Pharmacotherapy for Opioid Dependence in Correctional Settings: Research Findings and Recommendations

(1)

Pharmacotherapy for Opioid Dependence in Correctional Settings: Research

Findings and Recommendations

Robert P. Schwartz, M.D.

Rschwartz@friendsresearch.org Friends Research Institute

www.friendsresearch.org

(2)

Overview of Presentation

• Background

• Research on uses of pharmacotherapy for opioid dependence during incarceration

• Summary & Recommendations

(3)

Correctional Institutions

• Jail

•

Pre-trial detainees

•

Short sentences (< 1 year)

• Prison

•

Sentences > 1 year

(4)

Medications

Opioid Agonist Treatment (OAT) 1) Methadone

2) Buprenorphine

Opioid Antagonist Treatment to Prevent Relapse 3) Extended-release naltrexone (XR-NTX)

Opioid Antagonist to Reverse Overdose 4) Naloxone

(5)

Illicit Opioid Use is a Problem Among Inmates

High prevalence of a history of illicit opioid abuse among inmates (Perry et al., 2014):

• 20% in US

• 33% in UK

• 30% in France

(6)

Opioid Withdrawal

• Occurs among:

• Newly-arrested (out-of-treatment)

• Newly-arrested (in OAT)

• Prisoners actively using illicit opioids

• Untreated:

• ^Cruel

• ^Morbidity

• Creates an opioid market

• Reduces desire for OAT entry post-release (Mitchell et al. 2009)

Opioid Withdrawal Among Inmates

(7)

• Creates a market for drugs & corruption

• Overdose

• Hepatitis outbreaks (Taylor et al., 1995; Zamani et al., 2010)

Opioid Use Among Inmates

(8)

• Crime

• Re-incarceration

• HCV and HIV transmission

• Overdose death (Binswanger et al., 2007; Merral et al., 2010)

Post-release Relapse

(9)

Binswanger, et al., 2013, Annals of Internal Medicine

When Does Post-release OD Death Occur?

(10)

Pharmacotherapy for Opioid Dependent Inmates

•

OAT in prison is considered a best practice (WHO, 2009)

•

In the US:

•

Methadone: not widely available (Nunn et al., 2009)

•

Buprenorphine: used less frequently than methadone

•

Extended-release Naltrexone: recently available

• Outside the US:

•

Methadone: Australia, Canada, China, European Union, Iran, Malaysia and elsewhere (EMCDDA, 2009; Farnia et al, 2010)

•

Buprenorphine: France & Australia (Marzo et al., 2009)

•

Naltrexone Implant Trial: Norway (Lobmaier et al., 2010)

•

Naloxone: UK N-Alive Trial: (Strang et al., 2013)

(11)

Barriers to Implementing Medications

• Lack of knowledge

• Negative attitudes (especially re: OAT)

• Punitive framework

• Institutional focus

• Concerns about diversion

• Funding silos

• Lack of regulatory requirements

• Complex oversight

(12)

Indications for Pharmacotherapy for Inmates

1. Provide continuity of care during incarceration

•

For patients enrolled in community-based treatment

2. Initiate medication at detention

•

For out-of-treatment individuals

• To reduce heroin use during incarceration

• To reduce relapse after release

3. Initiate medication prior to release

•

For non-tolerant individuals with history of dependence

• To prevent relapse after release

(13)

Studies of Continuity of Care

Longitudinal non-random assignment

Magura et al., 1993; methadone in jail in New York City

McMillan et al., 2008; methadone in jail in ABQ, New Mexico

Random assignment

Rich et al. 2015; methadone in jail in Rhode Island

(14)

Continuity of MTP in New York*

Men (n = 199) Women (n = 38)

Returned to MTP 83% 79%

Retained in Treatment: 1 month 88% 80%

Retained in Treatment: 5 Months 57% 53%

* Magura et al., Journal of Drug Issues, 1993

• 237 MTP patients were maintained on methadone in NY City jail

• Referred back to their MTP at release

• Most returned to MTP within 24 hours

• Treatment retention was modest at 5 months

(15)

