Download Long-Acting Opioids and Short-Acting Opioids

PAIN MEDICINE
Volume 10 • Number S2 • 2009
Long-Acting Opioids and Short-Acting Opioids: Appropriate Use
in Chronic Pain Management
Perry G. Fine, MD,* Gagan Mahajan, MD,† and Mary Lynn McPherson, PharmD‡
*Pain Research Center, University of Utah School of Medicine, Salt Lake City, Utah; †Anesthesiology and Pain Medicine,
University of California, Davis School of Medicine, Sacramento, California; ‡School of Pharmacy, University of Maryland,
Baltimore, Maryland, USA
ABSTRACT
In recent years, opioid therapy for the management of chronic noncancer pain has become more
widely accepted following the publication of data demonstrating the efficacy of this class of drugs in
a variety of pain conditions, including osteoarthritis, neuropathic pain, and low back pain. An array
of short-acting and long-acting opioids has been formulated to help prescribers more effectively
tailor the management of chronic pain based on the quality and temporal profile of the pain as well
as the functional goals of the individual patient. Evidence suggests that both of these groups of
medications offer unique benefits to individual patients and that neither is more efficacious than the
other. Rather, both short-acting and long-acting opioids should be considered in the overall
pharmacotherapeutic treatment of patients with chronic noncancer pain.
Key Words. Chronic; Opioid; Pain Management
Introduction
I
n properly selected and monitored patients,
opioid analgesics are recognized as a widely
accepted and, sometimes, indispensable, class of
agents when used as part of a comprehensive, multimodal approach to the management of various
types of chronic pain [1,2].
Recent years have seen a move toward greater
use of these drugs in the management of the
diverse group of patients with chronic noncancer
pain [3–6]. Despite the historic stigmatization of
opioids and practitioners’ fears about prescribing
agents with abuse potential, these medications are
gradually becoming more accepted in the spectrum of noncancer pain syndromes, a concept that
has been endorsed by organizations including the
American Pain Society, American Academy of
Pain Medicine, and the American Geriatrics
Society, others [7,8]. This may be attributable to
greater clinical experience with this drug class, the
availability of different long-acting opioid (LAO)
Reprint requests to: Perry G. Fine, MD, Pain Research
Center, University of Utah School of Medicine, Salt Lake
City, UT 84108, USA. Tel: 801-585-7690; Fax: 801-5857694; E-mail: perry.fi[email protected].
and short-acting opioid (SAO) formulations allowing better tailoring of therapy to patient needs,
and an appreciation that all long-term therapies,
including interventional therapies, require consideration of risk–benefit ratios. In addition, agents
commonly prescribed for diverse chronic pain
conditions such as the cyclooxygenase-2-selective
nonsteroidal anti-inflammatory drugs (NSAIDs),
which promised analgesic efficacy without the
potential gastrointestinal side effects of nonselective NSAIDs, have been associated with a significant risk of cardiovascular adverse events [9],
turning attention back to the role of opioids in the
management of many chronic pain conditions.
Moreover, although management of neuropathic
pain remains clinically challenging, recent evidence supports a role for opioids in rationally constructed multidrug regimens for such conditions
as postherpetic neuralgia and painful diabetic
neuropathy [10].
Health care providers must turn to available
evidence and their own clinical experience for
guidance on how best to employ opioids in clinical
practice [1]. A number of controlled trials have
established the efficacy of different opioids in musculoskeletal conditions, including osteoarthritis
© American Academy of Pain Medicine 1526-2375/09/$15.00/S79 S79–S88
doi:10.1111/j.1526-4637.2009.00666.x
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Fine et al.
[11], low back pain [12,13], and various neuropathic pain conditions such as diabetic peripheral
neuropathy and postherpetic neuralgia [14].
However, clinical trials often fail to reflect real-life
practice [15] and may not offer practical guidance
on how to select and position available treatments
and formulations to best suit patient needs [16].
Recent meta-analyses and systematic reviews
[15–19] highlight the difficulties of appraising
clinical trial data in support of opioid treatments
and formulations in routine—and often longterm—chronic pain management.
