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APRIL 2018 | VOL 17, NO 4

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by an educational grant from Indivior Inc.
Introduction
ACTIVITY CHAIR
Genie L. Bailey, MD
Clinical Associate Professor of Psychiatry
and Human Behavior
Opioid Use Disorder:
Brown University
Providence, RI Challenges and Solutions
Director of Research and Director of
Medications for Addiction Treatment Division
Stanley Street Treatment & Resources, Inc.
to a Rising Epidemic
Fall River, MA
Disclosure: Genie L. Bailey, MD
Consulting Fee: Alkermes, Braeburn It is impossible to escape news reports about the opioid epidemic.
Speakers Bureau: Alkermes, BioDelivery,
Individuals with opioid use disorder (OUD); their friends, families, and
Indivior
Contracted Research (Paid to Institution): communities; and public and private organizations all express concerns
Braeburn, Indivior about the devastating effects of OUD and all commit to reduce them.
Updated reports on the epidemiology of OUD confirm the extent of the
FACULTY epidemic and identify factors that could advance prevention and treat-
Kevin P. Hill, MD, MHS ment. Countless reports of broad-spectrum investigational interven-
Assistant Professor of Psychiatry tions exemplify the challenges faced in this complex disease.
Harvard Medical School Solutions are being developed. Screening tools and clinical practice
Director of Addiction Psychiatry
guidelines are more evidence-based. An increased focus on the disease
Beth Israel Deaconess Medical Center
Boston, MA of addiction, patient characteristics, and patient preferences are expected
Disclosure: No relevant financial relationships
to improve treatment engagement, retention, and effectiveness. New
to disclose. treatment formulations are under development, and approved agents
are being investigated in head-to-head studies and in various settings.
Richard N. Rosenthal, MD
Understanding the epidemic and current state-of-the-art treatment
Professor of Psychiatry
Director of Addiction Psychiatry options is an important obligation for any clinician caring for patients
Stony Brook University Medical Center who have OUD or are at risk of developing OUD. Informing yourself
Department of Psychiatry and Behavioral of the current medical understandings of this disease can lead to more
Science effective and rewarding clinical experiences. It is our hope that diligent
Health Sciences Center attention to critical aspects of caring for these challenging patients can
Stony Brook, NY contribute to reaching a turning point in the OUD epidemic and can
Disclosure: No relevant financial relationships help replace the pervasive disheartening news with welcomed signs
to disclose.
of progress.
REVIEWER:
Ronald A. Codario, MD, EMBA, FACP,
FNLA, RPVI, CHCP
Opioid Use Disorder:
Disclosure: No relevant financial relationships
to disclose.
The Epidemic is Real
MEDICAL WRITER: Kevin P. Hill, MD, MHS
Valerie Zimmerman, PhD
Disclosure: No relevant financial relationships The opioid epidemic, which is particularly prevalent and challenging
to disclose. in the United States, is part of the general increased abuse and diver-
sion of prescription drugs.1 Medical emergencies related to opioid
VINDICO MEDICAL EDUCATION STAFF:
medications increased by 183% between 2004 and 2011. A plateau or
No relevant financial relationships to disclose.
slight decrease in prescription opioid diversion and abuse between
Signed disclosures are on file at Vindico 2011 and 2013 reported in one study is encouraging and might indi-
Medical Education, Office of Medical Affairs cate that some of the interventions that have been implemented are
and Compliance.
CO N T I N U E D O N PA G E S 3
CO N T I N U E D O N PA G E S 2

Supplement to Current Psychiatry | Vol 17, No 4 | April 2018 S1

OPIOID USE DISORDER:
CHALLENGES AND SOLUTIONS TO A RISING EPIDEMIC
C ON TIN U E D FROM PAGE S1
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disorder (OUD).
S2 April 2018 | Vol 17, No 4 | Supplement to Current Psychiatry
OVERVIEW:
Prescription and nonprescription opioid use disorder
(OUD) has reached epidemic proportions in the United
States. Patients with chronic pain are known to have a
higher prevalence of comorbid psychiatric disorders.
Psychiatrists and other health care professionals who
treat patients with mental disorders may lack the skills
necessary to recognize individuals who may have OUD
or be at risk for addiction to opioids. The adoption of
validated tools can help to identify those patients if
used consistently. An insufficient number of physicians
are trained and certified to provide medications for
addiction treatment to patients with OUD. New methods
of delivering this treatment can provide long-acting
therapy and may improve compliance, while reducing
the risk of abuse. Although psychiatrists typically are not
the primary prescribers of opioid medications, they often
treat psychiatric disorders in patients with chronic pain
who take prescription opioids. Therefore, education to
psychiatrists can provide  increased knowledge of risk
assessment strategies for patients receiving opioids.
Learning Objectives: Upon successful completion of this
activity, participants should be better able to:
• Assess the increasing prevalence of opioid use disorder
(OUD) among patients with chronic pain and/or
psychiatric disorders.
• Evaluate current assessment tools that assist in
identifying patients who are dependent on opioids, or
at risk of developing dependence.
• Compare efforts to improve patients’ ability to receive
medication-assisted treatment (MAT) and psychosocial
support.
• Assess the safety and efficacy of current and emerging
therapies for OUD.
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C ON TIN U E D FROM PAGE S1
effective.2 However, the epidemic is real. Between 2002
and 2011, an estimated 25 million people engaged in
nonmedical use (NMU) of pain relievers. Even in the
recent years that showed decreased NMU of prescrip-
tion opioids, the prevalence of prescription opioid use
disorder (OUD), frequency of use, and related mortal-
ity increased.2
OUD often can be characterized by 3 stages, usu-
ally beginning with prescription opioid drugs. Studies
have shown a parallel relationship between prescrip-
tion opioid analgesic availability through legitimate
pharmacy channels and their subsequent diversion,
abuse, and adverse outcomes.1 Stage 2 occurs when
a patient taking prescription opioid drugs transi-
tions to heroin. More recently, many patients reach
stage 3—turning to synthetic opioids such as fentanyl
and carfentanil.
Stage 1: Prescription Opioids
The path to addiction might begin with a patient pro-
curing a prescription refill legitimately or acquiring
the medications through any means when unable to
get prescriptions legitimately. Patients might take
drugs that other family members retained after not
taking the full prescription because people rarely dis-
pose of unused opioid medication. A recent systematic
review of 6 eligible studies reported that 67% to 92%
of patients who were prescribed postoperative opioids
did not use their entire prescription.3 In 2 studies that
examined storage safety, approximately three-fourths
of patients did not store their opioids in locked contain-
ers, and all studies reported low rates of anticipated
or actual disposal, with a maximum 9% of patients in
any study reporting that FDA-recommended disposal
methods were followed.3 Similarly, opioid use and
disposal was surveyed in the parents of 343 pediatric
patients who were prescribed opioid medication at
hospital discharge.4 Fewer than one-half (42%) of the
doses were consumed, and only 4% of families dis-
posed of leftover opioids.
Using US National Survey of Drug Use and Health
(NSDUH) data from 2005 to 2014, a recent study of
women of reproductive age women examined the
NMU of prescription opioids in the previous 30 days
in 8069 pregnant and 146,110 nonpregnant women
and found that 0.8% and 2.3%, respectively, had recent
opioid NMU.5 More of the pregnant women reported
a physician as their source of opioids for NMU com-
pared with nonpregnant women (46.2% vs 37.6%;
P = .004), whereas fewer pregnant women obtained
their NMU opioids from a friend or relative compared
with nonpregnant women (53.9% vs 75.0%; P = .001).
Numerically more pregnant women reported a drug
dealer as their source (14.6% vs 10.6%; P = .44).5
Clinicians can no longer conclude that a drug-naïve
patient receiving his/her first opioid prescription will
Supplement to Current Psychiatry | Vol 17, No 4 | April 2018
be issue-free for a few months, as evidence shows that
the transition to addiction can occur early and rapidly.6
In addition, the treatment window might be open for
only a brief interval. In a recent study of 625 patients
with chronic noncancer pain, having a current opioid
prescription was an independent risk factor for opioid
misuse (odds ratio, 4.06; 95% confidence interval [CI],
1.62-10.18; P = .003).6
Consequences of Opioid Use: Terminology
The important goal of maintaining a favorable balance
between risks and benefits with any medical treatment
is complicated in those with chronic use of opioids for
pain control, where adverse consequences include tol-
erance, physical dependence, addiction, and death.7
Opioids are effective in certain clinical scenarios, but
they are high-risk medications. Tolerance can be defined
as those who have reached an adaptive state that results
in decreased opioid effects.8 Physical dependence is
characterized by the manifestation of a class-specific
withdrawal syndrome that can occur when the opioid is
abruptly stopped, a rapid dose reduction is experienced,
blood levels of the drug are reduced through any cause,
or an antagonist is administered.
Addiction is characterized by impaired control over
drug use, compulsive use, continued use despite harm,
and craving. Historically, several definitions of addic-
tion have been used, which contributed to some of the
inconsistencies in reporting addiction data.9 In 2011,
the American Society of Addiction Medicine devel-
oped a long definition that provides expanded details
about each component of the definition, supplemented
by a summarized short definition (Figure 1, page S4).10
A simpler definition describes addiction as a primary,
chronic, relapsing brain disease characterized by loss
of control over one’s use of a drug; continued use of
the drug despite adverse consequences of use; and an
obsessive desire and/or compulsive seeking of the
drug. The simplest definition of addiction might be
the repeated use of a drug despite harm. Onset of drug
addiction usually occurs in adolescence, and, although
it is treatable and controllable, it usually is not curable.
The adverse consequences of opioid use also include
abuse, misuse, and diversion. Abuse is defined as any
use of an illegal drug or intentional self-administration
of a medication for nonmedical purposes, such as
altering one’s state of consciousness.8 Drug misuse is
defined as use of a medication other than as directed
or as indicated, whether willful or unintentional, and
whether harm results. Opioid misuse has been defined
as either (1) taking an opioid in a manner or dosage
other than prescribed or (2) taking another person’s
opioids, even if the use is for a legitimate medical
issue.6 Diversion is the intentional transfer of a con-
trolled substance from legitimate distribution and dis-
pensing channels.8
S3
OPIOID USE DISORDER:
CHALLENGES AND SOLUTIONS TO A RISING EPIDEMIC

FIGURE 1
Short Definition of Addiction

Addiction is a primary, chronic disease of brain reward, motivation, memory, and related circuitry.
Dysfunction in these circuits leads to characteristic biological, psychological, social, and spiritual
manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by
substance use and other behaviors.

