Transcript Presentation - Faculty of pain medicine

Opioid analgesics:
the most dangerous drugs in
the Western pharmacopoea?

Malcolm Dobbin
 Adjunct Senior Research Fellow
 Department of Forensic Medicine
 Monash University
ANZCA Faculty of Pain Medicine Refresher Course Day May 2015
Opioid analgesics

Risky drugs in normal clinical use*
Risky drug + risky use + wide exposure
=
 currently most dangerous drug

•
•
Davies EC et al. ADRs in hospital inpatients: A prospective analysis of 3695 patient episodes. PloS One 2009;4(2):e4439.
Seddon ME et al. The Adverse Drug Event Collaborative: a joint venture to measure medication-related patient harm.
NZ Med J 2013;126:9-20.
Opioid analgesic harm

Clinical practice

Collateral harm
•
•
Davies EC et al. ADRs in hospital inpatients: A prospective analysis of 3695 patient episodes. PloS One 2009;4(2):e4439.
Seddon ME et al. The Adverse Drug Event Collaborative: a joint venture to measure medication-related patient harm.
NZ Med J 2013;126:9-20.
The Ancients
Demeter giving poppy to Persephone.
(Knossos 1500 BC)
http://www.ancient-wisdom.co.uk/prehistoricdrugs.htm
Her son Dionysos with crown of poppies.
The Ancients
http://www.forumancientcoins.com/numiswiki/view.asp?key=flavian
Wisdom of the Ancients
 It
is better to suffer pain than to
become dependent on opium.
– Diagoras of Melos, 3rd Century B.C.
 Opium
should be completely avoided
(due to the risk of addiction).
– Erasistratus of Chios, 5th Century B.C.
Hippocrates discouraging the use
of primitive medical techniques
ἐπὶ δηλήσει δὲ
καὶ ἀδικίῃ
εἴρξειν
Abstain from
doing harm.
Hippocrates
ἐπὶ δηλήσει δὲ
καὶ ἀδικίῃ
εἴρξειν
ἐπὶ δηλήσει δὲ καὶ ἀδικίῃ εἴρξειν
Abstain from doing harm.
Latin: Primum non nocere.
First do no harm.
Paracelsus
Phillippus Aureolus Theophrastus Bombastus Von Hohenheim. 1493-1541
Paracelsus
• Alle Ding' sind Gift, und nichts ohn' Gift; allein die Dosis
macht, daß ein Ding kein Gift ist.
• “All things are poison, and nothing is without poison; only the
dose permits something not to be poisonous.”
• “The dose makes the poison.”
Hypnos and Thanatos, Sleep and His HalfBrother Death by John William Waterhouse. 1874
Increasing supply:
Opioid analgesics
Global opioid consumption: morphine
equivalents MEQ
Consumption data: INCB,
http://www.painpolicy.wisc.edu/global
Population data: UN World Population Prospects, 2010 revision,
ME conversion factors: WHO Centre for Drug Statistics Methodology.
total ME (mg/person)
Global opioid consumption: morphine
equivalents MEQ
70
60
58.11
6.4-fold increase since 1991
50
40
30
20
9.03
33.26
10
19
80
19
82
19
84
19
86
19
88
19
90
19
92
19
94
19
96
19
98
20
00
20
02
20
04
20
06
20
08
20
10
0
Consumption data: INCB,
http://www.painpolicy.wisc.edu/global
Population data: UN World Population Prospects, 2010 revision,
ME conversion factors: WHO Centre for Drug Statistics Methodology.
Global oxycodone supply disparity 2010
Canada (0.6%)
8%
Europe( 11.4%)
9%
Other (82.5%)
2%
A & NZ (0.4%)
2%
USA (5.1%)
79%
oxycodone consumption 2008
mg/capita
140
Canada
USA
120
100
Denmark
80
Australia
6 developed countries
accounted for 95% of
global consumption
60
Norway
40
20
Sweden
0
62 countries reporting
Source: International Narcotics Control Board, UN population data
Australia
70
70
60
50
number
opioids
preparations
40
30
20
10
11
8
4
0
1992
2007
Leong et al. Examination of opioid prescribing in Australia: 1992-2007. Int Med J 2009;39:676-81
Oxycodone supply: Australia 2010
40mg OxyContin
controlled release
tablet, 8968897, 8%
20mg OxyContin
controlled release
tablet, 13716410, 12%
10mg OxyContin
controlled release
tablet, 15614819, 14%
80mg OxyContin
controlled release
tablet, 5406898, 5%
30mg suppository,
295140, 0%
20mg OxyNorm
capsule, 4161429, 4%
10mg OxyNorm
capsule, 5296395, 5%
5mg Endone tablet,
55413518, 48%
5mg OxyNorm capsule,
4285573, 4%
tablets, capsules and suppositories: 113.2 million
Australian population:
22 million.
Opioid base supply:
Australia, 1991-2012
Kg
Opioid base supply:
Australia, 1991-2012
Kg
Trends in opioids supply:
Australia, 1991-2014
2.5 tonnes
Most opioid use:
high dose patients
 Healthcore
(commercial insurance)
– Top 5% (138+ MED/day) - 70% of total use
 Arkansas
Medicaid (Public)
– Top 5% (128+ MED/day) - 48% of total use
Edlund MJ et al. An Analysis of Heavy Utilizers of Opioids for Chronic Noncancer Pain in the
TROUP Study. J Pain Symptom Manage 2010:40:279-889.
Opioids:
place in illicit drug use
Global illicit drug use,
dependence: place of opioids.
Harm:

