oud patient withdrawal management and initiating relapse prevention … · 2020. 4. 1. ·...

Adam Bisaga, MD Professor of Psychiatry

Columbia University

Tuesday, March 31st, 2020 12:00 PM – 1:00 PM EST

OUD Patient Withdrawal Management and Initiating Relapse

Prevention with XR-Naltrexone

2

Webinar Housekeeping

Minimize or maximize the webinar

panel by selecting the orange arrow.

To be recognized, type your question

in the “Question” box and select

send.

3

Disclosures

• Alkermes: Received grant support (medication samples, funded

research)

• Unpaid consultancy: Alkermes, Go-Medical

The content of this activity may include discussion of off label or investigative drug uses.

The faculty is aware that is their responsibility to disclose this information.

4

Educational Objectives

At the conclusion of this activity participants should be able to:

Enhance their knowledge of the latest evidence-base for the

effectiveness of XR-naltrexone in treatment of opioid use

disorder

Identify patients that may benefit from the relapse-prevention

treatment using XR-naltrexone

Adopt new protocols for managing opioid withdrawal to initiate

antagonist-based relapse prevention treatment

5

Outline

1. Evidence for use of XR-naltrexone for relapse prevention

treatment following detoxification

2. Selection of patients

3. Strategies to initiate treatment

4. The evolving model of OUD care

6

XR-NALTREXONE FOR RELAPSE

PREVENTION TREATMENT FOLLOWING

DETOXIFICATION



DETOXIFICATION

7

OUD TREATMENT STRATEGY

• Most effective treatment involves a combination of

several approaches

– Pharmacological Treatment (MAT/MOUD -

medication + intervention to increase

medication adherence)

– Psychosocial/behavioral Therapies (helping

patients develop skills necessary to maintain

abstinence)

– Self Help/Mutual Help Groups (social network

supportive of abstinence and recovery)

– Recovery-oriented activities (help patients

develop satisfying lives)

8

MEDICATIONS FOR OUD (MOUD)

Methadone

Antagonist

μ ORμ OR

FullAgonist

Buprenorphine

XR-NaltrexonePartialAgonist

μ OR

Methadone

Antagonist

μ ORμ OR

FullAgonist

Buprenorphine


μ OR

Methadone

Antagonist

μ ORμ OR

FullAgonist

Buprenorphine


μ OR

O

pio

id R

ecep

tors

↓NMDA

κ OR

κ OR

n OR

9

Methadone

Antagonist

μ ORμ OR

FullAgonist

Buprenorphine


μ OR

Methadone

Antagonist

μ ORμ OR

FullAgonist

Buprenorphine


μ OR

FDA-APPROVED MEDICATIONS: AGONISTS

• Methadone (MET), buprenorphine (BUP) “Stabilizes” system’s functioning via constant stimulation of opioid receptors

Prevents withdrawal, relieves craving, stabilizes affect, minimizes pathological brain responses, blocks effects of other opioids

• Limitations BUP requires mild withdrawal to initiate

Potential for side-effects (overdose with MET)

Regulatory oversight

• Concerns Risk of misuse

and diversion

Difficult to retain

long-term

-3

-2

-1

0

1

2

3

4

5

0 5 1 0 1 5 2 0 2 5 3 0

HER

METH

BUP

10

Methadone

Antagonist

μ ORμ OR

FullAgonist

Buprenorphine


μ OR

FDA-APPROVED MEDICATIONS: ANTAGONIST

• Naltrexone “Stabilizes” system’s functioning after “resetting” opioid receptors

(post-withdrawal)

Blocks effects of exogenous opioids and re-development of physical

dependence, relieves craving, stabilizes affect

• Limitations Requires resolution of physical dependence before initiation

• Concerns Difficult to initiate and

difficult to retain

-3

-2

-1

0

1

2

3

4

5

0 5 1 0 1 5 2 0 2 5 3 0

HER

NTX

11

NALTREXONE: EFFECTIVENESS AND SAFETY

EFFECTIVENESS

XR-naltrexone is effective vs. oral naltrexone (2009, 2018)

XR-naltrexone is efficacious vs placebo injection (2006, 2011)

XR-naltrexone is effective vs. treatment-as-usual (2015,2016)

