal management • Opioids Opioids • NSAIDs and acetaminophen for osteoarthritisNSAIDs and acetaminophen for osteoarthritis• Transcutaneous electrical stimulation (TENS) unitsTranscutaneous electrical stimulation (TENS) units• Antidepressants and anticonvulsants for neuropathic painAntidepressants and anticonvulsants for neuropathic pain• Reconditioning exercisesReconditioning exercises
Wiedemer NL, et al. Pain Med. 2007;8(7):573-584.
Opioid Renewal Clinic: Results• OTAs increased: 63 OTAs increased: 63 214 214• Monthly UDTs increased: 80 Monthly UDTs increased: 80 200 200 • Oxycodone SA use decreasedOxycodone SA use decreased
• Quarterly costs: $130,000 Quarterly costs: $130,000 $5,000$5,000• Percent of opioids: 22.5% Percent of opioids: 22.5% 0.4%0.4%
• ER visits reduced 73%ER visits reduced 73%• Unscheduled PCP visits reduced 60%Unscheduled PCP visits reduced 60%• PCPs satisfied (questionnaire)PCPs satisfied (questionnaire)• 171/335 patients referred had aberrant drug-taking behaviors171/335 patients referred had aberrant drug-taking behaviors
• 45% adhered to OTA (resolved aberrant behaviors)45% adhered to OTA (resolved aberrant behaviors)• 38% self-discharged from ORC38% self-discharged from ORC• 13% referred for addiction treatment13% referred for addiction treatment• 4% consistently negative UDT4% consistently negative UDT
Wiedemer NL, et al. Pain Med. 2007;8(7):573-584.
Pharmacologic • Sequestered
antagonist• Bio-available
antagonist• Pro-drug
Combination Mechanisms
Physical• Difficult to crush• Difficult to extract
Aversive Component• Capsaicin – burning sensation• Ipecac – emetic• Denatonium – bitter taste
Deterrent Packaging• RFID – Protection• Tamper-proof bottles
Incre
asi
ng
Dir
ect
Ab
use
Dete
rren
ce Opioid Abuse-Deterrent
Strategies Hierarchy
Prescription Monitoring
Remaining Questions
• How much does the barrier approach deter How much does the barrier approach deter the determined abuser?the determined abuser?
• How much do agonist/antagonist How much do agonist/antagonist compounds retain efficacy?compounds retain efficacy?
• How much do agonist/antagonist How much do agonist/antagonist compounds pose serious adversity?compounds pose serious adversity?
WHAT IS WHAT IS ADDICTION?ADDICTION?
DoesDoesNotNot
NecessarilyNecessarilyEqualEqual
Physical Physical DependencDependencee
AddictionAddiction
Ed Salsizt
Pain and Pain and AddictionAddiction
DoesDoesNotNot
NecessarilyNecessarilyEqualEqual
Chronic Chronic PainPain
SufferinSufferingg
Ed Salsizt
Pain Treatment in Patients with an Addiction
Avoid the patient’s drug of choiceAvoid the patient’s drug of choice Consider safer longer acting Consider safer longer acting
opioidsopioids Use medication with lower street Use medication with lower street
valuevalue Avoid self administration, if Avoid self administration, if
possiblepossible Case managementCase management
Pain Treatment in Patients with an Addiction
Explain potential for relapseExplain potential for relapse Explain the rationale for the medicationExplain the rationale for the medication Educate the patient and the support Educate the patient and the support
systemsystem Encourage family/support system Encourage family/support system
involvementinvolvement Frequent follow-upsFrequent follow-ups Consultations and multidisciplinary Consultations and multidisciplinary
approachapproach
Must satisfy baseline opioid Must satisfy baseline opioid requirements before treating painrequirements before treating pain
The usual maintenance dose (e.g., The usual maintenance dose (e.g., methadone) will not control the painmethadone) will not control the pain
The usual methadone dose needs to be The usual methadone dose needs to be supplemented with appropriate supplemented with appropriate medication(s) for pain controlmedication(s) for pain control
May need slightly higher amounts for May need slightly higher amounts for slightly longer periods of timeslightly longer periods of time
Pain Control for Opioid Maintained Patients
Monitoring:Monitoring:
Regularly assess the 5 A’s:Regularly assess the 5 A’s: • AnalgesiaAnalgesia• Adverse effectsAdverse effects• Activity / functionActivity / function• Aberrant behaviorsAberrant behaviors• AffectAffect
•Commonly reported association of persistent pain with psychological illness.
•Direction of causality is unknown between persistent pain and affective illness.
•Indication are that psychological disorder is a common correlate of persistent pain, and that this association is observed in a wide range of cultural settings.
