Transcript The Unintended Consequences of Compassionate Care

Richard B. Riemer, D.O.
Medical Director, Schools Insurance Authority
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A historical perspective
Data supporting the “epidemic of prescription
drug overdose”
Innovations in Neuroscience: what we have
learned about addiction and drugs of
addiction including prescription opioids.
The Clinical Dilemma- the “carefully selected
patient”
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“The new science of mind is based
on the principle that our mind and
brain are inseparable… it constructs
our sensory experiences, regulates
thoughts and emotions and controls
our actions…our mind is a set of
operations carried out by our
brain…these same principles of unity
applies to mental disorders.”
Eric Kandel, MD
Nobel Prize Recipient in Physiology or
Medicine, 2000
New York Times, 9/9/2013
$2,500,000,000
2 Billion
$2,000,000,000
$1,500,000,000
$1,000,000,000
800 million
$500,000,000
$0
2000
2013
2013
885340
2004
299498
0
200000
400000
600000
800000
1000000
42
45
40
35
30
25
20
16
15
10
5
0
2002
2012
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In California,
workplace insurers
spent $252 million
on opioids in 2010
This represented
~30% of all
prescription costs,
twice that of 2002.
35%
30%
30%
25%
20%
15%
15%
10%
5%
0%
2002
2010
Source is Center for Behavioral Health Statistics and
Quality, Substance Abuse and Mental Health Services
Administration, Treatment Episode Data (TEDS), Data
received through 11.3.2010.
“Those who cannot
remember the past are
condemned to repeat it.”
Reason in Common Sense, p. 284
George Santayana
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Opioid addiction is rare in pain patients.
Physicians are needlessly allowing patients
to suffer because of “opiophobia”.
Opioids are safe and effective for chronic
pain.
Opioid therapy can be easily discontinued.
Dhalla, I.A., N. Persaud, and D.N. Juurlink, Facing up to the
prescription opioid crisis. BMJ, 2011. 343: p. d5142.
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Misperception: “drugs are safe”
Campaign: “under-treatment of pain”- new
standard of care.
Joint Commission: Pain the 5th Vital Sign
Since 2001: 12 units CME in Pain
Management
Perceived safety of long term opioids, No
Ceiling Dose and new extended release
formulations.
Protection from and relief of pain and suffering are a
fundamental feature of the human contract we make as parents,
partners, children, family, friends, and community members, as
well as a cardinal underpinning of the art and science of
healing. Pain is part of the human condition; at some point, for
short or long periods of time, we all experience pain and suffer
its consequences. While pain can serve as a warning to protect
us from further harm, it also can contribute to severe and even
relentless suffering, surpassing its underlying cause to become
a disease in its own domains and dimensions. We all may share
common accountings of pain, but in reality, our experiences
with pain are deeply personal, filtered through the lens of our
unique biology, the society and community in which we were
born and live, the personalities and styles of coping we have
developed, and the manner in which our life journey has been
enjoined with health and disease.
IOM-Relieving Pain In America (2011)
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>100 million Americans 1
Mean Prevalence of 35.5% for chronic pain of
any kind 2
Weighted mean prevalence of 11% for severe
chronic pain 2
1. Institute of Medicine Relieving Pain in America: A blueprint for transforming
prevention, care, education and research, 2011.
2. Opina M, Hartstall C. 2002. Prevalence of chronic Pain: An Overview. Alberta
Heritage Foundation for Medical Research. Alberta, CA.
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$8.4 billion spent on narcotic analgesics in
2010.
Narcotics: 11th most prescribed drug
Oxycontin accounted for $3.1 billion in sales
Hydrocodone/APAP was the most dispensed
medication in the U.S.- 131.2 billion
dispensed.
Enough Hydrocodone to give every US Adult
one 5 mg tablet every 4 hours for six weeks.
Behavior
Percentage
Addicted to opioids
3.3
Engaged in misuse
behaviors
Illicit Drug Use
11.5
14.5
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For every one overdose death from opioids:
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9 treatment admissions
30 Emergency Department Visits
118 met criteria for addiction
785 people over the age of 12 using drugs for nonmedical reasons
From 1971 to 2007: an 8-fold increase in
drug overdoses.
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National Survey: 2006-2008- users of
opioids for non-health-related purposes
revealed they obtain drugs from physicians
31% of the time.
Overdoses:
◦ 40% see multiple doctors
◦ 40% see one doctor, prescribed high doses
◦ 20% see one doctor, prescribed low dose
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Risk of OD 4-12 fold higher >100 MED’s
~50% of OD’s occur when opioids are
combined with other drugs (especially
BZDP’s).