Addiction is characterized by inability to consistently Abstain, impairment in Behavioral control,

Craving, Diminished recognition of significant problems with one’s behaviors and interpersonal
relationships, and a dysfunctional Emotional response. Like other chronic diseases, addiction often
involves cycles of relapse and remission. Without treatment or engagement in recovery activities,
addiction is progressive and can result in disability or premature death.

Source: American Society of Addiction Medicine.10

TABLE 1 DSM-5: Substance Use Disorder
Impaired Control
• Larger amounts or over longer period than intended
• Persistent desire or unsuccessful efforts to cut down
• Much time spent in acquiring, using, or recovering from
effects
• Craving or strong desire to use
Pharmacologic Criteria
• Tolerance
• Withdrawal
Social Impairment
• Failure to fulfill major role obligations
• Continued substance use despite persistent or recurrent
social or interpersonal problems
• Abandonment/reduction of important social, work, or
recreational activities
Risky Use
• Continued use despite knowledge of a substance-induced
physical or mental problem
• Hazardous situations
Source: American Psychiatric Association.13
Consequences of Opioid Use: Common
Adverse Events
Gastrointestinal and central nervous system-related
adverse events (AEs), such as constipation, nausea, and
somnolence/drowsiness, frequently are cited as lead-
ing to opioid therapy discontinuation, with 14% to 20%
mean incidence differences between opioid and placebo
group subjects in more than 30 studies.7 Fatigue, cogni-
tive dysfunction, dry mouth, sweating, and weight gain
also have been reported frequently. Other AEs include
respiratory depression, pruritus/dry skin/itching,
vomiting, delayed gastric emptying, sexual dysfunc-
tion, muscle rigidity and myoclonus, sleep disturbances,
diminished psychomotor performance, hyperalgesia,
dizziness/vertigo, multiple drug interactions, frac-
tures, and endocrinopathy with androgen deficiency.7,11
Prescribing clinicians should be alert for and manage
these common AEs.
DSM-5: Substance Use Disorder
DSM-IV, published in 1994, underwent a full revision to
DSM-5, which was published in 2013.12 In DSM-IV, sub-
stance abuse and substance dependence were separate
disorders that were combined into substance use disor-
der (SUD) in DSM-5, measured on a continuum from
mild to severe. Eleven symptoms are divided among
impaired control, social impairment, pharmacologic
criteria, and risky use (Table 1).13 Having 2 or 3 of these
symptoms in the previous 12 months is consistent with
mild SUD, whereas 4 or 5 is categorized as moderate,
and 6 or more symptoms indicates severe SUD.
Opioid Effectiveness
The effectiveness of short-term opioids for treating acute
and postoperative pain is well established.14 However,
although analgesic and functional improvement have
been reported, nonopioids might be as effective or more
effective.15-18 In addition, the quantity of opioids pre-
scribed often are more than what is needed.19 A system-
atic review and meta-analysis of short-term pain relief
experienced by patients with chronic low back pain con-
cluded that the modest relief obtained was not likely to
be clinically important.20
The efficacy of opioids for long-term treatment of
chronic pain is not well-established and characterized
by weak, insufficient evidence and mixed reports.20-22
An observational study of 333 pain clinic patients tak-
ing either opioid or nonopioid analgesics for at least
3 months reported similar pain intensity and treatment

S4 April 2018 | Vol 17, No 4 | Supplement to Current Psychiatry

FIGURE 2
Opioid and Heroin Overdose Deaths in the United States
30,000
Number of deaths
22,500
15,000
7,500
0
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Source: Rudd RA, et al44; Centers for Disease Control and Prevention.45
satisfaction between groups.23 Patients taking higher
opioid dosages had an increased risk-to-benefit ratio,
which included more psychological impairment with-
out improved pain relief. Although some patients may
benefit from long-term opioid treatment, there are no
criteria to identify these patients,24 and a long-term
study to explore risk factors would be unethical. In fact,
in a review of 34 studies of the long-term effectiveness
and risks of opioid therapy, none of the studies included
follow-up beyond 1 year.11 The 2016 Centers for Disease
Control and Prevention opioid prescription guidelines
for chronic pain emphasize that nonopioid therapy
is preferred.25
Several clinical practice guidelines acknowledge
the risks and limitations of opioid therapy and pro-
vide management recommendations based on cur-
rent evidence. However, several studies have shown
that most clinicians do not follow recommended
practices for prescribing opioids. A recent interven-
tional trial randomized 53 primary care clinicians
and their 985 patients who were receiving long-term
opioid therapy for pain to an intervention designed
to improve guideline adherence and decrease risk
of opioid misuse.26 Despite the possibility that a
Hawthorne effect (ie, subjects changing behavior
because they know they are being observed) might
increase guideline compliance in the control physi-
cians, only 37.8% of patients in that group received
guideline-concordant care compared with 65.9%
of intervention group patients (P < .001), leaving
one-third of the intervention group patients without
guideline-adherent treatment.
Heroin
Prescription opioids
Year
Epidemiology of the Opioid Epidemic
The United States has been particularly affected by
the opioid epidemic. Although it is home to only
5% of the world’s population, 80% of the world’s
opioid medications and 99% of the world’s hydroco-
done are prescribed in the United States.27 Although
one study reported that fewer than 1% of patients
who were prescribed opioids are “doctor shop-
pers,”28 acquiring their opioids from more than 1
prescription source, another study of overdose fatali-
ties reported that 21.4% of patients were associated
with doctor shopping.29 In addition, there is a strong
association between diversion of prescription opi-
oids and deaths due to overdose.29 Possible misuse
has been estimated to occur in approximately 20%
of patients prescribed opioids,30,31 reaching 33% if
opioids were started in patients before the twelfth
grade.32 Data from 472,200 persons aged 18 to 64 who
participated in the NSDUH revealed that the preva-
lence of NMU of prescription opioids decreased
from 5.4% to 4.9% between 2003 and 2013.2 However,
this was accompanied by an increased prevalence
of high-frequency use (≥200 days) and increased
prevalence from 12.7% to 16.9% of OUD among non-
medical users.
Health care costs for opioid misusers are
approximately 9-fold greater than for the general
population.30 Caring for the estimated 2 million indi-
viduals addicted to prescription opioid medications
and the 0.5 million addicted to heroin was estimated at
$25 billion in 2007, and costs to society were esti-
mated at $56 billion.2,33
Supplement to Current Psychiatry | Vol 17, No 4 | April 2018 S5
OPIOID USE DISORDER:
CHALLENGES AND SOLUTIONS TO A RISING EPIDEMIC
TABLE 2 Screening Tools for Opioid Use Disorder
Tool
PRESCREEN
NIDA Drug Use Screening Tool:
Quick Screen
CRAFFT (Part A)
Opioid Risk Tool
Brief Screener for Alcohol, Tobacco,
and other Drugs (BSTAD)
Screening to Brief Intervention
(S2BI)
FULL SCREEN
NIDA Drug Use Screening Tool
CAGE-AID
Drug Abuse Screen Test (DAST-10)
CRAFFT
Abbreviations: APA, American Psychiatric Association; NIDA, National Institute on Drug Abuse; NM, NIDA-modified.
Source: National Institute on Drug Abuse.50
Provider-related Opioid Overdose Risk Factors
Several provider-related factors contribute to opioid
overdoses. Prescribing opioids after a nonfatal overdose
is associated with repeat overdose. In one study of 2848
patients with a nonfatal opioid overdose, 91% were repre-
scribed opioids during a median follow-up of 299 days,
usually by the same clinician.34 The cumulative incidence
of repeat overdose at 2 years was 17%, 15%, and 9% for
patients receiving high, moderate, and low opioid dos-
ages, respectively, after the overdose compared with 8%
for those not receiving opioid prescriptions.
Long-acting opioids have been associated with a
greater risk of overdose and fatality compared with
short-acting formulations.35,36 Co-prescribing respiratory
depressants, particularly benzodiazepines, is a risk fac-
tor for opioid overdose.35-39 The possible association of
failure to perform risk and overdose monitoring has not
yet been studied.
Stage 2: Heroin: An Unintended Consequence
If persons are forced to acquire their drugs illegally, pre-
scription opioids quickly can become cost prohibitive
when the daily intake equates to $80 to $160 (approxi-
mately $1 per milligram). This facilitates a switch to the
considerably less expensive heroin, which usually is
administered via injection shortly after the individual
makes the transition.
A recent examination of NSDUH data from 2002 to
2014 revealed that between those time points, there
was a 4-fold increase in the odds of heroin use emerg-
ing among adults aged 18 to 25 with NMU of prescrip-
tion opioids (NMPO) and a 9-fold increase in the odds
S6 April 2018 | Vol 17, No 4 | Supplement to Current Psychiatry
Patient Age Administered By
Adult Adolescent Self Clinician
X See APA-adapted See APA-adapted X
NM ASSIST tools NM ASSIST tools
X X X
X X
X X X
X X X
X X
X X
X X X
X X X
of heroin use among young adults aged 26 to 34 with
NMPO.40 Similarly, in an older sample of 3396 US veter-
ans, with a mean age of 49.7 years, who were followed
between 2002 and 2012, 77% of the 500 who initiated
heroin use during follow-up reported previous or
current NMPO.41 In multivariate analysis, NMPO
remained independently associated with heroin initia-
tion (adjusted hazard ratio, 5.43; 95% CI, 4.01-7.35).
Nationally, drug overdoses are responsible for more
deaths annually than motor vehicle accidents.42 In 2013,
approximately 44,000 people died from drug overdoses,
including approximately 25,000 from opioid painkill-
ers and heroin; compared with approximately 30,000 in
vehicular crashes.43 The Centers for Disease Control and
Prevention reported 12,989 heroin overdose deaths in
the United States in 2015, representing a 7-fold increase
since 2000 (Figure 2, page S5).44,45 During that interval,
deaths attributed to opioid analgesics increased from
4400 to 25,608.
Stage 3: Fentanyl and Its Analogs:
Unprecedented Devastation
The synthetic opioid fentanyl and its analogs, includ-
ing sufentanil and carfentanil, pose even more danger.
Fentanyl is 50 times more potent than heroin and 100
times more potent than morphine, whereas carfentanil is
10,000 times more potent than morphine.46 The US death
rate from synthetic opioids other than methadone, which
includes drugs such as tramadol and fentanyl, increased
72.2% between 2014 and 2015 across all demograph-
ics and regions; however, the increase was considerably
greater in the Northeast (107.4%), Midwest (95%), and
 Case Presentation: Recognizing Opioid Use Disorder
Genie L. Bailey, MD
A 53-year-old man has a 4-year history of back pain
related to degenerative disc disease. He has been taking
hydrocodone/acetaminophen (7.5 mg/325 mg) 3 times
daily. Recently, because of complaints that the medica-
tion is not as effective as it was initially, he was prescribed
oxycodone/acetaminophen (10 mg/325 mg) every
6 hours. However, that regimen does not control his pain,
so he admits to taking 2 pills at a time for the past few
months. Accordingly, his prescription needs to be refilled
more frequently. He tried to convince his family physician
to prescribe a stronger medication; however, he recently
received a letter of dismissal from the physician because
of his repeated requests for early refills.
