Download Part 1 of 3 Trainers Donald Harrell Meg Rumfield

• Donald Harrell
• Meg Rumfield
• Claire Saadeh
Trainers • Karel Schram
Venue:
Joint Provider Surveyor
Training
City:
Grand Rapids
State:
Michigan
Date:
Tuesday, April 1, 2014
None of the trainers have
anything to disclose
Disclosure:
Part 1 of 3
1
Mary Williams
Case Study
Overview

42 year old female

Hypertension

Type 2 diabetes with painful
neuropathy

Chronic low back pain
2
Mary Williams
Case Study
Past Medical History

Type 2 diabetes mellitus x 8 years
– Painful diabetic neuropathy x 2 years

Hypertension

Chronic low back pain

Tobacco dependence

Alcohol dependence (in recovery 10 yrs)

Obesity
3
Mary Williams
Case Study
Current Medications

Metformin 1000 mg 2x/day

Lisinopril 10 mg 1x/day

Hydrochlorothiazide 12.5 mg 1x/day

Aspirin 81 mg 1x/day
Current Pain Medications

Oxycodone/APAP 5mg/325 mg
1-2 tablets every 4-6 hours
 Gabapentin 300 mg 3x/day
4
Mary Williams
Case Study
Previous Pain Medications

NSAIDs (inadequate pain relief and
upset stomach)

Acetaminophen (inadequate pain
relief)

Tricyclic antidepressants
(inadequate pain relief and dry
mouth)

Tramadol (inadequate pain relief)

Acetaminophen with codeine
(inadequate pain relief)
5
Mary Williams
Case Study
Social History

Receptionist - law office 20 hrs/week

Married - husband manages
hardware store

Children - ages 6, 12 and 15 years
6
Mary Williams
Case Study
Substance Use History

Alcohol dependence (in recovery for
past 10 years)

Tried marijuana in high school

No recent history of illicit drug use

Smokes tobacco 1 pack per day for
the past 25 years
Family History
 Family history of substance
abuse
– Mother died from complications of
alcoholic cirrhosis
7
Assessing Chronic Pain
and Opioid Misuse Risk
8
Learning Objectives: Presentation 1

Discuss prevalence of chronic pain in the US

Discuss prevalence of the use and misuse of
opioid analgesics

Describe the pharmacology, efficacy and safety
of opioid analgesics

Describe the components of a thorough opioid
misuse risk assessment for a potential candidate
for chronic opioid therapy
9
Mary Williams Case Presentation
 Visiting provider for first time
 Previous PCP moved out of state
Takes 4 to 8
oxycodone/
APAP tablets
per day for
chronic pain
– Makes it
possible for
her to go to
work
Best pain relief
8 tablets per
day
– Previous PCP
limit of 150
tablets per
month
– Afraid she
would become
“addicted”
She hopes to
get enough
medication
to
consistently
take 8
tablets per
day
10
Mary Williams Case Presentation
Very careful
not to run out
early
Gets anxious
if supply runs
out early in
month
Nausea,
vomiting and
diarrhea
upon running
out
Has enough
medication to
last one week
Brought in her
previous
medical
records
11
Mary Williams Case Presentation
 Severe pain in feet
Burning, numbness and tingling
 Trouble sleeping and “depressed”
because of her chronic pain
 Pain worse at night
States pain
is “20”
 Due to only taking 3-4 tablets/day
because it is end of month
on a scale
of 0 - 10
Range of Pain
0
None
1
2
3
4
5
6
7
8
9
10
Bad as
possible
11
12
13
14
15
16
17
18
19
20
12
Assessing Pain
13
Building Trust
Patient Issues
Patients will assume that
you don’t believe their pain complaints
Often demonstrated by
exaggerating pain scores
14
Building Trust
Patient Issues
Some patients with adequate pain relief
Believe it is not in their best interest to report pain relief
Fear that medication will be reduced
Fear that physician may decrease efforts
to diagnose problem
Evers GC, et al. Support Care Cancer. 1997 Nov;5(6):457-60.
15
Building Trust
Provider Strategies
 Assume patient fears you think pain is not real or not
very severe
 After you take a through pain history…
Show empathy for
patient experience
Educate patient about need
for accurate pain scores to
monitor therapy
Validate that you
believe pain is real
Discuss factors which
worsen pain and limit
treatment (i.e. substance
abuse, mental health)
Believing patient’s pain complaint does not mean
opioids are indicated
16
Pain Assessment

Pain scales
– Numeric rating
– Visual analog
– Faces scale

Multidimensional instruments
– McGill Pain Questionnaire
– Brief Pain Inventory (BPI)
Impractical for
routine use in
primary care
– Pain, Enjoyment, General activity (PEG) scale
Brevik H et al. Br J Anaesh 2008;101:17-24.
Krebs EE et al. J Gen Intern Med 2009;24(6):733-8.
17
Mary Williams
Case Study
PEG Scale Assessment
In the past week:
Pain on average?
0
1
2
3
4
5
6
7
8
9
As bad as
you can
imagine
No pain
0
10
1
2
Pain interfered with Enjoyment of
life?7
3
4
5
6
8
9
10
Completely
interferes
Does not interfere
Pain interfered with General activity?
0
1
2
Does not interfere
3
4
5
6
7
8
9
10
Completely
interferes
18
Mary Williams
Case Study
Physical

Normal vital signs

Weight 220 lbs (BMI 32 = obese)

No acute distress

Normal cardiopulmonary exam

Spine normal alignment, negative
straight leg test

No Achilles tendon reflex bilaterally

Diabetic foot exam:
– No lesions/ulcerations
– Palpable pulses
– Monofilament testing bilaterally 4/5
19
Scope of the Problem
100 Million in U.S. with
Chronic Pain
 42% with pain lasting
over one year


33% report pain as
disabling
63% have seen
primary care physician
for help
120
Prevalence
in Millions
100
100
80
60
40
20
19
21
CHD
Diabetes
0
Chronic
Pain
$600 Billion Annual Costs
 Healthcare expenses
 Lost income
 Lost productivity
American Academy of Pain Medicine www.painmed.org
Institute of Medicine. 2011 Relieving Pain in America. Washington DC
20
Chronic Pain is Complex
Genetic Predispositions
 Structure and function of the nervous system
 Molecular basis for response to pain and/or analgesia
Environmental Stressor Effects
Work, home
Social Effects
 Socially determined constructs of pain, suffering and
disability
 Beliefs about pain treatment
Apkarian AV et al. Pain 2011; 152 (3 Suppl): S49-S64.
Bennett RM. Mayo Clin Proc 1999;74:385-398.
21
Chronic Pain Affected by Co-Morbidities
Condition
Incidence
Chronic Pain Patients
Depression
33 - 54%
Anxiety
Disorders
Personality
Disorders
PTSD
Substance
Use Disorders
16.5 - 50%
References
Cheatle M, Gallagher R, 2006
Dersh J, et al., 2002
Knaster P, et al., 2012
Cheatle M, Gallagher R, 2006
Polatin PB, et al. 1992
31 - 81%
49% veterans
2% civilians
Fischer-Kern M, et al., 2011
Otis, J, et al., 2010
Knaster P, et al., 2012
Polatin PB, et al. 1992
15 - 28%
Cheatle M, Gallagher R, 2006
22
Psychiatric Co-Morbidities
Patient “A”Pain 8/10
Cultural
Background
Environmental
Stressors
Functional
Disability
Social
Disability
Physical
Injury
Genetics
Patient “B” Pain 8/10
Cultural
BackgroundEnvironmental
Stressors
Functional
Disability
Social
Disability
Cognitive
Dysfunction
Depression
& Anxiety
Gatchel RJ. Am Psychol. 2004 Nov;59(8):795-805.
Substance
Abuse
Physical
Injury
Genetics
Addiction
Depression
& Anxiety
23
Screening for Unhealthy Substance Use
Alcohol
“Do you sometimes drink beer wine or other alcoholic
beverages?”
“How many times in the past year have you had 5 (4 for
women) or more drinks in a day?”
(+ answer: > 0)
Drugs
“How many times in the past year have you used an
illegal drug or used a prescription medication for nonmedical reasons?”
(+ answer: > 0)
Smith PC, et al. Gen Intern Med. 2009 Jul;24(7):783-8.
Smith PC, et al. Arch Intern Med. 2010 Jul 12;170(13):1155-60.
24
Screening for Mental Illness
Patient Health Questionnaire (PHQ 2, PHQ 9)
Other psychiatric history – anxiety, PTSD
Suicidal, homicidal
Mental status and competency
25
Screening for Depression
PHQ2 Patient Health Questionnaire
Over the last 2 weeks, how
often have you been bothered
 Interpretation
by any of the following
– Positive if 3 or more points
problems?
1.Little interest or pleasure
in doing things
2.Feeling down, depressed,
or hopeless

