Clinicians should recognize that virtually any drug acting on the
central nervous system or any route of drug administration can be
abused. The effective management of patients with substance abuse
histories requires a comprehensive approach that accounts for the
biological, chemical, social, and psychiatric aspects of substance
abuse and addiction. This approach goes beyond simply avoiding
certain drugs or routes of administration and provides practical
means to manage risk during cancer treatment.
Although the most difficult issues in cancer care typically arise in
those who are actively abusing alcohol or other drugs, the following
principles can also apply to patients who are in drug-free recovery
and those who are in methadone maintenance programs. The guidelines
below are likely to be most helpful in the management of the active
drug abuser. The management, recognition, and documentation of
addiction-related outcomes may be helpful and necessary at various
times in all pain treatments.
Recommendations for the long-term administration of potentially
abusable drugs, such as opioids, to patients with a history of
substance abuse are based solely on clinical experience. Studies are
needed to determine the most effective strategies and to empirically
define patient subgroups who may be most amenable to different
approaches. The following guidelines broadly reflect the types of
interventions that may be considered in this clinical context (Table
Involve a Multidisciplinary TeamIn the population of
patients with cancer and substance abuse, pain and symptom management
often is complicated by multiple medical, psychosocial, and
administrative problems. A team approach can be very useful in
addressing these problems and avoiding provider burn-out. The most
effective team may consist of an oncologist, a physician with
expertise in pain/palliative care, nurses, social workers, and, if
possible, a mental health professional with expertise in addiction medicine.
Set Realistic Goals for TherapyThere is a high
recurrence rate for drug abuse and addiction. The risk of relapse is
higher because of the stress associated with cancer and the ready
availability of centrally acting drugs. Complete prevention of
relapses may be impossible in such a setting. If there is a general
understanding that compliance and abstinence are not realistic,
conflicts with staff in terms of management goals may be reduced.
Rather, the goal of team management might be the creation of a
structure for therapy that includes sufficient social/emotional
support and limit-setting to contain the harm done by relapses and to
render them less frequent.
Severe substance-use disorder and comorbid psychiatric diagnoses may
prevent a small subgroup of patients from complying with the
requirements of oncologic therapy. In such circumstances, clinicians
must reestablish limits on multiple occasions and attempt to develop
an increasing variety and intensity of supports. Frequent team
meetings and consultations with other clinicians may be needed.
Ultimately, appropriate expectations must be clarified and failing
Evaluate and Treat Comorbid Psychiatric DisordersThe
comorbidity of personality disorder, depression, and anxiety
disorders in alcoholics and other patients with substance-abuse
histories is extremely high. The treatment of anxiety and
depression can increase patient comfort and possibly diminish the
likelihood of relapse or aberrant drug-taking.
Prevent or Minimize Withdrawal SymptomsMany patients
with a history of drug abuse consume multiple drugs, and therefore a
complete drug-use history must be elicited to prepare for the
possibility of withdrawal. Delayed abstinence syndromes, such as may
occur following abuse of some benzodiazepine drugs, may pose a
particular diagnostic challenge. Clinicians must be familiar with the
signs and symptoms associated with withdrawal from opioids and other drugs.
Consider the Therapeutic Impact of ToleranceAs mentioned
in part 1 of this article (April 1998, p 517), tolerance is a complex
phenomenon,[2,3] and its impact on clinical management in this
context is likely to be highly variable. Patients who are actively
abusing drugs may have sufficient drug tolerance to influence the use
of prescription drugs subsequently administered for an appropriate
It is possible that exposure to a drug of abuse will induce
sufficient tolerance to the desired therapeutic effects and make pain
management more difficult. A survey of hospitalized patients on
methodone maintenance failed to identify any difference in the need
for postoperative analgesics between those with and without a
substance abuse history. However, anecdotal experience suggests
that some actively abusing patients who develop a therapeutic need
for an opioid or a sedative-hypnotic drug do require relatively high
initial doses or need rapid dose escalation to establish or retain
Similarly, clinical observation suggests that some patients receiving
methadone maintenance require relatively higher opioid doses to treat
acute pain and relatively rapid dose escalation at the start of
therapy to identify a useful dose for chronic cancer pain management.
From a practical perspective, the clinician must not only be cautious
in estimating the degree to which tolerance may be operating but also
remain cognizant of the potential need for relatively higher doses.
The starting dose of a therapeutic drug should be conservative, and
rapid dose titration with careful monitoring should be available.
