Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works...
-
Upload
truongkhanh -
Category
Documents
-
view
216 -
download
0
Transcript of Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works...
![Page 1: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/1.jpg)
Pharmacotherapy Works for
Opioid Use Disorders
in CJ Populations
Peter D. Friedmann, MD, MPH, FASAM, FACP Chief Research Officer
Baystate Health
Associate Dean for Research
University of Massachusetts Medical School – Baystate Health
![Page 2: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/2.jpg)
Dr. Peter Friedmann
Disclosures:
• In-kind research support from Alkermes
• Honorarium for Advisory Board from Indivior
![Page 3: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/3.jpg)
Roadmap
• Terminology
• Epidemics of incarceration and opioids
• Incarceration doesn’t treat the chronic,
relapsing disorder of addiction
• Opioid use disorders harmful in CJ
populations
• Pharmacotherapy works for opioid use
disorders in CJ populations
![Page 4: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/4.jpg)
Terminology
• Physiological dependence – Adaptation to chronic use of substance – Tolerance
• Decreased effect of substance after repeated use • Need for increased dose to achieve same effect
– Withdrawal syndrome • Characteristic symptoms on cessation of use
• Addiction: chronic, relapsing brain disease characterized by
• Compulsive use • Loss of Control • Use despite Consequences
![Page 5: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/5.jpg)
Abuse Potential
• Route of administration – Faster route has a greater abuse potential
• Injecting IV Injecting SQ Oral
• Drug Half life – Briefer half-life has a greater abuse potential
• Heroin Methadone
• Lipophilicity (faster into the brain)
– Higher lipophilicity greater abuse potential • Heroin Morphine Methadone
• Agonist activity • Full partial
![Page 6: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/6.jpg)
Roadmap
• Terminology
• Epidemics of incarceration and opioids
• Incarceration doesn’t treat the chronic,
relapsing disorder of addiction
• Opioid use disorders harmful in CJ
populations
• Pharmacotherapy works for opioid use
disorders in CJ populations
![Page 7: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/7.jpg)
“Opioid Epidemic”: Sales, Overdose Deaths and Treatment Admissions, U.S. 1999–2010
0
1
2
3
4
5
6
7
8
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Rate
Year
Opioid Sales KG/10,000 Opioid Deaths/100,000 Opioid Treatment Admissions/10,000
CDC. MMWR 2011. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm60e1101a1.htm?s_cid=mm60e1101a1_w..
![Page 8: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/8.jpg)
Opioid Use Disorders Common in CJ
Populations
• 20-23% U.S. inmates h/o opioid use • ~5-15% U.S. arrestees utox+ for
opioids • Jail inmates 12% regular use of
opioids
BJS, NCJ 213530, October 2006; NCJ 209588, July 2005. ONDCP, May 2013. Dolan , Hall &Wodak. The Provision of Methadone Within Prison Settings. In: Methadone Maintenance treatment and Other Opioid Replacement Therapies. Ward J, Mattick RP, Hall W, eds. Australia: Harwood Academic Publishers; 1998. pp. 379-396 8
![Page 9: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/9.jpg)
The Revolving Door…
• >12 million jail releases per year
• >700,000 prison releases per year – >200,000 opioid-addicted adults cycle
thru CJ system annually (Nunn et al. 2009)
![Page 10: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/10.jpg)
Roadmap
• Terminology
• Epidemics of incarceration and opioids
• Incarceration doesn’t treat the chronic,
relapsing disorder of addiction
• Opioid use disorders harmful in CJ
populations
• Pharmacotherapy works for opioid use
disorders in CJ populations
![Page 11: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/11.jpg)
Repeated exposure to
reinforcing agents Long-
Lasting Brain Effects
![Page 12: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/12.jpg)
Impaired Control 1. Larger amounts/longer than intended 2. Inability to cut down or control 3. Much time spent 4. Craving and urges
Social Impairment 5. Not able to function 6. Continued use despite interpersonal problems 7. Reduced activities
Risky Use 8. Use in dangerous circumstances 9. Continued use despite physical or psych. problems
Physiological Dependence 10.Tolerance 11.Withdrawal
Neuronal Changes Substance Use Disorder (DSM-V) (2-3: mild; 4-5: moderate; six or more: severe)
![Page 13: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/13.jpg)
Abstinence via incarceration
• Does not address substance
use disorder
• Still vulnerable to triggers on
reentry
• Decreases tolerance but not
craving – increased risk of overdose death
![Page 14: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/14.jpg)
Incarceration
does not
extinguish
addiction
• Opioids are immediate and reliable reinforcers • Learned associations (expectancies) are not
unlearned with coerced detention • Expectancies and responses re-triggered with
return to community environment
![Page 15: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/15.jpg)
• >½ relapse within 1year (Martin et al. 1999)
• 2/3rd return to custody within 3 years (Langan & Levin, 2002)
![Page 16: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/16.jpg)
Roadmap
• Terminology
• Epidemics of incarceration and opioids
• Incarceration doesn’t treat the chronic,
relapsing disorder of addiction
• Opioid use disorders harmful in CJ
populations
• Pharmacotherapy works for opioid use
disorders in CJ populations
![Page 17: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/17.jpg)
Post Release Dangers
• Relapse
• Recidivism
• Overdose
• Communicable diseases
• Other morbidity
![Page 18: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/18.jpg)
RR=12
RR=4 RR=3.2
Release from Prison - High Risk of Death
Binswanger IA et al. N Engl J Med 2007.
