Transcript FLUNISOLIDE HFA INHALER SYSTEM

The
Opioid Epidemic
Some Key issues for Physicians and other
Healthcare workers
Richard Ries MD
[email protected]
Harborview Medical Center and the University of
Washington
Seattle, Washington
Len Paul0zzi MD MPH
CDC Atlanta Georgia
Ries Conflict of Interest Statement


Dr Ries is on Speaker’s bureaus for
 Janssen, Reckitt-Benckiser, and Alkermes
Dr Ries has Grant funding from:
 NIH- NIDA-NIAAA
 Contingency Management Alcohol in
Mentally Ill
 Brief Interventions of Drug Abuse in Prim
Care
 PTSD-- Exposure +/- Sertraline
 CM for Alcohol in Native Am Indians
 RCT of Injectable Naltrexone is Severe Alc
 DOD- Suicide Prevention grant
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Mary presents with serious multiple
fractures after an auto crash
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32 y o w female with history of minor traumas (twisted ankle, back
spasms), ER scripts 2 years ago for 5 days of oxycodone
Stabilized fractures of L femur and tibia, L wrist, abrasions, but post
stabilization on standard opioid pain control, complains of pain,
shows sweating, diarhea, feels cold and shakes, blood pressure
elevates
Further info from family finds pt is prescribed oxycodone for chronic
back pain, also xanax for anxiety, often appears sleepy, they think
she might have a drug problem, and may be taking too much
medication or maybe not as prescribed
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3
Motor vehicle traffic, poisoning, and drug poisoning
(overdose) death rates
United States, 1980-2010
Motor Vehicle Traffic
Poisoning
Drug Poisoning (Overdose)
Deaths per 100,000 population
25
20
15
10
5
0
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
Year
Paulozzi - CDC NCHS Data Brief, December, 2011, Updated with 2009 and 2010 mortality data
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Death Rates for Drug Overdose by State, 2010
13.1
12.9
10.4
3.4
7.3
12.9
11.8
10.9
6.3
15.0
13.9
8.6
6.7
20.7
15.3
10.0 14.4
16.9
10.6
7.8
16.1
28.9
12.7
9.6
17.0
6.8
23.6
11.4
16.9
17.5
19.4
23.8
14.6
12.5
11.4
11.8
NH
VT
MA
RI
CT
NJ
DE
MD
DC
11.8
9.7
11.0
15.5
10.1
9.8
16.6
11.0
12.9
10.7
9.6
13.2
16.4
11.6
10.9
Age-adjusted rate per 100,000 population
3.4 - 10.9*
10.9* - 13.9
Footnote: *10.9 is in two ranges dueRRies
to rounding.
2014HI is 10.88 while WI is 10.94
14.0 - 28.9
Opioid analgesic overdose death rates
by sex and race , U.S., 2009
Source: National Vital Statistics System; crude rates
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Drug overdose deaths by major drug type,
US, 1999-2010
Opioids
Heroin
Cocaine
Benzodiazepines
2004
2006
18,000
16,000
Number of Deaths
14,000
12,000
10,000
8,000
6,000
4,000
2,000
0
1999
2000
2001
2002
2003
2005
2007
2008
2009
2010
Year
CDC/NCHS National Vital Statistics System, CDC Wonder. Updated with 2010 mortality.
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Journal of Analytical Toxicology, Volume 27, Number 2 March 2003
Oxycodone Involvement in Drug Abuse Deaths: A DAWNBased Classification Scheme Applied to an Oxycodone
Postmortem Database Containing Over 1000 Cases*
Authors: Cone E.J.1; Fant R.V.1; Rohay J.M.1; Caplan Y.H.2; Ballina M.3; Reder R.F.3; Spyker
D.3; Haddox J.D.
Of 1014 cases:
30 (3.3%) involved oxycodone as the single reported chemical entity;
of these,
The
vast majority (N = 889, 96.7%) were multiple drug abuse
deaths
The most prevalent drug combinations were
oxycodone in combination with benzodiazepines, alcohol,
cocaine, other narcotics, marijuana, or antidepressants.
Exhibit 2: Past Year Initiation of Non-Medical Use of Prescription-type
Psychopharmaceutics, Age 12 or Older: In Thousands, 1965 to 2005 1
3000
New Users (x 1000)
2500
2000
1500
1000
500
19
65
19
67
19
69
19
71
19
73
19
75
19
77
19
79
19
81
19
83
19
85
19
87
19
89
19
91
19
93
19
95
19
97
19
99
20
01
20
03
20
05
0
Analgesics
Tranquilizers
Stimulants
Sedatives
While Opiates have grown fastest, Benzos are
not far behind
Source: SAMHSA, OAS, NSDUH data , July 2007
Benzo’s the Hidden Drug
• While there are hundreds of recent articles on Prescription
Opiate problemsMost literature on Benzo Abuse/Dependence is > 10 years
old
•
Toxicology studies of Opiate deaths usually find Benzo’s
too –respiratory depression is additive.