The patient is married and owns a construction com-
pany. He smokes 1 pack of cigarettes daily, and he no
longer uses alcohol after being a heavy drinker in his 20s,
with a driving-under-the-influence arrest that resulted
in loss of employment. He denies buying drugs on the
street, crushing or snorting pills, or injecting his opioid
medication. However, a prescription drug monitoring
program search reveals that he has received prescrip-
tions for alprazolam and oxycodone from 2 different pro-
viders in the past 6 months. Drug tests were positive for
opioids and benzodiazepines.
MANAGEMENT APPROACH
The patient’s medication escalation could be due to inad-
equately controlled chronic pain or opioid use disorder
(OUD). As a first step to confirm the accurate diagnosis, a
pain evaluation is indicated. The finding that the patient
is seeing multiple physicians and has added benzodi-
azepine to his opioid use increases his risk for OUD. He
South (55.6%) compared with the West (12.5%).47 The rise
in deaths is driven by increases in fentanyl-involved over-
dose, most likely involving illicitly manufactured fen-
tanyl, which may be mixed with or sold as another drug,
such as heroin.48,49
Screening for Opioid Use Disorder
Identifying persons who have or are at risk for OUD
is an essential first step before a management plan can
be developed. Several reliable and evidence-based tools
are available to screen for OUD and other substance
use disorders through links on the National Institute
on Drug Abuse website (Table 2).50 Clinicians should
review the features and suitability of these screening
tools for their individual practices and select those with
the best fit to adopt as part of standard patient care.
Supplement to Current Psychiatry | Vol 17, No 4 | April 2018
may have added the benzodiazepine because of anxiety
over uncontrolled pain or withdrawal initiated when his
opioid medication is not available. It is clear the patient
has a physiological dependence on opioids; however, the
available information is inadequate to make a diagnosis
of OUD. Physiological dependence does not automati-
cally equal addiction.
Increasing medication on his own is another risk fac-
tor for adverse outcomes; therefore, a discussion with the
patient about how and when he decides to take more
medication is warranted. Because another physician dis-
missed the patient from his clinical practice, establishing
good patient–physician rapport can be a challenge. The
therapeutic alliance could be facilitated by the physician
acknowledging to the patient that he has a chronic pain
issue. If an alliance can be established, he may be more
willing to accept that opioids are not necessarily the best
treatment for chronic pain and accept a prescription for
physical therapy or advice concerning lifestyle changes.
Also, depression should be considered and ruled out.
If the patient is confirmed to have a chronic pain prob-
lem and meets the criteria for OUD, he may be a candi-
date for buprenorphine. Buprenorphine could provide a
steady-state blood level, manage his craving issues, and
potentially treat his pain.
In summary, the patient needs a compassionate
approach, with more investigation of his pain. He is mis-
using opioids and the health care system by seeking mul-
tiple prescribers; thus, he needs a treatment approach
that does not involve only increasing pain medications,
and he should be counseled to give other interventions
a trial.
Summary
The opioid epidemic continues to impact individuals,
the health care system, and society. New policies and
interventions might be starting to have effects, but if
they are not followed, the epidemic will continue and its
adverse consequences will increase. Clinicians should
familiarize themselves with and use the resources avail-
able—from opioid treatment guidelines through screen-
ing tools—that can help identify OUD. In addition,
clinicians should understand the availability, risks, and
benefits of OUD management options.
REFERENCES
1. Dart RC, Surratt HL, Cicero TJ, et al. Trends in opioid analgesic abuse
and mortality in the United States. N Engl J Med. 2015;372(3):241-248.
2. Han B, Compton WM, Jones CM, Cai R. Nonmedical prescription opi-
oid use and use disorders among adults aged 18 through 64 years in
the United States, 2003-2013. JAMA. 2015;314(14):1468-1478.
S7
OPIOID USE DISORDER:
CHALLENGES AND SOLUTIONS TO A RISING EPIDEMIC
3. Bicket MC, Long JJ, Pronovost PJ, Alexander GC, Wu CL. Prescription
opioid analgesics commonly unused after surgery: a systematic review.
JAMA Surg. 2017;152(11):1066-1071.
4. Monitto CL, Hsu A, Gao S, et al. Opioid prescribing for the treat-
ment of acute pain in children on hospital discharge. Anesth Analg.
2017;125(6):2113-2122.
5. Kozhimannil KB, Graves AJ, Jarlenski M, Kennedy-Hendricks A,
Gollust S, Barry CL. Non-medical opioid use and sources of opioids
among pregnant and non-pregnant reproductive-aged women. Drug
Alcohol Depend. 2017;174:201-208.
6. Hah JM, Sturgeon JA, Zocca J, Sharifzadeh Y, Mackey SC. Factors associated
with prescription opioid misuse in a cross-sectional cohort of patients with
chronic non-cancer pain. J Pain Res. 2017;10:979-987.
7. Manchikanti L, Kaye AM, Knezevic NN, et al. Responsible, safe, and
effective prescription of opioids for chronic non-cancer pain: American
Society of Interventional Pain Physicians (ASIPP) Guidelines. Pain
Physician. 2017;20(2 Suppl):S3-S92.
8. Chou R, Fanciullo GJ, Fine PG, et al; American Pain Society-American
Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines
for the use of chronic opioid therapy in chronic noncancer pain. J Pain.
2009;10(2):113-130.
9. Savage SR, Joranson DE, Covington EC, Schnoll SH, Heit HA, Gilson
AM. Definitions related to the medical use of opioids: evolution towards
universal agreement. J Pain Symptom Manage. 2003;26(1):655-667.
10. American Society of Addiction Medicine. Definition of addiction.
https://www.asam.org/for-the-public/definition-of-addiction. Accessed
December 25, 2017.
11. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-
term opioid therapy for chronic pain: a systematic review for a National
Institutes of Health Pathways to Prevention Workshop. Ann Intern Med.
2015;162(4):276-286.
12. American Psychiatric Association. DSM-5 fact sheets. From planning
to publication: developing DSM-5. https://www.psychiatry.org/
psychiatrists/practice/dsm/educational-resources/dsm-5-fact-sheets.
Accessed December 24, 2017.
13. American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association;
2013.
14. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk
DC. Opioids compared to placebo or other treatments for chronic low-back
pain. Cochrane Database Syst Rev. 2013 Aug 27;8:CD004959.
15. American Society of Anesthesiologists. Practice guidelines for acute
pain management in the perioperative setting: an updated report by
the American Society of Anesthesiologists Task Force on Acute Pain
Management. Anesthesiology. 2012;116(2):248-273.
16. Cantrill SV, Brown MD, Carlisle RJ, et al; American College of Emergency
Physicians Opioid Guideline Writing Panel. Clinical policy: critical issues in
the prescribing of opioids for adult patients in the emergency department.
Ann Emerg Med. 2012;60(4):499-525.
17. Moore P, Hersh E. Combining ibuprofen and acetaminophen for acute pain
management after third-molar extractions: translating clinical research to
dental practice. J Am Dent Assoc. 2013;144(8):898-908.
18. Derry S, Derry CJ, Moore RA. Single dose oral ibuprofen plus oxycodone
for acute postoperative pain in adults. Cochrane Database Syst Rev. 2013 Jun
26;6:CD010289.
19. Maughan BC, Hersh EV, Shofer FS, et al. Unused opioid analgesics
and drug disposal following outpatient dental surgery: A randomized
controlled trial. Drug Alcohol Depend. 2016;168:328-334.
20. Abdel Shaheed C, Maher CG, Williams KA, Day R, McLachlan AJ.
Efficacy, tolerability, and dose-dependent effects of opioid analgesics for
low back pain: a systematic review and meta-analysis. JAMA Intern Med.
2016;176:(7)958-968.
21. Chou R, Ballantyne JC, Fanciullo GJ, Fine PG, Miaskowski C. Research
gaps on use of opioids for chronic noncancer pain: findings from a review
of the evidence for an American Pain Society and American Academy of
Pain Medicine clinical practice guideline. J Pain. 2009;10(2):147-159.
22. Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. BMJ.
2015;350:g6380.
23. Elsesser K, Cegla T. Long-term treatment in chronic noncancer pain: results
of an observational study comparing opioid and nonopioid therapy. Scand
J Pain. 2017;17:87-98.
24. Hamunen K. Opioids in chronic pain — Primum non nocere. Scand J Pain.
2017;17:152-153.
25. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids
for chronic pain—United States 2016. JAMA. 2016;315(15):1624-1645.
26. Liebschutz JM, Xuan Z, Shanahan CW, et al. Improving adherence to long-
term opioid therapy guidelines to reduce opioid misuse in primary care: a
cluster-randomized clinical trial. JAMA Intern Med. 2017;177(9):1265-1272.
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27. Manchikanti L, Fellows B, Ailinani H, Pampati V. Therapeutic use, abuse,
and nonmedical use of opioids: a ten-year perspective. Pain Physician.
2010;13(5):401-435.
28. McDonald DC, Carlson KE. Estimating the prevalence of opioid
diversion by “doctor shoppers” in the United States. PLoS One. 2013;8(7):
e69241.
29. Hall AJ, Logan JE, Toblin RL, et al. Patterns of abuse among unintentional
pharmaceutical overdose fatalities. JAMA. 2008;300(22):2613-2620.
30. Ruetsch C. Empirical view of opioid dependence. J Manag Care Pharm.
2010;16(1 Suppl B):S9-S13.
31. Sullivan MD, Edlund MJ, Fan MY, Devries A, Brennan Braden J, Martin
BC. Risks for possible and probable opioid misuse among recipients of
chronic opioid therapy in commercial and Medicaid insurance plans: The
TROUP Study. Pain. 2010;150(2):332-339.
32. Miech R, Johnston L, O’Malley PM, Keyes KM, Heard K. Prescription
opioids in adolescence and future opioid misuse. Pediatrics. 2015;136(5):
e1169-1177.
33. Birnbaum HG, White AG, Schiller M, Waldman T, Cleveland JM, Roland
CL. Societal costs of prescription opioid abuse, dependence, and misuse in
the United States. Pain Med. 2011;12(4):657-667.
