Transcript Pain Med

Addressing the Barriers to
Effective Pain Management and
Issues of Opioid Misuse and Abuse
Earl Quijada, MD
Assistant Professor, Physical Medicine and Rehab
Linda Loma University
Linda Loma, California
Sponsored by The France Foundation
Supported by an educational grant from King Pharmaceuticals
Faculty Disclosure
It is the policy of The France Foundation to ensure balance, independence,
objectivity, and scientific rigor in all its sponsored educational activities. All
faculty, activity planners, content reviewers, and staff participating in this
activity will disclose to the participants any significant financial interest or
other relationship with manufacturer(s) of any commercial
product(s)/device(s) and/or provider(s) of commercial services included in
this educational activity. The intent of this disclosure is not to prevent a
person with a relevant financial or other relationship from participating in the
activity, but rather to provide participants with information on which they can
base their own judgments. The France Foundation has identified and
resolved any and all conflicts of interest prior to the release of this activity.
The following faculty have indicated they have no relationships with industry
to disclose relative to the content of this CME activity:
• Dr. Earl Quijada has nothing to disclose.
Educational Learning Objectives
• Identify the negative impact of persistent pain on
health and quality of life, methods to assess pain
levels, appropriate use of opioid medications, and
documentation required for compliance with
regulatory policies
• Integrate appropriate risk assessment strategies for
patient abuse, misuse, and diversion of opioids into
an overall management approach for acute and
chronic pain
• Describe the specific elements of new abuse
deterrent technologies associated with opioid
therapy, and assess their implications for clinical
practice
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.
Multiple Types of Pain
Examples
A. Nociceptive
Noxious
Peripheral
Stimuli
• Strains and sprains
• Bone fractures
• Postoperative
B. Inflammatory
• Osteoarthritis
• Rheumatoid arthritis
Inflammation
• Tendonitis
• Diabetic peripheral
neuropathy
C. Neuropathic
Multiple Mechanisms
Peripheral Nerve
Damage
• HIV-related polyneuropathy
• Fibromyalgia
D. Noninflammatory/
Nonneuropathic
Abnormal Central Processing
• Post-herpetic neuralgia
• Irritable bowel syndrome
No Known Tissue or
Nerve Damage
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
Long-Term Consequences of Acute Pain:
Potential for Progression to Chronic Pain
Sensitization
Surgery
or
injury
causes
inflammation
Peripheral
Nociceptive
Fibers
Transient
Activation
ACUTE
PAIN
Sustained
currents
Peripheral
Nociceptive
Fibers
Structural
Remodeling
CNS
Neuroplasticity
Hyperactivity
Sustained
Activation
CHRONIC
PAIN
Woolf CJ, et al. Ann Intern Med. 2004;140:441-451; Petersen-Felix S, et al. Swiss Med Weekly. 2002;132:273278; Woolf CJ. Nature.1983;306:686-688; Woolf CJ, et al. Nature. 1992;355:75-78.
Neuroplasticity in Pain Processing
100
Hyperalgesia3
Pain Sensation
80
60
heightened sense of
pain to noxious
stimuli
Injury
Allodynia
40
20
0
Normal Response
To Painful Stimulus
pain resulting from
normally painless
stimuli
innocuous
noxious
Stimulus Intensity
1. Woolf CJ, Salter MW. Science. 2000;288:1765-1768.
2. Basbaum AI, Jessell TM. The perception of pain. In: Kandel ER, Schwartz JH, et al. eds. Principles of Neural
Science. 4th ed. New York, NY: McGraw-Hill; 2000:479.