acute toxic effects (including OD);
 effects of intoxication (e.g. injury and violence)
 Dependence
 Adverse effects of sustained use
Degenhardt L et al. Extent of illicit drug use and dependence, and their contribution to the global
burden of disease. Lancet 2012;379:55-70.
Global illicit drug use and
dependence.
Cannabis users
Opioid users
Amphetamine
group users
Cocaine users
125-203 million
12-21 million
14-56 million
14-21 million
(2.8-4.5%)
(0.3-0.5%)
(0.3-1.3%)
(0.3-0.5%)

Illicit opioid use is a major cause of mortality from fatal overdose and
dependence

Opioids are responsible for the greatest burden of
death and illness
Degenhardt L et al. Extent of illicit drug use and dependence, and their contribution to the global
burden of disease. Lancet 2012;379:55-70.
Global illicit drug use and
dependence.

2010: 15.5 million opioid dependent people

Opioid dependence 9.2 million DALYs

Opioid dependence – substantial contributor to
global disease burden
Degenhardt L et al.The global epidemiology and burden of opioid dependence: results from the
global burden of disease 2010 study. Addiction 2014;109:1320–1333
First illicit drug use:
USA, 2008
million
2.5
2.2 2.2
2
1.5
1
1.2
0.9
0.7
0.7
0.6
0.5
0.4
0.2 0.1 0.1
0
n
pp
t
ts
rs asy
na ed)
ne lan
i
n
e
a
z
a
st
c a mu
iju n m uili
al
c
o
r
h
e
c
a
ti
o
q
n
i
s
n
n
m
(
tra
ic
s
e
lg
a
an
n
D
es
oi
r
LS tiv
he
da
e
s
P
C
P
Source: National Survey on Drug Use and Health 2008. (SAMHSA 2009)
Pain relievers USA, 2012
Non-medical use:
• lifetime
37 million (14.2%)
• last year 12.5 million (4.8%)
• last month 4.9 million (1.9%)
Dependence:
2004
1.4 million
2012
2.1 million
Source: National Survey on Drug Use and Health 2012. (SAMHSA 2013)
Grade 12 US students:
non-medical use in past year.
1 in 10
%
10
9
8
7
6
5
4
3
2
1
0
1 in 20
9.6
5.2
OxyContin
Vicodin
Source: Monitoring the Future: 2007. University of Michigan
Source of opioid pain relievers for non-medical use in
past year: US 2012
NSP survey:
Australia 2000-2010
NSP survey - last opioid injected: Australia,
2000 & 2010
7%
27%
Source: Australian NSP Survey National Data Report 1995-2010
Opioid injected: Australia 2010
Source: Australia Drug Trends 2010. IDRS p 10
PWID recent prescription drug injection *
%
* Illicit Drug Reporting System (IDRS) Victoria, 1999-2010.
May-12
Jan-12
Sep-11
5000
May-11
6000
Jan-11
7000
Sep-10
May-10
Jan-10
Sep-09
May-09
Jan-09
Sep-08
May-08
Jan-08
Sep-07
May-07
Jan-07
Sep-06
May-06
Jan-06
Sep-05
May-05
Jan-05
Sep-04
May-04
Jan-04
Sep-03
May-03
Jan-03
Sep-02
May-02
Jan-02