•
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Sales of Benzo’s are also increasing dramatically
•Simple
Tox screens often miss Clon- and Alprazolam
Characteristics of unintentional pharmaceutical
overdose deaths (N=295),
West Virginia, 2006
Characteristic
History of substance abuse
Pct.
78.3
Other mental illness
42.7
Nonmedical route of administration
22.4
Previous overdose
16.9
TOTAL
100.0
Sources: Hall et al, JAMA, 2008 and Toblin et al, J Clin Psych, 2010
11
Source Where Pain Relievers Were
Obtained for Most Recent Nonmedical Use
among Past Year Users Aged 12 or Older
2006
Source Where Respondent Obtained
Bought on
Drug Dealer/ Internet
0.1%
Stranger
More than 3.9%
One Doctor
1.6%
One Doctor
19.1%
Bought/Took
from Friend/Relative
14.8%
Other 1
4.9%
Free from
Friend/Relative
55.7%
Source Where Friend/Relative Obtained
More than One Doctor
3.3%
Free from
Friend/Relative
7.3%
One
Doctor
80.7%
Bought/Took from
Friend/Relative
4.9%
Drug Dealer/
Stranger
1.6%
Other 1
2.2%
Note: Totals may not sum to 100% because of rounding or because suppressed estimates are not shown.
1
The Other category includes the sources: “Wrote Fake Prescription,” “Stole from Doctor’s
Office/Clinic/Hospital/Pharmacy,” and “Some Other Way.”
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Opioid Abstinence Syndrome
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Symptoms: craving, anxiety, irritability, restlessness,
nervousness, insomnia, rhinorrhea, lacrimation, nausea,
abdominal cramps, myalgias, arthralgias
Signs: tachycardia, hypertension, mydriasis, piloerection,
diaphoresis, tremor
Depending on opioid abused, starts within 4-6 hours, full
intensity at 24 to 72 hours, can last for 7-14 days—
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Eg oxycodone vs methadone
Though less medically dangerous than alcohol or BZP,
appears to drive relapse to opioid use at much higher
rate.
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Clinical Opiate Withdrawal Scale (COWS) 1
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Resting Pulse Rate: (record beats per
minute)
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Measured after patient is sitting or lying for
one minute
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0 pulse rate 80 or below
1 pulse rate 81-100
2 pulse rate 101-120
4 pulse rate greater than 120
Sweating: over past ½ hour not accounted
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for by room
temperature or patient activity.
0 no report of chills or flushing
1 subjective report of chills or flushing
2 flushed or observable moistness on face
3 beads of sweat on brow or face
4 sweat streaming off face
Restlessness Observation during
assessment
0 able to sit still
1 reports difficulty sitting still, but is able to
do so
3 frequent shifting or extraneous movements
of legs/arms
5 Unable to sit still for more than a few
seconds
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Pupil size
0 pupils pinned or normal size for room light
1 pupils possibly larger than normal for room
light
2 pupils moderately dilated
5 pupils so dilated that only the rim of the iris is
visible
Bone or Joint aches If patient was having pain
previously, only the additional component
attributed
to opiates withdrawal is scored
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0 not present
1 mild diffuse discomfort
2 patient reports severe diffuse aching of joints/
muscles
4 patient is rubbing joints or muscles and is
unable to sit
still because of discomfort
Runny nose or tearing Not accounted for by cold
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symptoms or allergies
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0 not present
1 nasal stuffiness or unusually moist eyes
2 nose running or tearing
4 nose constantly running or tears streaming
down cheeks
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GI Upset: over last ½ hour
0 no GI symptoms
1 stomach cramps
2 nausea or loose stool
3 vomiting or diarrhea
5 Multiple episodes of diarrhea or
vomiting
Tremor observation of outstretched
hands
COWS p2
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0 No tremor
1 tremor can be felt, but not observed
2 slight tremor observable
4 gross tremor or muscle twitching
Yawning Observation during
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0 no yawning
1 yawning once or twice during
assessment
2 yawning three or more times during
assessment
4 yawning several times/minute
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assessment
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Anxiety or Irritability
0 none
1 patient reports increasing irritability
or anxiousness
2 patient obviously irritable anxious