3. Cervero F, Laird JMA. Pain. 1996;68:13-23.
Vicious Cycle of Uncontrolled Pain
Avoidance
Behaviors
Pain
Decreased
Mobility
Social
Limitations
Altered
Functional
Status
Diminished
SelfEfficacy
Breaking the Chain of Pain Transmission
5-HT = serotonin; NE = norepinephrine;
TCA = tricyclic antidepressant
1. Gottschalk A, Smith DS. Am Fam Physician. 2001;63:1979-1984; 2. Iyengar S, et al. J Pharmacol Exp Ther. 2004;311:576-584;
3. Morgan V, et al. Gut. 2005;54:601-607; 4. Reimann W, et al. Anesth Analg. 1999;88:141-145. Vanegas H, Schaible HG. Prog
Neurobiol. 2001;64:327-363; 6. Malmberg AB, Yaksh TL. J Pharmacol Exp Ther. 1992;263:136-146; 7. Stein C, et al. J Pharmacol
Exp Ther. 1989;248:1269-1275.
Multimodal Treatment
Pharmacotherapy
Physical Medicine
and Rehabilitation
Assistive devices,
electrotherapy
Complementary
and Alternative
Medicine
Opioids, nonopioids,
adjuvant analgesics
Strategies for
Pain and
Associated
Disability
Interventional
Approaches
Injections,
neurostimulation
Psychological
Support
Psychotherapy,
group support
Massage, supplements
Lifestyle Change
Exercise, weight loss
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.
Components of Chronic Pain
• Chronic pain
– Baseline persistent pain
– Breakthrough pain (BTP)
BTP
8
6
4
2
Time, h
• Each component of chronic pain needs to be
independently assessed and managed
Portenoy RK, et al. Pain. 1999;81:129-134; Svendsen K, et al. Eur J Pain. 2005;9:195-206.
5 AM
4
3
2
1
12 AM
11
10
9
8
7
6 PM
5
4
3
2
1
12 PM
11
10
9
8
7
0
Baseline
Pain
6 AM
Pain Level
10
Positioning Opioid Therapy
for Chronic Pain
• Chronic non-cancer pain: evolving perspective
– Consider for all patients with severe chronic pain, but
weigh the influences
 What is conventional practice?
 Are there reasonable alternatives?
 What is the risk of adverse events?
 Is the patient likely to be a responsible drug-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.
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)
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.
Alternatives
to Opioid
Therapy
Use of Psychotherapeutic
Cointerventions
(9.1)
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)
Continue Opioid Therapy
Monitoring (5.1-5.3)
Breakthrough Pain (12.1)
Implement Exit Strategy
Opioid-Related Adverse Effects
(8.1)
Chou R, et al. J Pain. 2009;10:113-130.
*Clinician accepting primary responsibility for a patient’s overall medical care.
Opioid Formulations
Type of Drug
Examples
Pure m-opioid receptor agonists
Morphine, hydromorphone, fentanyl,
oxycodone
Dual mechanism opioids
Tramadol, tapentadol
Rapid onset (transmucosal)
Fentanyl, alfentanil, sufentanil,
diamorphine
Immediate release
Tramadol, oxycodone
Modified release (long acting)
Morphine, methadone, oxycodone
Available with co-analgesic
Oxycodone, tramadol, codeine
Only available with co-analgesic
Hydrocodone
Formulation Points to Consider
• Dose-limiting issues and toxicity with co-analgesics
– 4 g/day acetaminophen limit
• Importance of titration
– Risk of overdose, challenges of dose conversion during rotation
•
•
•
•
•
Pharmacokinetics versus temporal patterns of pain
Adherence
Cost
Convenience
Caregiving issues
Domains for Pain Management Outcome:
The 4 A’s
•
•
•
•
Analgesia
Activities of Daily Living
Adverse Events
Aberrant Drug-Taking Behaviors
Passik SD, Weinreb HJ. Adv Ther. 2000;17:70-83.
Passik SD, et al. Clin Ther. 2004;26:552-561.
Federation of State Medical Boards
of the United States, Inc
Model Policy for the Use of Controlled Substances
for the Treatment of Pain
Federation of State Medical Boards House of Delegates, May
2004. http://fsmb.org. Accessed March 2010.
FSMB Model Policy
Basic 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
New Illicit Drug Use United States, 2006
2,500
New Users (thousands)
2,150
2,063
2,000
1,500
1,112
1,000
500
977
860
845
783
267
264
91
69
0
Marijuana
Cocaine
Stimulants
Sedatives
Pain
Tranquilizers
Ecstasy
Inhalants
LSD†
Relievers*
Heroin
PCP†
*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.