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Many of the Rx opioids are high risk
preparations:
◦ 3% fentanyl immediate release
◦ 17% fentanyl patches
◦ 10% methadone
Methadone: 2% of all opioids nationally, but
1/3rd of all deaths due to OD
45% of prescriptions in California WC were for
oxycodone- one of the most abused drugs.
Unpublished-Nickols, T., et al. 2012, RAND-David Griffen College of
Medicine/UCLA
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Small number of physicians represent outliers
with high-risk prescribing practices.
One percent of physicians who prescribed
opioids within CA WC were the source of 33%
of all opioid prescriptions.
Swedlow A, Ireland J, Johnson, G. Prescribing Patterns of
Schedule II Opioids in California Workers’ Compensation:
California WC Institute 2011.
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Is there any role for chronic opioid analgesia
(COT) in the treatment of chronic noncancer
pain (CNCP)?
Does the prescription of opioids to an injured
worker with noncancer pain worsen
outcomes?
Does the Rx of Opioids effect outcomes
(disability, pain severity, surgical risk, etc.)
How to determine the “carefully selected
patient”?
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Acute Pain
Chronic Pain
Opioids
Acute Pain
Chronic Pain
CNCP
COT
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Experts advocate use of COT for carefully
selected patients- how good are you?
Is it possible to identify patients with
predisposing factors that place them at risk
for Substance Abuse Disorder (SAD)?
Gut feelings- Physicians judged only 13.9% of
CPP prescribed opioids having aberrant drug
behaviors when 50% had positive UDT for
illicit drugs and 8.7% had no evidence of
opioid in their urine.
(Wassan, A.D. et al. Psychiatric history and psychological adjustement or risk
fractors for aberrant drug-related behavior among patients with chronic
pain. Clin. J. Pain, 2007: 23(4): 307-15.
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Patient self-report: notoriously unreliable.
Berndt et al found that 32% of patients
reports of prescription medication use did
not correspond with UDT.
Cook et al. found that self-reports compared
to urine tests, up to 50% of substance
abusers report falsely.
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Mixed predictors (+) in some
studies and (-) in others:
◦ Male sex, hx anxiety d/o; hx
of Rx drug abuse and race
(non-white)
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Variables rarely examined
but when they were, there
was some predictive value:
◦ (+) FHx of drug/illicit drug
use
◦ Hxchildhood sexual abuse
◦ Hx of DUI or drug convictions
◦ Lost or stolen Rx
◦ Supplemental sources of
drugs
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Not predictive:
socioeconomic status and
disability level.
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No one interview format or
instrument is superior to
any other in predicting
opioid misuse among CPP.
Strongest predictor:
personal hx of alcohol and
illicit drug use.
2 variables not predictive:
severity of pain and female
sex
Younger age, hx of legal
problems, (+) UDT
moderately positive
predictors
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despite our best attempt to
“profile” those at risk, it may
merely be the prescription and
use of opioids themselves which
best predicts poor outcomes!
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Does health care utilization and the
physicians initial management of workrelated LBP associate with the length of
disability.
Subtext: Does the prescription of opioids
affect total cost and length of disability.
Mahmud, M.A., et al., Clinical management and the duration of disability for workrelated low back pain. J Occup Environ Med, 2000. 42(12): p. 1178-87.
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An association between the avoidance of
prolonged opioid use (>7 days) and going off
disability was observed.
Mahmud, M.A., et al., Clinical management and the duration
of disability for work-related low back pain. J Occup
Environ Med, 2000. 42(12): p. 1178-87.
45
60
40
13
20
</=7 days
>7 days
</=7 days
0
Duration of Opioids
>7 days
Days of Disability
50
45
45
40
35
28
30
25
20
15
10
10
5
0
Imaging and Opioids
Imaging only
No imaging or opiods
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Prospective observational study correlated that
prescription of more then 7 days of opioids in the first 6
weeks after acute low back injury was associated with
increased risk (OR 2.2) of long-term (one year) work
disability.
Receipt of at least 2 opioid prescriptions in 6 weeks was
associated with increased risk (OR >/= 1.8) of long term
disability.
Receipt of >150 MED in six weeks associated with
doubling of 1-year disability.
Franklin, G.M., et al., Early opioid prescription and subsequent disability among workers with back injuries:
the Disability Risk Identification Study Cohort. Spine (Phila Pa 1976), 2008. 33(2): p. 199-204.