Once initiated, XR-naltrexone and buprenorphine are equally effective and safe (2017,2018)

SAFETY

XR-naltrexone and buprenorphine have comparable effects on mood (2017,2018,2019)

XR-naltrexone is not associated with depression/anhedonia (2010,2011,2015,2016,2019)

XR-naltrexone is not associated with excessive overdose (2010,2016,2017,2019)

12

NALTREXONE EFFECTIVENESS: ORAL VS. XR

• XR-naltrexone (injections, implants) are more effective than the oral

preparation because effectiveness is primarily dependent on adherence

XR-preparations should be the treatment of choice where available

Treatment with naltrexone should include behavioral strategies to improve

adherence

Time to dropout: XR- vs. oral naltrexone

Implant vs. oral naltrexone

13



DETOXIFICATION

XR-NALTREXONE:

PATIENT SELECTION AND STRATEGIES

FOR TREATMENT INITIATION

14

CANDIDATES FOR NALTREXONE

• Patients who are not interested or able to be on agonist maintenance

• Patients who are detoxified and abstinent but at risk for relapse

• Patients who failed prior treatment with agonists

• Patients successful on agonist but who want to discontinue them without risking relapse

• Patients with less severe form of a disorder?

• Young adults that are often unwilling to commit to a long-term agonist maintenance

• Individuals who use opioids sporadically (high-risk group)

15

NALTREXONE TREATMENT INITIATION

Naltrexone will precipitate

severe and prolonged

withdrawal (PW)

Naltrexone can be given with no

risk of PW

Using large amounts of

long-acting or potent agents

Using daily short acting

agents (heroin)

Using daily low dose/oral

agents Using opioids sporadically (high-risk)

Detoxified, or abstinent

>10 days

Physical

Dependence

Without

Physical Dependence

after confirming absence of physical depend.

using naloxone or naltrexone challenge

Maintained on methadone

Maintained on buprenorphine

Level of physical dependence at treatment outset is the main consideration

16

METHODS FOR INITIATING NALTREXONE

• No single best method but rather a set of approaches/tools that can

be individualized to the patient and treatment team experience

• Effective method will balance the degree of discomfort and the

duration of treatment

• Always confirm absence of opioids and physical dependence prior

to the first dose of naltrexone – Patient must understand the risks of precipitated withdrawal if underreporting

– Always perform naloxone challenge if unsure of the abstinence and the absence

of physiological dependence

DAYS 1 10

Wit

hd

raw

al S

ever

ity

17

NALOXONE CHALLENGE

• Naloxone is a short-acting opioid antagonist used to reverse overdose and to detect physiological dependence

• In dependent individuals, naloxone will precipitate withdrawal that usually emerges within 5-10 min and dissipates within 30 min

– Severity can be measured using standard instruments (e.g., COWS)

– Severity of withdrawal is proportional to the level of physical dependence and the dose of naloxone

– Any change from baseline, particularly appearance of objective signs, evidences positive test

• Naloxone is given IM (deltoid) at the 0.8-1.2 mg dose (2-3 cc) – To minimize risk of withdrawal, may administer in 2 stages, 0.4 mg followed by

0.8 mg

• With the negative test, full dose naltrexone can be started – Naltrexone should not be given after the positive test (it will precipitate

withdrawal lasting many hours), in that case naloxone challenge can be repeated the next day

18

APPROACHES TO MANAGE OPIOID WITHDRAWAL

• Agonist-assisted

• Symptomatic-treatment alone

• Rapid withdrawal using antagonist

• Ultra-Rapid withdrawal under anesthesia

19

AGONIST-ASSISTED

• Low doses of opiate agonist (MET 10-20 mg or BUP 4-8 mg) are given for 1-2 days to substitute for heroin and prevent severe withdrawal

• Subsequently agonist is tapered off slowly to minimize withdrawal

• Washout period needed (7-10 days) to eliminate residual dependence

• Adjunctive medications can be used to alleviate the residual withdrawal

• Allows for safe completion of detox over an extended period

• Can prevent severe complications in medically or psychiatrically ill patients, and in those with mixed-dependence

