Académique Documents
Professionnel Documents
Culture Documents
Available at www.mdedge.com/currentpsychiatry/opioidCME
Support Statement: This activity is supported
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
DISCLOSURES: OVERVIEW:
In accordance with the Accreditation Council for Prescription and nonprescription opioid use disorder
Continuing Medical Education’s Standards for Commercial (OUD) has reached epidemic proportions in the United
Support, all CME providers are required to disclose to the States. Patients with chronic pain are known to have a
activity audience the relevant financial relationships higher prevalence of comorbid psychiatric disorders.
of the planners, faculty, reviewers, and staff involved in Psychiatrists and other health care professionals who
the development of CME content. An individual has a treat patients with mental disorders may lack the skills
relevant financial relationship if he or she has a financial necessary to recognize individuals who may have OUD
relationship in any amount occurring in the past 12 or be at risk for addiction to opioids. The adoption of
months with a commercial interest whose products or validated tools can help to identify those patients if
services are discussed in the CME activity content over used consistently. An insufficient number of physicians
which the individual has control. are trained and certified to provide medications for
addiction treatment to patients with OUD. New methods
UNLABELED AND INVESTIGATIONAL USAGE: of delivering this treatment can provide long-acting
The audience is advised that this continuing medical therapy and may improve compliance, while reducing
education activity may contain references to unlabeled the risk of abuse. Although psychiatrists typically are not
uses of FDA-approved products or to products not the primary prescribers of opioid medications, they often
approved by the FDA for use in the United States. treat psychiatric disorders in patients with chronic pain
The faculty members have been made aware of their who take prescription opioids. Therefore, education to
obligation to disclose such usage. All activity participants psychiatrists can provide increased knowledge of risk
will be informed if any speakers/authors intend to discuss assessment strategies for patients receiving opioids.
either non-FDA approved or investigational use of
products/devices. Learning Objectives: Upon successful completion of this
activity, participants should be better able to:
ACCREDITATION: • Assess the increasing prevalence of opioid use disorder
Vindico Medical Education is accredited by the (OUD) among patients with chronic pain and/or
Accreditation Council for Continuing Medical Education to psychiatric disorders.
provide continuing medical education for physicians. • Evaluate current assessment tools that assist in
identifying patients who are dependent on opioids, or
CREDIT DESIGNATION: at risk of developing dependence.
Vindico Medical Education designates this enduring • Compare efforts to improve patients’ ability to receive
material for a maximum of 1.25 AMA PRA Category medication-assisted treatment (MAT) and psychosocial
1 Credit(s)™. Physicians should claim only the credit support.
commensurate with the extent of their participation in
• Assess the safety and efficacy of current and emerging
the activity.
therapies for OUD.
This enduring material is approved for 1 year from the date
of original release, April 1, 2018 to April 1, 2019. COPYRIGHT STATEMENT:
Created by Vindico Medical Education, 6900 Grove Road,
HOW TO PARTICIPATE IN THIS ACTIVITY AND OBTAIN Building 100, Thorofare, NJ 08086-9447. Telephone:
CME CREDIT: 856-994-9400; Fax: 856-384-6680. Printed in the USA.
To participate in this CME activity, you must read the Copyright © 2018 Vindico Medical Education. All rights
objectives and articles, complete the CME posttest, reserved. No part of this publication may be reproduced
and return the registration form and evaluation in their without written permission from the publisher. The
entirety. Provide only one (1) correct answer for each material presented at or in any of Vindico Medical
question. A satisfactory score is defined as answering Education continuing medical education activities does
7 out of 10 of the posttest questions correctly. Upon not necessarily reflect the views and opinions of Vindico
receipt of the completed materials, if a satisfactory score Medical Education. Neither Vindico Medical Education
on the posttest is achieved, Vindico Medical Education nor the faculty endorse or recommend any techniques,
will issue an AMA PRA Category 1 Credit(s)™ certificate commercial products, or manufacturers. The faculty/
within 4 to 6 weeks. authors may discuss the use of materials and/or products
that have not yet been approved by the US Food and Drug
Target Audience: The intended audience for this activity is Administration. All readers and continuing education
psychiatrists and other health care professionals involved participants should verify all information before treating
in the treatment of patients with prescription opioid use patients or utilizing any product.
disorder (OUD).
CME QUESTIONS?
