POCKET GUIDE MEDICATION-ASSISTED TREATMENT 

OF OPIOID USE DISORDER
 

 

Nearly 80 percent of individuals with an opioid use disorder do not receive

treatment. In the 2014 National Survey on Drug Use and Health (NSDUH),

435,000 respondents ages 12 or older reported current use of heroin.

Nonmedical use of pain relievers continues to be more widespread than heroin 

use—4.3 million NSDUH respondents reported nonmedical use of pain relievers

in the past month. Medication-assisted treatment (MAT) is an effective response

to opioid use disorder. It is the use of medications, in combination with

behavioral therapies, to provide a whole-patient approach to the treatment of

substance use disorders. Individuals receiving MAT often demonstrate dramatic

improvement in addiction-related behaviors and psychosocial functioning. 

The first barrier to accessing treatment is failure to recognize

substance use disorder. Screening, Brief Intervention, and

Referral to Treatment (SBIRT) is an approach in which screening

is followed up as appropriate with brief intervention to promote

healthy behavior change and with referral to treatment for

those needing more extensive care. (www.samhsa.gov/sbirt) 

Produced by the Substance Abuse and Mental Health Services Administration (SAMHSA). 
TREATMENT OF OPIOID USE DISORDER

Checklist for Prescribing Medication 

for the Treatment of Opioid Use Disorder 

Assess the need for treatment
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For persons diagnosed with an opioid use disorder, first determine the severity 

of patient’s substance use disorder. Then identify any underlying or co-occurring 

diseases or conditions, the effect of opioid use on the patient’s physical and

psychological functioning, and the outcomes of past treatment episodes. 

Your assessment should include: 

A patient history 

• Ensure that the assessment includes a medical and psychiatric history, a 

substance use history, and an evaluation of family and psychosocial supports. 

• Access the patient’s prescription drug use history through the state’s prescription

drug monitoring program (PDMP), where available, to detect unreported use 

of other medications, such as sedative-hypnotics or alcohol, that may interact 

adversely with the treatment medications. 

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TREATMENT OF OPIOID USE DISORDER

 

4 

• A physical examination that focuses on physical findings related to addiction 

and its complications. 

• Laboratory testing to assess recent opioid use and to screen for use of other 

drugs. Useful tests include a urine drug screen or other toxicology screen,

urine test for alcohol (ethyl glucuronide), liver enzymes, serum bilirubin, serum 

creatinine, as well as tests for hepatitis B and C and HIV. 

Educate the patient about how the medication works and the associated risks 

and benefits; obtain informed consent; and educate on overdose prevention. 

There is a potential for relapse and overdose on discontinuation of the medication.

Patients should be educated about the effects of using opioids and other drugs

while taking the prescribed medication and the potential for overdose if opioid

use is resumed after tolerance is lost. 

Evaluate the need for medically managed withdrawal from opioid 

Naltrexone patients must first be medically withdrawn from opioids. 
TREATMENT OF OPIOID USE DISORDER

 

Address co-occurring disorders 

Have an integrated treatment approach to meet the substance use, medical and 

mental health, and social needs of a patient. 

Integrate pharmacologic and nonpharmacologic therapies 

All medications for the treatment of the opioid use disorder should be prescribed 

as part of a comprehensive individualized treatment plan that includes counseling 

and other psychosocial therapies, as well as social support through participation 

in Narcotics Anonymous and other mutual-help programs. 

Refer patients for higher levels of care, if necessary 

Refer the patient for more intensive or specialized services if office-based treatment 

with buprenorphine or naltrexone is not effective or the clinician does not have 

the resources to meet a particular patient’s needs, Providers can find programs in 

their areas or throughout the United States by using SAMHSA’s Behavioral Health 

Treatment Services Locator at www.findtreatment.samhsa.gov. 

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TREATMENT OF OPIOID USE DISORDER 6 

Medications Approved in the Treatment 

of Opioid Use Disorder* 

Frequency of Administration 

Extended Release 

Injectable Naltrexone 

Monthly†

Methadone 

Daily 

Buprenorphine 

Daily (also alternative dosing

regimens)

Route of Administration
�

Extended Release 

Injectable Naltrexone

Intramuscular (IM) injection into

the gluteal muscle by a physician

or other health care professional.† 

Methadone

Orally as liquid concentrate, 

tablet or oral solution of diskette

or powder. 

Buprenorphine 

Oral tablet or film is dissolved

under the tongue.
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Who May Prescribe or Dispense

Extended Release 

Injectable Naltrexone 

Any individual who is licensed 

to prescribe medicines (e.g., 

physician, physician assistant, 

nurse practitioner) may prescribe

and/or order administration by

qualified staff. 

