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Medication and Behavioral Treatment

of Substance Use Disorders

Brian Fuehrlein, MD, PhD

Director, Psychiatric Emergency Room, VA

Connecticut and Assistant Professor of

Psychiatry, Yale University

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Brian Fuehrlein, Disclosures

I have no financial relationships to disclose.

The contents 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.

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Planning Committee, Disclosures

AAAP aims to provide educational information that is balanced, independent, objective and free of bias

and based on evidence. In order to resolve any identified Conflicts of Interest, disclosure information from

all planners, faculty and anyone in the position to control content is provided during the planning process

to ensure resolution of any identified conflicts. This disclosure information is listed below:

The following developers and planning committee members have reported that they have no

commercial relationships relevant to the content of this module to disclose: PCSS-MAT lead

contributors Frances Levin, MD and Adam Bisaga, MD; AAAP CME/CPD Committee Members Dean

Krahn, MD, Kevin Sevarino, MD, PhD, Tim Fong, MD, Tom Kosten, MD, Joji Suzuki, MD; and AAAP

Staff Kathryn Cates-Wessel, Miriam Giles, Carol Johnson and Justina Pereira.

All faculty have been advised that any recommendations involving clinical medicine must be based on

evidence that is accepted within the profession of medicine as adequate justification for their indications

and contraindications in the care of patients. All scientific research referred to, reported, or used in the

presentation must conform to the generally accepted standards of experimental design, data collection,

and analysis. The content of this CME activity has been reviewed and the committee determined the

presentation is balanced, independent, and free of any commercial bias. Speakers will inform the learners

if their presentation will include discussion of unlabeled/investigational use of commercial products.

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Target Audience

The overarching goal of PCSS-MAT is to make

available the most effective medication-assisted

treatments to serve patients in a variety of settings,

including primary care, psychiatric care, and pain

management settings.

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Educational Objectives

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

Identify the primary medications in the treatment of

alcohol use disorder

Define the primary medications in the treatment of opioid

use disorder

Describe the primary options for psychosocial treatment

and support

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Substance use disorder is a chronic relapsing and

remitting illness

A multimodal approach of medications and

psychosocial treatment and support is considered

the most effective for opioid and alcohol use

disorder

Withdrawal management is not treatment

Review

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Case Presentation #1

Bob is a 50-year-old male with chronic alcohol use disorder.

Recently completed court-ordered detox then

30-day residential treatment

Relapsed upon discharge from treatment

due to cravings

Ambivalent about sobriety

Lives alone

Diagnosed with cirrhosis and coronary artery disease

Has been prescribed low dose opioids for chronic back pain

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• Steve is a 27-year-old man diagnosed

with alcohol use disorder

• Recently completed a 90-day treatment

program and remains sober, but struggles

with cravings 2-3 times per week

• Generally prefers not taking medications but is willing to try

• Committed to recovery, attends daily AA meetings

• No medical problems

• Lives with a supportive family

Case Presentation #2

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Denise is a 40-year-old woman with alcohol use

use disorder

Recently arrested for 3rd DUI

Currently in court-ordered intensive outpatient

program

Denies cravings

Highly motivated by legal pressures

Inquired about a medication that will prevent her

from drinking

Lives with husband who is willing to do whatever

it takes to help her

No medical problems

Case Presentation #3

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Alcohol Use Disorder

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Disulfiram (Antabuse)

Approved in 1957 for alcohol use disorder

Aversive therapy, does not reduce cravings

Inhibits aldehyde dehydrogenase

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Increasing levels of acetaldehyde causes an

aversive reaction

Leads to tachycardia, flushing, nausea,

vomiting, hypotension

Within hours of first dose and days to weeks

after last dose

Must fully educate patients about these risks

Most effective with motivated patients

Most effective with supervised administration

Disulfiram (Antabuse)

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Starting and maintenance dose 250-500mg daily