Administer PHQ9 if positive

Efficacy
– Test Sensitivity: 83%
– Test Specificity: 92%
Scoring:
0
1
2
3
Not at all
Several days
More than half the days
Nearly every day
Kroenke K, Spitzer RL, Williams JB.Med Care. 2003 Nov;41(11):1284-92.
26
Mary Williams
Case Study
Screenings: Substance Abuse
and Depression

Screened negative for unhealthy
substance use and depression
27
Opioid Pharmacology
28
When are Opioids Indicated?
Pain is moderate to severe
Pain has significant impact on function
Pain has significant impact on quality of life
Non-opioid pharmacotherapy has failed
If already on opioids, is there documented benefit
29
Mary Williams
Case Study
YES Pain is moderate to severe
YES
Pain has significant impact
on function
YES
Pain has significant impact on
quality of life
YES
Non-opioid pharmacotherapy
has failed
NOT
KNOWN
If already on opioids, is there
documented benefit
30
Opioids
Diacetylmorphine (Heroin)
Oxymorphone
Natural (Opiates)
and Semisynthetic
Hydrocodone
Oxycodone
Hydromorphone
Synthetic
Methadone
Meperidine
Fentanyl
31
Opioid Chemical Classes with Examples
prototypical opioids
 Morphine, Codeine,
Hydromorphone, Hydrocodone,
Oxymorphone, Buprenorphine
Benzomorphans
 Pentazocine
Phenylpiperidines
 Fentanyl
Diphenylheptanes
 Methadone
Phenathrenes
Trescot AM et al. Pain Physician 2008;11:S133-S153.
32
Activation of Mu Receptors
Opioid Pharmacodynamics

Turn on descending inhibitory
systems in the midbrain

Prevent ascending
transmission of pain signal

Inhibit terminals of C-fibers in
the spinal cord

Inhibit activation of peripheral
nociceptors
McCleane G, Smith HS. Med Clin North Am. 2007 Mar;91(2):177-97. Image source: www.mayo.edu/proceedings
33
How Good are Opioids for Chronic Pain?

Most literature: surveys and uncontrolled case
series
 RCTs are short duration <8 months with small
samples <300 pts
 Mostly pharmaceutical company sponsored
 Outcomes
–
–
–
–
Better analgesia with opioids vs. controls
Pain relief modest
Mixed reports on function
Addiction not assessed
Ballantyne JC, Mao J. N Engl J Med. 2003 Nov 13;349(20):1943-53.
Kelso E, et al. Pain. 2004 Dec;112(3):372-80.
Eisenberg E, McNicol ED, Carr DB. JAMA. 2005 Jun 22;293(24):3043-52.
Furlan AD, et al. CMAJ. 2006 May 23;174(11):1589-94.
Noble M, et al. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD006605.
34
Variable Response to Opioids
Not all patients respond to
the same opioid in
the same way
Not all pain
responds to the
same opioid in the
same way
35
Variable Response to Opioids
Mu Receptor

G protein-coupled receptor family, signal via
second messenger (cAMP)

>100 polymorphisms in the human MOR gene

Mu receptor subtypes
Smith HS. Pain Physician 2008;11: 237-248.
36
Variable Response to Opioids
Opioid Pharmacokinetics

Opioid metabolism differs by individual opioid
and by individual patient

Most opioids are metabolized by the cytochrome
P450 (CYP) system
– Codeine may be ineffective in ~10% of Caucasians
due to genetic polymorphisms in CYP2D6

Trial of several opioids may be needed to find
acceptable balance between analgesia and
tolerability
Smith HS. Mayo Clin Proc. 2009 Jul;84(7):613-24.
37
Opioid Choices with Examples
Full mu
agonists
 Morphine, Oxycodone, Hydrocodone,
Hydromorphone, Fentanyl,
Methadone, Oxymorphone
Partial mu
agonist
 Buprenorphine
Opioids
Mixed
agonist/
antagonists
Dual
mechanism
opioid
analgesics
 Tramadol, Tapentadol
 Pentazocine
38
Opioid Formulations and Routes
Transdermal
 Immediate release (IR)
 Extended release/ Long
acting (ER/LA)
Oral
 Fentanyl
 Buprenorphine
 Buprenorphine
off-label use for
pain
Sublingual
39
Transdermal Preparations


Fentanyl and Buprenorphine
Convenient dosing
– Fentanyl every 72 hours
– Buprenorphine every 7 days




Slow onset and delayed offset
Requires predicable blood flow and adequate
subcutaneous fat
Absorption is altered with fever, broken skin, edema
Some with metal foil backing and not compatible
with MRI
40
Opioid Choice
Immediate Release (IR)








Morphine
Hydrocodone
Hydromorphone
Oxycodone
Oxymorphone
Tramadol
Tapentadol
Codeine
Extended Release /
Long-acting (ER/LA)
 Morphine
 Hydrocodone
 Hydromorphone
 Oxycodone
 Oxymorphone
 Tramadol
 Tapentadol



Methadone
Fentanyl transdermal
Buprenorphine
transdermal
41
Selected Opioids With
Unique Properties
42
Methadone is Different
CDC, Morbidity and Mortality Weekly Report (MMWR) July 6, 2012 / 61(26);493-497.
43
Methadone is Different
The problem…
 Long, variable, unpredictable half-life
– Analgesia 6-8 hours
– Serum t½ 20-100 hours

QTc prolongation, risk of torsade de points
Some possible advantages…
 Mu opioid agonist, NMDA receptor antagonist
– Potentially less tolerance, better efficacy in neuropathic
pain


No active metabolites
Inexpensive, small dosage units (5mg tablets)
Fredheim OMS et al. Acta Anaestheiol Scand. 2008;52:879-889.
44
Dual Mechanism Opioids
Tramadol
 Mu-opioid agonist and
NE and serotonin
reuptake inhibitor
 Seizure risk
 Physical dependence
 Not scheduled as
controlled substance
BUT has addiction
potential
Medical Letter April 2010
Tapentadol
 Mu-opioid agonist and
NE reuptake inhibitor
 Seizure risk
 Physical dependence
 Schedule II controlled
substance with
addiction potential
45
Resources on Specific Opioids
Providers
e.g., dosing, specific
product risks, limitations
for use in patients with
gastrointestinal problems
such as inability to
swallow, feeding tubes or
malabsorption issues
Patients
e.g., side effects, drugdrug interactions
including CNS
depressants, safe
disposal
• http://dailymed.nlm.nih.gov/dailymed
• www.accessdata.fda.gov/scripts/cder/drugsatfda/
• Package inserts on ER/LA website
• Adverse events to be reported to FDA
www.fda.gov/Drugs/InformationOnDrugs/ucm135151.htm
• Materials:
www.er-la-opioidrems.com/IwgUI/rems/products.action
• Medication guide given at the pharmacy
46
Opioid Risks
47
Issues Preventing Opioid Prescribing
Issues
Prevalence
Potential for patients to become addicted
89%
Potential for patients to sell or divert
75%
Opioid side effects
53%
Regulatory/law enforcement monitoring
40%
Hassle and time required to track/refill
28%
Upshur CC, Luckmann RS, Savageau JA. J Gen Intern Med. 2006 Jun;21(6):652-5.
48
Opioid Tolerance and Physical Dependence
Both tolerance and physical dependence are
physiological adaptations to chronic opioid exposure
Tolerance:
 Increased dosage needed to produce specific effect
– Develops readily for CNS and respiratory depression
– Less so for constipation
– Unclear about analgesia
Physical Dependence:
 Signs and symptoms of withdrawal by
abrupt opioid cessation, rapid dose
reduction
49
Opioid Safety and Risks
Allergies
Rare
Organ
Toxicities
Rare
Adverse
Effects
Common
Suppression of
hypothalamicpituitarygonadal axis
Nausea,
sedation,
constipation,
urinary retention,
sweating
>50 mg (MSO4
equivalents)
assoc. with 2x
increase
fracture risk
Benyamin R, et al. Pain Physician 2008; 11:S105-S120.
Saunders KW,, et al. J Gen Intern Med. 2010;25:310-315.
Pruritis (histamine
release)
Respiratory
depression –
sleep apnea
50
Respiratory Depression