Sep-01
May-01
Drug injected: Sydney Medically
Supervised Injecting Centre
Other Opioids
Heroin
Cocaine
Methampethamines
4000
3000
2000
1000
0
Talc pulmonary granulomatosis
Heroin-ambulance attendances:
Melbourne, 1998-9 to 2010-11
Lloyd B. Trends in alcohol and drug related attendances in Melbourne 2010/2011. Turning Point
Drug and Alcohol Centre, Fitzroy. 2012
Opioid-analgesic ambulance attendances:
Melbourne, 1998-9 to 2010-11
Lloyd B. Trends in alcohol and drug related attendances in Melbourne 2010/2011. Turning Point
Drug and Alcohol Centre, Fitzroy. 2012
DirectLine calls - opioids: 1999-2009
%
40
other opioid
35
32
30
25
*
25
20
20
15
29
28
26
27
32
31
30
31
18
14
10
14
10
heroin
5
7
8
9
13 12
12
11
20
10
20
09
20
08
20
07
20
06
20
05
20
04
20
03
20
02
20
01
20
00
20
19
99
0
Source: DirectLine, Turning Point Alcohol and Drug Centre. Victorian IDRS 2012.
Harm in clinical use
CNMP treatment
in practice
CNMP treatment in practice
Few specialists/clinics
 Increasing patients
 Most - GP
 Little training - pain management,
addiction
 Some reluctant to prescribe

CNMP treatment in practice

Barriers
– Short appointment times
– Lack of confidence
– Many non-reimbursed tasks
– Complex cases – many tasks
– Multiple comorbidities
CNMP treatment in practice:
adverse selection

High risk patients (MH or SU disorder) receive high
risk regimens
– High daily dose
– High potency opioids
– Chronic prescribing
– Concurrent sedative/hypnotics
Sullivan M et al. Opioid therapy for chronic pain in the United States: Promises and perils. Pain
2013;154:S94-S100.
Saunders KW et al. Concurrent Use of Alcohol and Sedatives among Persons Prescribed Chronic Opioid
Therapy: Prevalence and Risk Factors. J Pain 2012;13:266-75.
CNMP treatment in practice:
risk of lifelong opioids

90 days continuous treatment: 2/3rds remain on
opioids years later – predicted by:
– High daily opioid dose
– Opioid misuse
Sullivan M et al. Opioid therapy for chronic pain in the United States: Promises and perils. Pain
2013;154:S94-S100.
Martin BC et al. Long-term chronic opioid therapy discontinuation rates from the TROUP study. J
Gen Intern Med 2011;2:1450-7.
Acute opioid risks
Hospital ADEs
3695 patient episodes
 545 (14.7%) – ADR
 Half avoidable
 Commonest drugs:

– diuretics,
– opioid analgesics (16.1% of all ADRs),
– anticoagulants
Davies EC. Adverse Drug Reactions in Hospital In-Patients: A Prospective Analysis of 3695 PatientEpisodes. 2009; PLoS ONE 4(2): e4439
Hospital ADEs
1210 charts
 353 ADEs (28.9%)
 18 cases severe, (5 deaths)