6.2
5.6
2.9
1.8
1
0
1
2
3
>3
Percentage
9.20%
4.78%
0.74%
0
1 to 7
>7
Disability Duration
 Medical Costs
 Late Opioid Use
 Subsequent back surgery
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Webster, B.S., S.K. Verma, and R.J. Gatchel, Relationship between early
opioid prescribing for acute occupational low back pain and
disability duration, medical costs, subsequent surgery and late
opioid use. Spine (Phila Pa 1976), 2007. 32(19): p. 2127-32.
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January 2002-December 2003
Only acute LBP cases
N= 8443 cases (1/1/2002-12/31/2003)
Excluded CLBP, Tx within the past year, no
concurrent or serious injury, i.e. fx
The MEA (morphine equivalent amount)
within the first 15 days after onset of injury
was calculated.
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Group
Group
Group
Group
Group
I: (No opioids within the first 15 days)
II: 1-141 MEA
III: 141-225
IV: 226-450
V: >450
Disability Days
121.1
0
124.1
1-140
149.6
141-225
175.5
226-450
204.2
450+
Medical Costs
30,000
25,000
20,000
15,000
Medical Costs
10,000
5,000
0
0
1-140
141-225
226-450
450+
Surgery %
23.5
15.6
10.5
11.9
7.9
0
1-140
141-225
226-450
450+
Late Opioid
34.3
23.4
18.8
13.5
7.2
0
1-140
141-225
226-450
450+
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After controlling for age, gender, job tenure,
and injury severity, the findings indicate that
receipt of higher amount of morphine
equivalent medications in early treatment was
significantly associated with adverse
outcomes including higher medical costs and
prolonged disability, higher risk of surgery,
and continued use of opioids.
Innovations in ScienceA window into the living brain
Neuroanatomy 101
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Plays a central role in
reward circuit relying on
dopamine and serotonin.
Close relationships to the
VTA (s. nigra) which is
targed by opiates;
prefrontal cortex, locus
ceruleus (drives aberrant
drug seeking behaviors),
hippocampus, prefrontal
cortex, insular cortex.
Signals anticipation of
pain perception.
 MRI
Scan
 Functional MRI Scan (fMRI)
 DTI- Diffusion tensor imaging
 SPECT Scan (single-photon
emission computed tomagraphy)
 PET (positron emission
tomography)
Speed matters
Expectation Matters
Volkow N D et al. J. Neurosci. 2003;23:11461-11468
©2003 by Society for Neuroscience
Stimulant Dependent
siblings vs. Healthy
Non-dependent siblings
vs. healthy
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Addiction is “polygenic”
Genes influence:
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Brain development
Relevant neurotransmitter systems
Drug metabolic pathways
Neural circuitry
Cellular physiology
Behavioral patterns
Response to environmental stimuli
Individual’s personality traits
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MAO’s
◦ Deaminates NE, Epi,
Serotonin, dopamine
◦ Adult carriers of “lowactivity” MAOA, exposed
to child abuse, more
likely to develop
conduct D/O, antisocial
PD, violent behaviors.
◦ MAO-L: reduced volume
of ACC (pathway
disrupted in SUD)
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BDNF-Brain-derived
neurotrophic factor
BDNF (Val(66) Mety
genotype may
provoke drug
seeking behavior in
heroin users.
Low levels BDNF
impede
development of
serotonin neurons
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Example: “Gateway theory”- how early
exposure to a chemical or drug, may increase
risk for subsequent addiction (by increasing
gene transcription in brain circuits that
underlie addiction)
Example: prenatal exposure to cigarette
smoke associated with specific brain changes
and behaviors later in adolescence
(methylation of BDNF)
Hypothetical example: Injured worker with
pain.
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Dopamine and other neurotransmitters
Learning- synaptic plasticity and long-term
potentiation (LTP) and long-term depression
(LTD)
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Most research on neurobiological aspects of opioid
dependence on brain systems focused on illicit opioids
(e.g. heroin).
This study was unique: examines impact of long-term
prescription opioids, since this may cause a different
illness (pure, pharmacologically bred).
n=10: small, homogeneous population of patients
without dependence on alcohol, other drugs, comorbid
psychiatric or neurologic disease and NO Pain.
Compared morphologic and functional imaging (MRI,
DTI and fMRI)
Upadhyay, J., et al., Alterations in brain structure and functional
connectivity in prescription opioid-dependent patients. Brain, 2010.
133(Pt 7): p. 2098-114.