Depression of the medullary respiratory center
Decreased tidal volume and minute ventilation
Right-shifted CO2 response
Hypercapnea, hypoxia and decreased oxygen
saturation
Various agonist-type opioids do appear to differ in
potential for ventilatory depression in humans
Immediately life threatening
The key to remember is that sedation occurs before
respiratory depression therefore it is a warning sign
that the patient is overmedicated
Dahan A, et al. Anesthesiology 2010;112:226-238.
51
Managing Opioid Adverse Effects
Nausea and
vomiting
Sedation
Mostly during initiation
or change in dose
Constipation
Usually resolves in few days,
antiemetics, switch opioids
Decrease dose
Most common and
should be anticipated
Senna laxatives, bowel stimulants,
switch opioids; avoid bulking agents
Pruritis
Switch opioids, antihistamines
Urinary
Retention
Switch opioids
Benyamin R, et al. Pain Physician 2008;11:S105-S120.
52
Opioid Safety and Risks
Worsening
Pain
Withdrawal
mediated pain
Hyperalgesia in
some patients
Addiction
Overdose
At high doses
(ER/LA formulations
contain more opioid
than IR and increase
overdose risk)
When
combined with
other
sedatives
53
Rates of Prescription Opioid Sales, Deaths and
Substance Abuse Treatment Admissions
National Vital Statistics System, 1999-2008; Automation of Reports and Consolidated Orders System (ARCOS) of the Drug
Enforcement Administration (DEA), 1999-2010; Treatment Episode Data Set, 1999-2009.
54
New Users: Specific Illicit Drugs
3,000
2,567
2,361
2,500
2,179
2,000
1,500
1,000
1,2261,110
813 702
617
500
0
337
186 180
45
* Includes pain relievers, tranquilizers,
stimulants,
sedatives
Note:
The and
specific
drug refers to a drug that
was used for the first time, regardless of
whether it was the first drug used or not.
SAMSHA, 2009 National Survey on Drug Use and Health (September 2010).
55
Where Pain Relievers Were Obtained
Over 71% from Family or Friend
Prescribed by one doctor 17.3%
Other source 7.1%
Got from drug
dealer or stranger
Took from friend
or relative
without asking
4.4%
Over 71% from Family or Friend
4.8%
Bought from
friend or
relative
11.4%
55%
2010 National Survey on Drug Use and Health: SAMHSA, Office of Applied Studies; 2011
Obtained
free from
friend or
relative
56
Collateral Opioid Risk

Risks
– Young children ingestion and overdose
– Adolescents experimentation leading
to overdose and addiction

Mitigating risk
– Safe storage and disposal
– Educate family members
– Have poison control
number handy
57
Opioid Addiction Risk

True incidence and prevalence of addiction in
chronic pain populations prescribed opioids is
unknown due to different criteria used to define
addiction in different studies

The range in prevalence reported is 0-50%
Højsted J, Sjøgren P. Eur J Pain. 2007 Jul;11(5):490-518.
58
Opioid Misuse Risk
Known Risk Factors

Good
Predictors
for
problematic
prescription
opioid use

Young age (less than 45 years)
Personal history of substance abuse
– Illicit, prescription, alcohol, nicotine


Family history of substance abuse
Legal history
– DUI, incarceration


Mental health problems
History of sexual abuse
Akbik H, Butler SF, Budman SH, et al. J Pain Symptom Manage 2006;32(3):287-293.
Ives J, et al. BMC Health Serv Res. 2006 Apr 4;6:46.
Liebschutz JM et al. J Pain. 2010 Nov;11(11):1047-55.
Michna E, et al. J Pain Symptom Manage. 2004 Sep;28(3):250-8.
Reid MC, et al. J Gen Intern Med. 2002 Mar;17(3):173-9.
59
Why Patients Become Addicted to Opioids
Opioids activate mu receptors in midbrain =
“reward pathway” causing euphoria
 Dopaminergic system that is very reinforcing
 Most rewarding are fast onset opioids
 ER/LA should be less
rewarding if taken as
prescribed but are very
rewarding if adulterated
(e.g., crushed, chewed)
Kosten TR, George TP. Science and Practice Perspectives – July 2002:13-20.
60
Abuse Deterrent/Resistant Formulations
In Development
Physical
Barriers
Reducing
Drug Rewards
Opioid
Formulations
Agonistantagonist
Combinations
Aversive
Components
Routes of
Administration
Prodrugs
Currently there are NO PROVEN abuse
deterrent/resistant opioids or
formulations
Passik SD. Mayo Clin Proc. 2009 Jul;84(7):593-601.
Stanos SP et al. Mayo Clin Proc. 2012;87(7):683-694.
61
Drug-Drug Interactions
Profiles vary among the different opioids and opioid formulations
Central nervous system depressants (alcohol, sedatives, hypnotics, tricyclic
antidepressants)
 Can have potentiating effect on sedation and respiratory depression caused
by opioids
Some ER/LA opioid formulations
 May rapidly release opioid (dose dump) when exposed to alcohol
 Some drug levels may increase without dose dumping when exposed to
alcohol
Diuretics
 Opioids can reduce efficacy by inducing release of antidiuretic hormone (ADH)
Some Opioids (methadone, buprenorphine)
 Can prolong the QTc interval
Concomitant drugs that act as inhibitors or inducers of various cytochrome P450
enzymes
 Can result in higher or lower than expected blood levels of some opioids
FDA Blueprint: www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/ucm277916.pdf
62
Important Resource: DailyMed
http://dailymed.nlm.nih.gov/dailymed

Updated medication content and labeling
– Search and download

Reformatted drug labeling easier to read

National Library of Medicine (NLM) provides as
a public service; does not accept advertisements
63
Risk in Elderly

Drug-drug interactions

Drug-disease interactions
– CHF, chronic liver and renal disease
– Dementia

Decline in therapeutic index

Age-related predisposition to adverse drug
effects

Start low and go slow
American Geriatrics Society Panel. JAGS 2009;57:1331-1346.
64
Risk Assessment
65
Assess for Opioid Misuse Risk
Prior to Prescribing

Validated questionnaire

Urine drug testing

Check state prescription drug monitoring
program data (if available)

Review old medical records

Talk to previous provider (if possible)
66
Validated Questionnaires
ORT
Opioid Risk Tool
SOAPP Screener & Opioid Assessment for Patients with Pain
STAR
Screening Tool for Addiction Risk
SISAP Screening Instrument for Substance Abuse Potential
PDUQ
Prescription Drug Use Questionnaire
No “Gold Standard”
Lack of rigorous testing
Moore TM, et al. Pain Medicine 2009;10(8): 1426-1433.
67
Mary Williams
Case Study
Opioid Risk Tool Score
Femal
e
Family history of substance abuse