BUP taper NTX

5 Day 0 10 15

Withdrawal

agonist-assisted + opioid washout

NTX Induction

washout

20

SYMPTOMATIC TREATMENT ALONE

• A variety of adjunctive medications are used to decrease specific symptoms of withdrawal

• Autonomic arousal (clonidine, lofexidine)

• Anxiety/restlessness Benzodiazepines vs. non-controlled agents

• Insomnia

• Musculo-skeletal pain (NSAID’s)

• GI Distress (hydration, anti-nausea, anti-diarrhea, anti-spasmodics)

• No opioid agonist used so NTX can be started in ∼7 days

5 0 10 15

clonidine/bdz NTX

symptomatic only

washout

21

RAPID WITHDRAWAL USING LOW-DOSE ANTAGONIST

• Addition of an opioid antagonist accelerates detoxification • “Speeding” up the replacing of desensitized receptors with new, fully

active receptors

• BUP, naloxone, and naltrexone shorten OWS unlike clonidine or BDZs

• Withdrawal symptoms are prevented and alleviated with adjunctive medications

• Low-dose antagonist • Naltrexone is added few (1-3) days after the last dose of opioid starting

with very low doses (0.5-3 mg) to minimize precipitated withdrawal while accelerating time to the full dose tolerability

5 0 10 15

BUP clonidine/bdz

NTX low-dose antagonist + symptomatic

22

ULTRA-RAPID WITHDRAWAL UNDER SEDATION/ANESTHESIA

• Large dose of antagonist given during the first day • requires deep sedation (midazolam or GA) to decrease the experience

of precipitated withdrawal and symptomatic treatment

• Followed by full-dose NTX maintenance (almost 100% induction success)

• Not recommended by most guidelines because of higher rates of complications (including deaths)

• May be appropriate in selected, low risk cases when followed by XR-naltrexone

• Asturian method (outpatient, Carreno ea., 2002) • 12 hours opioid abstinence

• clonidine 0.45mg, famotidine, loperamide or octreotide, ondansetron, midazolam 22.5mg, clorazepate 50mg

• (1h) metoclopramide 10mg, naltrexone 50mg

• (1h) hyoscine 20mg, clonidine 0.3mg, metoclopramide 10 mg

23

COMPARING TWO METHODS OF INITIATING TREATMENT WITH XR-NALTREXONE: OUTPATIENT

• Individuals with OUD were randomly assigned to Standard (N=52) vs. Rapid (N=98) Method of outpatient induction onto XR-naltrexone

(Sullivan, Bisaga et al., 2017)

30% of patients

dropped out before

the injection during

the wait period

Odds: 2.9 (p=0.01)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pe

rce

nt

Re

ceiv

ing

Firs

t N

altr

exo

ne

In

ject

ion

Rapid

Method

Standard

Method

- Withdrawal severity was mild and comparable

- No difference on safety measures

BUP taper NTX

5Day 0 10 15

W it hdrawal N T X Induct ion

washout

50 10 15

BUP clonidine/bdz

NTX

W it hdrawal

N T X Induct ion

Standard Protocol (14 day)

Rapid Protocol (7 day)

VS

- Patients inducted using Rapid method had greater success

- Users of RX opioids were more likely to initiate XR-NTX

24

RAPID NALTREXONE INDUCTION (COLUMBIA PROTOCOL)

• Buprenorphine is administered as soon as opioid withdrawal emerge – start with low dose if positive for synthetic opioids (fentanyls)

• Standing doses of adjunctive medication to prevent withdrawal – rather than as needed

• Low starting doses of naltrexone (0.5-3mg) to minimize precipitated withdrawal – given in divided doses to assess tolerability

• Protocol may be modified (accelerated or slowed) depending on the tolerability of NTX titration (4-7 days) – higher rates of completion among users of prescription opioids

clonidine/bdz/zolp

BUP NTX

25

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

Buprenorphine admission 4-6 mg

Naltrexone 1-3 mg (.5+.5)

3-6 mg (1+1)

12.5 mg (3+3)

XR-naltrexone (6)

Supportive medications

clonidine 0.1-0.2 mg qid, clonazepam 0.5-1.0 mg tid, prochlorperazine, zolpidem, trazodone