4 patient so irritable or anxious that
participation in the
assessment is difficult
Gooseflesh skin
0 skin is smooth
3 piloerrection of skin can be felt or
hairs standing up on
arms
5 prominent piloerrection
Total scores
with observer’s initials
Score:
5-12 = mild;
13-24 = moderate;
25-36 = moderately severe;
more than 36 = severe withdrawal
Alcohol WD
CIWA-Ar
10 items
CIWA-AD
8 items
COWS scale in fill out form ---download
http://www.naabt.org/documents/cows_induction_flow_
sheet.pdf
RRies 2014
Medically Supervised Opioid
Withdrawal
 Methadone substitution and taper- not advised for
novice doctors….you have to know methadone half
lives and build up
 Clonidine
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-2 adrenergic agonist
Acts on autoreceptors in locus coeruleus to
decrease noradrenergic output
Major side effect hypotension
Push dose until withdrawal sx abate or diastolic
BP <60
Use adjunctive benzodiazepines, anti-emetics,
antidiarrheals
 Buprenorphine
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Key Medications in Acute Opioid Withdrawal
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Buprenorphine/Naltrexone
 16 mg x 1
 16 mg, 8 mg, 4 mg
 16 mg maintenance to outpt
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Sedation
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Gabapentin 400 tid – 800 tid esp if BZPs involved
Mirtazapine 7.5 or 14 mg ( more is less sedative)
Tizanidine to 4-12 mg tid ( muscle spasm and sedation)
Quetiapine 200 - 400 HS esp if agitated/psychotic
Olazapine 10 mg hs
“
“
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Autonomic stabilization
 Clonidine .1 tid to 1 mg tid over time
RRies 2014
Journal of Analytical Toxicology, Volume 27, Number 2 March 2003
Oxycodone Involvement in Drug Abuse Deaths: A DAWNBased Classification Scheme Applied to an Oxycodone
Postmortem Database Containing Over 1000 Cases*
Authors: Cone E.J.1; Fant R.V.1; Rohay J.M.1; Caplan Y.H.2; Ballina M.3; Reder R.F.3; Spyker
D.3; Haddox J.D.
Of 1014 cases:
30 (3.3%) involved oxycodone as the single reported chemical entity;
of these,
The
vast majority (N = 889, 96.7%) were multiple drug abuse
deaths
The most prevalent drug combinations were
oxycodone in combination with benzodiazepines, alcohol,
cocaine, other narcotics, marijuana, or antidepressants.
Opioids + Benzos
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Short acting Opioid and Long acting
Benzo ( Clonazepam or Diazepam)
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Classic opioid WD, migrating to
hyperadrenergic autonomic + anxiety and
possible seizures
Though not published, using combination
of Bup + anticonvulsant covers this
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Gabapentin 400 tid, or 600 tid helps both
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For those with Severe Opioid Dependence ----Withdrawal only (Detox)
---vs. Maintenance vs
----Block ?
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Withdrawal Only—
 High Relapse (90+ % ) whether fast or slow Detox
 Relapse incurred Morbidity, Mortality, Cost
 Not only costly, but ethical?
Maintenance
 Bup/Ntx- Training certification fits ACO Prim Care
 Methadone--- only in Federally certified clinics
Block – Naltrexone
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Oral– adherence issues, but OK after long term stabilization
Injectable– fits in with “abstinence model”, good at inpt DC
RRies 2014
Remaining in treatment (nr)
Treatment Retention and more…
20
15
Bup
75% retention
75% UTS negative
10
20% mortalityControl
in placebo group
5
Buprenorphine
0
0
50
100
150
200
250
300
Treatment duration (days)
Kakko J et al. Lancet 2003
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350
BMJ. 2003 May 3;326(7396):959-60.
Loss of tolerance and overdose mortality after
inpatient opiate detoxification: follow up study.
Strang J1, McCambridge J, Best D, Beswick T, Bearn J, Rees S, Gossop M.
Med Sci Law. 1990 Jan;30(1):12-6.
Mortality following release from prison.
Harding-Pink D.
Author information
Abstract
. The mortality rate during the first year after release was about 5 deaths/1000
person years, a rate over four times the age-adjusted rate in the
general population. The majority of deaths were due to overdose by opiate
drugs among young, frequently imprisoned drug abusers, and occurred within
the first few weeks after release.
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Arch Gen Psychiatry. 2011 Dec;68(12):1238-46. Epub 2011 Nov 7.
Adjunctive Counseling during Brief and Extended
Buprenorphine-naloxone Treatment for Prescription
Opioid Dependence: a 2-phase Randomized
Controlled Trial.
Weiss RD, Potter JS, Fiellin DA,.