Continuity of MTP in NM: No Change in Recidivism*

• ABQ, NM jail

• Observational study of 589 inmates

• Outcome measure: time from release to rebooking

• Continuity of methadone was not associated with rebooking

• Limitations: Did not examine reasons for non-medication in jail nor rates of MTP reentry after release

* McMillan, Lapham & Lackey, Addiction, 2008

(16)

Continued MTP v. Withdrawal in Jail: RCT*

2 group RCT compared forced withdrawal vs. continued methadone with 1 month post-release follow-up

• 223 adults enrolled in MTP at time of arrest

• Randomly assigned to continue MTP in jail or TAU

• TAU = slow methadone dose taper (3 mg/day)

•

45 of the 141 (32%) assigned to withdrawal were still on methadone at release

• Rich et al., 2015; Lancet

(17)

Baseline Characteristics

Continued MTP (n = 114)

Withdrawal (n = 109)

Total Sample ( n = 223)

Male (n/%) 87 (76%) 86 (79%) 173 (78%)

Age (mean/SD) 33 (8.0) 36 (8.7) 34 (8.4)

Days in Jail (mean/SD)

56 (47) 56 (42) 56 (45)

Time in MTP (weeks)

156 239 197

(18)

Outcomes

Continued MTP (n = 114)

Withdrawal (n = 109)

p

Dosed on D/C Day 111 (97%) 45 (41%) .0001

Opioid use (1 month) 9 (8%) 16 (18%) .033

Entered MTP 106 (96%) 68 (78%) .0001

Re-incarcerated 12 (11%) 8 (9%) .67

ITT Continuing Methadone : HR 2.04 (95% CI, 1.48-2.80) As treated: HR 6.61 (95% CI, 4.00 – 10.91)

(19)

Summary: Continuity of Care

•

The RCT by Rich showed benefit of continuity of care

•

Incarcerated individuals should have access to care equivalent to care available in the community

•

Yet, 88% of US jails forced MTP patients to discontinue treatment while detained (Fiscella et al., 2004)

•

More research on the value of continuity of care may not be warranted

•

Research is needed on approaches to:

•

Overcome implementation barriers

•

Improve treatment retention post-release

(20)

Studies on Initiating Medication at Arrest

There are 3 studies of OAT at arrest

Magura et al., 1993; jail in New York City

Random assignment

Magura et al., 2009; Jail in New York City

Schwartz et al., Recruiting: Jail in Baltimore, Maryland

(21)

Jail-Based MTP Evaluation: New York*

Design: Longitudinal, non-random assignment evaluation of two cohorts.

Inclusion Criteria:

(1) Methadone Maintenance Cohort - Opioid dependent

- Admitted to methadone treatment at Rikers Island - Misdemeanor charge or sentence < 1 year

(2) Methadone Detoxification Cohort (Control)

-

Eligible for, but did not receive, maintenance because of:

(a) low grade felony; (b) completed detox; or (c) no treatment slot

* Magura et al., Journal of Drug Issues,1993

(22)

Methods

Treatments:

Methadone Maintenance

- Methadone 30 mg daily - Limited counseling

- Referred to select community-based MTPs Methadone Detoxification

- Methadone x 7 days

Assessments at Baseline and 6 month post release:

- Demographics, drug use, treatment entry and retention

(23)

Participant Flow (Magura et al., 1993)

(24)

Follow-up Sample Demographics (N = 249)

Variable N/(%)

Race/Ethnicity

African American White/Other

Hispanic

156 (62.7%) 48 (39.6%) 147 (59.0%)

Gender

Male 139 (55.8%)

Mean Age (Yrs) 33

Drug Injection (Y/N) 193 (77.5%)

(25)

Outcomes at 6.5 Month Follow-up (N = 249)

* p < .001; ** p < .01

Variable Maintenance (n = 195) Control (n = 54) Attended any

community drug treatment program (n/%)*

166 (85%) 20 (37%)

In treatment (n/%)** 53 (27.2%) 5 (9%)

Any past month heroin Use (n/%)

60 (31%) 12 (22%)

Any past month drug injection (n/%)