– Opioids
– anticoagulants
– antibiotics
– NSAIDS
– Diuretics
(33%)
(10%)
(9%)
(5%)
(4%).
•Seddon ME et al. The Adverse Drug Event Collaborative: a joint venture to measure medication-related
patient harm. NZ Med J 2013;126:9-20.
Hospital ADEs
567 surgical patients
 27.5 ADEs and 4.2 preventable ADEs per 100
admissions (15.4 %).
 1 in 4 life-threatening
 Opioids and anticoagulants

de Boer M et al. Adverse drug events in surgical patients: an observational multicentre study. Int J Clin
Pharm. 2013;35:744-52
Post-operative
opioid respiratory depression

Anesthesia Closed Claims Project 1990-2009
9,799 claims
 357 acute pain claims
 92 claims - respiratory depression
 77% -severe brain damage or death
 Expensive

Lee AN et al. Postoperative opioid-induced respiratory depression: a closed claims analysis.
Anesthesiology. 2015;122:659-65
post-operative
opioid respiratory depression
Risk groups known
 ‘respiratory depression’ taught and monitored
 OIVI – includes airway collapse
 Snoring, gurgling signs ignored.
 oximetry and capnography monitoring
 Alarm fatigue

Opioid risks:
chronic non-cancer pain
Harm: increasingly recognised,
emerging.








Hyperalgesia
Endocrine dysfunction - hypogonadism
Immunosuppression
Opioid-induced bowel disorder
Sleep apnoea – central and obstructive
Difficulty managing acute & post-op pain
Dependence, addiction
Diversion – on-selling
Coma, OIVI and overdose
Most feared of all ADEs
 Incorrectly taught, perceived, as ‘respiratory
depression’
 Signs of airway collapse ignored: snoring, gurgling.
 Role of partial or mixed agonists
 Naloxone half life, modified release opioids,
methadone

OIVI
sleep apnoea
 obese patients
 Patients on >200 mg MED - evaluate for sleep
disordered breathing
 Dose-related death risk in COPD

Hospitalisation for heroin/other opioid
poisoning: Australia
2500
2000
1712
1500
1000
828
500
0
1998-99
heroin
2007-08
other opioids, methadone, other synthetic narcotics
Source: AIHW National Hospital Morbidity Database. http://d01.aihw.gov.au/cognos/cgi-bin/ppdscgi.exe?DC=Q&E=/AHS/pdx0708
Hospitalisation for heroin/other opioid
poisoning: Australia
80.3%
2500
2000
2261
1712
32.6%
1500
1000
828
554
500
0
1998-99
heroin
2007-08
other opioids, methadone, other synthetic narcotics
Source: AIHW National Hospital Morbidity Database.
http://d01.aihw.gov.au/cognos/cgi-bin/ppdscgi.exe?DC=Q&E=/AHS/pdx0708
Association:
dose and overdose
Odds ratio relative to low dose COT
Dose-related opioid overdose risk
10
*
8.9
8
*
*p<0.05
7.2
6
*
*
4
4.6
3.7
2
* *
*
1
1
1
1.9
1.9
*
2.9
2
1.3
1.2
0
GHRI study Ann Intern VHA study JAMA 2011
Med 2010
Ontario study Arch
Intern Med 2011
MED/day
1-19 mg
20-49 mg
50-99 mg
100 mg +
200+
Dose-related OD risk
Dunn KM et al. Opioid prescriptions for chronic pain and overdose. Ann Intern med 2010;152:85-92.
Spatial association:
supply and harm
Cited in: CDC opioid painkiller prescribing: where you live makes a difference.
http://www.cdc.gov/vitalsigns/pdf/2014-07-vitalsigns.pdf
Opioid OD death rates 2008
Kg opioid analgesics 2010
Correlation supply, harm
Modari: N
Carolina.
Drug Alc
Depend
2013;132:81
Misuse, addiction
Pharmaceutical opioid misusers
1. Intentionally seeking intoxicating effect: includes PWIDs,
others
2. “Accidental”, “respectable”, “functional” addicts, “hidden
addiction” - PLU.
– Highly functioning
– Employed, educated, family, social support, income OK, insight,
highly motivated when aware
– Suited to GP care
– AOD clinics – developed for heroin users
External locus of
control
Passik S D Mayo Clin Proc. 2009;84:593-601
Vulnerable Australians