RAPID NALTREXONE INDUCTION PROCEDURE: INPATIENT

26

RAPID NALTREXONE INDUCTION PROCEDURE: OUTPATIENT

Day 1 Day 2 Day 3 Day 4 Day 5

Buprenorphine 2+2+2mg (+2hs)

Naltrexone 1+2 mg 3+3 mg 6+6+12 mg

XR-NTX

Supportive medications

clonidine 0.1-0.2 mg qid, clonazepam 0.5-1.0 mg tid, prochlorperazine, zolpidem, trazodone

60% success

(Sibai et al., 2019)

0

2

4

6

8

10

12

14

BASELINE DAY1 DAY2 DAY3 DAY4 DAY5

0

10

20

30

40

50

60

70

80

90

100

BASELINE DAY1 DAY2 DAY3 DAY4 DAY5

Avera

ge C

ravin

g S

core (

0-1

00)

Avera

ge C

OW

S S

core

(0-48

)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

BASELINE DAY 1 DAY 2 DAY 3 DAY 4 DAY 5

Re

tain

ed

in T

rea

tme

nt

RX Opioids

Heroin

27

BUPRENORPHINE “BRIDGE” PRIOR TO RAPID INDUCTION

• An outpatient procedure appropriate for patients with severe use disorder (e.g., injecting large doses of heroin) and those who are not able to tolerate

more rapid transition onto naltrexone

• A period of treatment with buprenorphine allows patients to stabilize (stop) their drug use first prior to undergoing opioid withdrawal

STABILIZATION WITHDRAWAL/INDUCTION

29

PROTRACTED WITHDRAWAL: NALTREXONE FLU

• Patients who start naltrexone right after withdrawal commonly experience a “flu-like” symptoms (low-grade withdrawal)

Somatic complaints: insomnia, GI distress, hyperalgesia, anergia

Anxiety, irritability, dysphoria, anhedonia

Symptom severity correlated with naltrexone dose and timing

Severity may be lower if naltrexone initiation is postponed (but relapse risk)

• Partially alleviated with aggressive symptomatic treatment, Insomnia (v. frequent, often severe): zolpidem, trazodone, quetiapine

GI distress: H2 blockers

Anxiety/hyperarousal: clonazepam, clonidine, gabapentin

• Most of these symptoms remit by 2-4 weeks True prolonged symptoms are rare and likely reflect additional

psychopathology

30

OUD TREATMENT: TRANSITION TO A NEW MODEL OF CARE

31

OUD TREATMENT IN TRANSITION

• Chronic disorder model: different levels of care over time, medications and additional treatments needed may change over time

• Inpatient detoxification is no longer a primary treatment, phasing-out detox units to become medication-induction units

• Shift away from residential treatment towards (long-term) outpatient treatment

• Extended-release preparations and behavioral interventions to overcome nonadherence, the major challenge in medication treatment

• Focus on offering patient choice of medication: methadone vs. buprenorphine vs XR-naltrexone

32

OUD TREATMENT IN TRANSITION (2)

• Comprehensive treatment system (One-stop-shop)

• Expanding of care models (from low-threshold to comprehensive)

• Staged treatment: methadone buprenorphine XR-naltrexone

• Acceptance of other measures of treatment success than complete abstinence: harm-reduction framework

• Incorporating recovery framework and peer advocates

• Treatment of co-occurring disorders

(UNODC/WHO Int. Standards, 2016)

33

References

Comer, S. D., M. A. Sullivan, E. Yu, J. L. Rothenberg, H. D. Kleber, et al. (2006).

"Injectable, sustained-release naltrexone for the treatment of opioid dependence: a

randomized, placebo-controlled trial." Arch Gen Psychiatry 63(2): 210-218.

Hulse, G. K., N. Morris, D. Arnold-Reed and R. J. Tait (2009). "Improving clinical

outcomes in treating heroin dependence: randomized, controlled trial of oral or

implant naltrexone." Arch Gen Psychiatry 66(10): 1108-1115.

Hulse, G. K., R. J. Tait, S. D. Comer, M. A. Sullivan, I. G. Jacobs and D. Arnold-Reed

(2005). "Reducing hospital presentations for opioid overdose in patients treated with

sustained release naltrexone implants." Drug Alcohol Depend 79(3): 351-357.