80 (41%) 22 (41%)

(26)

Conclusion

• Initiating Methadone Treatment in Jail was feasible

•

Few attempts at diversion (“spit backs”)

•

No conflicts among inmates

•

Correction Officers reported patients calmer than others

•

Most patients offered methadone, accepted it and stayed on it while incarcerated (95%)

• Significantly higher treatment entry and retention rates compared to controls

•

Poor treatment retention even in methadone-treated group

• Limitation: High attrition rate and non-random assignment

(27)

• Context: A NYC jail with a well established MTP that did not routinely offer buprenorphine treatment

• 133 adult male inmates sentenced from 10 to 90 days at Rikers Island started on at least one dose of methadone for opioid withdrawal

•

Randomly assigned to Buprenorphine v. Methadone treatment

•

Assessment at baseline & 3 month post-release follow-up

 Magura et al., Drug & Alcohol Dependence, 2009

Initiating Methadone v. Buprenorphine at Arrest

(28)

Participant Flow

(29)

Baseline Characteristics ( N = 116)

Buprenorphine (n=60)

Methadone (n=56)

P

Age (years) 38.4 (7.9) 40.7 (9.1) ns

African American (%) 25% 25% ns

Hispanic 65% 62% ns

Days of heroin use in 30 days prior to incarceration

28.0 (6.4) 28.6 (4.8) ns

(30)

Outcomes

Buprenorphine (n=60)

Methadone (n=56)

P Discontinued for diverting medication 10% 1.8%

Completed treatment in jail 82% 75% ns

Attended Treatment at Release 48% 23% <.005

Re-incarcerated at 3 month f/u 40% 50% ns

Days heroin use in 30 days prior to f/u 13.7 (14.3) 14.4 (13.4) ns

(31)

Conclusion

• Total sample reported a 50% reduction in days of heroin use from baseline to follow-up

• 3-month follow-up outcomes were not significantly different between medication groups

• Buprenorphine administration required more time than methadone administration (15 minutes vs. 3 minutes) and it was more

expensive than methadone

• Diversion was more of a problem with buprenorphine treatment

• Relatively low treatment entry rates in both groups Limitation: No drug testing data

(32)

Study Locations

Friends PI Schwartz; NYU PI Lee; UCLA PI Farabee 32

(33)

Summary Of Initiating Medication

Magura’s research demonstrated feasibility of initiating methadone at the time of detention

• Post release entry and retention rates needed improvement

•

Low rates likely hampered further improvements in drug use

•

Patient Navigation may be a useful approach

• More research is need on approaches to increase:

•

Treatment entry rates post-release

•

Community treatment retention rates for this population

(34)

Continuity of Care & Initiating Medication: Studies with Mixed Samples

• Marzo et al., 2009; 47 remand prisons in France

• Favrod-Coune et al., 2013; remand prison in Geneva, Switzerland

Random Assignment

• None

(35)

Studies on Initiating OAT to Reduce Heroin Use During Incarceration

There are 2 such studies:

Heimer et al., 2005; prison in Puerto Rico

Random assignment

Dolan et al., 2003; prison in New South Wales, Australia

(36)

• MTP Eligibility: Inmates with heroin dependence in prison and a sentence of < 2 years

• 20 started on MTP in prison and compared to 40 randomly selected non-MTP patient prisoners

MTP in Puerto Rican Prison*

Prison MTP (n=20) Non MTP (n=40) Subset of Heroin using non MTP (23)

Heroin use in prison, baseline 20 (100%) 23 (57.5%) 23 (100%)

Daily use while in prison, baseline 18 (90%) 6 (15%) 26.1%

Heroin use in past 30 days, F/U 1/18 (5.6%) 15 (37.5%) 65.2%

Opioid positive test, F/U 1 (5%) 9 (22.5%) 39.1%

Methadone positive test, F/U 20 (100%) 0 0%

* Heimer et al., Drug and Alcohol Dependence, 2005

(37)

Conclusion

• Many prisoners were using heroin in this prison in Puerto Rico

• Methadone suppressed heroin use during prison sojourn

• Limitation:

•

Small sample size

•

No random assignment

•

No post-release F/U data

(38)

Methadone Treatment In Australian Prison: RCT*

Context: Prison MTP with a 6 month waiting list

Participants: 382 adults on prison MTP wait list Conditions: Randomly assigned to:

1) Wait list control for 4 months 2) Begin methadone treatment Follow-up: 4 months

* Dolan et al., Drug and Alcohol Dependence, 2003

(39)

Heroin Use In Prison

(Self-report or Opioid Positive Hair Test)

(40)

Syringe Sharing (%)

%

(41)

Conclusions

• This study showed clear benefits to providing methadone maintenance during incarceration to reduce in prison

heroin use and syringe sharing.

• It could be employed to reduce the likelihood of HIV or hepatitis outbreaks in prison.

(42)

Studies of OAT as Relapse Prevention

There are 7 studies of OAT for non-opioid tolerant prisoners:

Albizu-Garcia, 2007, Prison, Puerto Rico [buprenorphine]

Zaller et al., 2013; Prison, Rhode Island [buprenorphine]

Random assignment

Dole et al., 1969 Rikers Island Jail, NY [methadone]

Kinlock et al., 2009. Baltimore Prison, MD [methadone]

McKenzie et al., 2012. Rhode Island Prison [methadone]

Gordon et al, 2013. Baltimore Prison [buprenorphine]

Lee et al., 2015. New York Jail (extended release naltrexone]

(43)

Buprenorphine Treatment in Prison: In Puerto Rico*

• High rates of heroin use in prison

•

Open-label, pre- post design feasibility study

• 45 pre-release male inmates

• Buprenorphine provided by prison health staff

• Over 80% were opiate tolerant at induction

• Non-tolerant participants started at low dose (2/.5 mg.)

• 3 dropped out (2 nausea and 1 transfer to another prison)

* Albizu-Garcia et al., Journal of Addiction Medicine, 2007

(44)

Outcomes

• High rate post-release treatment entry at physician office- based practice

• 78% of participants were in treatment at 1 month post- release

• Low rate of opioid use post-release

• 25% opioid positive drug tests

Limitation: Small pilot study without control group

(45)

Buprenorphine Treatment in Prison: In Rhode Island*

• Two-group pilot feasibility study (N = 44)

•

Open-label, pre- post design feasibility study

• First cohort started buprenorphine in the community (n = 32)

• Second cohort started buprenorphine in prison (n = 12)

• 6 month F/U interview for self-reported drug use and treatment participation

* Zaller, McKenzie, Friedmann et al., Journal of Substance Abuse Treatment, 2013

(46)

Outcomes: Post-release & 6 Month F/U

• Starting buprenorphine in prison was feasible

Bup after release (n=32)

Bup in prison (n=11)

p

Attended first outpatient visit 25 (78%) 11 (92%) ns

In treatment at 6 month F/U 11 (34%) 10 (91%) .005

Non fatal OD 3 (12%) 0 ns

Heroin Use, past 30 days at F/U 6 (24%) 0 ns

Arrested 6 (17%) 0 ns

Limitation: Small pilot study, no drug testing

(47)

First Methadone Study in NYC Jail*

This landmark study sought to determine:

•

Inmates’ interest in methadone treatment prior to release

•

The effectiveness of initiating methadone treatment prior to release.

•Inclusion criteria: Adult male inmate at Rikers Island; willing to apply for methadone treatment; history of at least 5 years of heroin

addiction and 5 prior convictions.

•Exclusion criterion: Under community supervision after release.

•* Dole et al., NEJM, 1969

(48)

Methods

• 12 randomly selected adult male inmates w/history of opioid

dependence from among MTP applicants were started on methadone about 10 days prior to release.

•

Patients were not opioid tolerant at the time of dose induction

•

Methadone started at low dose: 10 mg po QD

•

Slowly increased (over 10 days) to about 35 mg prior to release

• Comparison group created of 16 randomly selected MTP applicants at Rikers Island Jail.