This article provides a constructivist view of
LAO and SAO preparations within chronic pain
management; this type of approach is characterized by an organized, structured approach to practice that focuses on attaining therapeutic goals
while minimizing potential harms. Examining the
current state of knowledge regarding these formulations can aid the clinician in generating a cohesive framework from which to apply sound clinical
judgment in the selection of appropriate agents
and dosage formulations.
Patient Assessment: A Key to
Successful Intervention
Comprehensive patient assessment is required
to allow proper consideration of the potential
Table 1
benefits and risks of the available pharmacotherapeutic treatment options, including drug choice,
routes, and dosing regimen [20–23]. This includes
a complete medical and psychological history,
differential diagnosis of presenting symptoms,
and analysis of relevant comorbid conditions
[20,21]. An important step in assessment for
potential opioid therapy, in particular, is a discussion about patient personal or family history of
substance abuse, as patients with such a historyj
are more likely to develop aberrant drug-taking
behaviors later in therapy [20,24].
The general principles of opioid prescribing are
summarized in Table 1 [25]. Prescribers may wish
to consider these key questions, based on Fine and
Portenoy, to help determine the appropriateness
of opioids in a particular patient [20]:
• What is the conventional management for this
type of pain within the immediate practice
setting and compared with national standards of
care?
• Are there other treatments with more favorable
risk–benefit ratios than opioids in terms of pain
control and improvement in function and
quality of life (QoL) in this type of patient with
this type of pain?
• Are there relatively high risks related to opioid
pharmacotherapy in this patient given their
Principles of opioid prescribing
Patient selection
Perform comprehensive
assessment
Full characterization of pain complaint
Evaluation-relevant comorbidities
Current substance abuse
Personal history of substance abuse
Family history of substance abuse
Opioid selection
Consider
Severity and pattern of pain
Age, medical comorbidities, individual differences, previous opioid experiences
Drug-specific differences
Route selection
Dosing
Monitoring
Use least invasive route possible
Consider patient characteristics and adherence
Initiating therapy
Consider previous dosing requirements and relative analgesic potencies
Start with lowest likely effective dose
Increasing dose
Increase in increments (30–100%)
Size of increment and time interval between increments influenced by severity of
pain, treatment side effects
Increase dose until adequate analgesia occurs or dose-limiting side effects occur
Schedule
Consider schedule: ATC or prn depending on temporal pain patterns
Rescue
Consider rescue medicine for BTP
Monitor
Efficacy, side effects of treatment
Aberrant behaviors, other responses over time
Consider modifications
Follow-up
Modify frequency and tailor to individual patient’s clinical, social circumstances
Source: Smith et al. [25].
ATC = around-the-clock; BTP = breakthrough pain; prn, as-needed.
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Opioids: Appropriate Use in Chronic Pain Management
Table 2 Universal precautions for assessment
of chronic pain
1. Differential diagnosis
2. Psychological assessment (including risk of addictive
disorders)
3. Informed consent
4. Treatment agreement or “opioid contract”
5. Assessment of pain level and function before and after
intervention
6. Appropriate trial of opioid with or without adjunctive
medication
7. Reassessment of pain score and level of function
8. Regular assessment of the four As of pain medicine:
analgesia, activities of daily living, adverse events,
aberrant behaviors
9. Periodic review of pain diagnosis and comorbid conditions
10. Documentation
Adapted from Gourlay et al. [26].
personal and medical history? This relates not
only to the risk of medication misuse, but
importantly, to the role that comorbidities or
drug interactions may play in therapy selection.
• Are there concerns about the responsible use of
medication over time? This risk assessment
applies to the patient as well as the patient’s
home and work environments (e.g., friends and
family). Appropriate use of a universal precautions approach (Table 2) [26] and validated tools
such as the Opioid Risk Tool [27] or the revised
Screener and Opioid Assessment for Patients
with Pain [28] can help with a structured risk
assessment in every patient being considered for
opioid therapy.