34. Larochelle MR, Liebschutz JM, Zhang F, Ross-Degnan D, Wharam JF.
Opioid prescribing after nonfatal overdose and association with repeated
overdose: a cohort study. Ann Intern Med. 2016;164(1):1-9.
35. Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional
Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in
chronic non-cancer pain: part I - evidence assessment. Pain Physician.
2012;15(3 Suppl):S1-S66.
36. Zedler B, Xie L, Wang L, et al. Risk factors for serious prescription opioid-
related toxicity or overdose among Veterans Health Administration
patients. Pain Medicine. 2014;15(11):1911-1929.
37. Jann M, Kennedy WK, Lopez G. Benzodiazepines: a major component in
unintentional prescription drug overdoses with opioid analgesics. J Pharm
Pract. 2014;27(1):5-16.
38. Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert AS. Benzodiazepine
prescribing patterns and deaths from drug overdose among US
veterans receiving opioid analgesics: case-cohort study. BMJ. 2015;
350:h2698.
39. Shah NA, Abate MA, Smith MJ, Kaplan JA, Kraner JC, Clay DJ.
Characteristics of alprazolam-related deaths compiled by a centralized
state medical examiner. Am J Addict. 2012;21(suppl 1):S27-S34.
40. Martins SS, Segura LE, Santaella-Tenorio J, et al. Prescription opioid use
disorder and heroin use among 12-34 year-olds in the United States from
2002 to 2014. Addict Behav. 2017;65:236-241.
41. Banerjee G, Edelman EJ, Barry DT, et al. Non-medical use
of prescription opioids is associated with heroin initiation among
US veterans: a prospective cohort study. Addiction. 2016;111(11):
2021-2031.
42. Hedegaard H, Chen L-H, Warner M. Drug-poisoning deaths involving
heroin: United States, 2000-2013. NCHS data brief, no 190. Hyattsville, MD:
National Center for Health Statistics; 2015.
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https://www-fars.nhtsa.dot.gov/Main/index.aspx. Accessed December
24, 2017.
44. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in drug and
opioid overdose deaths—United States, 2000-2014. MMWR Morb Mortal
Wkly Rep. 2016;64(50-51):1378-1382.
45. Centers for Disease Control and Prevention. Opioid data analysis.
https://www.cdc.gov/drugoverdose/data/analysis.html. Accessed
January 9, 2018.
46. O’Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden
RM. Deaths involving fentanyl, fentanyl analogs, and U-47700 - 10
states, July-December 2016. MMWR Morb Mortal Wkly Rep. 2017;
66(43):1197-1202.
47. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved
overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep.
2016;65(5051):1445-1452.
48. Gladden RM, Martinez P, Seth P. Fentanyl law enforcement submissions
and increases in synthetic opioid-involved overdose deaths - 27 states, 2013-
2014. MMWR Morb Mortal Wkly Rep. 2016;65(33):837-843.
49. Peterson AB, Gladden RM, Delcher C, et al. Increases in fentanyl-related
overdose deaths - Florida and Ohio, 2013-2015. MMWR Morb Mortal Wkly
Rep. 2016;65(33):844-849.
50. National Institute on Drug Abuse. Chart of evidence-based screening tools for
adults and adolescents. https://www.drugabuse.gov/nidamed-medical-
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drug-testing-resources/chart-evidence-based-screening-tools-adults.
Revised September 2017. Accessed December 25, 2017.
 Managing the Opioid Use Disorder Crisis
Richard N. Rosenthal, MD
T
he critical need to find solutions for the opioid
use disorder (OUD) crisis is universally acknowl-
edged. However, several barriers challenge the
efforts to control opioid misuse and reduce its harmful
impact on individuals, the health care system, and soci-
ety (Figure, page S10). These treatment provision barri-
ers are active in 3 domains: the treatment system, the
medical providers, and the patients themselves.
Treatment System
Access to the treatment system is limited by a defi-
ciency in evidence-based systematic screening. The
improved focus on value-based care has allowed for
increased identification and treatment of substance
use disorders (SUDs), and the availability of several
validated screening tools should contribute to reduc-
ing this barrier.1,2 Other obstacles include a lack of par-
ity in identification and management of OUD, failure
to provide service continuum for addiction treatment,
and inadequately trained staff.1,2 Cost and insurance
coverage, as well as legal and regulatory issues, can
limit access to treatment. The health care system also
is affected by traditional stigma and biases that could
lead to stereotypic thinking, limiting adequate patient
assessment.
Medical Providers
The prescriber role is unique and critical in managing
OUD. However, clinician training for SUD is not always
adequate, and many physicians continue to have a poor
understanding of the medications and guidelines for
addiction treatment.
A single physician should not be the sole authority;
addiction should be treated following a collaborative
care model similar to other chronic diseases, such as
diabetes.3 A multimodal, multidisciplinary team must
provide coordinated care with adequate communica-
tion among team members. The team could be inde-
pendent of or part of a coordinated network, preferably
integrated with behavioral health.
Treatment should be person centered and recov-
ery oriented, with a focus on safety and quality of life.
Cultural- and trauma-informed principles should be
followed. Success requires the active involvement of
patients, focusing on participation and empowerment,
not compliance. Management decisions should be
based on the patient’s informed choice.
Patients
Intrinsic factors, including denial and shame, keep
patients from pursuing treatment. Stigma and bias
Supplement to Current Psychiatry | Vol 17, No 4 | April 2018
might prevent persons with OUD from telling others
about their disorder. Persons with OUD fear losing their
employment and fear the impact that their OUD could
have on personal relationships if their disorder is dis-
covered. Patients themselves usually do not understand
that addiction is a chronic disease for which they should
adopt a recovery orientation; that is, they will never be
cured and must learn how to rehabilitate themselves as
part of their recovery.
The United States promulgated addiction privacy
regulations (42 CFR Part 2) in 1975, which, although
initially protecting patients from undue exposure
and discrimination, ultimately restricted patients
with addiction from taking advantage of health care
modernization.4 Compared with others without SUD,
patients with OUD do not benefit from integrated
systems and electronic medical records or the essen-
tial knowledge acquired over the past 40 years that
addiction cannot be treated effectively in isolation.
Accordingly, the Overdose Prevention and Patient
Safety (OPPS) Act is being considered, which will
amend the federal statute and align 42 CRF Part 2 with
the Health Insurance Portability and Accountability
Act (HIPAA) for purposes of treatment, payment, and
operations. It will allow for sharing addiction treat-
ment records within the health care system, following
HIPAA’s established privacy and security protections.
Prohibiting disclosure outside the health care sys-
tem would be retained, and provisions against using
addiction treatment records in criminal proceedings
would be strengthened. Although, there is opposition
from grassroots recovery organizations,5 professional
medical organizations such as the American Society
of Addiction Medicine support the OPPS as reflect-
ing efforts to improve patient access while protecting
against stigmatization.6
Psychosocial Factors in Recovery from
Substance Use Disorders
Medication is important, but it is not a substitute for
the work of recovery. A medication is intended to nor-
malize psychological and biophysical brain function,
allowing patients to normalize their learning and adap-
tation in the real world. Psychosocial treatment can be
an important part of the management plan for patients
with OUD or other SUDs.
Psychosocial treatment typically focuses on reduc-
ing stress and exposure to the conditioned cues associ-
ated with substance use. Stress could be reduced by
decreasing negative emotional states; increasing resil-
ience to stressors through support, remoralization,
S9
OPIOID USE DISORDER:
CHALLENGES AND SOLUTIONS TO A RISING EPIDEMIC
FIGURE
Barriers to Opioid Use Disorder Treatment
Limited access
• Lack of systematic screening
• Available service array
• Lack of parity
• Cost/coverage
• Inadequate
workforce
Treatment
system
Legal/regulatory
Stigma/bias
Treatment
provision
Denial/shame Limited access
Stigma/bias • Availability
Fear of: • Cost/coverage
• Being stigmatized
Patients
• Job, relationship losses
• Discrimination
MAT denotes medication for addiction treatment.
Source: Richard N. Rosenthal, MD.
and self-efficacy; and addressing psychiatric comorbid-
ity that increases relapse vulnerability.7,8
Cognitive-behavioral approaches could be par-
ticularly useful in reducing exposure to conditioned
cues for substance use.8 Rewards can be changed
by introducing “healthy pleasures”; that is, help-
ing patients normalize what they do to feel good
instead of turning to drugs. Often, patients are in a
negative emotional state and simply want to feel nor-
mal. The drug-use cycle could be broken if healthy
pleasures are adopted. Patients also should learn to
adopt refusal skills.8 They must learn how to say “no”
effectively to make this strategy protective. Avoiding
people, places, and things that are associated with
substance use also is important to reduce the risk
of relapse.
Several resources are available that provide access
to and review of several evidence-based psychosocial
interventions for SUDs. The US Substance Abuse and
Mental Health Services Administration (SAMHSA)
provides links to individual interventions through
its National Registry of Evidence-Based Programs
and Practices.9 In addition, the National Institute on
Drug Abuse lists evidence-based approaches to
behavioral as well as pharmacological therapies.10
Interventions are related to general and specific
patient groups and employ several strategies. Some
S10 April 2018 | Vol 17, No 4 | Supplement to Current Psychiatry
Limited evidence-based
knowledge and its application
reflecting a model of chronic
disease, outcomes,
collaboration, and
integration, with
Medical person-centered,
providers recovery-oriented, safety-focused,
cultural- and trauma-informed
principles, addressing disparities.
Poor understanding of medicines
for addiction treatment.
Limited understanding:
• Chronic disease model
• Recovery-orientation
• Multimodal approach
• Role of MAT
intervention examples include motivational enhance-
ment therapy, cognitive-behavioral therapy, con-
tingency management, community reinforcement,
supportive–expressive psychotherapy, and behav-
ioral couples therapy for alcoholism and drug abuse.
Limitations of Psychosocial Treatment
of Substance Use Disorder
Although individual and group counseling is part of
standard treatment, most persons with OUD relapse.11-13
Several limitations are associated with the psychoso-
cial treatment of SUD, including low adherence and
unknown optimum duration of treatment.14,15 In addi-
tion, psychosocial treatments can be stigmatizing.16
Barriers to performing effective trials of psychosocial
interventions include supervised provision of treat-
ment by expert therapists, which is not typical of the
real world.
Meta-analyses investigated adding psychosocial
interventions to OUD treatment during detoxification
and maintenance treatment. The first meta-analysis
included 11 trials of opioid detoxification that compared
any psychosocial intervention plus any pharmacologic
intervention with medication alone.17 Significantly
reduced dropouts, clinic absences during treatment,
and opioid use during treatment and at follow-up
were reported for psychosocial interventions. Available
evidence was inadequate to support a single psychoso-
cial approach. The authors concluded that developing
adjunct psychosocial approaches could increase detoxi-
fication effectiveness.