Contact us at CME@VindicoCME.com
effective.2 However, the epidemic is real. Between 2002 be issue-free for a few months, as evidence shows that
and 2011, an estimated 25 million people engaged in the transition to addiction can occur early and rapidly.6
nonmedical use (NMU) of pain relievers. Even in the In addition, the treatment window might be open for
recent years that showed decreased NMU of prescrip- only a brief interval. In a recent study of 625 patients
tion opioids, the prevalence of prescription opioid use with chronic noncancer pain, having a current opioid
disorder (OUD), frequency of use, and related mortal- prescription was an independent risk factor for opioid
ity increased.2 misuse (odds ratio, 4.06; 95% confidence interval [CI],
OUD often can be characterized by 3 stages, usu- 1.62-10.18; P = .003).6
ally beginning with prescription opioid drugs. Studies
have shown a parallel relationship between prescrip- Consequences of Opioid Use: Terminology
tion opioid analgesic availability through legitimate The important goal of maintaining a favorable balance
pharmacy channels and their subsequent diversion, between risks and benefits with any medical treatment
abuse, and adverse outcomes.1 Stage 2 occurs when is complicated in those with chronic use of opioids for
a patient taking prescription opioid drugs transi- pain control, where adverse consequences include tol-
tions to heroin. More recently, many patients reach erance, physical dependence, addiction, and death.7
stage 3—turning to synthetic opioids such as fentanyl Opioids are effective in certain clinical scenarios, but
and carfentanil. they are high-risk medications. Tolerance can be defined
as those who have reached an adaptive state that results
Stage 1: Prescription Opioids in decreased opioid effects.8 Physical dependence is
The path to addiction might begin with a patient pro- characterized by the manifestation of a class-specific
curing a prescription refill legitimately or acquiring withdrawal syndrome that can occur when the opioid is
the medications through any means when unable to abruptly stopped, a rapid dose reduction is experienced,
get prescriptions legitimately. Patients might take blood levels of the drug are reduced through any cause,
drugs that other family members retained after not or an antagonist is administered.
taking the full prescription because people rarely dis- Addiction is characterized by impaired control over
pose of unused opioid medication. A recent systematic drug use, compulsive use, continued use despite harm,
review of 6 eligible studies reported that 67% to 92% and craving. Historically, several definitions of addic-
of patients who were prescribed postoperative opioids tion have been used, which contributed to some of the
did not use their entire prescription.3 In 2 studies that inconsistencies in reporting addiction data.9 In 2011,
examined storage safety, approximately three-fourths the American Society of Addiction Medicine devel-
of patients did not store their opioids in locked contain- oped a long definition that provides expanded details
ers, and all studies reported low rates of anticipated about each component of the definition, supplemented
or actual disposal, with a maximum 9% of patients in by a summarized short definition (Figure 1, page S4).10
any study reporting that FDA-recommended disposal A simpler definition describes addiction as a primary,
methods were followed.3 Similarly, opioid use and chronic, relapsing brain disease characterized by loss
disposal was surveyed in the parents of 343 pediatric of control over one’s use of a drug; continued use of
patients who were prescribed opioid medication at the drug despite adverse consequences of use; and an
hospital discharge.4 Fewer than one-half (42%) of the obsessive desire and/or compulsive seeking of the
doses were consumed, and only 4% of families dis- drug. The simplest definition of addiction might be
posed of leftover opioids. the repeated use of a drug despite harm. Onset of drug
Using US National Survey of Drug Use and Health addiction usually occurs in adolescence, and, although
(NSDUH) data from 2005 to 2014, a recent study of it is treatable and controllable, it usually is not curable.
women of reproductive age women examined the The adverse consequences of opioid use also include
NMU of prescription opioids in the previous 30 days abuse, misuse, and diversion. Abuse is defined as any
in 8069 pregnant and 146,110 nonpregnant women use of an illegal drug or intentional self-administration
and found that 0.8% and 2.3%, respectively, had recent of a medication for nonmedical purposes, such as
opioid NMU.5 More of the pregnant women reported altering one’s state of consciousness.8 Drug misuse is
a physician as their source of opioids for NMU com- defined as use of a medication other than as directed
pared with nonpregnant women (46.2% vs 37.6%; or as indicated, whether willful or unintentional, and
P = .004), whereas fewer pregnant women obtained whether harm results. Opioid misuse has been defined
their NMU opioids from a friend or relative compared as either (1) taking an opioid in a manner or dosage
with nonpregnant women (53.9% vs 75.0%; P = .001). other than prescribed or (2) taking another person’s
Numerically more pregnant women reported a drug opioids, even if the use is for a legitimate medical
dealer as their source (14.6% vs 10.6%; P = .44).5 issue.6 Diversion is the intentional transfer of a con-
Clinicians can no longer conclude that a drug-naïve trolled substance from legitimate distribution and dis-
patient receiving his/her first opioid prescription will pensing channels.8
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.