Because of the variability in response to opioids
among individual patients, the relative risks associated with this class of drugs, and differing
degrees of prescriber comfort and experience
using opioids in chronic pain treatment, it is
important to consider a multidimensional and
multidisciplinary approach to ensure the provision
of appropriate care with these agents [29]. Some
patients can be treated in a primary care setting,
while others represent a more significant challenge and may best be referred to a specialist with
related specific experience in addiction or psychiatry. Commonly, there is a middle ground; many
patients can be comanaged with the assistance of
other specialists [26]. The use of non-opioid and
nonpharmacologic approaches should be considered and tailored for the individual patient [7].
LAOs and SAOs in Chronic Pain Management
Having decided that a patient is a suitable candidate for opioid-based therapy, the clinician has the
choice of a wide range of agents with distinct pharmacodynamic and pharmacokinetic characteristics, such as opioid receptor selectivity of full or
partial agonists, mixed agonist–antagonists, time
to analgesic onset, elimination half-life, and duration of analgesic effect [20,30]. It is important to
note that the agent selected for an initial opioid
trial will not necessarily form the basis of longer
term management. Interindividual variability in
biologic responses to particular opioids (including
the development of tolerance) preclude always
identifying the “best” opioid for a patient at the
outset of treatment [23,31,32].
Clinicians are presented not only with a choice
among a variety of opioid agonists, but also with
the decision to prescribe either a LAO or a SAO
[1,20,32]. Throughout this review, the term LAO
will be used to describe opioids that are inherently
long acting, such as methadone and levorphanol, as
well as modified-release formulations [20]. Table 3
describes some of the most commonly available
short-acting and long-acting formulations used for
the management of chronic pain [20,33–37].
The pharmacokinetic properties of LAOs allow
reduced frequency of dosing relative to SAOs and
typically provide analgesia over an 8–72-hour
dosing interval [38]. It has been suggested that
LAOs have the greatest utility in extended treatment of patients with consistent pain levels, and
those in whom non-opioid treatment has failed
to provide adequate or tolerable analgesia [39].
Table 3 Opioid formulations available for management
of chronic noncancer pain in the community setting
Drug
Codeine
Fentanyl
Hydrocodone
Hydromorphone
Levorphanol
Methadone
Morphine
Plasma
Half-Life,
Hours*
3
7–12
2–4
2–3
12–15
12–150
2–3
Oxycodone
2–3
Oxymorphone [33,34]
7–9.5
Propoxyphene [35]
Tramadol [36,37]
6–12
5–8
Formulation
Duration
of Effect,
Hours†
Oral
TD
TM
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
4–6
48–72
1–2
3–6
3–6
3–6
6–8
3–6
8–24
3–6
8–12
4–6
12
4–6
4–6
24
IR
CR, SR, ER
IR
CR
IR
ER
IR
ER
* Does not apply to modified-release or TD formulations.
† Refer to other sources for dosing strengths and recommendations.
Adapted from Fine and Portenoy [20] and APS [63].
CR = controlled release; ER = extended release; IR = immediate release;
SR = sustained release; TD = transdermal; TM = transmucosal.
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However, the evidence base for these ideas is not
strong [17], and appropriate selection relies primarily on clinical judgment and an evaluation of each
individual patient. Many LAOs are formulated
specifically to maintain analgesia through modified release of the active agent, which is designed
to provide relatively consistent and prolonged
plasma drug levels with fewer peak and trough
fluctuations compared with short-acting formulations of the same opioid [38]. In addition, LAOs
may offer the potential for improved compliance
with dosing schedule [40] and avoidance of patient
“clock-watching” between doses, although this
idea is supported more by clinical experience than
evidence.