Male
Alcohol
1
3
Illegal drugs
2
3
Prescription drugs
4
4
Personal history of substance abuse

Alcohol
3
3
Illegal drugs
4
4
Prescription drugs

1
5
3
0
ADHD, OCD, bipolar, schizophrenia
2
2
Depression
1
1
Age between 16-45 years
History of preadolescent sexual
abuse
5
1
Psychological disease
SCORING
0-3 Low Risk
4-7 Moderate Risk
>8 High Risk
Webster LR, Webster RM. Pain Med. 2005 Nov-Dec;6(6):432-42.
68
Opioid Misuse Risk Stratification
How should it be used?
Level of concern that should be communicated to the patient
 “Despite being in recovery from alcoholism, you are at higher
risk for developing problems with the opioid pain medication.”
Level of monitoring that should be implemented


Frequency of visits, urine drug testing, etc.
High risk patients may need to agree to random call-backs
Need for pain and/or addiction consultant
 If available
Some patients may be too risky for opioids analgesics
 e.g., patient with recent opioid addiction
69
Prescription Drug Monitoring Programs
Clinical tool
that
supports
safe
prescribing
and
dispensing
May help
prevent or
stop harm
from drug
diversion,
misuse and
abuse
Perrone J, Nelson LS. N Engl J Med 2012; 366:25:2341-2343.
Specifics
vary from
state to
state
Can
provide:
 Patient’s
prescription
history for
Schedule II–V
 Solicited reports
online; real time
or delay of days
to weeks
 Unsolicited
reports on
patients with
“questionable
activity”
70
Mary Williams
Case Study

Patient agrees to return in one
week

Provider has time to check
records and Prescription Drug
Monitoring Program (PDMP)

Patient has left a Urine Drug
Test (UDT)
71
Summary Points: Presentation 1
Opioids:
can
be beneficial for some
side
effects are common but can be managed
can
be harmful for some
carry
significant risk including overdose and addiction
misuse
risk can be assessed using systematic approach
which includes validated risk assessment questionnaires
72
Mary Williams Case Presentation
Review of Ms. Williams’
medical records
She is likely benefiting
from opioids
Progress notes, medication lists
are reconciled
States she is able to continue
working on current medications
Radiology reports
 Lumbar degenerative joint
disease
 Mild spinal stenosis
Moderate risk for prescription
opioid misuse based on the
Opioid Risk Tool score
No evidence of misuse of her
opioid prescriptions
Lack of adequate documentation
about pain and functional
benefits in her old record
73
Questions for Next Visit
Initiating Opioid Therapy Safely
Clinician Concerns:




Should I change her
opioid prescription?
Should I change the
opioid dose?
What about any other adjuvant
medications or therapies?
What sort of treatment plan
should I develop?
74
Part 2 of 3
75
Module 1 Case Summary:
Mary Williams

42 yo woman

Diabetic, hypertensive, obese,
smoker, with remote history of
alcohol dependence

Chronic neuropathic and back
pain

Regimen of gabapentin and
oxycodone/acetaminophen
for pain
76
Module 1 Case Summary:
Mary Williams
New primary care provider:
 Initial history and physical exam
 Assessments:
–
–
–
–
Pain and function
Mental health
Substance use
Opioid misuse risk
 Findings:
– Pain moderate to severe
– Impact on function and quality of life
– Some risk factors for opioid misuse77
Mary Williams
Case Study
In the interim…

Her medical records confirmed her
history and medication lists

Her urine drug test last time was
positive for oxycodone only

State prescription drug monitoring
program data showed for the past
12 months she had one prescriber
and went to one pharmacy
Office Visit 2

Pain score is unchanged from
previous week

Has run out of opioid prescription
78
Initiating Opioid Therapy Safely
79
Learning Objectives: Presentation 2

Describe universal precautions and their role
in chronic opioid therapy

Describe monitoring and documentation
strategies for chronic opioid therapy

Describe initiating opioid therapy

Apply counseling and communication
strategies to ensure appropriate and safe use of
opioid medications
80
Universal Precautions in Pain Medicine
Part of a Controlled Substance Policy for your Office

Opioid misuse risk prediction is imprecise
– Protects all patients
– Protects the public and community health

Consistent application of precautions
– Takes pressure off provider during time of stress
– Reduces stigmatization of individual patients
– Standardizes system of care

Resonant with expert guidelines
– American Pain Society/American Academy of Pain Medicine
– American Society of Interventional Pain Physicians
– Canadian National Pain Centre
Gourlay DL, Heit HA, Almahrezi A. Pain Med. 2005 Mar-Apr;6(2):107-12.
81
Common Universal Precautions






Comprehensive pain assessment including opioid
misuse risk assessment
Formulation of pain diagnosis/es
Opioid prescriptions should be considered a test or trial;
continued based on assessment and reassessment of
risks and benefits
Patient Prescriber Agreements (PPA) with informed
consent and plan of care
Regular face-to-face visits
Monitoring for adherence, misuse, and diversion
– Urine drug testing
– Pill counts
– Prescription drug monitoring program data (when available)

Clear documentation
Federation of State Medical Boards Guidelines 2004, www.fsmb.org
Gourlay DL, Heit HA, Almahrezi A. Pain Med. 2005 Mar-Apr;6(2):107-12.
Chou R, et al. J Pain. 2009;10(2):147-159.
82
Patient Prescriber Agreements (PPA)
Two Components
Informed Consent


Educational re:
potential risks
Establishes targeted
benefits or goals of
care
Plan of Care



Documents mutual
understanding of
clinical care plan
Takes pressure off
providers to make
individual decisions
Articulates monitoring
procedures and
responses to
unexpected findings

Efficacy not well
established

No standard or
validated form

Printed copy,
signed by both
patient and
prescriber, given
to the patient
may serve as a
Patient
Counseling
Document
Cheatle MD, Savage SR. Informed Consent: A Potential Obligation, J P&SM 2012. 44(1):105-116.
83
PPA Informed Consent
Common Components - Benefits
S
Targeted benefits/
goals of opioids:
 Reduce pain, not
eliminate
 Increased function
(individualized
and SMART
goals)
Specific
M
SMART
Goals
A
R
T
Nicolaidis C. Pain Med 2011;12(6):890-897.
Cheatle MD, Savage SR. J Pain Symptom Manage. 2012 Jul;44(1):105-16
Measurable
Actionoriented
Realistic
Time-sensitive
84
PPA Informed Consent
Common Components - Risk
Risks of opioids
Side effects (short and long term) – call provider
 Physical dependence, tolerance
 Drug interactions/over-sedation
 Potential for impairment e.g., risk of falls, working with
heavy machinery and driving
 Abuse, addiction, overdose with misuse
 Pregnancy and risk of Neonatal Abstinence Syndrome
 Possible hyperalgesia (increased pain)
 Victimization by others seeking opioids

Paterick TJ, et al. Mayo Clin Proc. 2008 Mar;83(3):313-9
Cheatle MD, Savage SR. J Pain Symptom Manage. 2012 Jul;44(1):105-16
85
PPA Plan of Care
Common Components






Engagement in other recommended pain care
and other treatment activities
Follow up visit and appointment policies
Monitoring polices - urine drug testing and pill
counts
Permission to communicate with key others –
providers, family members
No illegal drug use, avoid sedative use
Notifying provider of all other medications and
drugs including OTC and herbal preparations
Fishman SM, Kreis PG. Clin J Pain. 2002 Jul-Aug;18(4 Suppl):S70-5.
Arnold RM, Han PK, Seltzer D. Am J Med. 2006 Apr;119(4):292-6.
86
PPA Plan of Care
Common Components
Medication Management
 One prescriber, one pharmacy
 Use as directed (dose, schedule, guidance on missed doses)
– No adulteration of pills or patches
– ER/LA opioid analgesic tablets must be swallowed whole