TABLE 1 DSM-5: Substance Use Disorder vomiting, delayed gastric emptying, sexual dysfunc-
Impaired Control
tion, muscle rigidity and myoclonus, sleep disturbances,
diminished psychomotor performance, hyperalgesia,
• Larger amounts or over longer period than intended
dizziness/vertigo, multiple drug interactions, frac-
• Persistent desire or unsuccessful efforts to cut down tures, and endocrinopathy with androgen deficiency.7,11
• Much time spent in acquiring, using, or recovering from Prescribing clinicians should be alert for and manage
effects these common AEs.
• Craving or strong desire to use
Pharmacologic Criteria DSM-5: Substance Use Disorder
DSM-IV, published in 1994, underwent a full revision to
• Tolerance
DSM-5, which was published in 2013.12 In DSM-IV, sub-
• Withdrawal
stance abuse and substance dependence were separate
Social Impairment disorders that were combined into substance use disor-
• Failure to fulfill major role obligations der (SUD) in DSM-5, measured on a continuum from
• Continued substance use despite persistent or recurrent mild to severe. Eleven symptoms are divided among
social or interpersonal problems impaired control, social impairment, pharmacologic
• Abandonment/reduction of important social, work, or criteria, and risky use (Table 1).13 Having 2 or 3 of these
recreational activities symptoms in the previous 12 months is consistent with
Risky Use mild SUD, whereas 4 or 5 is categorized as moderate,
and 6 or more symptoms indicates severe SUD.
• Continued use despite knowledge of a substance-induced
physical or mental problem
Opioid Effectiveness
• Hazardous situations
The effectiveness of short-term opioids for treating acute
Source: American Psychiatric Association.13
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-
Consequences of Opioid Use: Common scribed often are more than what is needed.19 A system-
Adverse Events atic review and meta-analysis of short-term pain relief
Gastrointestinal and central nervous system-related experienced by patients with chronic low back pain con-
adverse events (AEs), such as constipation, nausea, and cluded that the modest relief obtained was not likely to
somnolence/drowsiness, frequently are cited as lead- be clinically important.20
ing to opioid therapy discontinuation, with 14% to 20% The efficacy of opioids for long-term treatment of
mean incidence differences between opioid and placebo chronic pain is not well-established and characterized
group subjects in more than 30 studies.7 Fatigue, cogni- by weak, insufficient evidence and mixed reports.20-22
tive dysfunction, dry mouth, sweating, and weight gain An observational study of 333 pain clinic patients tak-
also have been reported frequently. Other AEs include ing either opioid or nonopioid analgesics for at least
respiratory depression, pruritus/dry skin/itching, 3 months reported similar pain intensity and treatment
30,000
Heroin
Number of deaths
15,000
7,500
0
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Year
Source: Rudd RA, et al44; Centers for Disease Control and Prevention.45
satisfaction between groups.23 Patients taking higher Epidemiology of the Opioid Epidemic
opioid dosages had an increased risk-to-benefit ratio, The United States has been particularly affected by
which included more psychological impairment with- the opioid epidemic. Although it is home to only
out improved pain relief. Although some patients may 5% of the world’s population, 80% of the world’s
benefit from long-term opioid treatment, there are no opioid medications and 99% of the world’s hydroco-
criteria to identify these patients,24 and a long-term done are prescribed in the United States.27 Although
study to explore risk factors would be unethical. In fact, one study reported that fewer than 1% of patients
in a review of 34 studies of the long-term effectiveness who were prescribed opioids are “doctor shop-
and risks of opioid therapy, none of the studies included pers,”28 acquiring their opioids from more than 1
follow-up beyond 1 year.11 The 2016 Centers for Disease prescription source, another study of overdose fatali-
Control and Prevention opioid prescription guidelines ties reported that 21.4% of patients were associated
for chronic pain emphasize that nonopioid therapy with doctor shopping.29 In addition, there is a strong
is preferred.25 association between diversion of prescription opi-
Several clinical practice guidelines acknowledge oids and deaths due to overdose.29 Possible misuse
the risks and limitations of opioid therapy and pro- has been estimated to occur in approximately 20%
vide management recommendations based on cur- of patients prescribed opioids,30,31 reaching 33% if
rent evidence. However, several studies have shown opioids were started in patients before the twelfth
that most clinicians do not follow recommended grade.32 Data from 472,200 persons aged 18 to 64 who
practices for prescribing opioids. A recent interven- participated in the NSDUH revealed that the preva-
tional trial randomized 53 primary care clinicians lence of NMU of prescription opioids decreased
and their 985 patients who were receiving long-term from 5.4% to 4.9% between 2003 and 2013.2 However,
opioid therapy for pain to an intervention designed this was accompanied by an increased prevalence
to improve guideline adherence and decrease risk of high-frequency use (≥200 days) and increased
of opioid misuse.26 Despite the possibility that a prevalence from 12.7% to 16.9% of OUD among non-
Hawthorne effect (ie, subjects changing behavior medical users.