Mental health disorders
– 20% of adult population*
 Substance use disorders – personal
– 7% of adult population*
 Comorbidity prevalent
 Penetrative child sexual abuse #
– 2.0 to 6.7%
 Drug-related suicide risk
 Low SES, rural, smokers
* Source: National Survey of Mental Health and Wellbeing, 2007
# Aust Inst Family Studies: The prevalence of child abuse and neglect. 2013
Addiction, abuse

One opioid study based on standardised interviews (n=
801)
– 26% sought over-sedation
– 39% increased dose without prescription
– 8% obtained extra from other doctors
– 18% used for other than pain
– 12% hoarded pain medicines
Fleming et al Substance use disorders in a primary care sample receiving daily opioid therapy. J Pain 2007;8:573-82.
Addiction, abuse
38 articles
 Overall mean calculation range using 95% confidence
interval:

– Misuse
– Addiction
12.9-37.5%
3.2-17.3%
Vowles KE et al. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis
www.painjournalonline.com 2015;156:569-76.
Opioid-induced bowel disorder

Opioids affect GI motility
– Constipation, nausea, vomiting, bloating,
ileus, sometimes pain

Narcotic bowel syndrome
– abdo pain predominates

Stercoral perforation
Drossman D, Szigethy E. The Narcotic Bowel Syndrome: A Recent Update. AM J Gastroenterol
2014;10:22-30.
Davies A, Webber K. Stercoral Perforation of the Colon: A Potentially Fatal Complication of Opioid-Induced
Constipation. J Pain Symptom Manage 2015 Apr 3. pii: S0885-3924(15)00156-6. doi:
Bone metabolism
Role of endocrine system
 Opioids a/w significant BMD reduction*
 Interfere with osteoblast activity
 ? Monitor hormone levels
 Also -increased fall risk.

* Kinjo M et al. Bone mineral density in subjects using central nervous system-active
medications. Am J Med 2005;118:1414.
Falls, fracture risk

Miller
– Opioids: 120/1000 person years
– NSAIDs: 25/1000 person years
– Dose related

Saunders
– RR 1.28, dose related
Miller M et al. Opioid analgesics and the risk of fractures among older adults with arthritis. N Amer Geriatric Soc 2011.
Saunders KW et al. Relationship of opioid use and dosage levels to fractures of older chronic pain patients. JGIM 2010.
Opioid-induced dental problems
Xerostomia
 Dental caries
 Periodontitis
 Bruxism
 Acute necrotising gingivitis
 Tooth loss
 (High prevalence of smoking, neglect of dental
hygiene)

Cognitive impairment
(mental clouding)
Sedation
 Dose dependent

Increased supply
associated with:
 Increased
abuse
– (Cicero TJ et al. Relationship between therapeutic use and abuse of
opioid analgesics in rural, suburban and urban locations in the United
States. Pharmacoepidemiol Drug Saf 2007;16(8):827-40)
 Increased
medical emergencies
– (Dasgupta N et ak, Association between non-medical use and
prescriptive usage of opioids. Drug Alc Dep 2006;82:135-42.)
 Increased
drug poisoning deaths
– (Paulozzi LJ, Ryan GW. Opioid analgesics and rates of fatal drug
poisoning in the United States. Am J Prev Med 2006;31(6):506-11.)
Many patients function better
off opioids.