Methadone

SAMHSA-certified Opioid

Treatment Programs dispense

methadone for daily administration

either on site or, for stable patients,

at home. 

Buprenorphine 

Physicians must have board

certification in addiction medicine

or addiction psychiatry and/or

complete special training to qualify

for the federal waiver to prescribe

buprenorphine, but any pharmacy

can fill the prescription.

There are no special requirements

for staff members who dispense

buprenorphine under the

supervision of a waivered physician.

*Table highlights some properties of each medication. It does not provide complete information and is not intended as a substitute 

for the package inserts or other drug reference sources used by clinicians (see www.dailymed.nlm.nih.gov for current package inserts). 

For patient information about these and other drugs, visit the National Library of Medicine’s MedlinePlus (www.medlineplus.gov). 

Whether a medication should be prescribed and in what amount are matters to be discussed between an individual and his or her 

health care provider. The prescribing information provided here is not a substitute for the clinician’s judgment, and the National 

Institutes of Health and SAMHSA accept no liability or responsibility for use of the information in the care of individual patients. 

†Naltrexone hydrochloride tablets (50 mg each) are also available for daily dosing. 

TREATMENT OF OPIOID USE DISORDER 7 
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TREATMENT OF OPIOID USE DISORDER 8 

Pharmacologic Category
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Extended Release 

Injectable Naltrexone 

Opioid antagonist

Naltrexone displaces opioids from

receptors to which they have bound.

This can precipitate severe, acute

withdrawal symptoms if administered

in persons who have not completely

cleared opioid from their system. 

Patients who have been treated with

extended-release injectable naltrexone will have reduced tolerance to

opioids. Subsequent exposure to

previously tolerated or even smaller

amounts of opioids may result in

overdose.

Methadone

Opioid agonist 

Patients starting methadone should

be educated about the risk of

overdose during induction onto

methadone, if relapse occurs, or

substances such as benzodiazepines

or alcohol are consumed. During

induction, a dose that seems initially

inadequate can be toxic a few days

later because of accumulation in 

body tissues. For guidance on 

methadone dosing for all phases 

of MAT consult: TIP 43 (http://store.

samhsa.gov/product/TIP-43­

Medication-Assisted-Treatment-forOpioid-Addiction-in-OpioidTreatment-Programs/SMA12-4214) 

Buprenorphine 

Opioid partial agonist

Buprenorphine’s partial agonist

effect relieves withdrawal

symptoms resulting from cessation

of opioids. This same property

will induce a syndrome of acute

withdrawal in the presence of

long-acting opioids or sufficient

amounts of receptor-bound full

agonists. Naloxone, an opioid

antagonist, is sometimes added

to buprenorphine to make the

product less likely to be abused

by injection.
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Clinical Uses/Ideal Candidates
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TREATMENT OF OPIOID USE DISORDER 9 

Extended Release 

Injectable Naltrexone 

Prevention of relapse to opioid 

use disorder following opioid 

detoxification; studies suggest 

benefits for patients who are 

experiencing increased stress or 

other relapse risks (e.g., visiting 

places of previous drug use, loss 

of spouse, loss of job). 

Appropriate for patients who have 

been detoxified from opioids and 

who are being treated for a 

co-occurring alcohol use disorder. 

Extended-release naltrexone 

should be part of a comprehensive 

management program that includes 

psychosocial support. 

Other good candidates include 

persons with a short or less severe 

addiction history or who must 

demonstrate to professional licensing 

boards or criminal justice officials 

that their risk of opioid use is low. 

Methadone

Detoxification and maintenance 

treatment of opioid addiction. 

Patients who are motivated to 

adhere to the treatment plan and 

who have no contraindications to 

methadone therapy. 

Methadone should be part of a 

comprehensive management 

program that includes 

psychosocial support. 

Buprenorphine 

Treatment of opioid dependence. 

Patients who are motivated to 

adhere to the treatment plan and 

who have no contraindications to 

buprenorphine therapy. 

Buprenorphine should be part of 

a comprehensive management 

program that includes psychosocial 

support. 
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TREATMENT OF OPIOID USE DISORDER 10 

Contraindications
�

Extended Release 

Injectable Naltrexone 

Contraindicated in patients receiving 

long-term opioid therapy. 

Contraindicated in patients who are 

engaged in current opioid use (as indicated by self-report or a positive urine 

drug screen) or who are on buprenorphine or methadone maintenance 

therapy, as well as in those currently 

undergoing opioid withdrawal. 

Contraindicated in patients with a 

history of sensitivity to polylactideco-glycolide, carboxymethylcellulose, 

or any components of the diluent. 

Should not be given to patients whose 

body mass precludes IM 

injection with the 2-inch needle 

provided; inadvertent subcutaneous 

injection may cause a severe injection 

site reaction. 