Apply Appropriate Pharmacologic Principles to Treat Cancer PainTo
optimize long-term opioid therapy, well-accepted guidelines for
cancer pain management must be applied.[5,6] These guidelines
emphasize the importance of patient self-report as the basis for
dosing, individualization of therapy to identify a favorable balance
between efficacy and side effects, and the value of monitoring over
time. The concurrent treatment of side effects can optimize the
balance between analgesic and adverse effects.
The most important guideline for long-term opioid therapy,
individualization of the dose without regard to its size, can be
problematic in populations with histories of substance abuse.
Although it may be appropriate to exercise caution in prescribing
potentially abusable drugs to these populations, the decision to
forego the principle of dose individualization without regard to
absolute dose may increase the likelihood of undertreatment.[8,9] The
unrelieved pain that results can, in turn, lead to the development of
aberrant drug-related behaviors. Although these behaviors might be
best understood as pseudoaddiction (ie, distress and drug-seeking
behavior in patients with unrelieved cancer pain), their occurrence
confirms clinicians fears and encourages even greater caution
Given the dual role of methadone as a treatment for opioid
addiction and as an analgesic, clinicians who manage patients
with substance-abuse histories must understand the pharmacology of
this drug. The differences in the dosing of methadone for its two
indications are striking.
Abstinence can be avoided and opioid craving reduced with a single
daily dose. This is consistent with the long elimination half-life of
this drug. Analgesic effects after a dose, however, are usually much
briefer than would be expected, given the drugs half-life.
Indeed, one double-blind study demonstrated that the duration of
analgesia after a single dose of methadone is comparable to that
after morphine, an opioid with a short half-life. Although there
are exceptions, most patients appear to require a minimum of four
doses of methadone per day to achieve sustained analgesia.
Patients who are receiving methadone maintenance as a treatment for
opioid addiction can be administered methadone as an analgesic
outside of the guidelines of the addiction treatment program. This
typically requires a substantial change in therapy, including dose
escalation and multiple daily doses.
Although the management of such a change does not pose difficult
problems from a pharmacologic perspective, it can create considerable
stress for the patient and the clinicians involved in the treatment
of the addiction disorder. Some patients express a lack of faith in
the analgesic efficacy of methadone because the drug has been labeled
as addiction therapy, rather than a pain therapy. Others wish to
continue the morning dose for addiction, even if treatment during the
rest of the day uses the same drug at an equivalent or higher dose.
Some physicians who work at methadone clinics are willing to stay
involved and prescribe opioids, including methadone, outside of the
program, and others wish to relinquish care.
Select Drugs and Administration Routes for the Symptom and SettingAs
discussed previously, there is little reason to believe that the
common clinical lore about the differences in addiction liability
between short-acting and long-acting drugs or among different routes
of administration are relevant to the management of palliative
therapies in populations without substance abuse. In the population
of known substance abusers, however, it may be prudent to consider
There is no disadvantage to the use of a long-acting preparation, and
it is possible on theoretical grounds that the rapid onset and
decline of effects associated with short-acting drugs could
contribute to the development of aberrant drug-related behaviors.
Accordingly, it is appropriate during opioid therapy to rely, if
possible, on the use of long-acting drugs, such as oral methadone,
oral controlled-release or sustained-release opioid formulations, and
Recognize Specific Drug Abuse BehaviorsAll patients who
are prescribed potentially abusable drugs must be monitored over time
for the development of aberrant drug-related behaviors. The need for
this monitoring is especially strong in patients who have a remote or
current history of substance abuse, including alcohol abuse. If there
is a high level of concern about such behaviors, monitoring may
require relatively frequent visits and regular assessment of
significant others who can provide observations about patients
To facilitate the early recognition of aberrant drug-related
behaviors in patients who have been actively abusing drugs in the
recent past, regular screening of urine for illicit or licit but
unprescribed drugs may be appropriate. The patient should be informed
about this approach, which should be explained as a method of
monitoring that can be reassuring to the clinician and provide a
foundation for aggressive symptom-oriented treatments. Presented in
this way, it is a technique that enhances rather than threatens the
therapeutic alliance with the patient. Patients who protest
excessively may be unwilling or unable to enter a collaborative
relationship in which the clinician can be confident of responsible
drug-taking by the patient. Without such confidence, the clinician is
unlikely to respond to the patients unrelieved symptoms with
Utilize Nondrug Approaches as AppropriateA variety of
nondrug interventions may be useful in helping patients cope with the
cancer treatment. These include educational interventions designed to
assist patients in communicating with the staff about pain and
negotiating the complexities of the medical system, as well as
numerous cognitive techniques that enhance relaxation and aid in
coping. Nondrug interventions may be helpful adjunctive therapies but
should not be seen as substitutes for drugs targeted to pain,
depression, anxiety, or other physical or psychological symptoms.
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