Hooten WM et al. Treatment outcomes after multidisciplinary pain rehabilitation
with analgesic medication withdrawal for patients with fibromyalgia. Pain Med
2007
Miller NS et al. Effects of opioid prescription medication dependence and
detoxification on pain perceptions and self-reports. 2006.
Crisostomo RA et al. Withdrawal of analgesic medication for chronic low-back
pain patients: improvement in outcomes of multidisciplinary rehabilitation
regardless of surgical history. 2008.
Vorobeychik Y et al. Improved opioid analgesic effect following opioid dose
reduction. 2008.
Baron MJ et al. Significant pain reduction in chronic pain patients after
detoxification from high-dose opioids. 2006
Townsend CO et al. A longitudinal study of the efficacy of a comprehensive pain
rehabilitation program with opioid withdrawal: comparison of treatment outcomes
based on opioid use status at admission. 2008.
Ralphs JA et al. Opiate reduction in chronic pain patients: a comparison of
patient-controlled reduction and staff controlled cocktail methods. 1994.
Taylor CB et al. The effects of detoxification, relaxation and brief supportive
therapy on chronic pain. 1980.
maternal opioid use, NAS:
US 2000-09
Emergency Department visits:
USA 2004-2010
DAWN 2010 – national estimates of drug-related ED visits. SAMHSA 2012
Emergency Department visits:
USA 2004-2010
DAWN 2010 – national estimates of drug-related ED visits. SAMHSA 2012
Admissions by primary substance of abuse:
US TEDS 1997-2010
heroin: 5% increase
Prescription opioids: 1049% increase 2000-2011
6.5%
38% of all opioids
Source: Treatment Episode Dataset. (SAMHSA 2012)
Primary drug of concern: Qld
Opioid Treatment Program 01-06
Queensland Opioid Treatment Program. Annual Report. Medicines Regulation and Quality,
Queensland Health. Brisbane (2013)
Treatment episodes for opioid
dependence: W Australia
4500
4000
3500
3000
2500
no.
2000
1500
1000
500
0
3816
10%
2056
38%
1237
443
2000-01
heroin
2007-08
ppn opioids
Source: Submission No. 37, Part C. from Drug and Alcohol Office, 18 September 2009.
Drug poisoning deaths
USA 1999-2010
16,651
18,000
16,000
cocaine
14,000
heroin
12,000
opioid analgesics
10,000
8,000
4,030
6,000
4,000
2,000
SOURCE: CDC/NCHS, Online query system:
10
20
09
20
08
20
07
20
06
20
05
20
04
20
03
20
02
20
01
20
00
20
19
99
0
http://wonder.cdc.gov/mcd.html.
Drug poisoning deaths
USA 1999-2010
16,651
18,000
16,000
14,000
cocaine
12,000
opioid analgesics
heroin
10,000
8,000
4,030
6,000
4,000
2,000
SOURCE: CDC/NCHS, Online query system:
10
20
09
20
08
20
07
20
06
20
05
20
04
20
03
20
02
20
01
20
00
20
19
99
0
http://wonder.cdc.gov/mcd.html.
deaths
supply
Opioid supply and drug poisoning
deaths: Ohio 1997-2011
60
140
50
120
100
40
80
30
60
20
No. deaths
sales ($Cmillion)
OxyContin sales and oxycodone deaths: Ontario
40
10
20
0
0
03-'04
04-'05
05-'06
sales (C$million)
06-'07
07-'08
oxycodone deaths
Ontario Ministry of Health and Long Term Care, Ontario Centre of Forensic Sciences
Source: Vital signs: Overdoses of prescription opioid pain relievers- United States, 1999-2008. MMWR 2011
(Nov 1);60:1-6.
Oxycodone supply and unintentional
poisoning deaths: Victoria 2000-2010
Rintoul A, Dobbin M.
Oxycodone: supply trends and
deaths: Australia, 2001-2011
Overdose deaths involving opioids:
Victoria 2000
Pharmaceutical
opioids
only
Pharml
opioids
+
heroin
50
58
Heroin
Only
283
Overdose deaths involving opioids:
Victoria 2010
Pharmaceutical
opioids
only
Pharml
opioids
+
heroin
105
39
Heroin
only
100
Overdose deaths involving opioids:
Victoria 2012
Pharmaceutical
opioids
only
157
Pharml
opioids
+
heroin
53
Heroin
only
56
crime

