The monitoring of drug-related behavior is essential throughout the course
of opioid-therapy. The goals are to clarify whether any problematic behavior
has occurred, and if it has, to appropriately diagnose it as a first step
in management.
Most patients engage in responsible drug use over time. They adhere to
the practitioner’s instructions, and regularly communicate benefits
and problems. They do not substantively change therapy without prior discussion.
Some patients, however, engage in problematic drug-related behavior (also
termed “aberrant drug-related behavior” and non-adherence
behavior). Based on clinical experience, it is possible to describe a
large number of these problematic behaviors (Table 1). Some, such as occasional
unsanctioned dose escalation when symptoms flare, are probably quite common
and unlikely, by themselves, to indicate a diagnosis of addiction. Others,
such as injection of an oral formulation, are very serious and potentially
diagnostic of addiction.
Table 1: Problematic Drug-Related Behaviors and the Likelihood that
They Reflect An Underlying Addictive Disorder (.pdf)
If problematic drug-related behavior occurs, the clinician must reassess
the patient, posit a diagnostic formulation, and respond in a clinically-appropriate
manner. To develop a diagnostic formulation, there must be a clear understanding
of the varied phenomena related to chemical dependency and the differential
diagnosis they imply.
These phenomena include:
To establish a working diagnosis, this understanding of terminology must
be complemented by a comprehensive assessment of the drug-related behavior.
Based on this assessment, one or more of several broad diagnostic categories
should be applied (Table 2). In some cases, the diagnosis is clear from
a one-time evaluation of present and past behavior. In others, the complexity
of the case mandates a tentative diagnosis, confirmation of which must await
time to determine the response to new controls or medical interventions.
If the decision is made to continue prescribing, efforts to regain adherence
with the therapy must be instituted, and this must begin even if more time
is required to establish a diagnosis (see Responding to Problematic
Drug-Related Behavior).
Table 2: Differential Diagnosis of Problematic Drug-Related Behaviors (.pdf)
What is Tolerance?
Tolerance is a property of some drugs defined by the need for increasing
doses to maintain effects, which is induced by exposure to the drug. It
is a complex phenomenon that may involve both physiologic changes (known
as “pharmacologic” tolerance) and learning (known as “associative”
tolerance). Pharmacologic tolerance may be “pharmacokinetic”
(related to drug-induced changes in drug metabolim) or pharmacodynamic
(related to any number of changes that alter the concentration-response
relationship of the drug). Clinically relevant tolerance to opioid effects
is generally considered to be pharmacodynamic.
The mechanisms involved in the development of pharmacodynamic tolerance
are complex. Recent research has elucidated a mechanism that involves
the NMDA receptor and can be reversed by NMDA receptor blockers. Other
processes, such as changes in second messengers unrelated to the NMDA
receptor, changes in receptor number, and activation of parallel systems
that are anti-analgesic, also may be involved.
Tolerance may develop to any opioid effect and both the rate of development
and the degree of tolerance varies from effect to effect, and from individual
to individual.
Tolerance to adverse effects is a favorable phenomenon, which allows dose
escalation to levels associated with improved analgesia. Clinically relevant
tolerance to analgesic effects can occur and could be a major impediment
to the clinical use of opioid drugs. In the clinical setting, however,
the need for dose escalation has several potential drivers, only one of
which is tolerance. Progression of disease, a change in pain mechanism
(e.g., a shift from a nociceptive to a neuropathic mechanism), and psychological
processes that lead to increased pain all may lead to declining efficacy.
This observation suggests that the need for dose escalation can be ascribed
to tolerance only if an alternative explanation cannot be discerned.
Most patients who benefit from long-term opioid therapy require stable
doses for prolonged periods. Dose escalations from time to time may be
needed to recapture analgesia during episodes of increased pain. This
observation lends credence to the clinical perception that tolerance to
analgesic effects is rarely a major problem during opioid therapy for
chronic pain.
Tolerance to the positive psychic effects of a self-administered drug
has been postulated to be an important element in the genesis of addiction.
Patients who receive opioids for pain do not commonly express significant
effects of this type, and the development of tolerance to any mood effect
rarely influences the course of therapy. In short, addiction can occur
without evidence of tolerance and tolerance can be inferred in the clinical
setting without any of the behavioral problems consistent with abuse or
addiction.
References:
Nghiemphu LP, Portenoy RK: Opioid tolerance: a clinical perspective.
In Bruera EB, Portenoy RK (eds): Topics in Palliative Care, vol 5. New
York: Oxford University Press, 2000, pp 197-212.
What is Physical Dependence?
Physical dependence is a pharmacologic property defined solely by the
occurrence of an abstinence syndrome following abrupt dose reduction,
decreasing blood level of the drug, or administration of an antagonist.
The dose or duration of administration required to produce clinically
significant physical dependence in humans is not known. Studies suggest
that very little opioid exposure—as little as a single dose—can
result in some some degree of physical dependence. Most practitioners
assume that the potential for an abstinence syndrome exists after opioids
have been administered regularly for only a few days.