Should not be given to anyone allergic 

to naltrexone. 

Methadone

Contraindicated in patients who 

are hypersensitive to methadone 

hydrochloride or any other 

ingredient in methadone 

hydrochloride tablets, diskettes, 

powder or liquid concentrate. 

Contraindicated in patients with 

respiratory depression (in the absence 

of resuscitative equipment 

or in unmonitored settings) and 

in patients with acute bronchial 

asthma or hypercarbia. 

Contraindicated in any patient 

who has or is suspected of having 

a paralytic ileus. 

Buprenorphine 

Contraindicated in patients who are 

hypersensitive to buprenorphine or 

naloxone. 
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Warnings
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TREATMENT OF OPIOID USE DISORDER 

Extended Release 

Injectable Naltrexone

Use with caution in patients with 

active liver disease, moderate to severe 

renal impairment, and women of 

childbearing age. 

Discontinue in the event of symptoms 

or signs of acute hepatitis. 

As with any IM injection, extendedrelease injectable naltrexone should 

be used with caution in patients with 

thrombocytopenia or any coagulation 

disorder (e.g., hemophilia, severe 

hepatic failure); such patients should 

be closely monitored for 24 hours 

after naltrexone is administered. 

Patients may become sensitive to lower 

doses of opioids after treatment with 

extended-release injectable naltrexone. 

This could result in potentially lifethreatening opioid intoxication and 

overdose if previously tolerated larger 

doses are administered. 

Clinicians should warn patients that 

overdose may result from trying to 

overcome the opioid blockade effects 

of naltrexone. 

Methadone

Methadone should be used with caution 

in elderly and debilitated patients; 

patients with head injury or increased 

intracranial pressure; patients who 

are known to be sensitive to central 

nervous system depressants, such as 

those with cardiovascular, pulmonary, 

renal, or hepatic disease; and patients 

with comorbid conditions or 

concomitant medications that may 

predispose to dysrhythmia or reduced 

ventilatory drive. 

Methadone should be administered 

with caution to patients already at risk 

for development of prolonged QT 

interval or serious arrhythmia. 

The label includes a warning about 

somnolence that may preclude driving 

or operating equipment. 

Buprenorphine 

Caution is required in prescribing 

buprenorphine to patients with 

polysubstance use and those who 

have severe hepatic impairment, 

compromised respiratory function, 

or head injury. 

Significant respiratory depression and 

death have occurred in association 

with buprenorphine, particularly 

administered intravenously or in 

combination with benzodiazepines 

or other central nervous system 

depressants (including alcohol). 

Buprenorphine may precipitate 

withdrawal if initiated before patient 

is in opioid withdrawal, particularly 

in patients being transferred from 

methadone. 

The label includes a warning about 

somnolence that may preclude driving 

or operating equipment. 

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TREATMENT OF OPIOID USE DISORDER 12 

Use in Pregnant and Postpartum Women
�

Extended Release 

Injectable Naltrexone 

Pregnancy: FDA pregnancy 

category C‡ 

Nursing: Transfer of naltrexone and 

6ß-naltrexol into human milk has 

been reported with oral naltrexone. 

Because animal studies have shown 

that naltrexone has a potential for 

tumorigenicity and other serious 

adverse reactions in nursing infants, 

an individualized treatment decision 

should be made whether a nursing 

mother will need to discontinue 

breastfeeding or discontinue 

naltrexone. 

Methadone

Pregnancy: FDA pregnancy 

category C‡ 

Methadone has been used during 

pregnancy to promote healthy 

pregnancy outcomes for more than 

40 years. Neonatal abstinence 

syndrome may occur in newborn 

infants of mothers who received 

medication-assisted treatment with 

methadone during pregnancy. No 

lasting harm to the fetus has been 

recognized as a result of this therapy 

but individualized treatment 

decisions balancing the risk and 

benefits of therapy should be made 

with each pregnant patient. 

Nursing: Mothers maintained on 

methadone can breastfeed if they 

are not HIV positive, are not abusing 

substances, and do not have a disease 

or infection in which breastfeeding is 

otherwise contraindicated. 

Buprenorphine

Pregnancy: FDA pregnancy 

category C‡ 

Neonatal abstinence syndrome may 

occur in newborn infants of mothers 

who received medication-assisted 

treatment with buprenorphine 

during pregnancy. No lasting harm 

to the fetus has been recognized 

as a result of this therapy but 

individualized treatment decisions 

balancing the risk and benefits of 

therapy should be made with each 

pregnant patient. 