![Page 19: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/19.jpg)
Binswanger IA et al. N Engl J Med 2007.
Causes of Death Post-Prison Adjusted for Age, Sex, and Race
0
2
4
6
8
10
12
Re
lati
ve
Ris
k o
f D
ea
th
![Page 20: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/20.jpg)
Overdose deaths are the tip of the iceberg
SAMHSA NSDUH, DAWN, TEDS data sets
Coalition Against Insurance Fraud. Prescription for Peril. http://. Slide courtesy of Colleen Labelle
![Page 21: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/21.jpg)
Roadmap
• Terminology
• Epidemics of incarceration and opioids
• Incarceration doesn’t treat the chronic,
relapsing disorder of addiction
• Opioid use disorders harmful in CJ
populations
• Pharmacotherapy works for opioid use
disorders in CJ populations
![Page 22: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/22.jpg)
What Does It Feel Like to have Opioid Use D/O?
![Page 23: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/23.jpg)
‘Dope Sick’
![Page 24: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/24.jpg)
• ↓ positive reward • ↓negative
reinforcement • Extinguishes
expectancies associated w/use
Greenwald et al, Neuropsychopharmacol 28, 2003
Medication Attenuates Reinforcement
![Page 25: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/25.jpg)
MAT replaces a highly addictive,
unsafe drug with a less
addictive, safer one
Methadone, buprenorphine
• Lower abuse potential – Slower acting
– Long half-life
– Mild reinforcing/ rewarding
effect
• Block effects of short-
acting opiate
• Eliminate withdrawal
• Decrease craving – Rewarding enough that
people will take it
• Return to work, school,
family, etc
• Facilitate counseling
• Prevent overdose
deaths, HIV, viral
hepatitis
![Page 26: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/26.jpg)
What Does It Feel Like to Be on Opioid Replacement
Therapy?
![Page 27: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/27.jpg)
Impact of Methadone
Maintenance Treatment
• 7 trials → 4-fold ↑ stay in treatment
• 6 trials → 1/3rd ↓ opioid use
• ↓ death rates (Grondblah, ‘90)
• ↓ IDU (Ball & Ross, ’91; others)
• ↓ crime days (Ball & Ross, others)
• ↓ HIV seroconversion
• ↑ employment, health, social function
27 Mattick et al., Cochrane Review, 2009
![Page 28: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/28.jpg)
Methadone Effectiveness Gunne & Gronbladh, 1984
H H H H
H H H H
H H H H
H H H H
H
H H H H
H H H H
H H H H
H H H H
H
Methadone Regular Outpatient Rx.