(49)

Outcomes

N Lost Jail Readdicted Heroin Use

without

re-addiction

No Use

Methadone 12 0 3 (25%) 0 10 (83%) 2 (17%)

Control 16 1 (6%) 15 (94%) 15 (94%) 0 0

• Large number of program applicants entered waiting lists

• Follow-up interviews conducted at 7 – 10 months after release

(50)

Conclusions

• Initiating methadone prior to release for a sample of

previously detoxified individuals was desired & feasible

• Methadone as relapse prevention

• Early demonstration of effectiveness Limitations:

•

Small sample

•

No drug testing

(51)

Methadone Treatment for Prisoners: RCT*

• 211 adult pre-release prisoners in Baltimore were randomly assigned to:

1) Counseling in prison + passive referral

2) Counseling in prison + Methadone Post-release 3) Counseling in prison + Methadone Post-release

• F/U interviews at 1, 3, 6, and 12 months post-release

* Kinlock et al., Drug and Alcohol Dependence, 2007

(52)

Treatment

• One individual counseling session and 12 weekly group sessions

• Methadone started low (5 mg daily x 7 days)

• Methadone increase by 5 mg/week to target of

60 mg

(53)

(54)

Baseline Characteristics (N = 204)

Categorical Variables n (%)

Counseling Only (n = 64)

Counseling + Transfer (n = 69)

Counseling+Methadone

(n = 71)

African American 41 (64.1) 51 (73.9) 50 (70.4)

Caucasian 21 (32.8) 13 (18.8) 15 (21.1)

Other 2 (3.1) 5 (7.2) 6 (8.5)

Prior methadone treatment

15 (23.4) 17 (24.6) 15 (21.1)

Continuous Variables Mean (SD)

Age 40.7 (7.5) 40.3 (6.7) 39.9 (7.0)

Heroin use days 27.1 (7.8) 27.8 (6.1) 26.7 (8.9)

(55)

Outcomes

Counseling Only (n = 64)

Counseling + Transfer

(n = 69)

Counseling + Methadone (n = 71)

p

Entered MTP (within 30 days)

8.2% 48.4% 69.6% .0001

Days in MTP (past year)

23.1 91.3 166 < .01

Opioid positive (12 month F/U)*

65.6% 48.7% 25% < .01

Cocaine positive (12 month F/U)*

71.9% 66.6% 43.2% < .05

Re-arrest (past year)

50.8% 59.1% 52.9% ns

Overdose deaths 4 0 0

* Limited urine samples available CO (32); C+T (39), C + M (44)

(56)

Conclusion

• Treatment entry and retention rates superior for group starting medication in prison

• Second best approach would be to start just after release

•

Care must be taken with dosing of non-tolerant individuals

Positive drug tests were lower for group starting methadone in prison Limitation: Missing samples

• No difference in re-arrest

• Starting methadone in prison prior to release seemed promising

Limitations: Only men and much missing urine data

(57)

Methadone Prior v. Post-release: RCT

90 opioid non-tolerant adult inmates with history of opioid dependence in Rhode Island were randomly assigned to:

1) methadone prior to release with post-release MTP subsidy 2) Methadone after release with post-release MTP subsidy 3) Methadone after release without post-release MTP subsidy

•Methadone started LOW (5 mg) and increased SLOW (2 mg/day)

•6-month follow-up interviews

McKenzie et al, Substance Abuse, 2012

(58)

Methods

• “As treated” analysis

•

4 participants assigned to pre-release dosing did not start for logistical reasons and were analyzed with post-release data

•

During the study, a new federal grant provided MTP subsidy to all

participants and hence those participants who were randomly assigned to non-subsidy were analyzed with group receiving subsidy

• Average daily methadone was 33 mg at release

(59)

Demographics (N = 90)

Variable N/(%)

Race/Ethnicity

White Hispanic

45 (72.5%) 13 (21.0%)

Gender

Male 44 (71%)

Mean Age (Yrs) 40.7

Drug Injection (Y/N) 40 (64.5%)

(60)

Outcomes at 6 Month Follow-up (N = 90)

Variable

MTP in prison with subsidy

(n =21)

MTP after prison with subsidy

(n =32)

