- Define opioid dependence and opioid
- Describe the treatment of opioid
withdrawal syndrome including the use of the Clinical Opioid
Withdrawal Scale (COWS) and pharmacologic treatments.
- Appreciate the stigma associated with
opioid dependence and the potential impact on the quality of care
A 56-year-old man with
a long history of heroin use presented to the hospital with
abdominal pain, nausea, and vomiting. He said he had been using
less heroin than usual because of the gastrointestinal complaints
and felt that his symptoms were probably from heroin withdrawal. On
initial evaluation, he was dehydrated, but his vital signs were
unremarkable and his abdominal examination was benign. His complete
blood count, liver function tests, amylase, and lipase were all
normal, and an upright KUB radiograph showed no clear cause for his
abdominal pain. He was admitted to the hospital for treatment of
dehydration and opiate withdrawal and was given intravenous fluids,
methadone, and low doses of morphine intravenously for the
Later in the evening of
admission, he complained of increasing diffuse abdominal pain. He
also complained of excessive yawning and increased lacrimation. On
physical examination, he was tachycardic, tachypneic, and generally
restless, but had a nontender abdominal examination. He was given
increased methadone to treat presumed worsening opiate
Opioid dependence is a treatable chronic medical
illness that afflicts as many as 6 million persons in the United
States. Unfortunately, many providers are uncomfortable caring for
patients with opiate dependence, unwilling to do so, or simply
uninformed about appropriate treatment strategies. This case
provides an opportunity to discuss the basics of opiate dependence
and opiate withdrawal.
The medical disorder opioid dependence
is defined as a maladaptive pattern of use of illicit or
prescription opioids leading to clinically significant impairment
or distress as manifested by three or more diagnostic criteria in
the past 12 months.(1)
These diagnostic criteria include physical dependence, tolerance,
taking opioids in larger amounts or for longer periods than
intended, desiring to cut down or control use, dedicating a large
amount of time to procuring opioids or recovering from their
effects, giving up important activities because of their use, and
using opioids despite knowledge of harm. Unfortunately, the
terminology for this disorder is confusing. Physical dependence on
an opioid is just one of the seven criteria for the diagnosis of
opioid dependence, and patients who are not physically dependent on
opioids can still have opioid dependence if they meet three other
criteria. A common illicit opioid is heroin, but any opioid pain
medication can be "diverted" to illicit use, including hydrocodone
and long-acting oxycodone.
Opioid dependence is not a
trivial problem. More than 3 million Americans have used heroin in
According to the Office of National Drug Control Policy, there were
an estimated 810,000 to 1,000,000 individuals addicted to heroin in
the United States in the year 2000, representing the highest number
of heroin-addicted persons in this country since the late
Furthermore, the National Institute on Drug Abuse (NIDA) Monitoring
the Future Survey reported that as many as 10.5% of 12th graders
reported using hydrocodone within the last year.(4) Several factors contribute to this increased use.
First, in the late 1990s, the purity of heroin
increased—heroin purity now may be as high as 80%–90%
in large urban areas. The increase in purity has increased use of
heroin by noninjection routes of administration, including snorting
and smoking. Indeed, one survey found that only one third of new
users of heroin actually inject it.(3) Not
only are illicit opioids available and pure, they are cheap: it is
not unusual to be able to buy a supply of heroin (for one "hit")
for less than $10. Interestingly, this "street price" is much
cheaper than that of diverted prescription opioid
Another reason for the increase
in opioid dependence is the dramatic increase of drug diversion
(use of a drug outside the scope of its intended purpose). In 2000,
2 million people used prescription pain relievers for nonmedical
reasons for the first time (5),
and from 1999 to 2000, the Drug Abuse Warning Network (DAWN)
reported a 68% increase in illicit use of oxycodone
Furthermore, according to the DAWN
Mortality Data Report, hydrocodone ranked among the 10 most common
drugs related to deaths in 18 cities. Also, persons who misuse
prescription opioid medications are more likely to eventually use
illicit and illegal opioids that include heroin.
This increase in opioid
addiction has exacted tremendous medical and societal costs.
Illicit opioid use—either heroin use or prescription opioid
misuse—is associated with significant harm to individuals and
burdens limited health care resources. Major medical and
psychiatric illnesses often coexist with opiate addiction. For
example, depression, hepatitis infection (primarily hepatitis C),
and HIV are all common in patients who have opioid dependence.