Baseline
![Page 29: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/29.jpg)
Methadone Effectiveness Gunne & Gronbladh, 1984
P H H H
H
P H P
H H H H
H H H H
H H H
Methadone No Methadone
After 2 Years
1
3 2
1- Sepsis & endocarditis
2- Leg amputation
3- Sepsis
![Page 30: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/30.jpg)
Methadone Effectiveness Gunne & Gronbladh, 1984
H H H
H
P P
P
Methadone No Methadone
After 5 Years
![Page 31: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/31.jpg)
Function at Receptors:
Antagonists
Mu
receptor
occupies without activating
no abuse potential
blocks abused agonist opioid types
includes naloxone and naltrexone
Antagonist binding …
![Page 32: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/32.jpg)
Antagonist Activity Levels
%
Mu Receptor
Intrinsic
Activity
0
10
20
30
40
50
60
70
80
90
100
Opioid antagonists bind and occupy mu opioid receptors but result in no specific intrinsic activity regardless of dose
no drug high dose
DRUG DOSE
low dose
Antagonist (e.g. naloxone)
![Page 33: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/33.jpg)
Oral Naltrexone Treatment
• No reinforcement poor
adherence
• 6 trials → Ø effect stay in
treatment
• 3 trials → Ø effect on opioid use
33 Minozzi et al Cochrane Review, 2011
![Page 34: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/34.jpg)
Function at Receptors: Partial
Agonists Mu
receptor
activates the receptor at lower levels
is less reinforcing than full agonist
has less abuse potential than full agonist
includes buprenorphine
Partial agonist binding …
![Page 35: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/35.jpg)
Partial Agonist Activity Levels
no drug high dose
DRUG DOSE
low dose
%
Mu Receptor
Intrinsic
Activity
0
10
20
30
40
50
60
70
80
90
100
Full Agonist (e.g. heroin)
Partial Agonist (e.g. buprenorphine)
Like full agonists, partial agonist drugs increase mu activity at lower doses
At higher doses, even when partial agonist binds all mu receptors, maximal agonist effect is never achieved
Partial Agonist Effect Reinforces Adherence
![Page 36: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/36.jpg)
Buprenorphine Properties
• Opiate: derivative of thebaine • Partial-agonist
– Less reinforcing than a full agonist-milder effects – Safety – overdose ceiling effect
• Poor oral bioavailability – given sublingually • High affinity to the opiate receptor • Long duration of action (24-72hr) • Strong safety profile
– Little respiratory depression – Little overdose potential
![Page 37: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/37.jpg)
Impact of Buprenorphine
Maintenance Treatment
• 4 trials → 74% ↑ stay in
treatment
• 6 trials → 23% ↓ opioid use
37 Mattick et al., Cochrane Review, 2009
![Page 38: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/38.jpg)
RCT: Bup Detox vs. Maintenance Kakko et al., Lancet 2003
Treatment duration (days)
Rem
ain
ing in t
reatm
ent
(nr)
0
5
10
15
20
0 50 100 150 200 250 300 350
Bup 6 day detox
Bup Maintenance
All Patients: Group CBT Relapse Prevention, Weekly Individual
Counseling, 3x Weekly Urine Screens
N=20 per group
![Page 39: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/39.jpg)
Bup RCT: Mortality Kakko et al., Lancet 2003
Placebo Buprenorphine Cox
regression
Dead 4/20 (20%) 0/20 (0%) 2=5.9; P=0.015
![Page 40: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/40.jpg)
↑ Community Access to OAT
↓ Overdose Deaths
02
00
04
00
06
00
08
00
01
00
00
Pa
tien
ts tre
ate
d
0
100
200
300
Ove
rdose
dea
ths
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Year
heroin overdoses buprenorphine patients methadone patients
Schwartz et al, American Journal of Public Health, 2013
![Page 41: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/41.jpg)
Opiate Agonist Treatment in
Jails & Prisons
• Outside the US – Methadone: Australia, Canada, Europe, Iran
and elsewhere (EMCDDA, 2009; Farnia et al, 2010)
– Bup: France & Australia (Marzo et al., 2009)
– Considered a best practice (WHO, 2009)
• In the US – Methadone: not widely used (Nunn et al., 2009)
– Bup: used less frequently than methadone
![Page 42: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/42.jpg)
RCT of Forced Withdrawal in
Jail If Sentence ≤ 6 mos
Rich, McKenzie, Larney et al. Lancet. 2015
──Continued MMT (N=114) ----Forced withdrawal (N=109)
Logrank P<.001
P(P
ost-
Jail
MM
T C
linic
Att
endance)
![Page 43: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/43.jpg)
RCT of Pre-Release MMT:
Baltimore
0.0%
65.6%
17.3%
48.7%
36.7% 25.0%
0%
10%
20%
30%
40%
50%
60%
70%
% in Comm-Based Tx. % Opioid +
Pe
rce
nta
ge a
t 1
2-m
on
ths
Methadone Referral(N=64)
Methadone Transfer Post-Release (N=69)
Methadone Pre-and Post-Release (N=71)
Kinlock, Gordon, Schwartz et al. JSAT 2009.
![Page 44: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/44.jpg)
RCT of Pre-Release MMT:
Rhode Island
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
% MMT in 30days
% heroin +
Pe
rce
nta
ge a
t 1
2-m
on
ths
Pre-release + post-$$assistPost-$$ assist
Referral, no assist
P<.001
P=.09
McKenzie et al. Substance Abuse 2009.