In contrast, SAOs typically have durations of
action of 2–4 hours and often are used during
initial dose titration and for patients whose pain is
not consistent [38]. Titration with a SAO may
prevent long periods of discomfort for the patient
should side effects develop. Additionally, the starting dose for many patients may be less than the
lowest available strength of a prescribed LAO,
necessitating the use of a SAO for titration purposes. After dose initiation and titration is accomplished with SAOs, the patient is often converted
to an equivalent dose of a LAO, although some
patients may prefer to use these agents for aroundthe-clock (ATC) control of continuous pain as well
as for intermittent use on an as-needed (prn) basis
[38]. It should be noted that transdermal fentanyl
is specifically contraindicated in opioid-naïve
patients [41].
The group of SAOs known as rapid-onset
opioids (ROOs), including oral transmucosal fentanyl citrate and fentanyl buccal tablets, have been
designed as rescue medication for cancer-related
breakthrough pain (BTP), defined as sudden,
severe flares of pain that occur against a backdrop
of well-controlled baseline pain [42,43]. The pharmacokinetic and pharmacodynamic profiles of
ROOs provide for quick onset and offset of action
and allow for effective management of sudden and
intense episodes of pain [44,45]. Particular care,
however, should be taken when prescribing these
potent agents, which are currently Food and Drug
Administration (FDA) approved for cancer-related
BTP only. Their rapid onset of effect and lack of
a correlation between the baseline and breakthrough doses requires that they are titrated independently and that patients are opioid tolerant
as defined by the FDA [46–48]. Further, acceptance of the use of ROOs for the treatment of BTP
in patients with chronic noncancer pain is varied
Fine et al.
[43], although these agents have demonstrated
efficacy and safety in short-term studies of patients
with noncancer BTP [49,50], concerns remain
about their long-term effectiveness and potential
for abuse. It, however, remains to be determined
whether there is any greater or lesser risk of problematic drug-related behaviors in cancer and noncancer pain patients who have BTP. Therefore,
the decision to prescribe ROOs, regardless of
underlying pain pathophysiology, should follow
sound principles of practice for all opioid therapies, and include risk assessment, a benefit–risk
evaluation, and recognition that some patients
may have few, if any, BTP treatment alternatives
that are as efficacious as ROOs.
Relative Efficacy of LAOs and SAOs in
Long-Term Treatment
Few studies have directly compared LAOs and
SAOs for the management of chronic pain, and no
strong body of literature demonstrates more or
less benefit for either type of opioid preparation in
relation to analgesia, functionality, QoL, or aberrant behaviors. For example, a study comparing
controlled-release (CR) oxycodone administered
twice daily (every 12 hours) with immediaterelease (IR) oxycodone/acetaminophen dosed
every 6 hours in 167 subjects with chronic osteoarthritis demonstrated no significant differences
between the formulations on pain scores [11]. In
another study of CR vs IR oxycodone, similar
analgesic efficacy was observed for up to 10 days of
treatment in 47 patients with chronic back pain
[12]. Finally, two studies, comparing four timesdaily oxycodone IR with twice-daily oxycodone
CR in patients with cancer pain and low back pain,
concluded that both formulations can achieve
levels of stable analgesia in more than 80% of
patients [51]. Several literature reviews also failed
to identify clear differences in benefit between
LAOs and SAOs [15–19]. One of these reviews,
which focused on the efficacy and safety of these
groups of agents in noncancer pain, examined 16
randomized trials and 8 observational studies,
which together provided data on more than 2,500
patients. Insufficient evidence was found to determine whether one class was more effective or was
associated with better adverse event rates than the
other [17].
Clinical trials typically are constructed to
answer questions about a specific drug (proving
efficacy/equivalence of analgesia, profiling safety/
tolerability), rather than to identify the best
regimen, formulation, schedule, and long-term
Opioids: Appropriate Use in Chronic Pain Management
treatment plan to manage patient pain [52,53].
Moreover, clinical trials are frequently of relatively
short duration (commonly <16 weeks) and therefore cannot provide an evidence base in support
(or in refute) of long-term use of opioid therapy
[16]. It is not surprising, therefore, that reviews
and meta-analyses of the clinical trial literature
fail to provide concrete evidence supporting or
contraindicating long-term use of either type of
opioid in chronic pain. Many reviews attest to the
paucity of literature and inconsistency of findings,
which serves to cloud the evidence base for using
these drugs in daily practice [15,18,54]. The lack
of conclusive findings in these analyses points to
the need for individualization of care for each
patient, as no argument can be made that one or
another opioid is generally more effective [17].