Don’t abruptly discontinue opioids
Refill, renewal policies
Safe storage (away from family, visitors, pets), protected from
theft
Safe disposal (read product specific information for guidance)
No diversion, sharing or selling (illegal and can cause death in
others)
Fishman SM, Kreis PG. Clin J Pain. 2002 Jul-Aug;18(4 Suppl):S70-5.
Arnold RM, Han PK, Seltzer D. Am J Med. 2006 Apr;119(4):292-6.
87
Use a Health-Oriented, Risk-Benefit
Framework
Judge the opioid treatment –
not the patient
NOT…
• Is the patient good or
bad?
• Does the patient
deserve opioids?
• Should this patient be
punished or
rewarded?
• Should I trust the
patient?
Nicolaidis C. Pain Med. 2011 Jun;12(6):890-7.
RATHER…
Do the benefits of opioid
treatment outweigh the
untoward effects and
risks for this patient (or
society)?
88
Choosing Opioids
89
Opioid Choice
Considerations

Duration and onset of action
– Consider pattern of pain – incident, constant
– Fast on, fast off – most rewarding/addicting

Patient’s prior experience
– Mu polymorphisms – differences in opioid responsiveness
– Genomic differences in metabolism
– Resulting in differing effects and side effects



Patient’s level of opioid tolerance (always assess
before starting ER/LA formulations)
Route of administration
Cost and insurance issues
90
Immediate Release (IR) Opioids
When to Consider

No opioid tolerance/opioid naive
 Intermittent or occasional pain
 Incident or breakthrough pain with ER/LA
opioids
– May be manageable with non-opioid modalities,
behavioral interventions or meds
91
ER/LA Opioids
When to Consider

Opioid tolerance exists
 Constant significant pain is present
– Round the clock
– Protracted pain for hours

To stabilize pain relief when patient using
multiple doses IR opioids
92
Increased
Side effects
Withdrawal
Opioid Concentration
Theoretical Concern with IR Opioids
Pain
Opioid
Pain
Opioid
Pain
Opioid
Pain
Opioid
93
Withdrawal
Increased
Side effects
Opioid Concentration
Theoretical Benefit of ER/LA Opioids
Opioid
Opioid
94
IR vs ER/LA Uncertainties

Insufficient evidence to determine whether
ER/LA opioids are more effective or safer than
short-acting opioids
 Debate whether bolus dosing (IR) or continuous
exposure (ER/LA) are more likely to drive
challenges such as tolerance, hyperalgesia or
addiction
 Choose options that best meet patient needs –
individualize treatment
Chou R, Clark E, Helfand M. J Pain Symptom Manage. 2003 Nov;26(5):1026-48.
Argoff CE, Silvershein DI. Mayo Clin Proc. 2009 Jul;84(7):602-12.
95
Opioid Dosing
96
Opioid Dosing
>100-200mg
morphine
equivalents
Considered
higher dose
opioid therapy
by different
authors1,2,3
1.
2.
3.
4.
5.
6.
Higher doses
indicated in
some patients
 Manage as
higher risk
 Increase
monitoring
and support
Chou R, et al. J Pain. 2009;10(2):147-159.
Ballantyne JC, Mao J. N Engl J Med. 2003 Nov 13;349(20):1943-53.
Kobus AM, et al. J Pain. 2012 Nov;13(11):1131-8.
Huxtable CA, et al. Anaesth Intensive Care. 2011 Sep;39(5):804-23.
Brush DE. J Med Toxicol. 2012 Dec;8(4):387-92.
Lee M, et al. Pain Physician. 2011;14;145-161.
7.
8.
9.
10.
11.
12.
13.
Higher doses
more likely
associated
with :
 Tolerance4
 Hyperalgesia5,
6
 Reduced
function7,8
 Overdose9-13
Kidner CL, et al. J Bone Joint Surg Am. 2009 Apr;91(4):919-27.
Townsend CO, et al. Pain. 2008 Nov 15;140(1):177-89.
Dunn KM, et al. Ann Intern Med. 2010 Jan 19;152(2):85-92
Braden JB. Arch Intern Med. 2010 Sep 13;170(16):1425-32.
Bohnert AS, et al. JAMA. 2011 Apr 6;305(13):1315-21.
Gomes T, et al. Open Med. 2011;5(1):e13-22.
97
Paulozzi LJ. Pain Med. 2012 Jan;13(1):87-95.
Risk of Opioid Misuse
1
Percent
Use
Group Health Consort Study, 1997-2005; Dunn KM, et al. Ann Intern Med. 2010 Jan 19;152(2):85-92.
98
Rational Polypharmacy
Brain
Descending
Inhibition
(NE, 5HT)
Peripheral
Sensitization PNS
(Na+ channels)
NSAIDs
Opioids
TCA
Lidocaine
Woolf CJ. Ann Intern Med. 16 March 2004;140(6):441-451.
TCA
SSRI
SNRI
Tramadol
Opioids
Spinal
Cord
Central
Sensitization
(Ca++ channels,
NMDA receptor)
TCA
Gabapentin
Opioids
99
Exploit Synergism
7
5
4
3
2
1
0
Gilron I, et al.N Engl J Med. 2005 Mar 31;352(13):1324-34.
Morphine
Gabapentin
6
Dosage (mg)
Score for Pain Intensity
Rational Polypharmacy
Morphine, Gabapentin, or Their Combination for Neuropathic Pain
2500
50
2000
40
1500
30
1000
20
500
10
0
0
100
Multidimensional Care
It’s more than medications
Exercise
Modalities
Manual therapies
Orthotics
Cultivate
Well-being
NSAIDS
Anticonvulsants
Antidepressants
Topical agents
Opioids
Others
Restore
Function
Physical
Psychobehavioral
SELF
CARE
Medication Procedural
Improve
Quality of Life
Cognitive behavioral/ACT
Tx mood/trauma issues
Address substances
Mediation
Reduce
Pain
Nerve blocks
Steroid injections
TPIs
Stimulators
Pumps
101
Mary Williams
Case Study
Prescription Rationale

Patient known to tolerate oxycodone

Reported good analgesia on 8 tablets a day
(40mg)

Periodicity of effects (off-on) (i.e.,
withdrawal mediated pain) may drive pain

Analgesia may be improved with more
stable blood levels, perhaps at slightly lower
dose (30mg/day) (Titrate somewhat if
needed)

If poor analgesia or significantly higher
doses required, consider rotation to
alternative opioid

Follow closely, continue or discontinue
based on response
102
Office Visits
Pain Management Review

Assess progress towards goals
– Function
– Pain

Review engagement in self care
– Exercise, stress reduction, use of modalities (e.g.,
cold, heat, stretch)
– Recovery activities if indicated

Review non-opioid pain treatment
– Behavioral counseling
– Physical therapy
– Interventionalist treatment
103
Office Visits
Opioid Risk Review

How is patient actually using prescribed opioids?
– Take 24-hour inventory

Review emotional, psychiatric and social issues
 Health care use patterns
 Objective information
–
–
–
–

Observe for signs medication or substance misuse
Check PDMP (if available)
Urine drug tests
Pill counts
Revise treatment as indicated
104
Monitoring Strategies
105
Monitoring: Urine Drug Tests

Objective information that can provide
– Evidence of therapeutic adherence
– Evidence of use or non-use of illicit drugs

Subjective reports may not be accurate if patient
is:
– Challenged by substance use or mental health
disorders
– Or is purposely diverting

Natural medical discussion if framed as a
personal and public health issue
 Random, scheduled and/or when concerns arise
Heit HA and Gourlay DL. J Pain Symptom Manage 2004;27:260-267
Christo PJ et al. Pain Physician 2011;14:123-143
106
Why Drug Test?
Self-reported drug
use among pain
patients unreliable
 Fleming MF et al. J Pain 2007
 Fisbain DA et al. Clin J Pain 1999
 Berndt S, et al. Pain 1993
Behavioral
observations
detects only some
problems
 Wasan AJ et al. Clin J Pain 2007
 Katz NP et al. Anesth Analg 2003
May improve
adherence
(e.g., decreased illicit
drug use)
 Pesce A et al. Pain Physician 2011
 Starrels J et al. Ann Intern Med 2010
 Manchikanti L et al. Pain Physician 2006
Evolving standard
of care
 Chou R et al. J Pain 2009
 Tescot AM et al. Pain Physician
2008
 Federation of State Medical
Boards, 2004
107
Urine Drug Testing