Intent-to-Treat
• Arm 1 (N=29) – MMT 30 days before release – MMT linkage in community
(financial assistance) – 4 not treated before release
• Arm 2 (N=29) – MMT linkage in community
(financial assistance)
• Arm 3 (N=30) – MMT referral – No financial assistance for
MMT – 15 given ATR on release –>
as-treated crossed to Arm 2
![Page 45: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/45.jpg)
NYC Jail-to-Community Buprenorphine • More randomized participants
continued bup-nx at jail re-entry vs. methadone
- 48% vs. 23% (p<0.005) • Once in office-based bup-nx
treatment, no differences vs. non-jail patients
Same retention as non-jail
….self-reported heroin use
Lee 2009; Magura 2008
Same rates of urine + and…
![Page 46: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/46.jpg)
Bup Initiation Pre-Release
↑ Treatment Retention Post-Release
•N= 44
•73% postrelease; –27% pre-release
•Similar at baseline
•82% 6 month f/u
•Median community rx
9 vs 24 wks (p=.007)
•IDU 26% vs. 0%
(p=.05)
•Arrest 17% vs. 0
(p=.14)
Zaller, McKenzie, Friedmann et al. JSAT 2013
![Page 47: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/47.jpg)
Pre-, Post-Release MMT, Bup →
↓ post‐release mortality
Addiction
Volume 109, Issue 8, pages 1306-1317, 14 APR 2014 DOI: 10.1111/add.12536
http://onlinelibrary.wiley.com/doi/10.1111/add.12536/full#add12536-fig-0002
• Pre-release MAT lowered mortality by reducing overdose in Week 1
![Page 48: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/48.jpg)
Agonist Rx: Limited Uptake in CJ Settings
•Regulations and liability
•Mission –Security concerns
–Lack of qualified staff
–Budgets prioritize safety, not health care
•Stigma
•‘Drug-free’ treatment predominates –Medication treatment “available in the community”
–↓tolerance ↑overdose post-release
Nunn et al. 2009; Friedmann et al. 2012
![Page 49: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/49.jpg)
Agonist medications
underutilized in CJ Settings
•Illicit opiate use in detention – Corruption and violence
– HIV and hepatitis outbreaks
•Untreated opiate withdrawal in detention – Cruel and punitive
– Morbidity
– Reduces willingness to resume OAT post-
release
Mitchell et al., 2009; Rich Lancet 2015, Bruce 2008.
![Page 50: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/50.jpg)
Extended-Release Naltrexone
• Monthly IM injection • Must be completely
opioid-free
• Cumulative % confirmed opioid-free weeks:
- Median of 90% for XR-TNX vs. 35% for placebo
Krupitsky , Nunes, Ling et al. Lancet, 2011
![Page 51: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/51.jpg)
RCT of XR-NTX for Opioid
Dependence in Parole/Probation
• 5 site RCT
• Eligibility criteria – Adults with DSM-IV opioid dependence
– Parole, probation, incarceration in past 12 mo.
– Not seeking agonist treatment
• 6 month in-treatment phase
• Interviews, urine toxicology – In-treatment every 2 weeks
– End-of-treatment (27 weeks)
– 12 and 18 mos
• Relapse, rearrest/reincarceration, cost
Lee, Friedmann, Kinlock et al. Contemp Clin Trials 2015
![Page 52: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/52.jpg)
1. Pre-screened, n=2753;
2. Screened, n=437
TAU, n=155 XR-NTX, n=153
Randomization, N=308
FU every 2 weeks
End of Treatment Phase, 6 months, N=308
1° outcome: N=308
Study Flow
Final FU at 12, 18 months: on-going
Ineligible, n=129 Incomplete screen: 57
Opioids+: 25
Med/psyche/LFT:19
Recent overdose: 3
BMI>35: 2
![Page 53: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/53.jpg)
Time-to-Relapse • Relapse = self-report or urine tox evidence of >10 days of opioid use in a 4
week period, with a positive or missing urine test counted as 5 days of
opioid use.