Physical dependence is not problematic as long as patients are instructed
not to abruptly discontinue therapy after long-term use and no antagonist
drugs are administered.
The capacity for withdrawal, i.e., physical dependence, is often confused
with, or mislabeled, as “addiction.” This is a significant
error that must be avoided by health care professionals. Use of the term
reinforces the stigma associated with opioid therapy and should be abandoned.
Likewise, referring to the patient as “dependent” should also
be discouraged, since it creates confusion between physical dependence
and the type of psychological dependence that is associated with addiction.
Although physical dependence is neither necessary nor sufficient for addiction,
the phenomenon of physical dependence has been postulated to contribute
to the spiraling of aberrant drug-use that drives the addictive process
in predisposed individuals. A drug like an opioid might initially be taken
to gain a psychic effect. As a result of tolerance, a higher dose is needed
to regain the effect after a time, and this reinforces the frequency of
dosing and the search for higher doses. After physical dependence develops,
uncomfortable withdrawal occurs between doses, further driving drug craving,
this time to prevent the discomfort. This process is clinically observed
among those who develop opioid addiction; it appears to be rarely relevant
to patients who receive opioids for medical purposes, whether or not aberrant
drug use occurs.
What is Pseudoaddiction?
Pseudoaddiction refers to the development of problematic drug-related
behaviors that are driven by desperation surrounding unrelieved pain.
As originally coined, the term applied to the cancer population and to
less serious behaviors, such as frequent requests for dose escalation.
Over time, the meaning has been enlarged and it is now applied to virtually
any behavior and the cardinal characteristic is decline or disappearance
of the behavior when effective measures to relieve the pain (such as an
increase in drug dosage) are implemented.
In ascribing more overt and potentially harmful drug-related behaviors
to pseudoaddiction, there is a risk of ignoring a concurrent addiction.
This is a serious concern. It is important to recognize that addiction
and pseudoaddiction can coexist, and that the report of unrelieved pain
does not give license to behaviors that are inappropriate or illegal.
Even if the term pseudoaddiction is applied, it is necessary to gain control
over behaviors that place the patient, the physician, or others at risk.
References:
Portenoy RK, Payne R, Passik S: Acute and chronic pain. In Lowinson JH,
Ruiz P, Millman RB (eds): Comprehensive Textbook of Substance Abuse, Fourth
Edition. Baltimore: Williams and Wilkins, in press.
Abuse, Addiction and Dependence
Variation in the definitions of the terms “abuse,” “addiction”
and “dependence” has contributed to diagnostic confusion.
The clinician who is monitoring drug-related behavior over time must have
a clear understanding of these terms.
According to one definition, the term “drug abuse” should
apply to the use of any drug that is outside of accepted norms. Although
it is true that normative behavior reflects culture and is not constant,
this definition has utility in the clinical setting. It labels any use
of an illicit drug and any misuse of a prescribed drug as abuse.
The American Psychiatric Association’s Diagnostic and Statistical
Manual-4th revision (DSM-IV) offers a more clinical definition, designating
substance abuse as one of two Psychoactive Substance Use Disorders and
linking it with “Psychoactive Substance Dependence,” a term
intended to denote addiction. Substance abuse is defined as a maladaptive
pattern of drug use that results in harm or places the individual at risk.
The DSM-IV definition of Psychoactive Substance Dependence is defined
as a maladaptive pattern of drug use that persists at least one month
and includes at least three of nine criteria. Although the criteria include
descriptions of craving, compulsive use and use despite harm (which could
be used to establish the diagnosis in the absence of any other criteria),
they also refer to tolerance and physical dependence. This inclusion of
tolerance and physical dependence also characterizes older definitions
of “addiction” developed by expert committees of the World
Health Organization.
All of the latter definitions have been criticized by pain specialists,
who have been particularly disturbed by any reference to tolerance and
physical dependence, both of which may be normal biological responses
when opioids are used to treat pain. To address this criticism, a joint
Task Force of the American Academy of Pain Medicine, the American Pain
Society, and the American Society of Addiction Medicine created consensus
definitions. Addiction is:
| "a primary, chronic, neurobiologic 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." |
References:
American Pain Society. Definitions related to the use of opioids for
the treatment of pain: A consensus document from the American Academy
of Pain Medicine, the American Pain Society, and the American Society
of Addiction Medicine. ©1996-2003. Accessed online October 29, 2003.
http://www.ampainsoc.org/advocacy/opioids2
Kirsch KL, Whitcomb LA, Donaghy K, Passik SD. Abuse and addiction issues
in medically ill patients with pain: attempts at clarification of terms
and empirical study. Clin J Pain 2002;18:S52-S60.
Portenoy RK, Payne R, Passik S: Acute and chronic pain. In Lowinson JH,
Ruiz P, Millman RB (eds): Comprehensive Textbook of Substance Abuse, Fourth
Edition. Baltimore: Williams and Wilkins, in press.
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;26:655-667.
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