Urine drug screens are usually immunoassays
– Can be done at point of care or in a lab
– Quick and relatively inexpensive
– Need to know what is included in testing panel
– Risk of false negatives due to cut offs
– Risk of false positives due to cross reactions
– All unexpected findings should be sent for
confirmation by GC/MS
Reisfield GM et al. Bioanalysis 2009;1(5):937-952.
108
Urine Drug Testing

Gas Chromatography/Mass Spectroscopy
confirmation
–
–
–
–
Identifies specific molecules
Sensitive and specific
More expensive
Must be aware of opioid metabolism to interpret
Codeine
Hydrocodone
Oxycodone
Morphine
6-MAMa
Heroin
Hydromorphone
Oxymorphone
Not comprehensive pathways, but ,may explain the presence of apparently unprescribed drugs
6-MAM: 6-monoacetylmorphine; an intermediate metabolite
Peppin JF et al. Pain Medicine 2012;13:886-896
Heit HA, Gourlay DL. J Pain Symptom Manage. 2004 Mar;27(3):260-7.
Heit HA, Gourlay DL, Caplan YH. Urine Drug Testing in Clinical Practice; Pharmacom Group Inc., May 2010.
109
Urine Drug Testing
Caveats





One medical data point to integrate with others
Cannot discriminate elective use, addictive use
and diversion
Small risk for mislabeling, adulteration, other
error
Consult toxicologist/clinical pathologist before
acting if patient disputes findings
Dedicated deceivers can beat the system
Heit HA, Gourlay DL, Caplan YH. Urine Drug Testing in Clinical Practice; Pharmcom Group Inc., May 2010.
110
Monitoring: Pill Counts

Intended to:
– Confirm medication adherence
– Minimize diversion
Strategy
28 day supply (rather than 30 days)
Prescribe so that patient should have residual
medication at appointments
Ask patient to bring in medications at each visit
For identified risks or concerns, can request random
call-backs for immediate counts
111
Discussing Monitoring with Patients
112
Discussing Monitoring

Review the personal and public health
(community health) risks of opioid medications

Note medical responsibility to look for early signs
of harm

Discuss agreements, pill counts, drug tests, etc.
as ways that you are helping to protect patient
from getting harmed by medications

Use consistent approach, but set level of
monitoring to match risk
113
Mary Williams
Case Study
Past Medical History

Type 2 diabetes mellitus x 8 years
– Painful diabetic neuropathy x 2 years

Hypertension

Chronic low back pain

Tobacco dependence

Alcohol dependence (in recovery 10 yrs)

Obesity
114
Patients with Past Addiction History

Frame addiction as a challenging health issue

Express admiration for her recovery

Acknowledge patient’s desire to “never go there”
again

Encourage active recovery engagement

Discuss higher risk

Partner with patient to reduce risk
115
Patients with Past Addiction History
Tighten Structure of Care as Indicated

Setting of care (care coordination and
expertise)

Supports for substance/mental health recovery

Selection of treatments (less rewarding)

Supply of medications

Supervision intensity (frequency of visits, UDT,
pill counts, other monitoring and support)
Savage SR, Kirsch KL, Passik SD. Addict Sci Clin Pract. 2008 June; 4(2): 4–25
116
Office Systems
117
Optimize Office Systems
Save Time and Stress
Develop and
implement
 Office controlled
substance policies,
reflected in Patient
Prescriber
Agreement
 Management flow
sheet
 Lists of referral and support resources
(pain, mental health, addiction)
118
Optimize Office Systems
Save Time and Stress
Medical Assistant
or Receptionist
Assist in coordinating
care
Schedule, track and post
information in record
Flag concerns
–
–
–
–
–
–
Lab tests and results
Office visits
Physical Therapy
Counseling
Consultations
Etc.
Nursing Staff
Pharmacists
Review plan of care
with patient; provide
education
Use only one pharmacy
to fill prescriptions
Assess pain and
function; gather other
clinical information
Educate patients
regarding medications
Do pill counts
Partners for safety and
quality monitoring
Manage and monitor
prescription refills;
pharmacy liaison
Field patient calls
Random call backs
119
Mary Williams
Case Study
Follow-up

Patient reports somewhat more
consistent pain relief and
denies sedation
– But about 9 hours after her dose,
pain increases and interferes with
concentration

Provider increases ER/LA
oxycodone to 20mg every 12
hours to reduce end of dose
failure
120
Mary Williams
Case Study
Visit 2, cont.

In one week the nurse contacts
her and confirms that this has
been effective in improving pain
relief

Patient reports she is more
active and able to concentrate
on work
121
Documentation
122
Documentation

Detailed record can better inform care
 Protects prescriber when concerns arise
 Inclusions
–
–
–
–
–
Subjective reports (pt, family, co-care providers)
Standardized screens and assessments
Objective info (exams, labs, UDTs, pill counts, PDMP)
Clinical and diagnostic impressions
Rationale for all decision-making
• Special care: off-label, outside of guidelines, high risk pts

Templates in resource section this program
Passik SD, et al. Clin Ther. 2004;26:552-561
123
Federal and State Regulations
Federal
PAIN
Federal
ADDICTION
 May prescribe any opioid for pain
– Sublingual buprenorphine is off-label for pain
– Limits based on controlled substance class
– Refer to the DEA Practitioners’ Manual*
*www.deadiversion.usdoj.gov/pubs/manuals/pract/index.html
 Buprenorphine - must have 8 hours of training and
CSAT waiver/DEA X-number
 Methadone - must be part of licensed Opioid Treatment
Program
States
STATES

May have stricter regulations than Federal
 Useful state-specific information compiled by the FSMB
and available at:
– www.fsmb.org/PDF/grpol_pain_management.pdf
124
Summary Points: Presentation 2

Opioids are one tool in a multidimensional approach
that includes
– An active patient role in self-care
– Synergistic treatment






Initiate as a trial aimed at clear goals
Employ universal precautions with all patients
Tailor plan of care to the individual
Employ monitoring strategies to improve outcomes
Continue or discontinue treatment based on response
Document, document, document
125
Mary Williams
Case Study

Did well on regimen of ER/LA
oxycodone 20 mg bid with gabapentin
300 mg tid for the next 11 months

She then went to the ER of her local
hospital, requesting an early refill of
her oxycodone because she ran out
early

ER physician noted that she was in
moderate to severe opioid withdrawal
and gave her enough oxycodone to
last until her next primary care
provider appointment
126
Questions for Ongoing Monitoring
Assessing and Managing Aberrant Medication Taking Behavior
Provider Concerns:

How to address recent
aberrant behavior?

Is she addicted?

Has she developed a
tolerance to the opioids?

How do I accurately
assess this new behavior?
127
Part 3 of 3
128
Case Review: Mary Williams

Diabetic, obese, hypertensive, smoker
with remote history of alcohol
dependence
 Past year: took gabapentin and
oxycodone/acetaminophen for pain
 New primary care provider prescribes
ER/LA oxycodone
 Implements office policy
 Discusses opioid risks, goals of care
and monitoring
129
Mary Williams
Case Study
Summary to Date

Started on ER/LA oxycodone 15 mg bid,
titrated up and stabilized at 20 mg bid

For subsequent 11 months – all benefit
and no harm
– Coming every 28 days for refills (sees
nurse)
– PCP appointment every 2-3 months
– Adherent with monitoring
– Pain, function improved and stable

Then - ER visit for early refill and in
opioid withdrawal
130
Mary Williams
Case Study
Urgent PCP Office Visit for Early Refill

Leg and back pain has worsened in past
month
– Started taking an extra ER/LA oxycodone in
the afternoon and ran out early.