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 074293; 2007.
Definition of Terms
Misuse
• Use of a medication (for a medical purpose) other than as directed or as
indicated, whether willful or unintentional, and whether harm results or
not
Abuse
• Any use of an illegal drug
• The intentional self administration of a medication for a nonmedical
purpose such as altering one’s state of consciousness, eg, getting high
Diversion
• The intentional removal of a medication from legitimate and dispensing
channels
Addiction
• A primary, chronic, neurobiological disease, with genetic, psychosocial,
and environmental factors influencing its development and
manifestations
• Behavioral characteristics include one or more of the following:
impaired control over drug use, compulsive use, continued use despite
harm, craving
Pseudoaddiction
• Syndrome of abnormal behavior resulting from undertreatment of pain
that is misidentified by the clinician as inappropriate drug-seeking
behavior
• Behavior ceases when adequate pain relief is provided
• Not a diagnosis; rather, a description of the clinical intention
Katz NP, et al. Clin J Pain. 2007;23:648-660.
Prevalence of Misuse, Abuse,
and Addiction
Misuse 40%
Abuse: 20%
Addiction: 2% to 5%
Webster LR, Webster RM. Pain Med. 2005;6(6):432-442.
Total Pain
Population
Who Misuses/Abuses Opioids and Why?
Nonmedical
Use
• Recreational
abusers
• Patients with
disease of
addiction
Medical Use
• Pain patients
seeking more
pain relief
• Pain patients
escaping
emotional pain
Rx Opioid Users Are Heterogeneous
Nonmedical Users
Pain Patients
Passik SD, Kirsch KL. Exp Clin Psychopharmacol. 2008;16(5):400-404.
Risk Factors for
Aberrant Behaviors/Harm
Biological
• Age ≤ 45 years
• Gender
• Family history of
prescription drug
or alcohol abuse
• Cigarette
smoking
Psychiatric
• Substance use
disorder
• Preadolescent
sexual abuse
(in women)
• Major psychiatric
disorder
(eg, personality
disorder, anxiety
or depressive
disorder, bipolar
disorder)
Social
• Prior legal
problems
• History of motor
vehicle accidents
• Poor family
support
• Involvement in a
problematic
subculture
Katz NP, et al. Clin J Pain. 2007;23:103-118; Manchikanti L, et al. J Opioid Manag. 2007;3:89-100.
Webster LR, Webster RM. Pain Med. 2005;6:432-442.
Stratify Risk
Low Risk
• No past/current
history of
substance abuse
• Noncontributory
family history of
substance abuse
• No major or
untreated
psychological
disorder
Moderate Risk
High Risk
• History of treated
substance abuse
• Active substance
abuse
• Significant family
history of
substance abuse
• Active addiction
• Past/comorbid
psychological
disorder
Webster LR, Webster RM. Pain Med. 2005;6:432-442.
• Major untreated
psychological
disorder
• Significant risk
to self and
practitioner
10 Principles of Universal Precautions
1.
2.
3.
4.
5.
6.
7.
8.
Diagnosis with appropriate differential
Psychological assessment including risk of addictive disorders
Informed consent (verbal or written/signed)
Treatment agreement (verbal or written/signed)
Pre-/post-intervention assessment of pain level and function
Appropriate trial of opioid therapy adjunctive medication
Reassessment of pain score and level of function
Regularly assess the “Four A’s” of pain medicine: Analgesia, Activity,
Adverse Reactions, and Aberrant Behavior
9. Periodically review pain and comorbidity diagnoses, including addictive
disorders
10. Documentation
Gourlay DL, Heit HA. Pain Med. 2009;10 Suppl 2:S115-123.
Gourlay DL, et al. Pain Med. 2005;6(2):107-112.