because they know they are being observed) might Health care costs for opioid misusers are
increase guideline compliance in the control physi- approximately 9-fold greater than for the general
cians, only 37.8% of patients in that group received population.30 Caring for the estimated 2 million indi-
guideline-concordant care compared with 65.9% viduals addicted to prescription opioid medications
of intervention group patients (P < .001), leaving and the 0.5 million addicted to heroin was estimated at
one-third of the intervention group patients without $25 billion in 2007, and costs to society were esti-
guideline-adherent treatment. mated at $56 billion.2,33
Provider-related Opioid Overdose Risk Factors of heroin use among young adults aged 26 to 34 with
Several provider-related factors contribute to opioid NMPO.40 Similarly, in an older sample of 3396 US veter-
overdoses. Prescribing opioids after a nonfatal overdose ans, with a mean age of 49.7 years, who were followed
is associated with repeat overdose. In one study of 2848 between 2002 and 2012, 77% of the 500 who initiated
patients with a nonfatal opioid overdose, 91% were repre- heroin use during follow-up reported previous or
scribed opioids during a median follow-up of 299 days, current NMPO.41 In multivariate analysis, NMPO
usually by the same clinician.34 The cumulative incidence remained independently associated with heroin initia-
of repeat overdose at 2 years was 17%, 15%, and 9% for tion (adjusted hazard ratio, 5.43; 95% CI, 4.01-7.35).
patients receiving high, moderate, and low opioid dos- Nationally, drug overdoses are responsible for more
ages, respectively, after the overdose compared with 8% deaths annually than motor vehicle accidents.42 In 2013,
for those not receiving opioid prescriptions. approximately 44,000 people died from drug overdoses,
Long-acting opioids have been associated with a including approximately 25,000 from opioid painkill-
greater risk of overdose and fatality compared with ers and heroin; compared with approximately 30,000 in
short-acting formulations.35,36 Co-prescribing respiratory vehicular crashes.43 The Centers for Disease Control and
depressants, particularly benzodiazepines, is a risk fac- Prevention reported 12,989 heroin overdose deaths in
tor for opioid overdose.35-39 The possible association of the United States in 2015, representing a 7-fold increase
failure to perform risk and overdose monitoring has not since 2000 (Figure 2, page S5).44,45 During that interval,
yet been studied. deaths attributed to opioid analgesics increased from
4400 to 25,608.
Stage 2: Heroin: An Unintended Consequence
If persons are forced to acquire their drugs illegally, pre- Stage 3: Fentanyl and Its Analogs:
scription opioids quickly can become cost prohibitive Unprecedented Devastation
when the daily intake equates to $80 to $160 (approxi- The synthetic opioid fentanyl and its analogs, includ-
mately $1 per milligram). This facilitates a switch to the ing sufentanil and carfentanil, pose even more danger.
considerably less expensive heroin, which usually is Fentanyl is 50 times more potent than heroin and 100
administered via injection shortly after the individual times more potent than morphine, whereas carfentanil is
makes the transition. 10,000 times more potent than morphine.46 The US death
A recent examination of NSDUH data from 2002 to rate from synthetic opioids other than methadone, which
2014 revealed that between those time points, there includes drugs such as tramadol and fentanyl, increased
was a 4-fold increase in the odds of heroin use emerg- 72.2% between 2014 and 2015 across all demograph-
ing among adults aged 18 to 25 with NMU of prescrip- ics and regions; however, the increase was considerably
tion opioids (NMPO) and a 9-fold increase in the odds greater in the Northeast (107.4%), Midwest (95%), and
South (55.6%) compared with the West (12.5%).47 The rise Summary
in deaths is driven by increases in fentanyl-involved over- The opioid epidemic continues to impact individuals,
dose, most likely involving illicitly manufactured fen- the health care system, and society. New policies and
tanyl, which may be mixed with or sold as another drug, interventions might be starting to have effects, but if
such as heroin.48,49 they are not followed, the epidemic will continue and its
adverse consequences will increase. Clinicians should
Screening for Opioid Use Disorder familiarize themselves with and use the resources avail-
Identifying persons who have or are at risk for OUD able—from opioid treatment guidelines through screen-
is an essential first step before a management plan can ing tools—that can help identify OUD. In addition,
be developed. Several reliable and evidence-based tools clinicians should understand the availability, risks, and
are available to screen for OUD and other substance benefits of OUD management options.
use disorders through links on the National Institute
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20. Abdel Shaheed C, Maher CG, Williams KA, Day R, McLachlan AJ. https://www.cdc.gov/drugoverdose/data/analysis.html. Accessed
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Pain Medicine clinical practice guideline. J Pain. 2009;10(2):147-159. overdose deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep.
22. Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. BMJ. 2016;65(5051):1445-1452.
2015;350:g6380. 48. Gladden RM, Martinez P, Seth P. Fentanyl law enforcement submissions
23. Elsesser K, Cegla T. Long-term treatment in chronic noncancer pain: results and increases in synthetic opioid-involved overdose deaths - 27 states, 2013-
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cluster-randomized clinical trial. JAMA Intern Med. 2017;177(9):1265-1272. Revised September 2017. Accessed December 25, 2017.
T
he critical need to find solutions for the opioid might prevent persons with OUD from telling others
use disorder (OUD) crisis is universally acknowl- about their disorder. Persons with OUD fear losing their
edged. However, several barriers challenge the employment and fear the impact that their OUD could
efforts to control opioid misuse and reduce its harmful have on personal relationships if their disorder is dis-
impact on individuals, the health care system, and soci- covered. Patients themselves usually do not understand
ety (Figure, page S10). These treatment provision barri- that addiction is a chronic disease for which they should
ers are active in 3 domains: the treatment system, the adopt a recovery orientation; that is, they will never be
medical providers, and the patients themselves. cured and must learn how to rehabilitate themselves as
part of their recovery.
Treatment System The United States promulgated addiction privacy
Access to the treatment system is limited by a defi- regulations (42 CFR Part 2) in 1975, which, although
ciency in evidence-based systematic screening. The initially protecting patients from undue exposure
improved focus on value-based care has allowed for and discrimination, ultimately restricted patients
increased identification and treatment of substance with addiction from taking advantage of health care
use disorders (SUDs), and the availability of several modernization.4 Compared with others without SUD,
validated screening tools should contribute to reduc- patients with OUD do not benefit from integrated
ing this barrier.1,2 Other obstacles include a lack of par- systems and electronic medical records or the essen-
ity in identification and management of OUD, failure tial knowledge acquired over the past 40 years that
to provide service continuum for addiction treatment, addiction cannot be treated effectively in isolation.
and inadequately trained staff.1,2 Cost and insurance Accordingly, the Overdose Prevention and Patient
coverage, as well as legal and regulatory issues, can Safety (OPPS) Act is being considered, which will
limit access to treatment. The health care system also amend the federal statute and align 42 CRF Part 2 with
is affected by traditional stigma and biases that could the Health Insurance Portability and Accountability
lead to stereotypic thinking, limiting adequate patient Act (HIPAA) for purposes of treatment, payment, and
assessment. operations. It will allow for sharing addiction treat-
ment records within the health care system, following
Medical Providers HIPAA’s established privacy and security protections.
The prescriber role is unique and critical in managing Prohibiting disclosure outside the health care sys-
OUD. However, clinician training for SUD is not always tem would be retained, and provisions against using
adequate, and many physicians continue to have a poor addiction treatment records in criminal proceedings
understanding of the medications and guidelines for would be strengthened. Although, there is opposition
addiction treatment. from grassroots recovery organizations,5 professional
A single physician should not be the sole authority; medical organizations such as the American Society
addiction should be treated following a collaborative of Addiction Medicine support the OPPS as reflect-
care model similar to other chronic diseases, such as ing efforts to improve patient access while protecting
diabetes.3 A multimodal, multidisciplinary team must against stigmatization.6
provide coordinated care with adequate communica-
tion among team members. The team could be inde- Psychosocial Factors in Recovery from
pendent of or part of a coordinated network, preferably Substance Use Disorders
integrated with behavioral health. Medication is important, but it is not a substitute for
Treatment should be person centered and recov- the work of recovery. A medication is intended to nor-
ery oriented, with a focus on safety and quality of life. malize psychological and biophysical brain function,
Cultural- and trauma-informed principles should be allowing patients to normalize their learning and adap-
followed. Success requires the active involvement of tation in the real world. Psychosocial treatment can be
patients, focusing on participation and empowerment, an important part of the management plan for patients
not compliance. Management decisions should be with OUD or other SUDs.
based on the patient’s informed choice. Psychosocial treatment typically focuses on reduc-
ing stress and exposure to the conditioned cues associ-
Patients ated with substance use. Stress could be reduced by
Intrinsic factors, including denial and shame, keep decreasing negative emotional states; increasing resil-
patients from pursuing treatment. Stigma and bias ience to stressors through support, remoralization,
FIGURE
Barriers to Opioid Use Disorder Treatment
Limited access
Limited evidence-based
• Lack of systematic screening
knowledge and its application
• Available service array
reflecting a model of chronic
• Lack of parity
disease, outcomes,
• Cost/coverage
collaboration, and
• Inadequate
integration, with
workforce
Treatment Medical person-centered,
system providers recovery-oriented, safety-focused,
Legal/regulatory cultural- and trauma-informed
Stigma/bias principles, addressing disparities.