However, there is little support for special psycho-
social treatment as an adjunct during maintenance
therapy. The second meta-analysis included up to 35
eligible studies that compared any psychosocial inter­
vention plus any agonist with agonist alone for opioid
dependence.14 The outcomes assessed included reten-
tion in treatment (27 studies), abstinence during treat-
ment (8 studies), compliance (3 studies), psychiatric
symptoms (3 studies), depression (3 studies), number
of patients still in treatment at the end of follow-up
(3 studies), and abstinence at the end of follow-up (3
studies). Because all control interventions included
routinely offered counseling sessions, the authors
concluded that their study pursued the question of
whether more structured interventions provided any
additional benefit compared with standard psychoso-
cial support. For these outcomes, adding any psycho-
social support to standard maintenance treatment did
not provide significant additional benefit.
Medical Treatment is Necessary for Opioid
Use Disorder
Opioid detoxification alone generally is inadequate,
and detoxification followed by psychosocial treatment
is an insufficient clinical strategy. High relapse rates
typically occur after standard detoxification,11,13,18 which
are reported to reach ≥50% 1 to 2 months after discon-
tinuation of buprenorphine maintenance.11 A survey of
164 patients receiving inpatient opioid detoxification,
80% of whom had prior detoxifications, assessed their
desire for pharmacotherapy after discharge.18 The high
prevalence of prior detoxifications supports that detoxi-
fication alone does not protect from relapse to opioid
use. The most recent relapses occurred on the day of dis-
charge, within 1 month, or within 1 year for 27%, 65%,
and 90%, respectively, of survey participants. Almost
two-thirds (63%) of participants stated that they wanted
medication-assisted treatment (MAT) after discharge
from their current detoxification. A higher perceived
risk of relapse was associated with greater willingness
to receive aftercare medication. The authors concluded
that discussions regarding patient preference, including
relapse risk, might be beneficial for post-detoxification
abstinence.
The studies mentioned, as well as other studies,
support that detoxification is medical stabilization
not addiction treatment. Accordingly, “MAT” would
more appropriately be an acronym for Medication for
Addiction Treatment, as medication is the primary ther-
apy for OUD.19 This is supported in the 2016 Centers
for Disease Control and Prevention opioid prescribing
guidelines, which recommend that patients with OUD
Supplement to Current Psychiatry | Vol 17, No 4 | April 2018
be offered evidence-based treatment, such as MAT with
buprenorphine or methadone.20
General Principles for Providing Treatment for
Opioid Use Disorder
Patient characteristics before treatment have an impact
on management and outcomes. In a flexible-dosing
treatment trial, patient baseline characteristics were
associated with the buprenorphine dose employed.21
The multicenter study enrolled 748 patients seeking
treatment for opioid dependence, who were started
on buprenorphine, of whom 516 (69%) completed the
4-week stabilization/maintenance phase. A standard
3-day induction typically started with buprenorphine,
2 to 4 mg on day 1, 12 mg on day 2, and 16 mg on day 3.
Dosages could be adjusted at the weekly clinic visits
in 4-mg increments, ranging between 8 mg and 24 mg,
at the study physician’s discretion. No specific dosing
instructions were provided; physicians could consider
urine test results, participants’ self-reported opioid use,
as well as withdrawal, craving, and adverse events. By
week 4, all participants were on daily dosages of 8 mg
(9.3%), 16 mg (27.3%), or 24 mg (63.4%). Sites followed
their standard behavioral treatment procedures, with no
efforts to modify or standardize site-specific practices.
Final buprenorphine dosage was significantly
associated with days of heroin use in the 30-day pre-
induction period, averaging 17.2, 21.8, and 24.2 days
for participants, with final daily dosages of 8, 16, and
24 mg, respectively, of buprenorphine.21 Similarly, pro-
portions of participants with preinduction injection
drug use increased significantly with increasing final
buprenorphine dosages. In addition, baseline with-
drawal and craving scores were significantly lower
in the 8-mg group compared with both the 16- and
24-mg groups.
Buprenorphine maintenance dosages have been
noted to be significantly associated with abstinence
after buprenorphine maintenance therapy cessation. In
collapsed data from 5 studies that reported 10% to 50%
abstinence 1 month or more after buprenorphine main-
tenance therapy cessation, prior heroin use and taper
duration were not significantly associated with absti-
nence.11 However, lower mean maintenance dosages
were significantly related to higher abstinence rates at
follow-up.
Approved Medications for the Treatment
of Opioid Use Disorder
Several FDA-approved medication options are now
available for treating patients who have OUD, with
one approval in November 2017 and another pending
expected approval in 2018. The drugs are mu-opioid
receptor agonists and antagonists and are available in
formulations for daily use and extended-release dosage
formulations, lasting up to 6 months (Table, page S12).22-30
S11
OPIOID USE DISORDER:
CHALLENGES AND SOLUTIONS TO A RISING EPIDEMIC
TABLE Medications for Treating Opioid Use Disorder
Drug Dosage Formulation
MU-OPIOID RECEPTOR AGONISTS
Methadone Tablet/oral solution
Tablet
Buprenorphine
Implant
Buprenorphine extended release Injection
CAM2038, long-acting buprenorphine Injectiona
Film
Buprenorphine/naloxone
Tablet
MU-OPIOID RECEPTOR ANTAGONISTS
Tablet
Naltrexone
Injection
aPending FDA approval.
Source: Methadone hydrochloride22; buprenorphine extended‐release23; buprenorphine and naloxone24; buprenorphine25; buprenorphine hydrochloride26;
naltrexone hydrochloride27; buprenorphine and naloxone28; naltrexone extended-release29; US Food and Drug Administration.30
Benefits of Extended-Release Formulations
Issues associated with daily oral dosing, including
adherence and diversion, supported the rationale for
developing long-acting formulations.31 Extended-
release formulations can provide a longer duration of
mu-opioid receptor occupancy, reducing burden on
patients to adhere to a daily-dosing schedule. Patients
are unable to defeat the opioid blocking effects by
skipping doses. When administered in a health care
setting and distributed through a restricted distribu-
tion system, extended-release formulations can be
expected to reduce diversion, nonmedical use (NMU),
and accidental pediatric exposure associated with self-
administered products. Available extended-release
products use a systems approach; that is, they use
delivery systems such as depot injections and sub-
dermal implants to deliver the primary drug rather
than rely on modifications of the medication itself to
produce a compound with intrinsic extended-delivery
characteristics.
Methadone
Methadone is a schedule II, full mu-opioid agonist
that has been available since the 1960s. Studies report
a widely variable terminal half-life, ranging from 8 to
59 hours.22 Methadone is lipophilic; therefore, it can per-
sist in the liver and other tissues, prolonging treatment
effects despite low plasma drug concentrations.
Methadone is approved for treating opioid addiction,
with pill, liquid, and wafer formulations available for
oral daily dosing.32 Methadone can be dispensed only
through an opioid treatment program that is certified
by SAMHSA, which maintains an opioid treatment
program directory on its website.33
S12 April 2018 | Vol 17, No 4 | Supplement to Current Psychiatry
Administration Frequency
Oral Daily
Sublingual Daily
Subdermal 6 months
Subcutaneous Monthly
Subcutaneousa Weeklya/monthlya
Sublingual/buccal Daily
Sublingual Daily
Oral Daily
Intramuscular Monthly
Treatment is initiated at a low dosage that usually
should not exceed 40 mg.22 The dosage is adjusted dur-
ing the first week for optimal symptom control at the
time of expected peak activity, which occurs 2 to 4 hours
after dosing. Although accumulating tissue stores allow
the dose to be effective for a longer period, this also
presents a risk because of the cumulative effects dur-
ing early treatment. Therefore, caution and adequate
monitoring is essential. Maintenance dosages of 80 to
120 mg/d usually provide clinical stability. Methadone
should be provided for a minimum of 12 months; how-
ever, years of treatment might be required.32 To pre-
vent withdrawal syndrome, discontinuation must be
done gradually under a clinician’s supervision. Dosage
reductions usually should be <10% of the maintenance
dosage, with a 10- to 14-day interval between each dos-
age reduction.22
Safety
Methadone is safe and effective when taken as pre-
scribed.32 The most frequently observed adverse events
(AEs) include lightheadedness, dizziness, sedation,
nausea, vomiting, and sweating.32 Lower dosages may
be warranted to resolve these symptoms.
Major hazards of methadone therapy are respiratory
depression, with systemic hypotension occurring to a
lesser degree.22 An opioid antagonist, such as naloxone
or nalmefene, should be administered for clinically
significant respiratory or circulatory depression. Life-
threatening QT prolongation and serious arrhythmias
have been observed in patients taking methadone and
are more common among patients taking >200 mg/d.
When reported in patients on lower dosages, con-
comitant medications and/or clinical conditions such
as hypokalemia were contributing factors. However,
because of the strong evidence suggesting that metha-
done has the potential to elicit adverse cardiac conduc-
tion effects, close monitoring is necessary for patients
with risk factors for developing prolonged QT interval
and for those receiving high doses.
Acute methadone overdose can manifest as respira-
tory depression, somnolence progressing to stupor or
coma, skeletal–muscle flaccidity, cold and clammy skin,
and constricted pupils.22 Severe overdose could result
in apnea, circulatory collapse, cardiac arrest, and death.
Clinicians must be familiar with methadone drug
interactions, particularly the increased methadone
plasma concentrations and associated risk of fatal over-
dose that can result with concomitant treatment with
some cytochrome P450 (CYP) inhibitors.22 Similarly,
some CYP inducers effectively can decrease plasma
methadone concentrations, resulting in decreased
effectiveness.
Buprenorphine
Buprenorphine is a schedule III narcotic, which has
been available since 2002 as a sublingual tablet for treat-
ing opioid use disorder with a single daily dose.25 It
subsequently has been approved in additional dosage
formulations and combinations, with the most recent
FDA approval received in November 2017 for subcuta-
neous injection.