Concerned “body has become used to
current dose”; doesn’t seem to work all
day anymore
– Husband says she has become “addicted”

Difficult to go to work due to severe pain

Trouble sleeping as sheets touching her
feet now cause pain

Requests increase in her dose
131
Assessing and Managing
Aberrant Medication Taking
Behavior
132
Learning Objectives: Presentation 3

Assess differential diagnosis for aberrant
medication taking behavior
– Pain relief vs drug seeking

Assess lack of benefit, increased risk and/or harm

Determine whether to continue, change or
discontinue opioid therapy

If changing opioids, determine how to rotate
opioids

If discontinuing opioids, determine whether and how
to taper opioids
133
Managing Expectations
134
Opioids and Unrealistic Expectations
Patients often have unrealistic expectations that…
Opioids always equal chronic
pain relief therefore
more opioids equal
more pain relief
Often
results in
unsanctioned
dose escalation
or continued requests
for higher doses
Need to re-educate:
 Realistic goals
 Potential severe risks
and harm with opioids
135
Opioids and Misunderstandings


Family members (and
patients) often misunderstand
the differences
Need to re-educate
Physiologic adaptations
to chronic opioid
therapy
Physical
Dependence
Tolerance
Addiction
Maladaptive behavior
associated with opioid misuse
Savage SR et al. J Pain Symptom Manage. 2003;26:655-667.
136
Monitoring for Misuse
137
Monitoring for Opioid Misuse

Patient questionnaire
– Current Opioid Misuse Measure (COMM)

Other strategies
– Pill counts (scheduled vs random)
– Urine drug tests (scheduled vs random)
– Prescription drug monitoring program data

History from “reliable” family members
– Beware of family members with secondary gain for
giving inaccurate information
138
Current Opioid Misuse Measure (COMM)
Assessing Opioid Misuse Risk
Key Elements:

17 items

Takes ~10 minutes to
complete
Over-sedation
Helps for deciding level of
monitoring
Multiple prescribers

Score range: 0 – 68
Active mental health
issues

Scores >9 detect probable
opioid misuse with sensitivity
of 77% and specificity of 66%
Compulsive use

Butler SF, Budman SH, Fernandez KC, et al. Pain. 2007;130:144-156.
Consequences of overuse
Medication misuse
Obtaining meds from
someone else
Loss of control
139
Mary Williams
Case Study
COMM Score Results

Her COMM score was 12

Confirms concern about misuse
140
Aberrant Medication-Taking Behaviors
Differential Diagnosis
Pain Relief
Seeking
Drug Seeking
 Disease progression
 Addiction
 Poorly opioid
responsive pain
 Other psychiatric
diagnosis
 Withdrawal
mediated pain
 Opioid analgesic
tolerance
 Opioid-induced
hyperalgesia
Pain Relief and
Drug Seeking
 Criminal intent
(diversion)
(e.g. pain with comorbid addiction,
patient taking some
for pain and diverting
some for income)
141
Opioid Tolerance
Pain Relief Seeking

Right shift of the dose-response curve
 Tolerance to antinociceptive effects are
demonstrated in animal models but less
common in clinical settings
 Longitudinal studies in cancer and noncancer
populations find opioid doses typically stabilize
for extended periods
 Increased dose overcomes decreased analgesic
effectiveness
Schug SA, et al. Drug Saf 1992; 7(3):200-213.
Portenoy RK and Foley KM. Pain 1986; 25(2): 171-186.
Chang G, et al. Med Clin N Am. 2007;91:199-211.
Joseph EK et al. J Neurosci. 2010;30(13):4660-4666
142
Opioid-Induced Hyperalgesia
Pain Relief Seeking

Enhanced pain sensitivity to same opioid dose

Increased sensitivity can be overcome with
increased opioid dose temporarily

Paradoxically more opioid will worsen pain

Central and peripheral sensitization of
pronociceptive process
Chang G, et al. Med Clin N Am. 2007;91:199-211.
Lee M et al. Pain Physician 2011;14:145-161.
143
Opioid Tolerance vs OpioidInduced Hyperalgesia
144
Tolerance and Opioid-Induced Hyperalgesia
A
100
B
C
12
15
75
50
AC
AB
25
0
-25
-50
0
3
6
9
Dose
Angst MS, Clark JD. Anesthesiology. 2006 Mar;104(3):570-87.
145
Aberrant Medication-Taking Behavior
Drug Seeking
146
Drug Seeking
Differential Diagnosis
Addiction
Psychiatric
Diagnosis
Diversion
• Organic mental
syndrome
• Personality
disorder
• Chemical coping
• Depression/
anxiety/situational
stressors
• Psychosocial or
emotional issues
147
Drug Seeking
Addiction
Clinical syndrome presenting as…
Loss of Control
Compulsive use
Continued use despite harm
Craving
Aberrant
Medication
Taking Behaviors
(pattern and severity)
Addiction is NOT the same as physical dependence
Biological adaptation with signs and symptoms
of withdrawal (e.g., pain) if opioid is abruptly stopped
Savage SR, et al. J Pain Symptom Manage. 2003;26:655-667.
148
Concerning Behaviors for Addiction
Spectrum: Yellow to Red Flags
o
o
o
o
o
o
o
o
o
Requests for increase opioid dose
Requests for specific opioid by name, “brand name only”
Non-adherence w/ other recommended therapies (e.g., PT)
Running out early (i.e., unsanctioned dose escalation)
Resistance to change therapy despite AE (e.g. over-sedation)
Deterioration in function at home and work
Non-adherence w/ monitoring (e.g. pill counts, urine drug
tests)
Multiple “lost” or “stolen” opioid prescriptions
Illegal activities – forging scripts, selling opioid prescription
Modified from Portenoy RK. J Pain Symptom Manage. 1996 Apr;11(4):203-17.
149
Other Psychiatric Diagnoses
Drug Seeking
Psychiatric
Diagnosis
Chemical Coping
 Patients knowingly or unknowingly
inappropriately use opioids to treat a comorbid
disease such as depression or anxiety
 Usually self-medicating a mental health
disorder or stress
Others



Organic mental syndrome schizophrenia
Personality disorder; borderline personality
Depression/anxiety/situational stressors
Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guideline for Practitioners. 1st
Edition. North Branch, MN: Sunrise Press; 2007.
150
Drug Seeking
Diversion
Doctor Shoppers
Visit by an
individual
with or
without
legitimate
medical
need
To several
doctors
Each of whom
writes a
prescription for
controlled
substances
Followed by
visiting
multiple
pharmacies
Sometimes
paying cash
ER/LA opioids can be converted into rapid-onset
(immediate release) opioids by altering the tablet or patch
Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guideline for Practitioners. 1st
Edition. North Branch, MN: Sunrise Press; 2007.
151
Risk Benefit Framework
For Continuing or Discontinuing Opioids
Benefit
Pain
Function
Quality of Life
Risk/Harm
Misuse
Addiction
Overdose
Adverse Effects
152
Lack or Loss of Benefit






Reassess factors affecting pain
Re-attempt to treat underlying disease and
co-morbidities
Consider escalating dose as a “test”
Consider adding adjuvant medications for
synergy
Consider adding breakthrough medications
Consider opioid rotation
153
Consider Breakthrough Medication
Immediate
Release Opioid
(Mu agonist)
Immediate
Release Opioid
(dual mechanism)
Non-Opioid
Medications
 Same molecule
 Different molecule
 Tapentadol
 Tramadol
 NSAIDS
 Acetaminophen
 Adjuvant meds
Davies AN et al. European J of Pain 2009;13:331-338.
154
Consider Opioid Rotation