Violence and crime are also associated with opioid
We are told that the patient in
this case has a long history of heroin use and likely suffers from
the disorder of opioid dependence. The patient's symptoms as
described are consistent with classic opioid withdrawal. Opioid
withdrawal is defined diagnostically as three or more symptoms that
include dysphoric (negative) mood, nausea or vomiting, muscle
aches, runny nose or watery eyes, dilated pupils, goose bumps or
sweating, diarrhea, yawning, fever, and insomnia. In my clinical
experience, patients sometimes complain of abdominal cramping or
bony pain ("Doc, it's in my bones"), but overt abdominal pain (as
seen in this case) is less common. The withdrawal symptoms cause
significant distress to the individual and often impair functioning
in activities of daily living. Opioid withdrawal symptoms may be so
severe and aversive that many opioid-dependent individuals continue
to use the drugs only to avoid withdrawal. The nature and severity
of the opioid withdrawal syndrome depend on the individual, the
opioid pharmacology (short- vs. long-acting), and the standard dose
used. Research has recently shown benefit for monitoring opioid
withdrawal using objective measures such as the Clinical Opioid
Withdrawal Scale (COWS).(7) An
objective measure was not used in this case, but given the
constellation of symptoms, a presumptive diagnosis of opioid
withdrawal was made.
How should this patient's opiate
withdrawal be treated? Because opioid withdrawal syndrome, while
aversive, is not deadly, many insurers will not pay for a
hospitalization for only treatment of opioid withdrawal. Partly for
this reason, opiate withdrawal is generally managed in the
outpatient setting in methadone treatment facilities (or in
licensed opioid agonist therapy [OAT] programs). Occasionally,
patients like this one are admitted to a nonmethadone facility
(e.g., hospital) for another illness, and opioid dependence
treatment using opioids is necessary to help treat the primary
illness (e.g., an acute myocardial infarction in a patient with
heroin withdrawal). Management of opioid withdrawal in these
patients can be difficult. The primary concern should be managing
the acute medical illness and stabilizing the patient undergoing
opioid withdrawal. In the case of a patient with an acute illness
and opioid withdrawal (like the patient who presented in our case)
who does not want long-term treatment for their opioid dependence,
a short, tapering "detoxification" course of opioids is often used.
In both outpatient and inpatient settings, both methadone and
buprenorphine can be used to treat opioid withdrawal as well as to
provide longer term maintenance treatment for opiate
Emerging evidence suggests that
a short, decreasing dose course of either methadone or
buprenorphine can ameliorate the symptoms of withdrawal while acute
medical issues are addressed. Doses used depend on several factors
including the patient's level of physical opioid dependence, the
type of opioids illicitly used, and the nature of the acute medical
illness. Typically, detoxification treatment lasts less than 2
weeks, and there are several protocols available and
Emerging research has also outlined detoxification protocols using
buprenorphine and its potential preferential benefits as a
first-line pharmacologic agent.(9-17)
If long-term treatment of opioid
dependence is a goal for patients needing detoxification for an
acute medical illness, patients should be offered maintenance OAT
during their hospitalization. It is well established that
maintenance OAT is preferred over detoxification to reduce the
morbidity and mortality of the disease of opioid
Most providers are aware that methadone is the mainstay of
pharmacologic treatment of opioid dependence, but methadone can
only be prescribed for opioid dependence treatment within OAT
programs or when patients with opiate dependence are admitted to an
acute care hospital for other medical issues. Buprenorphine is
another effective medical treatment of opioid dependence (e.g.,
maintenance OAT) and can also be used as a pharmacologic treatment
of opioid withdrawal syndrome. In 2002, Congress amended the Drug
Abuse Treatment Act (DATA 2000), allowing credentialed and Drug
Enforcement Administration (DEA)-waivered physicians to prescribe
buprenorphine and buprenorphine/naloxone (both Schedule III
medications) for OAT in office-based practices.(19) Like methadone OAT for use in licensed methadone OAT
programs, buprenorphine administered in office-based practices is
effective at reducing illicit opioid use, drawing patients into
treatment, and reducing harm associated with comorbid medical and
Clinical studies suggest that patients maintained on buprenorphine
for a period of time do better than patients who are merely
"detoxified" using buprenorphine.(18)
In this case, the provider's
original working diagnosis was opioid withdrawal syndrome. Even
when this diagnosis is strongly suspected, a full and complete
history and physical examination as well as appropriate laboratory
studies should be performed. Other medical disorders, such as pain
syndromes, can mimic opioid withdrawal syndrome. In addition, many
patients with opiate dependence present with comorbid conditions of
HIV, hepatitis C, or skin infections—all consequences of
intravenous injection of illicit opioids. These disorders may
require specific treatment or may influence the treatment of other
In the patient in this case, the
overt abdominal pain would lead me to consider other diagnoses. The
patient's yawning, lacrimation, tachycardia, tachypnea, and general
restlessness are consistent with opioid withdrawal. His nontender
abdominal examination also would be consistent with this diagnosis.