Buprenorphine is a partial agonist at the mu-opioid
receptor, with a mean elimination half-life of 31 to
35 hours.22 It has a high affinity for the mu-receptor,
which allows it to block the effects of exogenous opi-
oids.34 If buprenorphine is administered before the
agonist effects of other opioids have subsided, with-
drawal signs and symptoms may be precipitated.25
Although its opioid effects rise with initial dosage
increases, a ceiling is reached at which the effects, such
as respiratory depression, level off and do not increase
with increased dosages. This reduces its potential for
overdose and contributes to its low toxicity compared
with full mu-receptor agonists.34 Treatment should be
started at least 12 hours after taking short-acting opi-
oids and after mild-to-moderate withdrawal symp-
toms have emerged, equivalent to a Clinical Opiate
Withdrawal Scale score of at least 9. Induction typically
is completed in 3 to 4 days; in some studies, extend-
ing induction over several days was associated with a
higher patient dropout rate during induction.25 During
maintenance, the dosage of sublingual buprenorphine
should be adjusted by 2- to 4-mg increments or dec-
rements to achieve a level that retains the patient in
treatment and suppresses opioid withdrawal signs
and symptoms. Depending on the individual patient,
maintenance dosages typically range between 4 and
24 mg/d; higher dosages have not been shown to pro-
vide additional benefit.
Supplement to Current Psychiatry | Vol 17, No 4 | April 2018
Buprenorphine produces opioid-type physical
dependence with chronic use, and abrupt discontinua-
tion will produce signs and symptoms of withdrawal.25
This withdrawal syndrome usually is milder than
that observed with full agonists and might be delayed
in onset.
Safety
Buprenorphine is safe and effective when taken as
directed. Patients taking concomitant CYP inhibitors
or inducers should be monitored for a potential need
for dosage adjustments. Common gastrointestinal AEs
include constipation, nausea, and vomiting.25 Headache,
pain, and insomnia were reported in approximately
20% to 30% of patients taking buprenorphine.
Although buprenorphine has been reported to
increase the QT interval, its effect is not clinically sig-
nificant.34 Deaths involving the drug are fewer than
deaths involving methadone and other prescription
full mu-opioid agonists.35 However, buprenorphine has
been associated with significant respiratory depression
and deaths and should be used with caution in patients
who have compromised respiratory function.25 Notably,
this risk is elevated when buprenorphine is taken intra-
venously or in combination with benzodiazepines or
other central nervous system depressants, including
alcohol. Patients should be warned of the potential dan-
ger associated with misuse of buprenorphine and self-
administration of concomitant depressants. Naloxone
treatment and reestablishment of adequate ventilation
might be part of respiratory depression management.
More detailed information is needed to help under-
stand the fatalities occurring with all partial or full mu-
agonist treatments for OUD.35 Improving fatal substance
overdose collection systems is warranted to allow for
comprehensive assessment of all potential contributors
to fatal outcomes, determination of whether drugs were
prescribed to the decedents, and establishment of the
substance use as being new or chronic.
Prescribing Buprenorphine: Requirements
for a Buprenorphine Waiver
Buprenorphine is the first medication to treat opioid
dependency that can be dispensed in physician offices,
community hospitals, health departments, and correc-
tional facilities by qualified US physicians.36 However,
clinicians who wish to prescribe buprenorphine for
treatment of OUD must first obtain a waiver from the
Drug Enforcement Administration (DEA).36 It is illegal
for narcotics, including other forms of buprenorphine
indicated for treating pain, to be used off-label to treat
opioid addiction.
Under federal law, prescribing and dispensing
buprenorphine products that are specifically indicated
for opioid addiction requires a waiver from obtaining
a separate DEA registration as a Narcotic Treatment
S13
OPIOID USE DISORDER:
CHALLENGES AND SOLUTIONS TO A RISING EPIDEMIC
Program.37-41 Initially, waivers were available only for
physicians who meet specific requirements; however,
in 2016 it became possible for qualifying nurse practi-
tioners and physician assistants to acquire a waiver. A
physician must receive 8 hours of approved training
or have specific board certification, whereas all nurse
practitioners and physician assistants must complete
24 hours of approved training. Individual physicians
can have no more than 30 patients in opioid depen-
dence treatment at any time during the first year. If
applicable, the physician could submit a second notifi-
cation of the need and intent to treat up to 100 patients
1 year after the initial notification is submitted. As part
of recent regulation changes, if buprenorphine treat-
ment has been provided to 100 patients for at least
1 year, physicians can apply to increase their limit to
275 patients. The SAMSHA website hosts a buprenor-
phine treatment practitioner locator, with search capa-
bility by city, state, and zip code.42
Buprenorphine: 6-month Subdermal Implant
A subdermal buprenorphine implant received FDA
approval in 2016 to treat opioid dependence in
patients who have achieved sustained clinical stabil-
ity on low-to-moderate transmucosal buprenorphine.26
Each treatment consists of 4 implants, each containing
buprenorphine 80 mg, which are inserted on the inner
side of the upper arm. The implants are removed after
6 months, and implants should be inserted only 1 time
in each upper arm, for a maximum of 2 treatments.
Implants must be removed by a health care provider
who is certified to perform the insertions. The implant is
not indicated for patients starting treatment or who have
not reached prolonged clinical stability. Prescribers must
have a buprenorphine waiver, and the implants are
available only through a restricted Risk Evaluation and
Mitigation Strategy (REMS) program because of FDA
concerns about the risk of implant complications, such
as migration, protrusion, expulsion, and nerve dam-
age.26 Health care providers must undergo live training
to be certified in implant insertion and removal.43
PRO-814: Buprenorphine Implant Versus
Sublingual Buprenorphine
The PRO-814 trial was a noninferiority study that
compared the 6-month implant with daily sublin-
gual buprenorphine as maintenance treatment for
opioid-dependent patients with stable abstinence.44 The
multicenter study enrolled 177 outpatients who had
been prescribed daily sublingual buprenorphine for
≥6 months, were abstinent while taking ≤8 mg/d for
≥90 days, and were determined to be clinically stable
by their physicians. Participants were randomized to
receive 4 placebo implants plus sublingual buprenor-
phine or sublingual placebo plus 4 buprenorphine
80-mg implants. The primary endpoint was difference
S14 April 2018 | Vol 17, No 4 | Supplement to Current Psychiatry
in proportion of responders, defined as ≥4 of 6 months
without an opioid-positive urine test based on self-
report and monthly plus 4 random tests. The absolute
8.8% difference in responders between implant (96.4%)
and sublingual (87.6%) buprenorphine groups sup-
ported noninferiority (P <. 001; P = .03 for superiority).
Cumulative opioid abstinence was maintained by 85.7%
and 71.9% of implant and sublingual group patients,
respectively, over the 6-month study interval (P = .03).
The significant difference emerged after 3 months and
was sustained through 6 months. Changes in measures
of craving and withdrawal were not significantly dif-
ferent between groups from baseline to the end of treat-
ment (P ≥ .43). Medication- and implant-related AEs
were consistent with the safety profile of buprenor-
phine and the implantation procedure. The study was
not powered to detect AE differences between groups.
The PRO-814 study supported efficacy of the implants
for abstinence maintenance in opioid-dependent
adults who are clinically stable on sublingual
buprenorphine ≤8 mg/d.44 Transitioning from the sub-
lingual formulation to the implant was not clinically
destabilizing. However, generalizability might be lim-
ited because of study participants who were primar-
ily white (94.9%), and most were employed, with at
least a high school education, and were dependent on
prescription opioids. Studies in new targets, including
criminal justice and other hard-to-reach populations,
are warranted.45
Buprenorphine + Naloxone
A combination formulation of buprenorphine and the
mu-opioid receptor antagonist naloxone is available
as a single daily-dose sublingual film and tablet.24,28
The FDA approved the film in 2002 and the tablet in
2013.46 Naloxone has no clinically significant effects
when administered sublingually and does not inter-
fere with the effects of buprenorphine.24,28 Physiological
and subjective effects of buprenorphine and buprenor-
phine/naloxone (BPN/NX) were similar at equivalent
buprenorphine doses. Including naloxone in the for-
mulation was thought to be a deterrent to its misuse
as an injection. Among opioid substitution therapy
clients interviewed in Australia, fewer reported inject-
ing BPN/NX film (3%) and tablets (2%) compared with
those claiming to regularly inject their buprenorphine-
only medication (25%).47
The film is available in 4 dose strengths, ranging from
2 to 12 mg buprenorphine, with a 4:1 ratio between
buprenorphine and naloxone.24 The 6 dose formula-
tions of the tablet have a similar ratio, with buprenor-
phine doses ranging from 0.7 to 11.4 mg.28 However, the
bioavailability is different between the 2 products; for
example, the 5.7-mg/1.4-mg sublingual tablet provides
the equivalent buprenorphine exposure as one 8-mg/
2-mg film dose and 12% lower naloxone exposure.28
Both are suitable for induction and maintenance treat-
ment.24,28 Treatment also requires filing a Waiver
Notification Form and acquiring certified training.28
Recent FDA Actions: Extended-Release
Injectable Buprenorphine
Two liquid depot formulations that transform into
a solid (RBP-6000) or viscous liquid-crystal gel
(CAM2038) on contact with bodily fluids following
subcutaneous injection were recently reviewed by the
FDA.30,31,48,49 The interface between the solid or gel and
bodily fluids provides the rate-limiting step in the dif-
fusion of buprenorphine into the bloodstream. Both
formulations rely on biodegradation for predictable
release rates of incipient buprenorphine. Subcutaneous
formulations have the advantages of rapid establish-
ment of effective plasma drug levels and potential flex-
ibility in dosing that is in-between the daily sublingual
formulations and the 6-month implant. There also is
added flexibility in dosing intervals.
RBP-6000: FDA-Approved Monthly Injection
In November 2017, RBP-6000 (buprenorphine extended
release) received FDA approval for monthly subcutane-
ous injection in the abdomen for treating moderate-to-
severe OUD in patients who initiated treatment with
a transmucosal buprenorphine product, with a mini-
mum 7-day dosage adjustment period.23,50 After 2 ini-
tial monthly dosages of 300 mg, the dosage should be
reduced to 100 mg monthly as a maintenance dosage.
The dosage may be increased to 300 mg for patients,
with the potential benefits outweighing the risks. It also
is available only on a REMS program, and health care
settings and pharmacies that order and dispense the
injection must be REMS-certified and compliant.
The injection has a terminal half-life of 43 to
60 days because of slow release of buprenorphine from
the injection site.23 Therefore, it is not surprising that
withdrawal syndrome was not observed in the month
after injection discontinuation. Simulation models sug-
gest that therapeutic levels of buprenorphine remain
in the plasma for 2 to 5 months after injecting 100 or
300 mg. Therefore, patients who discontinue the injec-
tions should be monitored for withdrawal signs and
symptoms, and treatment with transmucosal buprenor-
phine should be considered if warranted.
During clinical development of RBP-6000, favorable
results were obtained from phase 1 and 2 safety, dose-
ranging, and repeat-dosing studies. Monthly 300-mg
subcutaneous injections rapidly achieved effective
buprenorphine exposure after the initial injection and
maintained effective levels in chronic treatment.49 In
subjects with OUD, RBP-6000 blocked the effects of
hydromorphone opioid challenge.