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Results:
◦ 3T MRI: Reduced amygdala volume
(bilaterally)
◦ MRI/Diffusion weighted imaging: Reduced
FA in white matter tracts connected to
amygdala, corpus callosum, and internal
capsule.
◦ Functional MRI: Reduced FA correlated
with fMRI that showed reduced
connectivity between corresponding
structures: insula, amygdala and nucleus
accumbens.
Significant group-level FA decreases in white matter pathways.
Upadhyay J et al. Brain 2010;133:2098-2114
© The Author (2010). Published by Oxford University Press on behalf of the Guarantors
of Brain. All rights reserved. For Permissions, please email:
[email protected]
Resting-state functional connectivity changes in opioid-dependent
subjects in insula.
Upadhyay J et al. Brain 2010;133:2098-2114
© The Author (2010). Published by Oxford University Press on behalf of the Guarantors
of Brain. All rights reserved. For Permissions, please email:
[email protected]
Resting-state functional connectivity in opioid-dependent subjects
in amygdala.
Upadhyay J et al. Brain 2010;133:2098-2114
© The Author (2010). Published by Oxford University Press on behalf of the Guarantors
of Brain. All rights reserved. For Permissions, please email:
[email protected]
Resting-state functional connectivity in opioiddependent subjects in nucleus accumbens.
Upadhyay J et al. Brain 2010;133:2098-2114
© The Author (2010). Published by Oxford University Press on behalf of the Guarantors
of Brain. All rights reserved. For Permissions, please email:
[email protected]
Only longitudinal study (n=10)
 CLBP w/o Radiculopathy vs. Placebo
 13 areas with changes in brain volume,
6 correlate with dose
 Design: MRI volumetric study- pre-MS,
after one month of MS and ~4-6
months after discontinuation of MS.
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Younger, J.W., et al., Prescription opioid analgesics
rapidly change the human brain. Pain, 2011.
152(8): p. 1803-10.
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This group of patients with CLBP (n=10)) w/o
radiculopathy, SOD, prior opioids, ψ, neuropathic
pain compared to placebo group (n-9)
A before and after study, prospective, with
imaging prior to, after one month and on average
6 months post treatment with escalating doses of
opioids up to 120 MED/day ceiling.
Morphologic study-volumetric changes
measured.
Younger JW, et al. Prescription Opioid analgesics
rapidly change the human brain.
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A total of 13 structures demonstrated
significant regional volumetric gain or loss
over the 1-month of treatment.
Volumetric change in 6 of those regions
correlated with morphine dose, in particular
the right amygdala. (see next slide)
Other areas with significant reduction in size
(not dose related) were the right
hippocampus, b/l rostroventral pons and
right medial orbital gyrus of the orbitofrontal
cortex.
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This study measured changes up to 4.7
months on average (3.8-6.1 months after
cessation of the drug).
A quick and robust return to pre-opioid
volume levels would suggest that the drugs
impacts were transient and easily negated by
discontinuation of the drug.
HOWEVER, drug induced changes were
PERSISTENT!
This may underlie the difficulty with fully
recovering from adverse affects of opioids.
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No RCT examine pain control with doses
>180 to 200 MED
Dose-Response relationship observed: higher
doses assoc. with greater risks.
Even low doses are associated with increased
risk (one study as low as 50 MED/day.
Risk greatest above 100 MED/day: fatal OD
~20 t0 200% increased risk and 1100%
increased risk of serious or fatal OD.
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Vaccines to prevent opioid addiction
Medications that inhibit pain only in the
peripheral nervous system
Opioids that treat only pain without addiction
or side-effects
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Martin Brady, Executive Director and Debra
Russell, Schools Insurance Authority, Sacramento,
CA (www.sia-jpa.org)
National Institute of Drug Abuse
(www.drugabuse.gov)
Substance Abuse and Mental Health Services
Administration (www.samhsa.gov)
Physicians for Responsible Opioid Prescribing
(www.supportprop.org)
Centers for Disease Control (www.cdc.gov)
National Rx Abuse Summit
(www.nationalrxdrugabusesummit.org)
Questions?
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RECURRENT PAIN
ATTENTIONAL
FIXATION/RUMINATION
STRESS NEGATIVE EMOTION
TEMPORARY RELIEF FROM OPIOIDS
CONDITIONED REINFORCEMENT OF
OPIOID USE
OPIOID ATTENTIONAL BIAS
OPIOID CRAVING
TEMPORARY RELIEF FROM OPIOID USE
HYPERALGESIA
INSENSITIVITY TO NATURAL REWARD
LOSS OF CONTROL OVER OPIOID USE