Few contest the efficacy, as demonstrated in clinical studies and in routine care, of opioids in relieving the discomfort of chronic pain syndromes, but
many question the relevance of published clinical
trial data in the routine, and often long-term,
management of chronic pain [1,2].
Although review of clinical trial data suggests
that many patients discontinue long-term opioid
therapy due to either insufficient pain relief or
adverse effects, the same studies establish that
there are many patients who clearly respond well
[15]. Both issues, while often not completely
analyzed due to the constraints of trial protocols,
may be corrected in real-world clinical practice
through opioid rotation, dose titration, or administration of additional pharmacologic or nonpharmacologic therapies (see Multimodal Analgesia in
this supplement) [1,21–23].
Practical Considerations in Deciding on an
Appropriate Treatment Strategy
Patients with chronic pain represent a highly heterogeneous group in terms of age, pain etiology
and symptoms, comorbidities, and ability to tolerate discomfort. In addition, the biopsychosocial
nature of pain, impact of adverse effects of treatment, context of treatment (e.g., interdisciplinary
rehabilitative model vs single modality medical
model), and patient preferences affect the relative
merits of any treatment choice. Decisions depend
on pain fluctuation, activity levels, functional
goals, social circumstances, and other variables
[20], including patient adherence and medication
use behaviors. Although LAOs offer less frequent
dosing, which can improve compliance [38] it is
important not to choose an agent merely on the
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presumption that perceived “convenience” will
promote adherence [38], or that patients prescribed SAOs for ATC dosing may only use the
medication reactively, after pain levels increase,
thereby reducing overall daily pain control [40].
Similarly, it is important not to restrict the use of
SAOs only for acute pain.
The lack of a consistent evidence base requires
a flexible approach that tailors choice of opioid
formulation to individual needs, goals, clinical
context, and social environment, all of which may
be important for constructing a pain management
plan and the derived outcomes of treatment [20].
For example, in carefully selected patients and
with appropriate monitoring, LAOs may provide
relief for patients whose pain interferes with their
ability to sleep through the night [55], or for
patients in whom the peak–trough effects of SAOs
cause end-of-dose failure, causing pain to recur
before the next scheduled dose. Other patients
with chronic pain may prefer the faster onset
of most SAOs and the psychological comfort of
controlling pain with more frequent dosing, particularly in cases of more intermittent pain. Comprehensive patient assessment plays a key role in
the anticipation of these factors. Finally, empirical
observation suggests that individual patients with
chronic pain may have specific preferences based
upon their own experiences with either a LAO or
SAO [5,17,19,31].
Practical Issues in Opioid Initiation, Titration,
and Rotation
The goal of opioid-based therapy, like all other
treatments, is to optimize the balance between
benefit and risk. Proper initiation and titration of
dosage are keys to achieving this goal.
A low-dose SAO often is favored for initial
opioid therapy [38]; because of their short halflives and IR profiles, SAOs can be titrated to
effective analgesia more rapidly and—in an
unmonitored setting—safely than a LAO [20].
Titration to a new dose should not occur until
after drug plasma levels have reached steady state
(approximately five half-lives), which, for LAOs, is
longer than for SAOs [20]. A patient’s response to
previous opioid trials in terms of efficacy and side
effects also can be informative, allowing for more
appropriate selection of an initial opioid and dose
for that patient [20]. There is some support for use
of LAOs in initial titration for opioid-experienced
patients, although this strategy requires close
monitoring for adverse effects [55].