A 24-week, double-blind, randomized, multicenter
phase 3 trial assessed the efficacy, safety, and tolerabil-
Supplement to Current Psychiatry | Vol 17, No 4 | April 2018
ity of multiple subcutaneous injections of RBP-6000.50
The trial enrolled 504 subjects with moderate-to-severe
OUD (≥4 symptoms) who were seeking medication
treatment. Before starting treatment, subjects were
inducted and dose adjusted to 8 to 24 mg sublingual
buprenorphine film for 1 to 2 weeks. Three treatment
groups included 6 RBP-6000 300-mg injections at 28-day
intervals, 2 RBP-6000 300-mg injections followed by 4
100-mg injections, or placebo. Both dosage regimens
had significantly greater cumulative distribution func-
tion percentages of opioid-negative urines with no self-
reported opioid use during study months 2 through 6
(P < . 0001). RBP-6000 was well-tolerated, with no new
or unexpected safety findings. The safety profile was
consistent with currently marketed FDA-approved
transmucosal buprenorphine preparations, except for
anticipated injection site reactions. These results were
included with the data submitted to the FDA, which led
to its approval on November 30, 2017.48
CAM2038: Pending a Final FDA Decision
A small, 3-week, phase 2 trial reported immediate and
sustained opioid blockade and withdrawal suppression
following 2 weekly doses of 24 or 32 mg CAM2038.51 A
pivotal phase 3 efficacy study examined noninferiority
of the CAM2038 responder rate with that of sublingual
BPN/NX in 428 patients.30 Following screening, patients
were randomized to sublingual BPN/NX in the active
control group or weekly CAM2038 injections during
12 weeks of phase 1, followed by 3 monthly injections
of CAM2038 in the treatment group during phase 2.
Noninferiority (P < .001) to the sublingual medication
was observed in the CAM2038 group on responder rate,
defined as having no evidence of illicit opioid use at ≥8
of 10 prespecified time points over Weeks 9 to 24, and 2
must be at weeks 12 and 24.52 More urine samples were
negative for illicit opioids in the CAM2038 compared
with control group participants (P < .001). In addition,
CAM2038 demonstrated superiority (P = .004) over
weeks 5 to 24 for negative urine tests for illicit opioids
plus patient self-reports. Retention was similar between
groups during the 24-week trial. These data were part of
the application submitted to the FDA in 2017 to support
weekly and monthly formulations for subcutaneous
injection in the buttock, thigh, abdomen, or upper arm by
a health care provider.30 An advisory committee for the
FDA recommended approval of CAM2038 in November
2017, and the FDA decision is expected in 2018.53
Naltrexone
Naltrexone is a competitive mu-opioid antagonist that
blocks the euphoric and sedative effects of opioids.54
Effect duration has been shown to follow a dose-
response relationship, with 50, 100, and 150 mg of nal-
trexone blocking the pharmacologic effects of IV heroin
25 mg for 24, 48, and 72 hours, respectively.27
S15
OPIOID USE DISORDER:
CHALLENGES AND SOLUTIONS TO A RISING EPIDEMIC
Case Presentation: Treating Opioid Use Disorder
Genie L. Bailey, MD
A 28-year-old woman presents with a friend. She was
referred after an overdose rescue in the emergency
department 3 days ago. She started using metham-
phetamine in her early 20s and soon added prescrip-
tion pain pills. She stopped methamphetamine use
after 1 year; however, she continued to use opioid pain
medication at increasing dosages. She began injecting
heroin 3 months ago.
When she runs out of opioids, she experiences severe
cravings and withdrawal symptoms. She smokes mari-
juana to help with these symptoms. She smokes at least
1 pack of cigarettes per day—a habit she started when
she was 13 years old. She has a history of binge drinking
as a teenager, but she now drinks infrequently and has
not had more than 3 drinks at a time for more than 1 year.
She has no records in the Prescription Drug
Monitoring Program, implying that she obtains her
drugs from the street.
Physical examination reveals a heart rate of 105 bpm
and blood pressure of 132/84 mm Hg. She has fresh
needle tracks in the antecubital area of the left arm.
Initially approved for treating alcohol addiction,
the safety and efficacy of naltrexone has been widely
studied. A meta-analysis reported a 17% reduced risk
of heavy drinking with naltrexone compared with pla-
cebo, with an approximate 4% decrease in number of
drinking days.55 Several secondary outcomes also
were significantly improved compared with placebo;
however, return to any drinking was similar between
naltrexone and placebo.
Given that patients with OUD typically are ambiva-
lent about taking mu-antagonist medications, it is not
surprising that daily self-administered oral naltrexone
has mixed results for treating opioid addiction. A meta-
analysis concluded that oral naltrexone was not supe-
rior to treatment with placebo or no pharmacological
agent in detoxified patients with opioid addiction for all
outcomes assessed.56 However, the authors noted that
barely one-fourth (28%) of participants were retained in
treatment in the 13 studies, suggesting that these stud-
ies did not allow an adequate scientific evaluation of
oral naltrexone treatment for opioid dependence.
Extended release of a mu-opioid antagonist would
have the advantage of avoiding adverse events, such
as euphoria, dependence, respiratory depression, and
overdose death, that may be associated with use and
misuse of agonist drugs and would avoid NMU and
accidental pediatric exposure. An extended-release
S16 April 2018 | Vol 17, No 4 | Supplement to Current Psychiatry
MANAGEMENT APPROACH
This patient has signs of opiate withdrawal and is seek-
ing help for her 8-year addiction, making her a good
candidate for medication. She is accompanied by a
friend, indicating that she has support. Her recent con-
version to IV use and the overdose rescue experience
put her at very high risk. Any treatment will increase the
likelihood of her survival.
Buprenorphine is an evidence-based, office-based
option for this patient, and it might be lifesaving. If
she adheres to treatment, the risk of a repeat over-
dose is reduced. Sublingual buprenorphine is a pre-
ferred initial treatment, which allows for frequent
visits (generally 1 per week in the beginning of treat-
ment) to establish a positive therapeutic alliance and
motivate the patient’s engagement in her treatment.
Depending on the specific situation, the amount of
medication prescribed can be extended or the patient
could be transitioned to an extended-release formu-
lation. Additional psychosocial supports should be
offered and encouraged.
formulation was approved by the FDA for treating alco-
hol dependence in 2006.29 In 2010, the indication was
supplemented to include prevention of relapse to opioid
dependence after opioid detoxification. The formulation
is delivered by deep gluteal IM injection of 380 mg every
4 weeks or once monthly and can be administered by
any health care provider who is licensed to prescribe
medications.29 Patients should be opioid-free before
starting treatment. A minimum of 7 to 10 days without
opioids is recommended to avoid precipitating opioid
withdrawal that can be severe enough to require hospi-
talization. Abrupt discontinuation of naltrexone is not
associated with withdrawal syndrome.
Adverse Events
Treatment-emergent AEs that were more frequent
in the naltrexone injection group than in the placebo
group during clinical development for alcohol depen-
dence were similar to those observed in the safety study
performed in patients with opioid dependence.29 Any
injection-site reaction was reported in 65% of patients
receiving naltrexone injection compared with 50% of
those with placebo injections. The AEs included gas-
trointestinal disorders (nausea, vomiting, diarrhea,
and abdominal pain), somnolence or sedation, dizzi-
ness, headache, musculoskeletal and connective tissue
disorders, and depression. Regardless of treatment, all
patients with alcohol or opioid dependence should be
monitored for development of depression or suicidal
thinking. In controlled trials of naltrexone injection for
alcohol dependence, suicide-related AEs were more
common in the naltrexone group compared with pla-
cebo (1% vs 0%). In a small, open-label, safety study,
depressed mood, suicidal ideation, or suicide attempt
was reported by 5% of opioid-dependent patients
treated with extended-release naltrexone and by 10% of
those treated with oral naltrexone.
Opioid Use Disorder Treatment Medications:
Comparisons
Most studies report that methadone and buprenor-
phine are equally effective for treating opioid depen-
dence.57-59 Some studies also report similar AEs between
the 2 drugs58,60; however, some describe more AEs
associated with methadone use, including respiratory
depression and more severe neonatal abstinence syn-
drome.57,61 In nonrandomized studies, patients treated
with buprenorphine performed better in cognitive tests
compared with those taking methadone.62 In addition,
persons presenting to emergency departments after
NMU of methadone had higher hospitalization rates,
greater intensive care utilization rates, and considerably
worse medical outcomes, including death, compared
with persons presenting after NMU of buprenorphine.63
National databases in England and Wales were studied
for deaths associated with more than 17 million metha-
done and 2.6 million buprenorphine/buprenorphine-
naloxone prescriptions.64 Methadone had a significantly
greater risk of fatal overdose compared with buprenor-
phine (relative risk ratio: 6.23).
A recent 24-week, open-label trial was the first in the
United States to compare naltrexone and buprenor-
phine head-to-head.65 Opioid relapse-free survival of
extended-release naltrexone (XR-NTX) and sublingual
buprenorphine/naloxone (BUP/NX) was examined in
570 inpatients with OUD who were followed as outpa-
tients. Initiation of XR-NTX was less successful (72%)
compared with BUP/NX (94%; P < .0001). Accordingly,
in the intent-to-treat population, 24-week relapse
rates were greater for XR-NTX (65%) compared with
BUP/NX (57%), most of which were accounted for by
early relapse in 89% of the XR-NTX induction failures.
In the per-protocol analysis, including only success-
fully inducted patients, 24-week relapse events were
similar between the 2 groups. The authors concluded
that in patients for whom treatment was initiated, both
medications were equally safe and effective. They
noted that further efforts are warranted to facilitate
induction to XR-NTX, which may be more challenging
in outpatient settings, and to improve treatment reten-
tion for both medications.
A 12-week study in Norway also compared the
2 drugs; however, randomization was done after
Supplement to Current Psychiatry | Vol 17, No 4 | April 2018
detoxification.66 The trial was completed by 66% of
the 159 patients enrolled. Retention was noninferior
in the XR-NTX compared with the BUP/NX group.
Noninferiority was supported for number of opioid-
negative urine drug tests and use of heroin and other
illicit opioids, whereas superiority analysis showed sig-
nificantly lower use of heroin and other illicit opioids in
the XR-NTX group.
Summary
Medical treatment is a necessary component of multi­
disciplinary team management of OUD. Several
evidence-based psychosocial therapy options can be
considered for inclusion as part of the management
plan. Two extended-release buprenorphine formula-
tions were approved by the FDA in the past 2 years,
expanding options and increasing therapy effects dura-
tion following a single mu-opioid agonist treatment.