Initial Visits
•
•
•
•
•
•
•
Initial comprehensive evaluation
Risk assessment
Prescription monitoring assessment
Urine drug test
Opioid treatment agreement
Opioid consent form
Patient education
McGill Short Form Pain Questionnaire
Results of Short and Long
Form tests correlate well for
postsurgical pain
r = 0.67 - 0.86, P  0.002
Melzack R. Pain. 1987;30:191-197.
Principles of Responsible Opioid Prescribing
• Patient Evaluation
–
–
–
–
–
–
–
Pain assessment and history
Directed physical exam
Review of diagnostic studies
Analgesic and other medication history
Personal history of illicit drug use or substance abuse
Personal history of psychiatric issues
Family history of substance abuse/psychiatric
problems
– Assessment of comorbidities
– Accurate record keeping
Fine PG, Portenoy RK. Clinical Guide to Opioid Analgesia, 2nd edition, 2007.
Principles of Responsible Opioid Prescribing
Treatment Plan
• I have resolved key points before initiating opioid therapy
– Diagnosis established and opioid treatment plan developed
– Established level of risk
– I can treat this patient alone/I need to enlist other consultants to
co-manage this patient (pain or addiction specialists)
• I have considered nonopioid modalities
– Pain rehabilitation program
– Behavioral strategies
– Non-invasive and interventional techniques
Principles of Responsible Opioid Prescribing
Treatment Plan (cont)
•
•
•
•
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
Algorithm for the
Management of Chronic Pain
Pain frequency
Frequency flares of constant disturbing pain
Infrequent flares < 4 days per week
Analgesics
Ineffective or
require
excessive
doses
Short-acting
opioids
Physical therapy
Flare
management:
oscillatory
movements,
distraction
techniques,
trigger point
massage
Additional features
Psychology
Relaxation
Stress
management
Neuropathic
pain, burning
quality, nerve
injury, neuralgia
First line
Antidepressants:
TCA, SSRI
Antiepileptics:
gabapentin,
lamotrigine
Structural
pathology with
disability and
or overuse of
analgesics
Physical therapy Occupational
therapy
Psychology
Reconditioning
Body mechanics
Stretching
Work
exercises
simplification
Pacing skills
Cognitive
restructuring
Relaxation
Stress
management
Adjunctive
Capsaicin cream
Mexiletine
Long-acting
opioids
Long-acting
opioids
TCA = tricyclic antidepressants: SSRI = selective serotonin reuptake inhibitors
Marcus DA. Am Fam Physician. 2000;61(5):1331-1338.
Medical Records
• Maintain accurate, complete, and current records
–
–
–
–
–
–
–
–
–
Medical Hx & PE
Diagnostic, therapeutic, lab results
Evaluations/consultations
Treatment objectives
Discussion of risks/benefits
Tx and medications
Instructions/agreements
Periodic reviews
Discussions 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.
Considerations
• What is conventional practice for this type of pain or pain patient?
• Is there an alternative therapy that is likely to have an equivalent or
better therapeutic index for pain control, functional restoration, and
improvement in quality of life?
• Does the patient have medical problems that may increase the risk
of opioid-related adverse effects?
• Is the patient likely to manage the opioid therapy responsibly?
• Who can I treat without help?
• Who would I be able to treat with the assistance of a specialist?
• Who should I not treat, but rather refer, if opioid therapy is a
consideration?
Fine PG, Portenoy RK. Clinical Guide to Opioid Analgesia. Vendome Group, New York, 2007.
Initiation of
Therapy for
Chronic Pain
Marcus DA. Am Fam Physician. 2000;61(5):1331-1338.
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.
Differential Diagnosis of Aberrant
Drug-Taking Attitudes and Behavior
• Addiction (out-of-control, compulsive drug use)
• Pseudoaddiction (inadequate analgesia)
• Other psychiatric diagnosis
– Organic mental syndrome
(confused, stereotyped drug-taking)
– Personality disorder (impulsive, entitled, chemical-coping
behavior)
– Chemical coping (drug overly central)
– Depression/anxiety/situational stressors
(self-medication)
• Criminal intent (diversion)
Passik SD, Kirsh KL. Curr Pain Headache Rep. 2004;8:289-294.
