Definitions Related to the
Use of Opioids for the Treatment of Pain
The American Academy of Pain Medicine, The American Pain Society
and the American Society of Addiction Medicine
Consensus Document
BACKGROUND
Clear terminology is necessary for effective communication regarding
medical issues. Scientists, clinicians, regulators and the lay public
use disparate definitions of terms related to addiction. These disparities
contribute to a misunderstanding of the nature of addiction and
the risk of addiction, especially in situations in which opioids
are used, or are being considered for use, to manage pain. Confusion
regarding the treatment of pain results in unnecessary suffering,
economic burdens to society, and inappropriate adverse actions against patients and professionals.
Many medications, including opioids, play important roles in the
treatment of pain. Opioids, however, often have their utilization
limited by concerns regarding misuse, addiction and possible diversion for non-medical uses.
Many medications used in medical practice produce dependence, and
some may lead to addiction in vulnerable individuals. The latter
medications appear to stimulate brain reward mechanisms; these include
opioids, sedatives, stimulants, anxiolytics, some muscle relaxants, and cannabinoids.
Physical dependence, tolerance and addiction are discrete and different
phenomena that are often confused. Since their clinical implications
and management differ markedly, it is important that uniform definitions,
based on current scientific and clinical understanding, be established
in order to promote better care of patients with pain and other
conditions where the use of dependence-producing drugs is appropriate,
and to encourage appropriate regulatory policies and enforcement strategies.
RECOMMENDATIONS
The American Society of Addiction Medicine (ASAM), the American
Academy of Pain Medicine (AAPM), and the American Pain Society (APS)
recognize the following definitions and recommend their use:
ADDICTION
Addiction is a primary, chronic, neurobiologicneurobiological
disease, with genetic, psychosocial, and environmental factors influencing
its development and manifestations. It is characterized by behaviors
that include one or more of the following: impaired control over
drug use, compulsive use, continued use despite harm, and craving.
PHYSICAL DEPENDENCE
Physical dependence is a state of adaptation
that often includes tolerance and is manifested by a drug class
specific withdrawal syndrome that can be produced by abrupt cessation,
rapid dose reduction, decreasing blood level of the drug, and/or
administration of an antagonist.
In the case of sedative drugs, spontaneous withdrawal may occur
with continued use. Tolerance Tolerance is a state of adaptation
in which exposure to a drug induces changes that result in a diminution
of one or more of the drug's effects over time.
DISCUSSION
Most specialists in pain medicine and addiction medicine
agree that patients treated with prolonged opioid therapy usually
do develop physical dependence and sometimes develop tolerance,
but do not usually develop addictive disorders. However, the actual
risk is not known and probably varies with genetic predisposition,
among other factors. Addiction, unlike tolerance and physical dependence,
is not a predictable drug effect, but represents an idiosyncratic
adverse reaction in biologically and psychosocially vulnerable individuals.
Most exposures to drugs that can stimulate the brain's reward center
do not produce addiction. Addiction is a primary chronic disease
and exposure to drugs is only one of the etiologic factors in its development.
Addiction in the course of opioid therapy of pain can best be assessed
after the pain has been brought under adequate control, though this
is not always possible. Addiction is recognized by the observation
of one or more of its characteristic features: impaired control,
craving and compulsive use, and continued use despite negative physical,
mental and/or social consequences. An individual's behaviors that
may suggest addiction sometimes are simply a reflection of unrelieved
pain or other problems unrelated to addiction. Therefore, good clinical
judgment must be used in determining whether the pattern of behaviors
signals the presence of addiction or reflects a different issue.
Behaviors suggestive of addiction may include: inability to take
medications according to an agreed upon schedule, taking multiple
doses together, frequent reports of lost or stolen prescriptions,
doctor shopping, isolation from family and friends and/or use of
non-prescribed psychoactive drugs in addition to prescribed medications.
Other behaviors which may raise concern are the use of analgesic
medications for other than analgesic effects, such as sedation,
an increase in energy, a decrease in anxiety, or intoxication; non-compliance
with recommended non-opioid treatments or evaluations; insistence
on rapid-onset formulations/routes of administration; or reports
of no relief whatsoever by any non-opioid treatments.
Adverse consequences of addictive use of medications may include
persistent sedation or intoxication due to overuse; increasing functional
impairment and other medical complications; psychological manifestations
such as irritability, apathy, anxiety or depression; or adverse
legal, economic or social consequences. Common and expected side
effects of the medications, such as constipation or sedation due
to use of prescribed doses, are not viewed as adverse consequences
in this context. It should be emphasized that no single event is
diagnostic of addictive disorder. Rather, the diagnosis is made
in response to a pattern of behavior that usually becomes obvious over time.
Pseudoaddiction is a term which has been used to describe patient
behaviors that may occur when pain is undertreated. Patients with
unrelieved pain may become focused on obtaining medications, may
"clock watch," and may otherwise seem inappropriately "drug seeking."
Even such behaviors as illicit drug use and deception can occur
in the patient's efforts to obtain relief. Pseudoaddiction can be
distinguished from true addiction in that the behaviors resolve
when pain is effectively treated.
Physical dependence on and tolerance to prescribed drugs do not
constitute sufficient evidence of psychoactive substance use disorder
or addiction. They are normal responses that often occur with the
persistent use of certain medications. Physical dependence may develop
with chronic use of many classes of medications. These include beta
blockers, alpha-2 adrenergic agents, corticosteroids, antidepressants
and other medications that are not associated with addictive disorders.
When drugs that induce physical dependence are no longer needed,
they should be carefully tapered while monitoring clinical symptoms
to avoid withdrawal phenomena and such effects as rebound hyperalgesia.
Such tapering, or withdrawal, of medication should not be termed
detoxification. At times, anxiety and sweating can be seen in patients
who are dependent on sedative drugs, such as alcohol or benzodiazepines,
and who continue taking these drugs. This is usually an indication
of development of tolerance, though the symptoms may be due to a
return of the symptoms of an underlying anxiety disorder, due to
the development of a new anxiety disorder related to drug use, or
due to true withdrawal symptoms.
A patient who is physically dependent on opioids may sometimes continue
to use these despite resolution of pain only to avoid withdrawal.
Such use does not necessarily reflect addiction.
Tolerance may occur to both the desired and undesired effects of
drugs, and may develop at different rates for different effects.
For example, in the case of opioids, tolerance usually develops
more slowly to analgesia than to respiratory depression, and tolerance
to the constipating effects may not occur at all. Tolerance to the
analgesic effects of opioids is variable in occurrence but is never
absolute; thus, no upper limit to dosage of pure opioid agonists can be established.
Universal agreement on definitions of addiction, physical dependence
and tolerance is critical to the optimization of pain treatment
and the management of addictive disorders. While the definitions
offered here do not constitute formal diagnostic criteria, it is
hoped that they may serve as a basis for the future development
of more specific, universally accepted diagnostic guidelines. The
definitions and concepts that are offered here have been developed
through a consensus process of the American Academy of Pain Medicine,
the American Pain Society, and the American Society of Addiction Medicine.