Kelty, E., D. Joyce and G. Hulse (2019). "A retrospective cohort study of mortality rates

in patients with an opioid use disorder treated with implant naltrexone, oral

methadone or sublingual buprenorphine." Am J Drug Alcohol Abuse: 1-7.

Hulse, G. K., N. Morris, D. Arnold-Reed and R. J. Tait (2009). "Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone." Arch Gen Psychiatry 66(10): 1108-1115. Sullivan, M. A., A. Bisaga, M. Pavlicova, K. M. Carpenter, C. J. Choi, K. Mishlen, F. R. Levin, J. J. Mariani and E. V. Nunes (2019). "A Randomized Trial Comparing Extended-Release Injectable Suspension and Oral Naltrexone, Both Combined With Behavioral Therapy, for the Treatment of Opioid Use Disorder." Am J Psychiatry 176(2): 129-137. Comer, S. D., M. A. Sullivan, E. Yu, J. L. Rothenberg, H. D. Kleber, K. Kampman, C. Dackis and C. P. O'Brien (2006). "Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial." Arch Gen Psychiatry 63(2): 210-218. Krupitsky, E., E. V. Nunes, W. Ling, A. Illeperuma, D. R. Gastfriend and B. L. Silverman (2011). "Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial." Lancet 377(9776): 1506-1513. Lee, J. D., R. McDonald, E. Grossman, J. McNeely, E. Laska, J. Rotrosen and M. N. Gourevitch (2015). "Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial." Addiction 110(6): 1008-1014. Lee, J. D., P. D. Friedmann, T. W. Kinlock, E. V. Nunes, T. Y. Boney, R. A. Hoskinson, Jr., D. Wilson, R. McDonald, J. Rotrosen, M. N. Gourevitch, M. Gordon, M. Fishman, D. T. Chen, R. J. Bonnie, J. W. Cornish, S. M. Murphy and C. P. O'Brien (2016). "Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders." N Engl J Med 374(13): 1232-1242. Tanum, L., K. K. Solli, Z. E. Latif, J. S. Benth, A. Opheim, K. Sharma-Haase, P. Krajci and N. Kunoe (2017). "Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial." JAMA Psychiatry 74(12): 1197-1205. Lee, J. D., E. V. Nunes, Jr., P. Novo, K. Bachrach, G. L. Bailey, S. Bhatt, S. Farkas, M. Fishman, P. Gauthier, C. C. Hodgkins, J. King, R. Lindblad, D. Liu, A. G. Matthews, J. May, K. M. Peavy, S. Ross, D. Salazar, P. Schkolnik, D. Shmueli-Blumberg, D. Stablein, G. Subramaniam and J. Rotrosen (2018). "Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial." Lancet 391(10118): 309-318. Mysels, D. J., W. Y. Cheng, E. V. Nunes and M. A. Sullivan (2011). "The association between naltrexone treatment and symptoms of depression in opioid-dependent patients." Am J Drug Alcohol Abuse 37(1): 22-26. Latif, Z. E., J. Saltyte Benth, K. K. Solli, A. Opheim, N. Kunoe, P. Krajci, K. Sharma-Haase and L. Tanum (2019). "Anxiety, Depression, and Insomnia Among Adults With Opioid Dependence Treated With Extended-Release Naltrexone vs Buprenorphine-Naloxone: A Randomized Clinical Trial and Follow-up Study." JAMA Psychiatry 76(2): 127-134. Ngo, H. T., R. J. Tait and G. K. Hulse (2011). "Hospital psychiatric comorbidity and its role in heroin dependence treatment outcomes using naltrexone implant or methadone maintenance." J Psychopharmacol 25(6): 774-782. Zaaijer, E. R., L. van Dijk, K. de Bruin, A. E. Goudriaan, L. A. Lammers, M. W. Koeter, W. van den Brink and J. Booij (2015). "Effect of extended-release naltrexone on striatal dopamine transporter availability, depression and anhedonia in heroin-dependent patients." Psychopharmacology (Berl) 232(14): 2597-2607. Krupitsky, E., E. Zvartau, E. Blokhina, E. Verbitskaya, V. Wahlgren, M. Tsoy-Podosenin, N. Bushara, A. Burakov, D. Masalov, T. Romanova, A. Tyurina, V. Palatkin, T. Yaroslavtseva, A. Pecoraro and G. Woody (2016). "Anhedonia, depression, anxiety, and craving in opiate dependent patients stabilized on oral naltrexone or an extended release naltrexone implant." Am J Drug Alcohol Abuse: 1-7. Kelty, E., D. Joyce and G. Hulse (2019). "A retrospective cohort study of mortality rates in patients with an opioid use disorder treated with implant naltrexone, oral methadone or sublingual buprenorphine." Am J Drug Alcohol Abuse: 1-7. Morgan, J. R., B. R. Schackman, Z. M. Weinstein, A. Y. Walley and B. P. Linas (2019). "Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort." Drug Alcohol Depend 200: 34-39. Hulse, G. K., R. J. Tait, S. D. Comer, M. A. Sullivan, I. G. Jacobs and D. Arnold-Reed (2005). "Reducing hospital presentations for opioid overdose in patients treated with sustained release naltrexone implants." Drug Alcohol Depend 79(3): 351-357. Tait, R. J., H. T. Ngo and G. K. Hulse (2008). "Mortality in heroin users 3 years after naltrexone implant or methadone maintenance treatment." J Subst Abuse Treat 35(2): 116-124. Morgan, J. R., et al. (2019). "Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort." Drug Alcohol Depend 200: 34-39. O'Brien, C. P., et al. (2011). "Long-term opioid blockade and hedonic response: preliminary data from two open-label extension studies with extended-release naltrexone." Am J Addict 20(2): 106-112. Latif, Z. E., et al. (2019). "Anxiety, Depression, and Insomnia Among Adults With Opioid Dependence Treated With Extended-Release Naltrexone vs Buprenorphine-Naloxone: A Randomized Clinical Trial and Follow-up Study." JAMA Psychiatry 76(2): 127-134. Krupitsky, E., et al. (2016). "Anhedonia, depression, anxiety, and craving in opiate dependent patients stabilized on oral naltrexone or an extended release naltrexone implant." Am J Drug Alcohol Abuse: 1-7. Zaaijer, E. R., et al. (2015). "Effect of extended-release naltrexone on striatal dopamine transporter availability, depression and anhedonia in heroin-dependent patients." Psychopharmacology (Berl) 232(14): 2597-2607.