Treatment
provision Poor understanding of medicines
for addiction treatment.
and self-efficacy; and addressing psychiatric comorbid- intervention examples include motivational enhance-
ity that increases relapse vulnerability.7,8 ment therapy, cognitive-behavioral therapy, con-
Cognitive-behavioral approaches could be par- tingency management, community reinforcement,
ticularly useful in reducing exposure to conditioned supportive–expressive psychotherapy, and behav-
cues for substance use.8 Rewards can be changed ioral couples therapy for alcoholism and drug abuse.
by introducing “healthy pleasures”; that is, help-
ing patients normalize what they do to feel good Limitations of Psychosocial Treatment
instead of turning to drugs. Often, patients are in a of Substance Use Disorder
negative emotional state and simply want to feel nor- Although individual and group counseling is part of
mal. The drug-use cycle could be broken if healthy standard treatment, most persons with OUD relapse.11-13
pleasures are adopted. Patients also should learn to Several limitations are associated with the psychoso-
adopt refusal skills.8 They must learn how to say “no” cial treatment of SUD, including low adherence and
effectively to make this strategy protective. Avoiding unknown optimum duration of treatment.14,15 In addi-
people, places, and things that are associated with tion, psychosocial treatments can be stigmatizing.16
substance use also is important to reduce the risk Barriers to performing effective trials of psychosocial
of relapse. interventions include supervised provision of treat-
Several resources are available that provide access ment by expert therapists, which is not typical of the
to and review of several evidence-based psychosocial real world.
interventions for SUDs. The US Substance Abuse and Meta-analyses investigated adding psychosocial
Mental Health Services Administration (SAMHSA) interventions to OUD treatment during detoxification
provides links to individual interventions through and maintenance treatment. The first meta-analysis
its National Registry of Evidence-Based Programs included 11 trials of opioid detoxification that compared
and Practices.9 In addition, the National Institute on any psychosocial intervention plus any pharmacologic
Drug Abuse lists evidence-based approaches to intervention with medication alone.17 Significantly
behavioral as well as pharmacological therapies.10 reduced dropouts, clinic absences during treatment,
Interventions are related to general and specific and opioid use during treatment and at follow-up
patient groups and employ several strategies. Some were reported for psychosocial interventions. Available
Program.37-41 Initially, waivers were available only for in proportion of responders, defined as ≥4 of 6 months
physicians who meet specific requirements; however, without an opioid-positive urine test based on self-
in 2016 it became possible for qualifying nurse practi- report and monthly plus 4 random tests. The absolute
tioners and physician assistants to acquire a waiver. A 8.8% difference in responders between implant (96.4%)
physician must receive 8 hours of approved training and sublingual (87.6%) buprenorphine groups sup-
or have specific board certification, whereas all nurse ported noninferiority (P <. 001; P = .03 for superiority).
practitioners and physician assistants must complete Cumulative opioid abstinence was maintained by 85.7%
24 hours of approved training. Individual physicians and 71.9% of implant and sublingual group patients,
can have no more than 30 patients in opioid depen- respectively, over the 6-month study interval (P = .03).
dence treatment at any time during the first year. If The significant difference emerged after 3 months and
applicable, the physician could submit a second notifi- was sustained through 6 months. Changes in measures
cation of the need and intent to treat up to 100 patients of craving and withdrawal were not significantly dif-
1 year after the initial notification is submitted. As part ferent between groups from baseline to the end of treat-
of recent regulation changes, if buprenorphine treat- ment (P ≥ .43). Medication- and implant-related AEs
ment has been provided to 100 patients for at least were consistent with the safety profile of buprenor-
1 year, physicians can apply to increase their limit to phine and the implantation procedure. The study was
275 patients. The SAMSHA website hosts a buprenor- not powered to detect AE differences between groups.