Pain and Affective Disorders
JAMA. 1998;280:147-151Ed Salsizt
1.1. AddictionAddiction
2.2. PseudoaddictionPseudoaddiction
3.3. Other psychiatric disorderOther psychiatric disorder
4.4. EncephalopathyEncephalopathy
5.5. Family disturbanceFamily disturbance
6.6. Criminal intentCriminal intent
7.7. Exacerbation of pain syndromeExacerbation of pain syndrome
8.8. Side effect(s) of opioidSide effect(s) of opioid
Differential Diagnoses ofAberrant Drug Related Behaviors
Aberrant Drug Related Behaviors - Less Predictive of an Addiction
1.1. Aggressively complaining of the need for more Aggressively complaining of the need for more drugdrug
2.2. Drug hoarding during periods of reduced painDrug hoarding during periods of reduced pain
3.3. Requesting specific drugsRequesting specific drugs
4.4. Openly acquiring similar drugs from other Openly acquiring similar drugs from other medical sources if primary provider is absent medical sources if primary provider is absent or under-treatedor under-treated
5.5. Unsanctioned dose escalation or other non-Unsanctioned dose escalation or other non-compliance on one or two occasionscompliance on one or two occasions
1.1. Selling prescription drugsSelling prescription drugs
2.2. Prescription forgeryPrescription forgery
3.3. Stealing or “borrowing” drugsStealing or “borrowing” drugs
4.4. Obtaining prescription drugs form non-Obtaining prescription drugs form non-medical sourcesmedical sources
5.5. Concurrent abuse of alcohol or illicit Concurrent abuse of alcohol or illicit drugsdrugs
6.6. Multiple dose escalations or other non-Multiple dose escalations or other non-compliance with therapycompliance with therapy
Aberrant Drug Related Behaviors - Predictive of an Addiction
7. 7. Multiple episodes of prescription “loss”Multiple episodes of prescription “loss”
8. 8. Prescriptions from other clinicians/EDs Prescriptions from other clinicians/EDs without seeking primary prescriberwithout seeking primary prescriber
9. 9. Deterioration in function that appears to Deterioration in function that appears to be related to drug usebe related to drug use
10. 10. Resistance to change in therapy despite Resistance to change in therapy despite significant side effects from the drug significant side effects from the drug
Aberrant Drug Related Behaviors - Predictive of an Addiction
1.1. Syndrome of opioid Syndrome of opioid abuse/dependenceabuse/dependence
2.2. Other substance use disorderOther substance use disorder
3.3. Other psychiatric disorderOther psychiatric disorder
4.4. Exacerbation of pain syndromeExacerbation of pain syndrome
5.5. Other medical problemOther medical problem
6.6. Side effect of opioidSide effect of opioid
Differential Diagnosis of Functional Downturn
A Way Out A Way Out
Drug Abuse Treatment Act Drug Abuse Treatment Act (DATA) 2000 Schedule III (DATA) 2000 Schedule III
substancessubstances ADDICTION: ADDICTION:
Obtain DEA waiver; MD/DOObtain DEA waiver; MD/DO 30 patients only for addiction30 patients only for addiction
2007: 30/100 pt limit2007: 30/100 pt limit Once daily dosingOnce daily dosing
PAIN: PAIN: Any provider with a schedule III DEA Any provider with a schedule III DEA
can prescribe. can prescribe. Divided dosing.Divided dosing.
Open label study 95 consecutive patients on long term Open label study 95 consecutive patients on long term opioid therapy (LTOA) failing treatment based on:opioid therapy (LTOA) failing treatment based on: Increased painIncreased pain Decreased Functional CapacityDecreased Functional Capacity Emergence of opioid addiction (8%)Emergence of opioid addiction (8%)
Induced on buprenorphine 4-16mg (8mg mean dose)Induced on buprenorphine 4-16mg (8mg mean dose) 86% Experienced moderate to substantial pain relief86% Experienced moderate to substantial pain relief
Mood and function improvedMood and function improved 8% Discontinued due to side effects or increased pain8% Discontinued due to side effects or increased pain
Buprenorphine: Pain Buprenorphine: Pain DosageDosage
OFF LABELOFF LABEL Opioid NaïveOpioid Naïve
1-2 mg BID- QID (3-6mg/day)1-2 mg BID- QID (3-6mg/day) Opioid TolerantOpioid Tolerant
4mg TID-QID (12-16mg/day)4mg TID-QID (12-16mg/day) 24mg/day upper limits24mg/day upper limits 32mg/day maximum dose32mg/day maximum dose
CostCost Suboxone 8mg $5.97 Costco $2.15 Suboxone 8mg $5.97 Costco $2.15
FSSFSS Suboxone 2 mgSuboxone 2 mg
0 1 2 4 8 16 3210
11
12
13
14
15
16
17
Bre
ath
s/M
inu
te
PL Buprenorphine (mg, sl)
Human respiratory rate
Adapted from Walsh et al., 1994
Ceiling effect on Ceiling effect on respiratory depressionrespiratory depression
Buprenorphine-Buprenorphine-Benzodiazepine Relative Benzodiazepine Relative