34

References

Krupitsky, E., E. V. Nunes, W. Ling, A. Illeperuma, D. R. Gastfriend and B. L. Silverman (2011).

"Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled,

multicentre randomised trial." Lancet 377(9776): 1506-1513.

Krupitsky, E., E. Zvartau, E. Blokhina, E. Verbitskaya, V. Wahlgren, G . Et al. (2016). "Anhedonia,

depression, anxiety, and craving in opiate dependent patients stabilized on oral naltrexone or an

extended release naltrexone implant." Am J Drug Alcohol Abuse: 1-7.

Latif, Z. E., J. Saltyte Benth, K. K. Solli, A. Opheim, N. Kunoe, P. Krajci, K. Sharma-Haase and L. Tanum

(2019). "Anxiety, Depression, and Insomnia Among Adults With Opioid Dependence Treated With

Extended-Release Naltrexone vs Buprenorphine-Naloxone: A Randomized Clinical Trial and Follow-

up Study." JAMA Psychiatry 76(2): 127-134.

Lee, J. D., E. V. Nunes, Jr., P. Novo, K. Bachrach, G. et al. (2018). "Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial." Lancet 391(10118): 309-318. Lee, J. D., P. D. Friedmann, T. W. Kinlock, E. V. Nunes, T. Y. Boney, R. A. Hoskinson, Jr., D. Wilson, et al. (2016). "Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders." N Engl J Med 374(13): 1232-1242.



35

References



Lee, J. D., R. McDonald, E. Grossman, J. McNeely, E. Laska, J. Rotrosen and M. N. Gourevitch (2015)."Opioid

treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized

effectiveness trial." Addiction 110(6): 1008-1014.

Morgan, J. R., B. R. Schackman, Z. M. Weinstein, A. Y. Walley and B. P. Linas (2019). "Overdose following

initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a

United States commercially insured cohort." Drug Alcohol Depend 200: 34-39.