Nursing: Buprenorphine and its 

metabolite norbuprenorphine are 

present in low levels in human milk 

and infant urine. Available data are 

limited but have not shown adverse 

reactions in breastfed infants. 
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Potential for Abuse and Diversion
�

Extended Release 

Injectable Naltrexone 

No

Methadone 

Yes 

Buprenorphine 

Yes 

‡

Animal studies have shown an adverse effect on the fetus and there are no adequate, well-controlled studies in humans, but potential 

benefits may warrant use of the drug in some pregnant women despite potential risks. 

TREATMENT OF OPIOID USE DISORDER 13 
 

 

 

 

 

 

TREATMENT OF OPIOID USE DISORDER 14 

Clinical Opiate Withdrawal Scale 

This tool can be used in both inpatient and outpatient settings to reproducibly rate

common signs and symptoms of opiate withdrawal and monitor these symptoms over time. 

Resting Pulse Rate: beats/minute 

Measured after patient is sitting or lying for one minute. 

0 pulse rate 80 or below 

1 pulse rate 81-100 

2 pulse rate 101-120 

4 pulse rate greater than 120 

Sweating: Over past 1/2 hour not accounted for by 

room temperature or patient activity. 

0 no report of chills or flushing 

1 subjective report of chills or flushing 

2 flushed or observable moistness on face 

3 beads of sweat on brow or face 

4 sweat streaming off face 

Restlessness: Observation during assessment. 

0 able to sit still 

1 reports difficulty sitting still, but is able to do so 

3 frequent shifting or extraneous movements of legs/arms 

5 unable to sit still for more than a few seconds 

GI (Gastrointestinal) Upset: Over last 1/2 hour. 

0 no GI symptoms 

1 stomach cramps 

2 nausea or loose stool 

3 vomiting or diarrhea 

5 multiple episodes of diarrhea or vomiting 

Tremor: Observation of outstretched hands. 

0 no tremor 

1 tremor can be felt, but not observed 

2 slight tremor observable 

4 gross tremor or muscle twitching 

Yawning: Observation during assessment. 

0 no yawning 

1 yawning once or twice during assessment 

2 yawning three or more times during assessment 

4 yawning several times/minute 
 

 

 

 

 

 

Pupil Size: 

0 pupils pinned or normal size for room light 

1 pupils possibly larger than normal for room light 

2 pupils moderately dilated 

5 pupils so dilated that only the rim of the iris is visible 

Bone or Joint Aches: 

TREATMENT OF OPIOID USE DISORDER 15 

If patient was having pain 

previously, only the additional component attributed 

to opiates withdrawal is scored. 

If patient was having pain

previously, only the additional component attributed

to opiates withdrawal is scored. 

0 not present 

1 mild diffuse discomfort 

2 patient reports severe diffuse aching of joints/muscles 

4 patient is rubbing joints or muscles and is unable to sit 

still because of discomfort 

Runny Nose or Tearing: Not accounted for by cold 

symptoms or allergies. 

0 not present 

1 nasal stuffiness or unusually moist eyes 

2 nose running or tearing 

4 nose constantly running or tears streaming down cheeks 

Anxiety or Irritability: 

0 none 

1 patient reports increasing irritability or anxiousness 

2 patient obviously irritable or anxious 

4 patient so irritable or anxious that participation in the 

assessment is difficult 

Gooseflesh Skin: 

0 skin is smooth 

3 piloerrection of skin can be felt or hairs 

standing upon arms 

5 prominent piloerrection 

TOTAL SCORE:

The total score is the sum of all 11 items. 

SCORE: 5-12 = mild; 13-24 = moderate;

25-36 = moderately severe;

more than 36 = severe withdrawal

Initials of person completing assessment:

http://www.drugabuse.gov/sites/default/files/files/ClinicalOpiateWithdrawalScale.pdf 

Source: Wesson, D. R., & Ling, W. (2003). The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs, 35(2), 253–9. 
 

Disclaimer 

Nothing in this document constitutes an indirect or direct endorsement by the Substance 

Abuse and Mental Health Services Administration (SAMHSA) or the U.S. Department of Health 

and Human Services (HHS) of any non-federal entity’s products, services, or policies and any 

reference to a non-federal entity’s products, services, or policies should not be construed as 

such. No official support of or endorsement by SAMHSA or HHS for the opinions, resources, 

and medications described is intended to be or should be inferred. The information presented 

in this document should not be considered medical advice and is not a substitute for individualized 

patient or client care and treatment decisions. 

Electronic Access and Printed Copies 

This publication may be downloaded or ordered at store.samhsa.gov. Or call SAMHSA at

1-877-SAMHSA-7 (1-877-726-4727) (English and Español). 

Information contained in this guide is condensed from the SAMHSA publication Clinical Use 

of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use Disorder: A Brief 

Guide (SMA14-4892R), which is available at http://store.samhsa.gov. 

For more information visit:

http://www.samhsa.gov

SMA16-4892PG