Identifying Who Is at Risk
for Opioid Abuse and Diversion
•
•
•
•
•
•
•
•
Predictive tools
Aberrant behaviors
Urine drug testing
Prescription monitoring
programs
Severity and duration of pain
Pharmacist communication
Family and friends
Patients
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.
Risk Assessment Tools
• Addiction Behaviors Checklist (ABC)
– Evaluate and monitor behaviors indicative of
addiction related to prescription opioids in patients
with chronic pain
• Addiction Severity Index (ASI)
– Assess current and lifetime substance-use
problems and prior treatment
• Current Opioid Misuse Measure (COMM)
– Periodically monitor aberrant medication-related
behaviors in patients with chronic pain currently on
opioid therapy
Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14.
Risk Assessment Tools (cont)
• Drug Abuse Screening Test (DAST-10)
– Screen for probably drug abuse or dependence
• Pain Medication Questionnaire (PMQ)
– Assess risk for opioid medication misuse in patients with
chronic pain
• 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
Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14.
Risk Assessment Tools (cont)
• Diagnosis, Intractability, Risk, Efficacy (DIRE)
– Predict the analgesic efficacy of, and patient compliance to,
long-term opioid treatment in the primary care setting
• Screener and Opioid Assessment for Patients with
Pain-Revised (SOAPP-R)
– Predict aberrant medication-related behaviors in patients with
chronic pain considered for long-term opioid therapy
»
»
»
»
Empirically-derived, 24-item self-report questionnaire
Reliable and valid
Less susceptible to overt deception than past version
Scoring:  18 identifies 90% of high-risk patients
Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14.
Butler SF, et al. J Pain. 2008;9:360-372.
ORT Validation
Mark each box that applies
1.
Male
1
3
2
3
4
4
3
3
4
4
5
5
Family history of substance abuse
– Alcohol
– Illegal drugs
– Prescription drugs
2.
Female
• Exhibits high degree of
sensitivity and specificity
• 94% of low-risk patients did
not display an aberrant
behavior
Personal history of substance abuse
– Alcohol
– Illegal drugs
– Prescription drugs
3.
Age (mark box if 16-45 years)
1
1
4.
History of preadolescent sexual abuse
3
0
5.
Psychological disease
2
2
1
1
– ADD, OCD, bipolar, schizophrenia
– Depression
N = 185
ADD, attention deficit disorder; OCD, obsessive-compulsive disorder.
Webster LR, Webster RM. Pain Med. 2005;6:432-442.
• 91% of high-risk patients did
display an aberrant behavior
SOAPP
Chris Jackson
Name:_________________
Date:___________
9/16/09
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? 0
1 2
О
3
4
2. How often do you smoke a cigarette within an hour after you wake up?
0 1 2 3 4
3. How often have you taken medication other than the way that it was
prescribed?
0 1 2 3 4
О
4. How often have you used illegal drugs (for example, marijuana, cocaine,
etc.) in the past five years?
0
1
2
3
4
5. How often in your lifetime have you had legal problems or been
arrested?
0 1 2 3 4
Please include any additional information you wish about the above answers.
Thank you
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
-
Risk Assessment Tools Highlights
• ORT, SOAPP & DIRE
– Best assess abuse potential among those being
considered for long-term opioid therapy
• COMM & PMQ
– Characterize degree of medication misuse or
aberrant behavior once opioids are started
• DAST-10 & PMQ
– More suitable for assessing current alcohol and/or
drug abuse than potential for such abuse
Passik SD, et al. Pain Med. 2008;10 Suppl 2:S145-166.
Urine Drug Testing
• When to test?
– Randomly, annually, PRN
• What type of testing?
– POC, GS/MS
• How to interpret
– Metabolism of opioids
– False positive and negative results
• What to do about the results
– Consult, refer, change therapy, discharge
The Role of UDT
• UDT in clinical practice may
– Provide objective documentation of
compliance with treatment plan by
detecting presence of a particular drug
or its metabolites
– Assist in recognition of addiction or
drug misuse if results abnormal
• Results are only as reliable as testing laboratory’s
ability to detect substance in question
Heit HA, Gourlay DL. J Pain Symptom Manage. 2004;27:260-267.