Morgan, J. R., et al. (2019). "Overdose following initiation of naltrexone and buprenorphine medication

treatment for opioid use disorder in a United States commercially insured cohort." Drug Alcohol Depend

200: 34-39.

Mysels, D. J., W. Y. Cheng, E. V. Nunes and M. A. Sullivan (2011). "The association between naltrexone treatment and symptoms of depression in opioid-dependent patients." Am J Drug Alcohol Abuse 37(1): 22-26. Ngo, H. T., R. J. Tait and G. K. Hulse (2011). "Hospital psychiatric comorbidity and its role in heroin dependence treatment outcomes using naltrexone implant or methadone maintenance." J Psychopharmacol 25(6): 774-782.

36

References



O'Brien, C. P., et al. (2011). "Long-term opioid blockade and hedonic response: preliminary data from two

open-label extension studies with extended-release naltrexone." Am J Addict 20(2): 106-112.

Sullivan, M. A., A. Bisaga, M. Pavlicova, K. M. Carpenter, C. J. Choi, et al. (2019). "A Randomized Trial

Comparing Extended-Release Injectable Suspension and Oral Naltrexone, Both Combined With Behavioral

Therapy, for the Treatment of Opioid Use Disorder." Am J Psychiatry 176(2): 129-137.

Tait, R. J., H. T. Ngo and G. K. Hulse (2008). "Mortality in heroin users 3 years after naltrexone implant or

methadone maintenance treatment." J Subst Abuse Treat 35(2): 116-124.

Tanum, L., K. K. Solli, Z. E. Latif, J. S. Benth, A. Opheim, et al. (2017). "Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial." JAMA Psychiatry 74(12): 1197-1205.

Zaaijer, E. R., L. van Dijk, K. de Bruin, et al. (2015). "Effect of extended-release naltrexone on striatal

dopamine transporter availability, depression and anhedonia in heroin-dependent patients."

Psychopharmacology (Berl) 232(14): 2597-2607.

37

PCSS Mentoring Program

PCSS Mentor Program is designed to offer general information to clinicians

about evidence-based clinical practices in prescribing medications for

opioid use disorder.

PCSS Mentors are a national network of providers with expertise in

addictions, pain, evidence-based treatment including medications for

addiction treatment.

• 3-tiered approach allows every mentor/mentee relationship to be unique

and catered to the specific needs of the mentee.

• No cost.

For more information visit:

https://pcssNOW.org/mentoring/

https://pcssnow.org/mentoring/

38

PCSS Discussion Forum

Have a clinical question?

http://pcss.invisionzone.com/register

http://pcss.invisionzone.com/registerhttp://pcss.invisionzone.com/register

39

PCSS is a collaborative effort led by the American Academy of Addiction

Psychiatry (AAAP) in partnership with:

Addiction Technology Transfer Center American Society of Addiction Medicine

American Academy of Family Physicians American Society for Pain Management Nursing

American Academy of Pain Medicine Association for Multidisciplinary Education and

Research in Substance use and Addiction

American Academy of Pediatrics Council on Social Work Education

American Pharmacists Association International Nurses Society on Addictions

American College of Emergency Physicians National Association for Community Health Centers

American Dental Association National Council for Behavioral Health

American Medical Association The National Judicial College

American Osteopathic Academy of Addiction

Medicine Physician Assistant Education Association

American Psychiatric Association Society for Academic Emergency Medicine

American Psychiatric Nurses Association

40

Session Evaluation and Certificate

• Instructions will be provided in an email sent to participants an hour after the

live session

• Certificates are available to those who complete an evaluation

• Recordings of today’s webinar can be accessed at:

www.pcssNOW.org and education.psychiatry.org

http://www.pcssnow.org/education.psychiatry.org

41

Educate. Train. Mentor

www.pcssNOW.org

[email protected]

@PCSSProjects

www.facebook.com/pcssprojects/

Funding for this initiative was made possible (in part) by grant no. 1H79TI081968 from SAMHSA. The views expressed in written conference materials or

publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does

mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.
http://www.pcssnow.org/mailto:[email protected]://www.twitter.com/PCSSProjectshttps://twitter.com/PCSSprojectshttps://twitter.com/PCSSprojectshttp://www.facebook.com/pcssprojects/

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