Metabolized through liver and LFTs should be checked and monitored

Patients should be alcohol free for >12 hours

Occasional aversive reactions from hidden alcohol sources are possible

Must educate patient about the possibility of a severe reaction with

alcohol consumption

Severe myocardial disease, coronary occlusion and severe liver

disease are contraindications while psychosis is a relative

contraindication

Disulfiram (Antabuse)

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Naltrexone

Orally available mu opioid

receptor antagonist, not to be

confused with naloxone

Alcohol causes endogenous

opioid release and reinforcing

effects

Naltrexone reduces cravings and the positive reinforcing effects of

alcohol

Naltrexone reduces amount consumed when drinking

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Naltrexone

Orally once daily starting and maintenance dose is 25-50mg

Patients must be opioid free for >7 days for standard opioids and 10-14 days for long acting opioids like methadone

Obtain baseline liver function tests including AST, ALT, and total bilirubin prior to instituting naltrexone (oral or injectable) therapy. Only initiate therapy if liver function tests (LFTS) are lower than 5x the upper limit of normal (ULN).

Obtain follow-up AST and ALT levels approximately 8-12 weeks after initiation of naltrexone with quarterly monitoring thereafter

Side effects are generally mild and include nausea, headache, dizziness, fatigue and insomnia

Hepatotoxicity is a black box warning though is rare

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Extended Release Naltrexone (VivitrolTM)

• Once-a-month and injectable into gluteal muscle

Injection site reactions are a possible side effect

Consider a trial of oral naltrexone

Avoids first-pass metabolism hence total dose is lower (380mg)

Patients should not be prescribed opioids and this should be confirmed with a

urine drug screen or naloxone challenge

Patients had longer time of sobriety and fewer drinking days per month

Particularly effective following at least 4 days of abstinence, though may also be

used in those actively drinking

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Acamprosate (CampralTM)

NMDA receptor modulator and GABA/glutamate

stabilization

May also stabilize the hypothalamic pituitary axis

These actions offer neuroprotection and reduce the

post-acute withdrawal symptoms of anxiety and

irritability, which may contribute to a relapse

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Acamprosate (CampralTM)

Reduces the risk of return to drinking

Increases the duration of abstinence

Likely as effective as naltrexone

Well tolerated and not metabolized through the liver

Gastro-intestinal side effects are most common

Therapeutic dose is 666mg TID (6 pills per day)

Adherence is the primary problem

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Topiramate (TopamaxR)

Off-label use for alcohol use disorder to reduce post-acute withdrawal symptoms and craving

Facilitates GABA and antagonized glutamate and may decrease dopamine activity in the reward pathway and reduce withdrawal symptoms

Has shown efficacy in doses 75-300 mg daily and is better tolerated if titrated slowly

Compared to placebo, reduced drinks per day, number of heavy drinking days and days of abstinence

Primary side effect is cognitive slowing

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Gabapentin (NeurontinR)

• Indicated for seizure disorder, restless leg syndrome and

postherpetic pain

• Off-label use for alcohol use disorder (among other things)

GABA receptor agonist

Very mild side effect profile and very well tolerated

Dosed up to 1200 mg TID

Results are promising

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Medication Assisted Treatment

for Opioid Use Disorder

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Methadone

What does methadone have to do with this?

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Methadone

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Methadone Pharmacology

Full mu opioid receptor agonist

Half life 24 - 36 hours

Increased risk of respiratory depression and

overdose when mixed with alcohol and/or

benzodiazepines

Very effective at doses >80 - 140mg once daily

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CASAColumbia. (2012). Addiction medicine: Closing the gap between science and practice.