Dove B, Webster LR. Avoiding Opioid Abuse while Managing Pain: a Guide for Practitioners.
North Branch, MN: Sunrise River Press; 2007.
Positive and Negative
Urine Toxicology Results
• Positive forensic testing
– Legally prescribed
medications
– Over-the-counter
medications
– Illicit drugs or unprescribed
medications
– Substances that produce
the same metabolite as that
of a prescribed or illegal
substance
– Errors in laboratory analysis
• Negative compliance testing
–
–
–
–
Medication bingeing
Diversion
Insufficient test sensitivity
Failure of laboratory to test for
desired substances
Heit HA, Gourlay DL. J Pain Symptom Manage. 2004;27:260-267.
Urine Drug Testing
• Initial testing done with class-specific immunoassay drug
panels
– Typically do not identify individual drugs within a class
• Followed by a technique
such as GC/MS
– To identify or confirm the
presence or absence of a
specific drug and/or its
metabolites
Heit HA, Gourlay D. J Pain Sympt Manage. 2004:27:260-267.
UDT Immunoassay Screening
• Lab Testing or POCT
– Drug class
– High sensitivity,
low specificity
– Rapid results
– Not quantitative
POCT, point-of-care testing
Hammett-Stabler CA, Webster LR. A Clinical Guide to Urine Drug Testing. Stamford, CT: PharmaCom Group
Inc; 2008.
Detection of Opioids
• Opiate immunoassays detect morphine and
codeine
– Do not detect synthetic opioids
 Methadone
 Fentanyl
– Do not reliably detect semisynthetic opioids




Oxycodone
Hydrocodone
Buprenorphine
Hydromorphone
• GC/MS will identify these medications
Heit HA, Gourlay D. J Pain Sympt Manage. 2004:27:260-267.
UDT Laboratory-Based Tests
• GC/MS, LC/ MS,
ELISA
– High sensitivity,
high specificity
– Expensive
– Quantitative
– 1-3 days for
results
RESULTS OF CONTROLLED SUBSTANCE UDT:
WORKPLACE
Donor Name: Jack
Donor ID #: 1897221
Specimen ID #: 1897221-112
Accession #: None assigned
Random
Date collected: 04/11/2008
Date received: 04/15/2008
Class or Analyte
Result
AMPHETAMINES
BARBITUATES
BENZODIAZEPINES
CANNABINOIDS
COCAINE
METHADONE
OPIATES
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
NEGATIVE
POSITIVE
Validity Test
Result
CREATININENORMAL at 33.4 mg/dL
SPECIFIC GRAVITY
NORMAL
pH
NORMAL
Reason for test:
Time collected: 1648
Date reported: 04/15/2008
Screen Cut-Off
1,000 ng/ml
200 ng/ml
200 ng/ml
50 ng/ml
300 ng/ml
150 ng/ml
100 ng/ml
Normal Range
≥ 20 mg/dL
≥ 1.003
4.6-8.0
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.
Opioid Metabolism
Not comprehensive
pathways, but may
explain presence
of apparently
unprescribed drugs
Heroin
6-MAM
C-6G
Codeine
Morphine
Minor
Hydrocodone
Dihydrocodeine
M-3G
Minor
Hydromorphone
Dihydromorphone
Gourlay D, et al. http://www.familydocs.org/assets/171_UDT%202006.pdf. Accessed March 2010;
Cone EJ, et al. J Anal Toxicol. 2006;30:1-5; Heit HA, Gourlay D. Personal Communication. 2008.