RESULTS:
Phase 1 ( 2 week detox measured at 12 weeks),
successful outcomes -ie 10 weeks after detox
6.6%
(43 of 653) had
Phase 2 (12 week detox) 49.2% ie end of detox but still on med
Success rates 8 weeks after completing the buprenorphine-naloxone
taper (phase 2, week 24) dropped to 8.6% (31 of 360),
again with no counseling difference.
.
RRies 2014
Best Treatment by FAR--• Prevention -- Prevention – Prevention
• Avoid Opioids in most non-severe
syndromes
• Use Opioids like Steroids…aggressively
with built in short taper for most acute
cases
• The US uses more presc opioids than
most of the rest of the world combined
RRies 2014
Spine (Phila Pa 1976). 2008 Jan 15;33(2):199-204. doi: 10.1097/BRS.0b013e318160455c.
Early Opioid Prescription and Subsequent Disability
among workers with back injuries: the Disability Risk
Identification Study Cohort.
Franklin GM1, Stover BD, Turner JA, Fulton-Kehoe D, Wickizer TM; Disability Risk
•
•
To examine whether prescription of opioids within 6 weeks of low back
injury is associated with work disability at 1 year.
Nearly 14% (254 of 1843) of the sample were receiving work disability
•
After adjustment for pain, function, injury severity, and other baseline
covariates, receipt of opioids for more than 7 days (odds ratio = 2.2; 95%
confidence interval, 1.5-3.1) and receipt of more than 1 opioid prescription
were associated significantly with work disability at 1 year.
•
•
CONCLUSION:
Prescription of opioids for more than 7 days for workers with acute
back injuries is a risk factor for long-term disability. Further research
is needed to elucidate this association.
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Outcomes:
Buprenorphine, Methadone, LAAM:
Treatment Retention
Percent Retained
100
80
73% Hi Meth
60
58% Bup
40
53% LAAM
20
20% Lo Meth
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Study Week
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Intrinsic Activity: Full Agonist (Methadone), Partial
Agonist (Buprenorphine), Antagonist (Naloxone)
100
90
Full Agonist
(Methadone)
80
70
Intrinsic Activity 60
Partial Agonist
(Buprenorphine)
50
40
30
20
10
Antagonist (Naloxone)
0
-10
-9
-8
-7
Log Dose of Opioid
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-6
-5
-4
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Naltrexone for Opioid Dependence
 Most ideal pharmacologic treatment
 Requires complete withdrawal before initiation or
severe withdrawal will be precipitated
 Requires Naloxone challenge test
 Risk of OD if medication stopped
 In general poor patient compliance with oral form
but superb treatment for selected patients
 Now available in long acting injection
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Lancet. 2011 Apr 30;377(9776):1506-13.
Injectable Extended-release Naltrexone for Opioid
Dependence: a Double-blind, Placebo-controlled,
Multicentre Randomised Trial.
Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL.
FINDINGS:
6 month study of 250 patients
(n=124).
randomly assigned to XR-NTX (n=126) or placebo
% Weeks abstinent
XR-NTX
90·0%
Placebo Inj
versus 35·0%
Opioid-free days
99·2%
versus 60·4%
(p=0·0004)
Decreased craving –10.1
versus -0.7
(p<0·0001)
Retention days
vs
(p=0·0042)
168
96 days
(p=0·0002)
Two patients in each group discontinued owing to adverse events. No XR-NTX-treated
patients died, overdosed, or discontinued owing to severe adverse events.
RRies 2014
12 step facilitation …is a method to help get
patients to 12 step meetings and maximize
their benefit
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Why get people to 12 step meetings?
 20-50% of trauma( med-surg) and psychiatric in and outpts will
have current, history or episodic substance problems
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Substance treatment may be unavailable or even if used, 12
step will likely be involved
Positive effects include not only the group support and
socialization, but key psychological/therapeutic content
elements.
Addiction is a chronic potentially relapsing disease….Usual
TREATMENT is not usually structured for this BUT AA is
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Alcohol Abstinence Rates at 8 Years by Duration
of Meeting Attendance in the First Year
80
71.3
Percent Abstinent
70
60
50
56.2
40
30
42.7
35.3
20
10
0
None
(n = 201)
1-16
17-32
33+
(n = 89)
(n = 89)
(n = 94)
Weeks of Participation in AA year 1.
Moos, et al., 2004
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x 2 = 25.5, p < .01
Best Treatment by FAR--
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Prevention -- Prevention – Prevention
Avoid Opioids in most non-severe
syndromes
Use Opioids like Steroids…aggressively
with built in short taper for most acute
cases
The USA uses more presc opioids than
most of the rest of the world combined
RRies 2014
Your Case Examples:
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1.
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2.
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3.
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