phine treatment practitioner locator, with search capa- The PRO-814 study supported efficacy of the implants
bility by city, state, and zip code.42 for abstinence maintenance in opioid-dependent
adults who are clinically stable on sublingual
Buprenorphine: 6-month Subdermal Implant buprenorphine ≤8 mg/d.44 Transitioning from the sub-
A subdermal buprenorphine implant received FDA lingual formulation to the implant was not clinically
approval in 2016 to treat opioid dependence in destabilizing. However, generalizability might be lim-
patients who have achieved sustained clinical stabil- ited because of study participants who were primar-
ity on low-to-moderate transmucosal buprenorphine.26 ily white (94.9%), and most were employed, with at
Each treatment consists of 4 implants, each containing least a high school education, and were dependent on
buprenorphine 80 mg, which are inserted on the inner prescription opioids. Studies in new targets, including
side of the upper arm. The implants are removed after criminal justice and other hard-to-reach populations,
6 months, and implants should be inserted only 1 time are warranted.45
in each upper arm, for a maximum of 2 treatments.
Implants must be removed by a health care provider Buprenorphine + Naloxone
who is certified to perform the insertions. The implant is A combination formulation of buprenorphine and the
not indicated for patients starting treatment or who have mu-opioid receptor antagonist naloxone is available
not reached prolonged clinical stability. Prescribers must as a single daily-dose sublingual film and tablet.24,28
have a buprenorphine waiver, and the implants are The FDA approved the film in 2002 and the tablet in
available only through a restricted Risk Evaluation and 2013.46 Naloxone has no clinically significant effects
Mitigation Strategy (REMS) program because of FDA when administered sublingually and does not inter-
concerns about the risk of implant complications, such fere with the effects of buprenorphine.24,28 Physiological
as migration, protrusion, expulsion, and nerve dam- and subjective effects of buprenorphine and buprenor-
age.26 Health care providers must undergo live training phine/naloxone (BPN/NX) were similar at equivalent
to be certified in implant insertion and removal.43 buprenorphine doses. Including naloxone in the for-
mulation was thought to be a deterrent to its misuse
PRO-814: Buprenorphine Implant Versus as an injection. Among opioid substitution therapy
Sublingual Buprenorphine clients interviewed in Australia, fewer reported inject-
The PRO-814 trial was a noninferiority study that ing BPN/NX film (3%) and tablets (2%) compared with
compared the 6-month implant with daily sublin- those claiming to regularly inject their buprenorphine-
gual buprenorphine as maintenance treatment for only medication (25%).47
opioid-dependent patients with stable abstinence.44 The The film is available in 4 dose strengths, ranging from
multicenter study enrolled 177 outpatients who had 2 to 12 mg buprenorphine, with a 4:1 ratio between
been prescribed daily sublingual buprenorphine for buprenorphine and naloxone.24 The 6 dose formula-
≥6 months, were abstinent while taking ≤8 mg/d for tions of the tablet have a similar ratio, with buprenor-
≥90 days, and were determined to be clinically stable phine doses ranging from 0.7 to 11.4 mg.28 However, the
by their physicians. Participants were randomized to bioavailability is different between the 2 products; for
receive 4 placebo implants plus sublingual buprenor- example, the 5.7-mg/1.4-mg sublingual tablet provides
phine or sublingual placebo plus 4 buprenorphine the equivalent buprenorphine exposure as one 8-mg/
80-mg implants. The primary endpoint was difference 2-mg film dose and 12% lower naloxone exposure.28
Initially approved for treating alcohol addiction, formulation was approved by the FDA for treating alco-
the safety and efficacy of naltrexone has been widely hol dependence in 2006.29 In 2010, the indication was
studied. A meta-analysis reported a 17% reduced risk supplemented to include prevention of relapse to opioid
of heavy drinking with naltrexone compared with pla- dependence after opioid detoxification. The formulation
cebo, with an approximate 4% decrease in number of is delivered by deep gluteal IM injection of 380 mg every
drinking days.55 Several secondary outcomes also 4 weeks or once monthly and can be administered by
were significantly improved compared with placebo; any health care provider who is licensed to prescribe
however, return to any drinking was similar between medications.29 Patients should be opioid-free before
naltrexone and placebo. starting treatment. A minimum of 7 to 10 days without
Given that patients with OUD typically are ambiva- opioids is recommended to avoid precipitating opioid
lent about taking mu-antagonist medications, it is not withdrawal that can be severe enough to require hospi-
surprising that daily self-administered oral naltrexone talization. Abrupt discontinuation of naltrexone is not
has mixed results for treating opioid addiction. A meta- associated with withdrawal syndrome.