Detection Times of Common Drugs of Misuse
Drug
Approximate Retention Time
Amphetamines
• 48 hours
Barbiturates
Benzodiazepines
• Short-acting (eg, secobarbital), 24 hours
• Long-acting (eg, phenobarbital), 2–3 weeks
• 3 days if therapeutic dose is ingested
• Up to 4–6 weeks after extended dosage (≥ 1 year)
• Moderate smoker (4 times/week), 5 days
Cannabinoids
• Heavy smoker (daily), 10 days
• Retention time for chronic smokers may be 20–28 days
Cocaine
• 2–4 days, metabolized
Ethanol
• 2–4 hours
Methadone
• Approximately 30 days
Opiates
• 2 days
Phencyclidine
Propoxyphene
• Approximately 8 days
• Up to 30 days in chronic users (mean value = 14 days)
• 6–48 hours
Gourlay DL, Heit HA. Pain Med. 2009;10 Suppl 2:S115-123.
Risk Evaluation and Mitigation Strategies
Position of the FDA
• The current strategies for intervening with [the problem of
prescription opioid addiction, misuse, abuse, overdose and
death] are inadequate
• New authorities granted under FDAAA: [FDA] will now be
implementing Risk Evaluation and Mitigation Strategies
(REMS) for a number of opioid products
• [FDA expects] all companies marketing these products to
[cooperate] to get this done expeditiously
• If not, [FDA] cannot guarantee that these products will
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.
States with PMPs
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.
Identifying and Managing Abuse
and Diversion
•
•
•
•
•
•
Assessing risk and aberrant behaviors
Performing scheduled and random UDTs
Utilization of PMPs
Assessing stress and adequacy of pain control
Developing good communication with pharmacists
Receiving input from family, friends, and other patients
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
Setting
– Primary care
– Managed by nurse practitioner and clinical pharmacist
– Philadelphia VA pain clinic
Structured program
– Electronic referral by PCP
• Signed Opioid Treatment Agreement
• UDT
– Support from multidisciplinary pain team: addiction psychiatrist,
rheumatologist, orthopedist, neurologist, and physiatrist
– Multimodal management
•
•
•
•
•
Opioids
NSAIDs and acetaminophen for osteoarthritis
Transcutaneous electrical stimulation (TENS) units
Antidepressants and anticonvulsants for neuropathic pain
Reconditioning exercises
Wiedemer NL, et al. Pain Med. 2007;8(7):573-584.
Opioid Renewal Clinic: Results
• OTAs increased: 63  214
• Monthly UDTs increased: 80  200
• Oxycodone SA use decreased
– Quarterly costs: $130,000 $5,000
– Percent of opioids: 22.5% 0.4%
• ER visits reduced 73%
• Unscheduled PCP visits reduced 60%
• PCPs satisfied (questionnaire)
• 171/335 patients referred had aberrant drug-taking behaviors
– 45% adhered to OTA (resolved aberrant behaviors)
– 38% self-discharged from ORC
– 13% referred for addiction treatment
– 4% consistently negative UDT
Wiedemer NL, et al. Pain Med. 2007;8(7):573-584.
Opioid Abuse-Deterrent
Strategies Hierarchy
Increasing Direct Abuse Deterrence
Combination Mechanisms
Pharmacologic
•
•
•
Sequestered antagonist
Bio-available antagonist
Pro-drug
Aversive Component
•
•
•
Capsaicin – burning sensation
Ipecac – emetic
Denatonium – bitter taste
Physical
•
Difficult to crush
•
Difficult to extract
•
•
RFID – Protection
Tamper-proof bottles
Deterrent Packaging
Prescription Monitoring
Electronic Track and Trace RFID
• Secures integrity of drug supply chain by providing accurate
drug "pedigree"
– A record documenting that the drug was manufactured and
distributed under secure conditions. We particularly advocated for the
implementation of and noted that radio-frequency identification
(RFID) is the most promising
• RFID technology
– Tiny radio frequency chip containing essential data in the form of an
electronic product code (EPC)
– Each discrete product unit has a unique electronic serial number
– Product can be tracked electronically through every step of the supply
chain
RFID, radiofrequency identification
Physical Deterrent: Viscous Gel Base
• SR oxycodone formulation: Remoxy™
– Deters dose dumping
 Accessing entire 12-h dose of CR medication at 1 time
– Difficult to crush, break, freeze, heat, dissolve
 The viscous gel-cap base of PTI-821 cannot be injected
 Resists crushing and dissolution in alcohol or water
Aversive Component
• Capsaicin
– Burning sensation
• Ipecac
– Emetic
• Denatonium
– Bitter taste
• Niacin
– Flushing, irritation
Pharmacologic Deterrent: Antagonist
• Sequestered antagonist
• Bioavailable antagonist
• Antagonists are released
only when agent is
crushed for extraction
–
Oral-formulation
sequestered antagonist
becomes bioavailable
only when sequestering
technology is disrupted;
targeted to prevent
intravenous abuse
Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guide for Practitioners. 1st ed. North
Branch, MN: Sunrise River Press; 2007.