ContraindicationContraindication CNS depressants and sedatives (eg, CNS depressants and sedatives (eg, benzodiazepinesbenzodiazepines):): All oAll opioids pioids have additive sedative effects when have additive sedative effects when
used in combination with other sedativesused in combination with other sedatives Increased potential for respiratory depression, Increased potential for respiratory depression,
heavy sedation, coma, and death (France, IV heavy sedation, coma, and death (France, IV aprazolam and buprenorphine)aprazolam and buprenorphine)
Despite favorable safety, use caution with Despite favorable safety, use caution with concomitant psychotropics (eg, concomitant psychotropics (eg, benzodiazepines)benzodiazepines)
Disadvantages:Disadvantages:Buprenorphine for PainBuprenorphine for Pain
Disadvantages of buprenorphine Disadvantages of buprenorphine over pure mu agonists:over pure mu agonists:
Binds so well to Binds so well to mumu receptor that receptor that other opioids have little effectother opioids have little effect
No prn short acting opioids for No prn short acting opioids for breakthrough painbreakthrough pain
Ceiling on effectivenessCeiling on effectiveness 24 mg “yellow light24 mg “yellow light 32mg “red light 32mg “red light
Ed Johnson Ed Johnson Phd, Personal Phd, Personal CommunicationCommunication
Surgery, Trauma? FENTANYL? Surgery, Trauma? FENTANYL?
Buprenorphine: Buprenorphine: Dosage Dosage FormsForms
Buprenex:Buprenex: Buprenorphine IM formulation * Buprenorphine IM formulation *
Suboxone 8/2 mg, 2/0.5mgSuboxone 8/2 mg, 2/0.5mg ** **Buprenorphine/Naloxone sublingual tabletBuprenorphine/Naloxone sublingual tablet
Subutex 2mg, 8mgSubutex 2mg, 8mg****Buprenorphine sublingual tabletBuprenorphine sublingual tablet
Transdermal Buprenorphine Transdermal Buprenorphine Not FDA approved in the USNot FDA approved in the US
Implant Implant InvestigationalInvestigational
**Intramuscular form FDA approved for pain Intramuscular form FDA approved for pain **Sublingual form FDA approved for addiction**Sublingual form FDA approved for addiction
If non-opioids are ineffective, may If non-opioids are ineffective, may need to increase or stop need to increase or stop buprenorphine and add a pure Mu buprenorphine and add a pure Mu agonist for pain (OR-fentanyl)agonist for pain (OR-fentanyl)
May need to switch to pure Mu May need to switch to pure Mu agonist for maintenance (baseline agonist for maintenance (baseline requirements)requirements)
Care needed if/when buprenorphine Care needed if/when buprenorphine is restarted for maintenanceis restarted for maintenance
Buprenorphine maintained patientsBuprenorphine maintained patients
Case Presentation - PL
Unable to taper at homeUnable to taper at home Referred to Inpatient Detox for Referred to Inpatient Detox for
Induction to BuprenorphineInduction to Buprenorphine Significant difficult in getting to Significant difficult in getting to
moderate withdrawal statemoderate withdrawal state Inducted on 24mg of BuprenorphineInducted on 24mg of Buprenorphine Remains on this dose 2 years later.Remains on this dose 2 years later.
Conclusion
• Use of opioids may be necessary for pain relief• Balanced multimodal care
– Use of opioids as part of complete pain care– Anticipation and management of side effects– Judicious use of short and long acting agents– Focus on persistent and breakthrough pain– Maintain standard of care
H&P, F/U, PRN referral, functional outcomes, documentation
• Treatment goals– Improved level of independent function– Increase in activities of daily living– Decreased pain
• PharmacovigilancePharmacovigilance• Functional outcomesFunctional outcomes• Standard medical practiceStandard medical practice• FSMB policyFSMB policy
• Open IssuesOpen Issues• What is meant by pain management?What is meant by pain management?• Who needs what treatment?Who needs what treatment?• Do universal approaches work?Do universal approaches work?• Does it improve outcomes?Does it improve outcomes?
• For patientsFor patients• For regulatorsFor regulators
Conclusion (cont)
Some ResourcesSome Resources www.AOAAM.orgwww.AOAAM.org www.pcss-b.orgwww.pcss-b.org www.painedu.comwww.painedu.com
PainEdu ManualPainEdu Manual Opioid Risk Management SupplementOpioid Risk Management Supplement
www.pain.comwww.pain.com Links to many pain sitesLinks to many pain sites
www.legalsideofpain.comwww.legalsideofpain.com Current status of laws regarding opioid RxCurrent status of laws regarding opioid Rx
www.partnersagainstpainwww.partnersagainstpain Purdue site with access to patient Purdue site with access to patient
management formsmanagement forms