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Although there is some literature on rapid titration with CR formulations, these observations
were made under closely monitored conditions in
patients with cancer rather than noncancer pain
[55,56]. One of the few studies to address use of
LAOs vs SAOs in patients with noncancer pain
suggests that, although dose titration with LAOs
may offer some utility in carefully selected cases, it
carries a potential for increased adverse effects,
particularly nausea and emesis, relative to SAOs
[51]. The risk of respiratory depression can be
significant if opioids are not carefully titrated, and
this risk is heightened in patients who are not
opioid experienced [20]. Importantly, the guidance
offered here relates to usual outpatient care, and
not pain crises, in which inpatient admission or
close supervision may be indicated [20]. In all
clinical settings where opioid therapy is initiated
and doses are increased, safety is the first priority.
Some formulations are not appropriate, and
indeed, could be dangerous, when used for treatment initiation. For example, transdermal fentanyl
patches carry a black box warning against use in
opioid-naïve patients [41]. Because of the high
drug concentration and rate of delivery, this formulation can cause severe respiratory depression
in patients who are not opioid experienced [41].
Methadone is characterized by significantly different and complicated pharmacodynamic and pharmacokinetic properties compared with those of
other opioids. For example, methadone has a long
and variable half-life (12–120 h), with steady-state
serum concentrations achieved after 4–5 half-lives
[20,57]; therefore, time and patience are required
when adjusting methadone doses. Furthermore,
conversion to methadone from other opioids
demands significantly greater attention to dosing
due its unpredictable pharmacokinetics and the
potential for torsade de pointes, serotonin toxicity,
and numerous known drug–drug interactions that
result from its complicated mechanism of action
and uncertain metabolism [20,57,58].
Once an opioid and formulation have been
selected, the dosage should be titrated individually
to the level that provides maximal analgesia with
minimal adverse effects for each patient. Dosage
adjustment may be required several times during a
course of therapy should tolerance, new pain syndromes, or severe adverse effects develop. Dose
escalation of ATC opioids should be made
gradually; in general, it is recommended that a
dose be increased 30–50%, or up to 100% [20], if
pain is uncontrolled, the patient’s history indicates
an ability to tolerate such an increase, and a
Fine et al.
responsible caregiver is available to monitor for
serious adverse effects. The opioid dose usually is
not increased before achieving steady-state serum
concentrations, which vary depending on the
opioid and the formulation. In the case of a patient
receiving opioids both ATC and prn, the supplemental opioid is added to the fixed-dose amount.
Careful assessment of patient response to the new
regimen is required during titration, and it is recommended that the method and timing of titration be consistent irrespective of the specific
opioid or formulation. Of note, if patients are
receiving both a LAO and a SAO, both opioids
should be titrated concurrently [20].
Ongoing Assessment, Switching, and Maintenance
Ongoing patient assessment is an essential aspect
of opioid therapy. The “4 A’s”—analgesia, activities of daily living, adverse effects, and aberrant
behaviors—were developed to provide a framework for health care providers to routinely assess
critical outcome measures and gauge treatment
success [59]. The “4 A’s” emphasize that pain
relief, functional goals, side effects of treatment,
and adherence to the treatment plan should be
routinely evaluated and documented to allow
the clinician to adjust the therapeutic regimen
accordingly. Consistent reassessment is particularly important in the community setting where
primary care physicians often assume large
responsibility for patient follow-up, including
administering therapeutic regimens, determining
their efficacy, monitoring adverse events, checking
on adherence, and evaluating the effects of pain
management strategies on patients’ QoL [59].
Achieving a balance between analgesic and
adverse effects is often a matter of trial and error,
and is unique in each individual patient. Even
when the initial opioid formulation successfully
controls pain, a change in therapy (beyond upward
titration) may be required due to a change in clinical status or social circumstances, emergence
of new pain pathology, behavioral issues, comorbidities, drug–drug interactions, side effects, or
analgesic tolerance [26,60]. The management of
poorly responsive pain is complex and may require
more aggressive treatment, identification of an
opioid with a more favorable balance between
analgesia and side effects, or use of multiple
pharmacologic and nonpharmacologic strategies
in combination [20]. Alternatively, the individual
patient’s pain may not be opioid responsive, necessitating the implementation of predefined exit
Opioids: Appropriate Use in Chronic Pain Management
strategies from opioid therapy and administration
of alternative analgesic approaches [20].