Time–to-relapse
(median weeks) 10.5 5.0 <0.0001 HR .48 (.35,.66)
![Page 54: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/54.jpg)
XR-NTX Adherence and Attendance
• Of planned XR-NTX injections received: – 1st: 97% (1 declined; 2 failed narcan)
– 2nd: 88%
– 3rd::79%
– 4th: 73%
– 5th: 67%
– 6th: 61% (1 had allergic reaction after 5th)
• Mean 11 of 14 bi-weekly visits completed – No difference between arms
– 75% had week 27 end-of-treatment assessment
![Page 55: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/55.jpg)
Results at 6 months:
TAU Sought More Agonist Treatment
XR-NTX TAU P value RR( 95%CI)
% Participating in
outpatient program for
drug/alcohol 62.33% 65.03% 0.63 0.96 (0.81, 1.14)
% Entering hospital for
detox 2.74% 2.11% 0.73 1.30 (0.30, 5.69)
% Entering residential
program for detox or
SA services 8.90% 10.56% 0.63 0.84 (0.42, 1.71)
% Reported suboxone
treatment month 1-6 7.53% 25.35% <0.001 0.30 (0.16, 0.56)
% Reported methadone
treatment month 1-6 3.42% 11.27% 0.01 0.30 (0.11, 0.81)
Lee, Friedmann, Kinlock et al. Submitted.
![Page 56: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/56.jpg)
Results at 6 months:
No Differences in Secondary Outcomes
XR-NTX TAU P value
RR ( 95%CI)
Cocaine use days % 3.32% 3.87% 0.70 0.89
(0.42, 1.58)
Avg # drinks/week 1.59, CI
(0.73, 2.46)
1.23, CI
(0.76, 1.70)
0.47
% injection drug use 5.93% 8.62% 0.43 RR 0.69
(0.27, 1.75)
RAB Sex Risk Scores at
6 mo (mean) 2.75 2.86 0.68
Self-reported re-
incarceration
30
(19.61%) 27 (17.42%) 0.62
RR 1.13
(0.70, 1.80)
Lee, Friedmann, Kinlock et al. Submitted
![Page 57: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/57.jpg)
Effect attenuated but still significant 6-month post-
treatment (12-mo f/u)
TAU
NTX
P=0.0006 Van
der Waerden 2
sided test
Lee, Friedmann, Kinlock et al. Submitted
![Page 58: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/58.jpg)
No increase in overdose during 6 months
post-treatment
XR-NTX TAU P value
Overdose (death
or hospitalization) 0 7 0.015
Overdose deaths 0 3 0.248
Death, all cause 2 5 0.448
Lee, Friedmann, Kinlock et al. Submitted
![Page 59: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/59.jpg)
XR-NTX in Parole/Probation
• All had high rates of outpt counseling
• Over ¼ of controls reported agonist rx
• XR-NTX ↓opioid misuse & relapse. – ↑Time-to-relapse and the % of weeks
abstinent
– ↓ overdoses out to 12 months
– No differences in secondary outcomes • cocaine and alcohol use, HIV risk, CJ outcomes
Lee, Friedmann, Kinlock et al. Submitted
![Page 60: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/60.jpg)
XR-NTX in Community CJ
• Well-tolerated, feasible and safe
• Effective at preventing relapse &
overdose
• Likely effective in populations not seeking
or able to access agonist therapies
• Like other meds, no detected effect on
cocaine, CJ outcomes
![Page 61: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/61.jpg)
Discussion
• Incarceration does not treat chronic, relapsing disorder of addiction – Significant prevalence of opioid use in
CJ population – Community reentry is the rule – High risk for relapse and overdose
• Methadone, Bup, XR-NTX effective – ↓ opioid use in CJ populations
– ↓ overdose short-term
![Page 62: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/62.jpg)
Discussion
• Expand agonist tx. in jail/prison with
linkage to community rx. – continued or initiated
– humane
– ↑ post-release linkage to effective
treatment
– ↓ post-release opioid use, overdose
• Need more studies to examine how
best to implement in CJ settings
![Page 63: Pharmacotherapy Works for Opioid Use Disorders in CJ … · 2018-06-07 · Pharmacotherapy Works for Opioid Use Disorders ... • Pharmacotherapy works for opioid use disorders in](https://reader030.fdocument.pub/reader030/viewer/2022021801/5b4686097f8b9a3a058b923b/html5/thumbnails/63.jpg)
THANK YOU!
•Josh Lee, NYU
•Robert Schwartz, Friends
•Josiah Rich, Brown
•David Farabee, UCLA
NIDA esp. DESPR, Services Research Branch
Colleagues who’ve shared slides
Questions?? Comments?? [email protected]
•CJDATS collaborative
•XR-NTX collaborative R01s
Collaborators