Methadone Mechanism of Action

Being a full agonist with a long half-life, methadone

suppresses signs and symptoms of opioid withdrawal by

reaching a steady-state level with once daily dosing

It eliminates opioid cravings

May also serve to block the reinforcing effects of illicit

opioids

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Methadone Delivery

For treatment of OUD, methadone must

be administered in a federally regulated

opioid treatment program

Patients are seen daily for administered

dosing with gradually increasing take home

privileges on symptom improvement

Once per week visits is the least restrictive

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Methadone Side Effects

Respiratory depression, particularly with benzos or alcohol

Prolonged QTc at doses >100mg, if seen daily

Weight gain

Constipation

Decreased testosterone

Dry mouth

Urinary retention

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Buprenorphine

DATA 2000 permitted scheduled III-V

medications to treat opioid use disorder in an

office-based setting

Buprenorphine is schedule III

Synthetic opioid that functions as a partial agonist at the mu opioid receptor

Partial agonist effect serves to reduce cravings and eliminate withdrawal

Unlike full agonists, partial agonists create a ceiling effect at higher doses – thus no increased respiratory depression or euphoria at higher doses

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Buprenorphine Pharmacology

Compared to methadone, buprenorphine has a reduced overdose potential and improved

safety profile

Partial agonist may precipitate withdrawal if taken by someone who is taking daily doses of a

full agonist – need to be in mild withdrawal before taking first dose

Buprenorphine has a high affinity to the mu receptor and results in blocking other opioids

This may result in precipitated withdrawal

• This blocks other full agonist misuse

Formulated with naloxone (4:1 ratio) to reduce misuse and diversion – naloxone is not

bioavailable unless injected

Available in tablets, films, and long-acting implant

Buprenorphine is as effective as methadone except for treatment retention

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Extended-Release Naltrexone

Opioid antagonist

Provides complete blockade of the mu opioid receptors (though may be

overridden in emergency situations for acute pain control)

Counterintuitively, may actually reduce cravings for opioids (different

mechanism than methadone/buprenorphine)

Studies are underway to determine efficacy compared to buprenorphine

and methadone

Daily oral naltrexone is generally not recommended for OUD given

problems with medication adherence

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Pharmacotherapy for Opioid Use Disorder

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: Methadone Full Agonist: Methadone

Partial Agonist: Buprenorphine

Antagonist: Naltrexone

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Behavioral Treatment and

Psychosocial Supports for SUDs

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Evidence-Based Therapy

Evidence-based therapy should be used in conjunction with medications when possible.

For substances without an approved medication, evidence-based therapy can be one of the primary means of sobriety.

Evidence-based therapies include CBT1, CRAFT2 and CM3

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Cognitive Behavioral Therapy

• In maladaptive behavioral patterns, learning

plays a critical role

• Teach patients to identify and correct problematic

behaviors by applying learned skills

• Anticipating problems and enhancing self control

by developing coping strategies

• Exploring consequences, self monitoring for

cravings early and identifying risky situations

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CRAFT

Community Reinforcement and Family Training

Increase family compliance with an

intervention to increase the rate of treatment

for the patient

• Motivation building, functional analysis,

communication skill training, life enrichment

and other skills

• Targets the family of those with substance

use disorders

• Has been shown to improve engagement in

treatment

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Contingency Management

Highly effective in increasing treatment retention and promoting abstinence

Provides tangible rewards to reinforce positive behaviors, such as abstinence

Voucher based reinforcement involves vouchers that are exchanged for goods and services

Vouchers increase in value with more negative urine drug screens

Prize incentives provide chances to win cash prizes

Each negative urine is a chance to win

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Psychosocial Recovery Supports

Psychosocial recovery supports, while not evidence-

based therapies, are potentially very important and very

helpful.

When medications and other evidence-based therapies

are not available, psychosocial supports may be all that

is available

The primary psychosocial supports include Alcoholics

Anonymous, SMART Recovery and supportive

psychotherapy

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Alcoholics Anonymous

Founded in 1935

“Primary purpose is to stay sober and help other alcoholics achieve sobriety”

“The only requirement for AA membership is a desire to stop

drinking”

No cost, no side effects, readily available and may greatly benefit the patient

Nearly all patients with a substance use disorder will be familiar with AA, their providers should be too

AA is the primary psychosocial support available

Tonigan, S., et al. Participation and involvement

in Alcoholics Anonymous, 2003

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Alcoholics Anonymous

The recovery program

• Meetings (90 in 90)