analysis concluded that oral naltrexone was not supe-
rior to treatment with placebo or no pharmacological Adverse Events
agent in detoxified patients with opioid addiction for all Treatment-emergent AEs that were more frequent
outcomes assessed.56 However, the authors noted that in the naltrexone injection group than in the placebo
barely one-fourth (28%) of participants were retained in group during clinical development for alcohol depen-
treatment in the 13 studies, suggesting that these stud- dence were similar to those observed in the safety study
ies did not allow an adequate scientific evaluation of performed in patients with opioid dependence.29 Any
oral naltrexone treatment for opioid dependence. injection-site reaction was reported in 65% of patients
Extended release of a mu-opioid antagonist would receiving naltrexone injection compared with 50% of
have the advantage of avoiding adverse events, such those with placebo injections. The AEs included gas-
as euphoria, dependence, respiratory depression, and trointestinal disorders (nausea, vomiting, diarrhea,
overdose death, that may be associated with use and and abdominal pain), somnolence or sedation, dizzi-
misuse of agonist drugs and would avoid NMU and ness, headache, musculoskeletal and connective tissue
accidental pediatric exposure. An extended-release disorders, and depression. Regardless of treatment, all
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2011;68(12):1238-1246. probuphinerems.com/wp-content/uploads/2016/02/train-slides.pdf. Accessed
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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
10. The following are barriers I face most often in my current practice that impact my ability to
Last Name First Name Degree 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 □ □ □
Mailing Address Lack of systems-based coordination of care involving an interprofessional team □ □ □
Access to clinical trials □ □ □
Integrating/utilizing electronic health records □ □ □
City State Zip Code Implementing value-based metrics/quality measures □ □ □
Insurance/financial restrictions □ □ □
Lack of patient engagement □ □ □
Date of Birth (used for tracking credits ONLY)
Lack of patient adherence/compliance to therapy □ □ □
11. How confident are you in your ability to manage your patients with OUD?
Phone Number FAX Number □ Extremely Confident
□ Very Confident
□ Somewhat Confident
*E-mail Address □ Not at All Confident
□ Does Not Apply
Enduring Activity Evaluation 12. What educational topics would be of value to you for future CME activities? Please be specific.
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? 13. Please indicate your degree:
□ 1 to 9 □ 10 to 20 □ 21 to 30 □ More than 30 □ N/A □ MD/DO □ PA □ Other Health Care
2. How many years have you been treating patients who are taking opioid medications? □ PharmD/RPh □ RN/BSN/MSN □ Industry
□ 1 to 9 □ 10 to 30 □ 21 to 30 □ More than 30 □ N/A □ NP □ PhD □ Other:_________________
3. How many years have you been treating patients with opioid use disorder (OUD)? 14. Please indicate your primary specialty:
□ 1 to 9 □ 10 to 30 □ 21 to 30 □ More than 30 □ N/A □ General Psychiatry □ Psychology □ Pharmacy
4. Approximately how many patients with OUD do you see per month? □ Addiction Psychiatry □ Internal Medicine □ Nursing
□ 1 to 9 □ 10 to 30 □ 21 to 30 □ More than 30 □ N/A □ Adult Psychiatry □ Family Practice/ □ Industry
5. Please rate the overall educational quality of this activity (from 1 = Poor; 5 = Excellent). □ Nursing General Practice □ Other:_________________
□ 1 □ 2 □ 3 □ 4 □5 □ Geriatric Psychiatry □ Research ______________________
□ Child & Adolescent
6. Do you believe this program: Yes No N/A Psychiatry
Achieved its identified educational goals and learning objectives? □ □ □
15. Please indicate your primary professional/practice setting:
Covered content that is relevant and will be useful to your practice? □ □ □ □ Office/Private Practice □ Hospital
Increased your awareness of gaps in evidence-aligned care? □ □ □ □ Research □ Academic
Advanced your knowledge of practice changes that may improve gaps □ Residency □ Fellowship
in patient care within your health care system? □ □ □ □ Urgent Care □ Fed/State Govt.
Will increase your competence in managing these patients? □ □ □ □ Pharmacy □ Industry
Inspired you to engage/coordinate care within your health care system □ Administration □ Other:______________________________
to improve health care delivery? □ □ □ * Required field
Used teaching methods and educational formats that were effective for learning? □ □ □
Will improve your ability to communicate with patients/caregivers? □ □ □ Please return the CME Registration Form before the test expires to:
Provided you with resources to use in your practice and/or with your patients? □ □ □ Vindico Medical Education
Addressed and provided strategies for overcoming barriers to optimal patient care? □ □ □ PO Box 36 Thorofare, NJ 08086-0036
Was presented objectively and was free of commercial bias*? □ □ □ or Fax to: 856-384-6680
*If you indicated that the activity was not free of commercial bias, please provide
additional comments here: Questions about CME?
Contact us at CME@VindicoCME.com or Call us at 856-994-9400 ext. 504