Obtain or traffick crimes
–
–
–
–
–
–
–

Fraudulent representation (Dr shopping)
Identity fraud
Forgery
Coercion – Dr, pharmacist, patient
Theft
pharmacy break–in, ram raid, armed robbery
Trafficking (including on-selling)
Intoxication crimes
– Culpable driving – deaths
– Rambo effect
– shoplifting
Harm: trafficking
Drug
Price
Heroin per cap
$45-90
Methamphetamine per point
$30-65
Cocaine per cap
$50-125
Cannabis per gram
$10-25
Opioids
methadone 10mg tab
MS Contin, Kapanol 100mg
$5-20
Ecstasy tablet
$20-50
$20-50
$30-50
Pill Mills Florida



Florida prescribed ten times more oxycodone pills
than all other states combined.
98 of top 100 opioid-dispensing prescribers in US.
DEA Operation Pill Nation: $2.2 million cash, 70
exotic vehicles.
Source: Kuehn B. CDC: Major disparities in opioid prescribing among States JAMA 2014;Aug 6th
Computer forgery
2005
5 months
3 States
173 doctors
287 visits
425 prescriptions for
narcotics, morphine
425 x 20 = 8,500 tabs
8,500 x $20 = $170,000
$114 million per year
Pharmacy armed robbery
OxyContin – pharmacy response
Pharmacy armed robbery Victoria
Culpable driving
12 caps heroin, shot of speed 10 codeine tabs, 10 Xanax tabs
Drug, opioid poisoning US.
16917
4030
142,812 deaths
The end
Reasons for increased supply
Opiophobia
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opiophilia
1861-5 Morphine addiction – Civil War “The soldiers’ disease”
1914. Harrison Narcotic Act
1980 Porter & Jick
1986 Portenoy & Foley
1990 Melzack R. The tragedy of needless pain (Sci American article)
1996 American Pain Society: Pain-the 5th vital sign
1996 Purdue market OxyContin
1997 AAPM & APS consensus statement
1998 Veterans Administration: Pain-the 5th vital sign
2001 Joint Commission on Accreditation of Health Care Organisations.
Pain-the 5th vital sign 2001
2004 Federation of State Medical Boards
2007 Purdue fined $640 million
Reasons
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Experience with acute and cancer pain
Palliative care physicians
Professional and patient advocacy pain organisations
Reaction to under-prescribing
Concern about NSAIDS
 Compassion
– -proximate vs distal (ultimate)
Porter & Jick 1980
Portenoy & Foley 1986
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38 patients - pain service
Management problem - 2 patients (prior drug abuse).
“.. opioid maintenance therapy … safe, salutary and more
humane”.
Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: Report of 38 cases.
Pain 1986;25:171-86.
Medication safety in hospital.
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Hospitalisations: most commonly medicine classes: antibacterials, opioids, diuretics, antineoplastic agents,
antithrombotics, cardiac therapy
 31% of those admitted for faecal impaction (n=6851) were
dispensed highly or multiple anticholinergic agents, or
opioids at the time of the admission
 The US Institute of Safe Medication Practices - major
high-alert medications subject to administration error.
(insulin, opioids, injectable KCl, IV anticoagulants
(heparin) and NaCl solutions above 0.9 %)
Roughead
2013
L, Semple S, Rosenfeld E. Literature Review: Medication Safety in Australia. ACSQHC.
Australian Commission on Safety and Quality in
Healthcare: High risk medicines
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A
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Roughead
2013
Anti-infectives
Potassium and other electrolytes
Insulin
Narcotics and other sedatives
Chemotherapeutic agents
Heparin and other anticoagulants
Systems
L, Semple S, Rosenfeld E. Literature Review: Medication Safety in Australia. ACSQHC.
The tragedy of needless pain 1990
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“'Yet the fact is that when patients take morphine to
combat pain…
– rare to see addiction”.
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“The goal is nothing short of rescuing people whose
lives ….ruined by pain”.
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Melzack R. The tragedy of needless pain. Scientific Amer 1990;262 (2):
1996
1997