• Sponsorship

• Step work

• Commitments

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Alcoholics Anonymous

Meetings

• 90 meetings in 90 days is the minimum

recommended starting point

• Meetings are widely available, often

have themes and many attend daily

meetings indefinitely

Sponsorship

• “A sponsor is one person to turn to without embarrassment

when doubts, questions or problems linked to alcoholism

arise”

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Alcoholics Anonymous

Step work

• Step 1: We admitted we were

powerless over alcohol and our lives

had become unmanageable

• There are twelve steps that should be

worked through as part of the recovery

program

Commitments

• Commitment can be small, i.e., will make coffee at a particular meeting, or large, i.e., becoming a sponsor

• This shows responsibility to something or someone other than self

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SMART Recovery

Self Management And Recovery Training

Alternative or supplement to AA

Non confrontational motivational, behavioral and cognitive methods

Meetings are integral to the program

SMART recovery relies less on religion and

spirituality

Four point program

• Building motivation

• Coping with urges

• Problem solving

• Lifestyle balance Horvath, T. and Yeterian, J. “SMART Recovery: Self-Empowering, Science-Based

Addiction Recovery Support. Journal of Groups in Addiction Recovery, 7:102-117, 2012

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Supportive Recovery Psychotherapy

The primary goal is to strengthen the ability to cope with stressors

Close, empathetic listening

Reinforcing and strengthening resilience

Building and maintaining self-esteem

Encourage sharing of feelings and thoughts

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Summary

Medications are an integral part of substance use

disorder treatment

Only a handful of medications are currently

approved, with others under investigation

Psychosocial supports may be used in conjunction

with medications and may be particularly important

when medications or behavioral treatments are not

available

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References

Fuehrlein and Gold. Medication assisted recovery in alcohol and

opioid dependence. Directions in Psychiatry. 33(2):15-29, 2013

Horvath, T. and Yeterian, J. “SMART Recovery: Self-Empowering,

Science-Based Addiction Recovery Support. Journal of Groups in

Addiction Recovery, 7:102-117, 2012

Meyers, R. and Smith, J. Clinical Guide to Alcohol Treatment: The

Community Reinforcement Approach. Guildford Press, 1995

Newman, C. Cognitive Therapy of Substance Abuse. The

Guildford Press, 1993

Tonigan, S., et al. Participation and involvement in Alcoholics

Anonymous, 2003

Prendergast, M., et al. Contingency management for treatment of

substance use disorders: a meta-analysis. Addiction,

101(11):1546-1560, 2006

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PCSS-MAT Mentoring Program

PCSS-MAT Mentor Program is designed to offer general information to

clinicians about evidence-based clinical practices in prescribing

medications for opioid addiction.

PCSS-MAT Mentors are a national network of providers with expertise in

addictions, pain, evidence-based treatment including medication-

assisted 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:

pcssmat.org/mentoring

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PCSS Discussion Forum

Have a clinical question?

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Funding for this initiative was made possible (in part) by grant no. 1U79TI026556-01 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.

PCSS-MAT is a collaborative effort led by the American Academy of Addiction Psychiatry (AAAP) in

partnership with the: Addiction Technology Transfer Center (ATTC); American Academy of Family

Physicians (AAFP); American Academy of Pain Medicine (AAPM); American Academy of Pediatrics

(AAP); American College of Emergency Physicians (ACEP); American College of Physicians (ACP);

American Dental Association (ADA); American Medical Association (AMA); American Osteopathic

Academy of Addiction Medicine (AOAAM); American Psychiatric Association (APA); American

Psychiatric Nurses Association (APNA); American Society of Addiction Medicine (ASAM); American

Society for Pain Management Nursing (ASPMN); Association for Medical Education and Research in

Substance Abuse (AMERSA); International Nurses Society on Addictions (IntNSA); National

Association of Community Health Centers (NACHC); and the National Association of Drug Court

Professionals (NADCP).

For more information: www.pcssmat.org

Twitter: @PCSSProjects

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PCSS-MAT: Training, Mentoring, Resources