However, prescribing intravenous morphine would generally not be my
initial treatment of choice for opioid withdrawal if that was the
only medical condition needing attention. Detoxification using
buprenorphine (or potentially methadone) would better assist in
transitioning care from a detoxification treatment to longer term
maintenance therapy using buprenorphine or methadone. Although that
would represent my usual practice, in this case, because the
patient has abdominal pain of unclear etiology, intravenous
morphine may be a good option. As a short-acting treatment, I would
be able to monitor the acuity of abdominal pain to determine
whether it was due to atypical opioid withdrawal. In addition,
introduction of buprenorphine in this patient, who may need
surgical management of his acute condition, may complicate his
perioperative pain management. Buprenorphine is a partial opioid
agonist, and as a result of its high receptor affinity, traditional
doses of perioperative pain medications may not readily displace
buprenorphine from the opioid receptor and thus may not have the
necessary analgesic effect.(27)
The bottom line is that, at this
point, it would be appropriate to evaluate the patient for other
causes of his abdominal pain and worsening
Despite increasing the methadone, the
patient's abdominal pain persisted and worsened. A covering
physician was contacted overnight about the abdominal pain. The
nurse told the physician that the patient had asked for something
stronger for the pain. Because the daytime physician had earlier
described the patient as a "strung out shooter," the covering
physician believed that the patient was either drug seeking through
his complaints of pain or not receiving enough methadone. Instead
of reevaluating or reexamining the patient, the covering physician
ordered another increase in the dose of methadone. Overnight, the
patient continued to have diffuse abdominal pain and
In the morning, the patient's abdominal pain
became severe, his tachycardia worsened, and his blood pressure
decreased, indicating a possible infection (septic shock). He was
given aggressive intravenous fluids, and his abdominal computed
tomography scan (CT) revealed a perforated colon, likely from
diverticulitis. The patient then underwent successful colonic
resection and was discharged from the hospital 2 weeks
The patient's worsening condition in the face of
opioid agonist therapy should have given the covering physician
pause, and another diagnosis should have been strongly entertained.
Unfortunately, the stigma associated with having an alcohol or drug
use problem can contribute to misdiagnosis or delays in diagnosis.
There is general consensus that physicians and other health care
providers have negative perceptions about patients with alcohol and
other drug disorders (28-30)—attitudes that may result in worse health
outcomes. For example, 23% of HIV-infected patients had physicians
with negative attitudes toward patients who were injection drug
users. Injection drug users who were cared for by physicians with
negative attitudes had a significantly lower adjusted rate of
treatment with highly active antiretroviral therapy than
non–injection drug users who were cared for by such
physicians or injection drug users who were cared for by physicians
with positive attitudes.(28)
Although not stated explicitly in the case presentation, the
covering provider may have been biased by the description of the
patient as a "strung-out shooter" and treated him differently.
Physicians also have lower satisfaction in
treating patients with alcohol and other drug disorders than in
treating those with other medical illnesses.(31) This is somewhat surprising. Comparing alcohol and
drug disorder diseases with other chronic care diseases, relapse
rates to unhealthy behavior (e.g., alcohol use in an
alcohol-dependent patient; poor diet control in a patient with
diabetes) are comparable.(32)
Fewer than 40% of patients adhere to their antihypertensive
regimens, fewer than 30% of patients adhere to the recommended diet
or behavioral changes, and 50%–70% of hypertensive patients
experience a relapse of their disease annually. These rates are
comparable to a relapse rate between 40%–60% for alcohol and
other drug use disorders.(32-34)
Considering the effects of
alcohol and other drug use disorders on patients and their
environment, and the effective evidence-based treatments that are
available for these disorders, it is unfortunate that health care
providers may not appropriately screen, identify, and treat them.
How do clinicians ensure that patients with alcohol and other drug
use receive equal, high-quality care? In my experience, the first
step is to recognize that alcohol and other drug disorders are
chronic medical illnesses that are never quickly fixed. Improved
education in substance abuse disorders for trainees and practicing
clinicians may also improve the quality of care. Hospitals and
health care systems should consider structured mechanisms to ensure
appropriate treatment of opioid dependence and opioid
- Opioid dependence is a chronic,
treatable medical condition.
- The Clinical Opioid Withdrawal Scale
(COWS) can be a useful objective measure of opioid
- Methadone and buprenorphine treatments
are available for both opioid dependence and opioid withdrawal
- Providers should be suspicious of
atypical presentations of opioid withdrawal and evaluate patients
Adam J. Gordon, MD, MPH
Assistant Professor of Medicine, Advisory Dean
University of Pittsburgh School of Medicine
Faculty Disclosure: Dr. Gordon has
declared that neither he, nor any immediate member of his family,
has a financial arrangement or other relationship with the
manufacturers of any commercial products discussed in this
continuing medical education activity. In addition, his commentary
does not include information regarding investigational or off-label
use of pharmaceutical products or medical devices.
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