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(pain) is frequently inadequately treated, leading to
enormous social cost in the form of lost productivity,
needless suffering, and excessive healthcare
expenditures.
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Impediments to the use of opioids include concerns
about addiction, respiratory depression and other
side effects, tolerance, diversion, and fear of
regulatory action.
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Studies indicate that the de novo development of
addiction when opioids are used for the relief of pain
is low.
Pain: The Fifth Vital Sign
Joint Commission on Accreditation of Health Care
Organisations.
 2001
 Pain under-treated in hospitals
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. "Some clinicians have inaccurate and exaggerated concerns" about
addiction, tolerance and risk of death, the guide said. "This attitude
prevails despite the fact there is no evidence that addiction is a
significant issue when persons are given opioids for pain control."
OxyContin promotion
GAO. OxyContin abuse and diversion and efforts to address the problem. US Government Accounting Office. 2003
Van Zee A. The promotion and marketing of OxyContin: commercial triumph, public health tragedy. Amer J Public Health 2009;99:221-
In Guilty Plea, OxyContin Maker to Pay
$600 Million 2007
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misled regulators, doctors and patients about the drug’s risk of
addiction and its potential to be abused.
pleaded guilty today as individuals to misbranding, a criminal
violation. They agreed to pay a total of $34.5 million in fines.
pleaded guilty today as individuals to misbranding, a criminal
violation. They agreed to pay a total of $34.5 million in fines.
Purdue Pharma contended that OxyContin, because of its timerelease formulation, posed a lower threat of abuse and addiction
to patients than do traditional, shorter-acting painkillers like
Percocet or Vicodin.
That claim became the linchpin of the most aggressive
marketing campaign ever undertaken by a pharmaceutical
company for a narcotic painkiller.
http://www.nytimes.com/2007/05/10/business/11drug-web.html?pagewanted=all&_r=0
Russel Portenoy
Under-treatment of pain is a tragedy: so is addiction
 "We didn't know then what we know now."
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A Pain-Drug Champion Has Second Thoughts.
http://online.wsj.com/article/SB10001424127887324478304578173342657044604.html
Presentation
Increasing supply – reasons
 Increasing supply
 Benefits
 Costs
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– Acute
– Chronic
– Community (non-patient)
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The Prevention Paradox
Benefits: controversial
Most studies – uncontrolled case series
 Doses low-moderate
 Randomised trials short duration (<8/12)
 Unclear whether prolonged opioid Tx is effective controversial
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Benefits: weak evidence
 Back pain
- most prevalent condition for opioids
 Fibromyalgia
– other treatments
 Headache
– risk of medication overuse headache (MOH)
Benefits: recent guidelines
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American Pain Society/American
Academy of Pain Medicine (2009)
– Low quality evidence - 21/25
recommendations
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Canadian Guidelines (2010)
– 3/24 recommendations based on RCTs
– consensus opinion - 19 based
solely, partly
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…. opioid treatment …does not seem to
fulfil …key outcome …goals: pain relief,
improved quality of life and improved
functional capacity.
Eriksen et al. Critical issues on opioids and chronic non-cancer pain:
an epidemiological study. Pain 2006;125:172-9
Conclusion:
• Evidence on long-term opioid therapy
for chronic pain is very limited,
• but suggests an increased risk of
serious harms that appears to be
dose-dependent.
U.S. Agency for Healthcare Research and Quality (AHRQ). The Effectiveness
and Risks of Long-term Opioid Treatment of Chronic Pain. July 2014