The monthly naltrexone injection approved by the FDA
in 2010 remains the only available extended-release
mu-opioid antagonist. Clinicians should be aware of
the risks and benefits of each formulation, carefully con-
sidering individual patient baseline characteristics and
conducting diligent monitoring during treatment to
allow adequate response to AEs and changes in patient
outcomes and behavior.
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37. Drug Enforcement Administration. DEA requirements for DATA waived
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dwp_buprenorphine.htm. Accessed December 28, 2017.
38. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of
Buprenorphine in the Treatment of Opioid Addiction. Rockville, MD: Substance
Abuse and Mental Health Services Administration; 2004.
39. American Society of Addiction Medicine. Nurse practitioners and physician
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practice-resources/nurse-practitioners-and-physician-assistants-prescribing-
buprenorphine. Accessed December 28, 2017.
40. Substance Abuse and Mental Health Services Administration. Apply to
increase patient limits. https://www.samhsa.gov/medication-assisted-
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Accessed December 28, 2017.
41. Substance Abuse and Mental Health Services Administration. Qualify for a
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buprenorphine-waiver-management/qualify-for-physician-waiver.
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42. Substance Abuse and Mental Health Services Administration. Buprenorphine
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1197-1205.
Opioid Use Disorder:
Challenges and Solutions to a Rising Epidemic
CME Instructions for Claiming Credit
1. Proceed to the CME Registration Form.
Type or print your name, address, and date
of birth in the spaces provided.
2. Answer each posttest question by entering
it in the Answer Sheet space provided on
the Registration Form. Be sure to retain a
copy of your answers for your records.
3. Complete the evaluation portion of the
CME Registration Form. CME Registration
Forms will be returned to you if the
evaluation is not completed.
4. CME Registration Forms will not be
accepted after the expiration date.
Return the CME Registration Form
before the test expires to:
 Vindico Medical Education
PO Box 36
Thorofare, NJ 08086-0036
or fax to: 856-384-6680.
5. For downloadable handouts, patient
education tools, and online resources,
please visit:
VindicoCME.com/EducationalTools
6. The CME test will be available for download
and fax or mail submission (within 1 month
of mailing date) at:
 www.mdedge.com/currentpsychiatry/
opioidCME

CME Posttest
1. Between 2004 and 2011, medical emergencies related to opioid 6. All the following are key principles of treating opioid use
drugs increased by _________ . disorder except:
A. 103% A. A multimodal, multidisciplinary team must provide coordinated
B. 123% care, with adequate communication among team members.
C. 183% B. A single physician should be the sole authority.
D. 223% C. The team may be independent of or part of a coordinated
network, preferably integrated with behavioral health.
2. Opioid use disorder can often be characterized by 3 stages, D. Treatment should be person centered and recovery oriented,
usually beginning with _________ . with a focus on safety and quality of life.
A. Illicit drug use
7. Which of the following best describes the mechanism of action
B. Excessive recreational drug use
of buprenorphine, which contributes to its low toxicity, reducing
C. Prescription opioid drugs the potential for overdose?
D. A patient taking prescription opioid drugs, then transitioning to A. Partial antagonist at the mu-opioid receptor
heroin
B. Partial agonist at the mu-opioid receptor
3. In contrast to physical dependence, tolerance can be defined as: C. Full mu-opioid agonist
A. The manifestation of a class-specific withdrawal syndrome that D. Full mu-opioid antagonist
occurs when the opioid is abruptly stopped
8. Which of the following best describes the mechanism of action
B. The manifestation of a class-specific withdrawal syndrome that
for methadone, which may contribute to its side effects of
occurs with a rapid dose reduction of the opioid
respiratory depression and QT prolongation?
C. The manifestation of a class-specific withdrawal syndrome that
A. Full mu-opioid antagonist
occurs when the blood levels of the opioid decline
B. Partial mu-opioid antagonist
D. Reaching an adaptive state that results in decreased opioid
effects C. Partial mu-opioid agonist
D. Full mu-opioid agonist
4. Although it is home to only 5% of the world’s population, _____%
of the world’s opioid medications are prescribed in the United 9. Extended-release injectable buprenorphine provides all the
States. following benefits in treating patients with OUD except:
A. 99 A. Poor patient compliance and increased risk of misuse
B. 80 with treatment
C. 65 B. Predictable release rates
D. 50 C. Rapid establishment of effective plasma drug levels
D. Potential flexibility in dosing
5. Which of the following represents the first step to accurately
confirm the diagnosis of opioid use disorder? 10. A 25-year-old man presents with a friend. He had an overdose
A. Perform a pain evaluation rescue in the emergency department 4 days ago. He has a
history of cocaine use that started in his teens and then added
B. Recognize that physiological dependence automatically equals
prescription pain pills. He stopped cocaine use 6 months ago but
addiction
continued to use opioid pain medication at increasing doses and
C. Establish a hard-line approach to the patient began injecting heroin 4 months ago. In addition to counseling
D. Discourage the patient from ever using opioids and psychosocial support, which of the following would be the
best approach to treating his OUD?
A. Alprazolam
B. Sertraline
C. Aripiprazole
D. Buprenorphine

Supplement to Current Psychiatry | Vol 17, No 4 | April 2018 S19

Opioid Use Disorder:
Challenges and Solutions to a Rising Epidemic
CME Registration Form
Answer Sheet
1 2 3 4 5 6 7 8 9 10
*Time spent on this activity: Hours ☐ Minutes ☐
(Includes reading articles and completing the learning assessment and evaluation.)
This information MUST be completed in order for the quiz to be scored.
THE MONOGRAPH AND TEST EXPIRE APRIL 1, 2019
PRINT OR TYPE
Last Name First Name Degree
Mailing Address
City State Zip Code
Date of Birth (used for tracking credits ONLY)
Phone Number FAX Number
*E-mail Address
Enduring Activity Evaluation
Your evaluation of this activity is extremely important, as it allows us to plan for future
educational programs. Please take a moment to answer the following questions.
1. How many years have you been treating patients with comorbid pain disorders?
□ 1 to 9 □ 10 to 20 □ 21 to 30 □ More than 30 □ N/A
2. How many years have you been treating patients who are taking opioid medications?
□ 1 to 9 □ 10 to 30 □ 21 to 30 □ More than 30 □ N/A
3. How many years have you been treating patients with opioid use disorder (OUD)?
□ 1 to 9 □ 10 to 30 □ 21 to 30 □ More than 30 □ N/A
4. Approximately how many patients with OUD do you see per month?
□ 1 to 9 □ 10 to 30 □ 21 to 30 □ More than 30 □ N/A
5. Please rate the overall educational quality of this activity (from 1 = Poor; 5 = Excellent).
□ 1 □ 2 □ 3 □ 4 □5
6. Do you believe this program: Yes No N/A
Achieved its identified educational goals and learning objectives? □ □ □
Covered content that is relevant and will be useful to your practice? □ □ □
Increased your awareness of gaps in evidence-aligned care? □ □ □
Advanced your knowledge of practice changes that may improve gaps
in patient care within your health care system? □ □ □
Will increase your competence in managing these patients? □ □ □
Inspired you to engage/coordinate care within your health care system
to improve health care delivery? □ □ □
Used teaching methods and educational formats that were effective for learning? □ □ □
Will improve your ability to communicate with patients/caregivers? □ □ □
Provided you with resources to use in your practice and/or with your patients? □ □ □
Addressed and provided strategies for overcoming barriers to optimal patient care? □ □ □
Was presented objectively and was free of commercial bias*? □ □ □
*If you indicated that the activity was not free of commercial bias, please provide
additional comments here:
Yes No
7. Future activities concerning this subject matter are necessary. □ □
8. Approximately what percentage of the activity’s content was NEW to you?
□ 0% □ 25% □ 50% □ 75% □ 100%
9. A
 s the result of completing this educational activity, Do
I plan to make the following changes to my practice: Yes No Already N/A
Assess patients with chronic pain and/or psychiatric disorders
for evidence of OUD.
□ □ □ □
Incorporate assessment tools that assist in identifying patients who
are dependent on or at risk for opioid dependence. □ □ □ □
Establish systems in practice that allow for patients to receive
medication-assisted treatment (MAT). □ □ □ □
Apply the safety and efficacy of current and emerging therapies
for OUD when determining treatment regimens. □ □ □ □
Function within an interprofessional team to continually assess practice
patterns to ensure they align with the latest evidence-based care. □ □ □ □
Other planned changes to practice (please provide below):
If you do not intend to make changes to your practice, please indicate why:
10. The following are barriers I face most often in my current practice that impact my ability to
provide optimal care: Yes No N/A
Lack of applicable evidence-based guidelines for my current practice/patients □ □ □
Lack of time to stay up-to-date on the latest evidence-based care □ □ □
Lack of systems-based coordination of care involving an interprofessional team □ □ □
Access to clinical trials □ □ □
Integrating/utilizing electronic health records □ □ □
Implementing value-based metrics/quality measures □ □ □
Insurance/financial restrictions □ □ □
Lack of patient engagement □ □ □
Lack of patient adherence/compliance to therapy □ □ □
11. How confident are you in your ability to manage your patients with OUD?
□ Extremely Confident
□ Very Confident
□ Somewhat Confident
□ Not at All Confident
□ Does Not Apply
12. What educational topics would be of value to you for future CME activities? Please be specific.
13. Please indicate your degree:
□ MD/DO □ PA □ Other Health Care
□ PharmD/RPh □ RN/BSN/MSN □ Industry
□ NP □ PhD □ Other:_________________
14. Please indicate your primary specialty:
□ General Psychiatry □ Psychology □ Pharmacy
□ Addiction Psychiatry □ Internal Medicine □ Nursing
□ Adult Psychiatry □ Family Practice/ □ Industry
□ Nursing General Practice □ Other:_________________
□ Geriatric Psychiatry □ Research ______________________
□ Child & Adolescent
Psychiatry
15. Please indicate your primary professional/practice setting:
□ Office/Private Practice □ Hospital
□ Research □ Academic
□ Residency □ Fellowship
□ Urgent Care □ Fed/State Govt.
□ Pharmacy □ Industry
□ Administration □ Other:______________________________
* Required field
Please return the CME Registration Form before the test expires to:
Vindico Medical Education
PO Box 36 Thorofare, NJ 08086-0036
or Fax to: 856-384-6680
Questions about CME?
Contact us at CME@VindicoCME.com or Call us at 856-994-9400 ext. 504
OFFICE USE ONLY
Enduring material: Other
April 1, 2018 CPY-J964