Remaining Questions
• How much does the barrier approach deter the
determined abuser?
• How much do agonist/antagonist compounds
retain efficacy?
• How much do agonist/antagonist compounds
pose serious adversity?
Patient Case Studies
Case Study 1
• A 56-year-old healthy male with acute back pain
• Conservative therapy ineffective
• Dx with acute thoracic compression fractures
• Persistent pain 6/10 and activity related pain 10/10
• ORT 5
• UDT consistent therapy
• PMP: no opioids
• Rx started with hydrocodone 10 mg/APAP q 4 hours
• Titrated to 50 mg CR morphine/naltrexone BID
Case Study 1 (cont)
• Monitoring
– Weekly visits until stable
– Prescribe only enough medication until next visit
• RX
– Short acting for BTP
– CR formulation (with less street attractiveness)
– Vertebroplasty partially effective
• Six month follow-up
–
–
–
–
Much improved; pain 2/10, => tapered of opioids by 70%
No aberrant behaviors
PMP showed no aberrant behavior
Monthly UDT consistent with therapy
Case Study 2
• 38-year-old female actress with ovarian cancer and
peripheral neuropathy from therapy
• ORT score was 9
• Urine drug test: THC, amphetamines
• History of oxycodone addiction, ADD, sexual abuse
• Smokes 1 pack per day since the age of 12
• Consumes 20 drinks per week
• PMP: several opioid prescriptions from different providers
Case Study 2 (cont)
• RX
–
–
–
–
•
Instructed to D/C THC
OTA
Pregabalin 600 mg/day
Methadone was slowly titrated to 10 mg qid, Education for Safe Use
Two weeks later
– Patient said she couldn’t tolerate methadone
– Asked for oxycodone
– Pregabalin is causing confusion and severe memory impairment,
can’t remember her lines in performance
Case Study 2 (cont)
• High risk determines what type of monitoring/therapy
– Can oxycodone be safely prescribed?
• Abnormal PMP suggest substance abuse or diversion
– UDT and PMP role in monitoring? Frequency?
• What to do about THC?
– What if it is medical marijuana?
• Positive UDT amphetamine due to ADD treatment?
– Can UDTs differentiate methamphetamine from Adderall?
• What multi-therapeutic approaches should be taken?
• Should opioids be prescribed?
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
Conclusion (cont)
• Pharmacovigilance
–
–
–
Functional outcomes
Standard medical practice
FSMB policy
• Certain
–
It is required
• Uncertain
–
–
–
–
What is meant by pain management?
Who needs what treatment?
Do universal approaches work?
Does it improve outcomes?
 For patients
 For regulators
Online Resources
Resource
American Academy
of Pain Medicine
American Pain Society
Federation of State
Medical Boards
American Academy of
Pain Management
PMQ
Opioid Management Plan
Opioid Treatment
Agreement
Web Address
http://www.painmed.org/clinical_info/guidelines.html
http://www.ampainsoc.org/pub/cp_guidelines.htm
http://www.ampainsoc.org/links/clinician1.htm
http://www.fsmb.org/RE/PAIN/resource.html
http://www.aapainmanage.org/literature/Publications.php
http://www.permanente.net/homepage/kaiser/pdf/59761.pdf
McGill Pain Questionnaire (Melzack R. Pain.1987;30:191-197)
http://www.aafp.org/afp/20000301/1331.html
http://www.lni.wa.gov/ClaimsIns/Files/OMD/agreement.pdf.