Switch to another opioid as means of restoring
analgesic efficacy or limiting adverse effects
Based on large intra-individual variation in
response to different opioids
Different variants of mu-opioid receptors
Based on surveys and anecdotal evidence
Promising but needs validation
Inturrisi CE. Clin J Pain. 2002 Jul-Aug;18(4 Suppl):S3-13.
Fine PG and Portenoy RK. J Pain Symptom Manage 2009;38:418-425.
155
Opioid Conversion Tables





Derived from relative potency ratios using
single-dose analgesic studies in opioid naïve
patients
Based on limited doses or range of doses
Does not reflect clinical realities of chronic opioid
administration
Are not reliable due to individual
pharmacogenetic differences
Assume no cross tolerance and start every new
opioid at a dose used for opioid naïve patients
Webster LR, Fine PG. Pain Med. 2012 Apr;13(4):562-70
Pereira J, et al. J Pain Symptom Manage. 2001 Aug;22(2):672-87.
156
Continued Lack of Benefit
Remember:
Not all pain is opioid responsive
More opioid is not always better
More opioid may increase risk of adverse effects
Patient may have developed opioid induced
hyperalgesia and will improve off opioids
157
Discussing Continued Lack of Benefit
Stress how much you believe /empathize with patient’s
pain severity and impact
Express frustration re: lack of good pill to fix it
Focus on patient’s strengths
Encourage therapies for “coping with” pain
Show commitment to continue caring about patient and
pain, even without opioids
Schedule close follow-ups during and after taper
158
Pain Management Specialist
159
Pain Management Specialist
When to Refer
When…
 unsure of treatment options
 interventional treatment may be considered
 unsure how to safely rotate to different opioid
 uncomfortable with managing risk
 unsure how to manage aberrant behaviors
160
How to Find a Pain Management Specialist

State Medical Association web sites

American Academy of Pain Medicine web site
– www.painmed.org
161
Too Much Risk
Opioid-related
 Adverse events
– Side effects; toxicity
 Opioid induced
hyperalgesia
– increased dose or
opioid rotations without
benefit
 Addiction
Psychosocial
 Psychiatric instability
 Unsafe housing or storage
 Nonadherent with
monitoring procedures
 Nonadherent with office
procedures
 Use of other non opioid
drugs of abuse
 Diversion or criminal
behavior
162
Possible Addiction
Stay in the Risk/Benefit mindset:

Give specific and timely feedback why patient’s behaviors
raise your concern for possible addiction e.g., loss of control,
compulsive use, continued use despite harm

Remember patients may suffer from both chronic pain and
addiction

May need to “agree to disagree” with the patient

Benefits no longer outweighing risks

“I cannot responsibly continue prescribing opioids as I feel it
would cause you more harm than good.”

Always offer referral to addiction treatment
163
Addiction Medicine Specialist
When to Refer
When patient:
 is using illicit drugs
 is experiencing problems with other prescription
drugs (benzodiazepines)
 abuses or is addicted to alcohol
 agrees they have an opioid addiction and wants
help
 has dual or trio diagnosis of pain, addiction, and
psychiatric disease
164
Making Addiction Treatment Referrals

Substance Abuse and Mental Health
Services Administration (SAMHSA)
treatment locator
 State resources (Department Public Health)
– Acute treatment services (detoxes)
– Medication assisted treatment
• Methadone maintenance treatment programs
• Office-based opioid treatment with buprenorphine or
naltrexone

AA/NA free, widely available and effective
165
Possible Diversion

Discuss why you are concerned about diversion
– e.g., nonadherence with pill counts, Urine Drug Test
negative for prescribed opioid

Discuss your inability to prescribe when there is
any chance of diversion
166
Discontinuation of Opioids

Do not have to prove addiction or diversion only assess and reassess the risk-benefit ratio

If patient is unable to take opioids safely or is
nonadherent with monitoring then discontinuing
opioids is appropriate even in setting of benefits

Need to determine how urgent the
discontinuation should be based on the severity
of the risks and harms
167
Always Plan for Potential “Exit Strategy”

Emphasize criteria for tapering in initial patient-prescriber
agreement
– Documentation of lack of pain reduction and/or lack of functional
improvement
– Documentation of opioid medication or prescription misuse or
abuse
– Positive urine drug test for any illegal substance
– Failure to comply with all aspects of treatment program


Distinguish between abandoning opioid therapy,
abandoning pain management, and abandoning patient
Taper off opioid therapy, with or without specialty
assistance
168
Discontinuing Opioids
Determine Degree of Physical Dependence to Determine Withdrawal
Risk
Higher intensity withdrawal from:
 Higher steady state levels
 Longer term exposure
 Faster rate of medication clearance
– Long vs. short half life agents
169
Tapering Opioids
Immediate Release Opioids

Decide if you need a taper at all
– Is there physical dependence?

Decrease strength or number of tablets each
week

Build up alternative pain treatment modalities
170
Tapering Opioids
ER/LA Opioids

Decrease by 10-20% each week
– Long acting pill formulations dictate increments of
dose decrease that are possible
– Rate of decrease determined by circumstances of
withdrawal: emergency vs. controlled taper

Can use short acting opioids to treat
“breakthrough” symptoms

Build up alternative pain treatment modalities
171
Opioid Exit Strategy – Possible Paths
Patient’s behavior
consistent with
drug addiction
 Refer for addiction
management or
comanagement
Patient unable
or unwilling to
cooperate with
outpatient taper
 Provide sufficient
opioid for
1-month taper
 Refer to inpatient or
outpatient program
or similar service,
as available
No apparent
addiction problem
Patient able to
cooperate with
office-based taper
 Taper gradually
over 1-2 months
 Implement
non-opioid pain
management
(psychosocial
support, CBT,
PT, non-opioid
analgesics)
CBT, cognitive behavioral therapy; PT, physical therapy.
Katz N. Patient Level Opioid Risk Management: A Supplement to the PainEDU.org Manual. Newton, MA: Inflexxion, Inc.; 2007.
Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guideline for Practitioners. 1st Edition. North Branch,
MN: Sunrise Press; 2007.
172
Using Risk/Benefit Mindset to Avoid Pitfalls
Keep in the Risk/Benefit mindset when responding to:

But I really, really need opioids.

Don’t you trust me?

I thought we had a good relationship/
I thought you cared about me?

If you don’t give them to me, I will
drink/use drugs/hurt myself

Can you just give me enough to find a new doc?
173
Next Steps
174
Mary Williams Case Study
Opioid Rotation from Oxycodone: Options
Different opioid chemical
class
Methadone
 Full mu agonist and
NMDA antagonist
 May have improved
efficacy in
neuropathic pain
 Inexpensive and
small dosages
Fentanyl Patch
Same opioid chemical
class
Oxymorphone or
morphine or
hydromorphone
Buprenorphine
Patch
 Partial mu agonist
 Good safety profile but
possible less analgesic
efficacy
 Full mu agonist
175
Mary Williams Case Study
ER/LA Oxycodone to Methadone: Example
Taper ER/LA oxycodone
over 2-3 weeks
 Use IR oxycodone for
bridge until
therapeutic dose of
methadone is
achieved
 Use clonidine
(tablets or patch)
if symptoms of
withdrawal during
rotation
Titrate methadone slowly over 3-4
weeks
Analgesia duration is 4-8 hours while
serum half life is up to 100 hours
resulting in sedation and respiratory
depression until tolerance develops
Begin dose at 2.5 mg TID or 5 mg BID
Can titrate dose to 5mg TID
Do not increase dose more
frequently than weekly
176
Mary Williams
Case Study
Over Next 6 Months

Her pain and function improved

She was adherent with the treatment
and monitoring

There was no aberrant medication
taking behavior
177
Summary Points: Presentation 3

Aberrant medication taking behavior can signify
pain-relief or drug seeking behaviors or a
combination of both

It is important to fully assess and then respond
to aberrant behaviors

Decisions to continue or discontinue opioids
should be based on reassessment of the risks
and benefits of the treatment
178