MTP after prison no subsidy

(n = 9) p

Attended MTP within 30 days

(n/%)*

18 (85.7%) 13 (40.6%) 2 (22.2%) < .001

In treatment at F/U (n/%)**

14 (66.7%) 15 (46.9%) 4 (44.4%) ns

Heroin use past 30 days (n/%)

3 (14.4%) 18 (56.3%) 4 (44.4%) .008

Re-arrest past 6 months (n/%)

7 (33.3%) 9 (28.1%) 2 (22.2%) ns

(61)

Conclusion

• Group starting methadone in prison had higher rate of post-

release treatment entry and lower rates of opioid positive tests (similar to Kinlock and co-workers’ findings)

• Treatment retention was not significantly different

•

This area needs more research on approaches to improve retention (as in the case of continuity of care)

• Arrest rates at follow-up not significantly different

•

Arrest may be more of a function of policing and poverty

(62)

Buprenorphine in Corrections

• Buprenorphine as compared to methadone may have:

•

Less stigma

•

Fewer regulatory barriers in US

•

Better safety profile

(63)

211 male and female pre-release inmates in Baltimore with histories of heroin dependence prior to incarceration were randomly assigned to:

1. Counseling + Buprenorphine in prison with referral to continue buprenorphine in the community

2. Counseling Only in Prison with referral to buprenorphine in the community

Pre-release Buprenorphine Treatment for Prisoners: RCT*

*Gordon, Kinlock, Schwartz et al., Drug & Alcohol Dependence, 2014

(64)

Buprenorphine Dosing

• Most participants were non-tolerant

• Planned dose induction started low and went slow

•

Dose increased weekly unless otherwise indicated

• 1, 2, 3, 4, 6, 8, 12, 16 mg daily x 7 days

• Switched to 32 every other day, then thrice weekly

• Close observation for diversion: 19 cases diversion (17.9%)

(65)

Participant Characteristics (N = 211)

Variables

Age (Mean/SD) 39.1 (8.8)

African American White

70.1%

25.6%

Male 70.1%

Prior OAT 47%

Days of heroin use, 30 days prior to incarceration (Mean/SD)

24.5 (10.1)

(66)

Prison & Community Treatment Entry Outcomes

p = .006

p=.01

(67)

Conclusion

• Starting buprenorphine in prison, as with starting methadone in prison (Kinlock and McKenzie studies), was associated with significantly higher rates of post-release treatment entry

• Attempted diversion was a problem (as with Magura and co-

workers’ study) that may hamper use of buprenorphine in prison settings

• 12 month treatment outcomes will be reported soon

(68)

Extended-Release Naltrexone (XR-NTX) to Prevent Relapse After Release from Jail

• Pilot random assignment study

• 34 sentenced inmates in NYC jail with h/o opioid dependence

•

Did not want OAT

• Random assignment to:

1) XR-NTX injection prior to release and offered two further injections one month apart in the community

2) Treatment-as-usual with one counseling session and referral information

• F/U at 1, 2, 3, 4, and 8 weeks after release Lee et al., Addiction, 2015

(69)

Outcomes

XR-NTX (n=16) TAU (n=17) p

Opioid relapse weeks 1 – 8

8 (50%) 16 (93%) < .03

% Negative urine drug tests

59% (34/57) 24% (15/62) < .0001

Starting XR-NTX was a feasible and promising intervention

(70)

Limitations & Future Direction

• Small sample

• Limited follow-up period

• Large two-site random assignment study

underway as part of SOMATICS study

(71)

Future Directions

• Implementation and policy research on increasing medication penetration in jails in US

• Trials to test approaches to increase treatment entry post-release

• Trials to test approaches to increase treatment retention for individuals re-entering community care post-release

• Ongoing trials will provide data on use of extended release

naltrexone among inmates and probationers, patient navigation, and naloxone provided post-release

(72)

Thank you for your attention

• Contact:

•

Email: Rschwartz@friendsresearch.org

•

Web: www. Friendsresearch.org

•

Office Phone: 410-837-3977 Ext 276

•

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•

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