An inadequate response also may be due to the
presence of unrecognized and/or untreated BTP,
which is often managed with a prn short-acting or
rapid-onset rescue opioid. The dose of the shortacting medication is generally 5–15% of the total
daily opioid dose [20], whereas, as mentioned
earlier, ROOs require an independent titration
strategy; studies have found that there is no correlation between the baseline and rapid-onset dose
[46]. Differentiating between the baseline pain and
flares of BTP is critical, as frequent BTP episodes
may indicate inadequate treatment of persistent
baseline pain [46]. When escalating the dose of the
regularly scheduled opioid, it is important to
remember that the rapid-acting or SAO dose may
require a similar increase [46].
Adjustments to an analgesic regimen also may
be related to patient preferences [17]. For
example, a SAO may be used for initial dose titration in patients whose treatment goals include
eventual maintenance using a LAO. Some patients
may find that once their pain is adequately controlled, they would prefer a treatment using an
alternative route of administration. General principles for switching include consulting an equianalgesic table for guidance on dosing, determining
the clinically relevant start point for the switch,
and consideration of further dose adjustments and
rescue medication for BTP. One should be cautious, however, when referring to an equianalgesic
table as many are based on studies conducted in
opioid-naïve patients, suggesting that these tables
may not be useful in treating opioid-experienced
patients. Moreover, interindividual variability and
incomplete cross-tolerance resulting from genetic
polymorphisms and alternative isoforms of opioid
receptors demand that care be taken when switching between opioids [61]. Patient responsiveness
to each new agent should be reassessed according
to both therapeutic response and side effects [20].
Risk management, vigilance for aberrant behaviors, and signs of dependency and misuse of opioid
therapies are discussed in greater detail in Current
Risk Assessment and Management Paradigms in
this supplement. Primary care practitioners, as
well as pain specialists, must be aware of these
issues and discuss them with patients at all
stages of opioid-based pain management. The
prescriber can help assess risk and aberrant behaviors through measures such as random urine drug
testing, utilization of prescription monitoring
programs, and random pill counts [21,28,62].
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Throughout patient management, thorough
patient documentation of all aspects of the treatment protocol, clinical evaluation, and outcomes
of management strategies is essential [26].
Conclusions
Detailed attention to appropriate agent selection
and dosing regimen, careful titration, and vigilant
ongoing assessment has led to the increased acceptance of opioids as a safe and effective component
of the multimodal treatment of chronic noncancer
pain. In the absence of a set of patient characteristics or predictive test for successful opioid treatment, a short-term trial is the only way the
clinician can determine the efficacy and safety of
this medication class in a specific patient. An
opioid trial has the greatest chance of success if
incorporated into an overall management plan
that includes structured follow-up to evaluate continued effectiveness over time. Opioid treatment
may be further optimized through the inclusion of
behavioral, psychological, functional, rehabilitative, and appropriate interventional therapies,
along with adjuvant analgesics, when indicated.
In addition, the availability of SAO and LAO
formulations allows for tailoring of therapy to
patient needs. Individualization of therapy can
help reduce an overreliance on rigid dosing schedules, allowing patients to focus on activities of
daily life rather than their pain or their medication
use. This becomes part of an overall behavioral
conditioning program, aimed at reducing “illness
behavior” and correcting perceptions of disability
and fragility that often are associated with chronic
pain.
There are a number of data gaps and unmet
patient needs in the management of chronic pain.
Published evidence supports the efficacy and safety
of opioid medications but often fails to provide
practical guidance for agent selection or the predictability of long-term benefit. Well-constructed,
methodologically sound, long-term trials of opioid
therapy in heterogeneous populations are needed.
Such trials will help the clinician contribute to the
goal of improving pain control in the many patient
groups currently experiencing suboptimal pain
management or inappropriate exposure to an
otherwise efficacious class of analgesic agent. In
the absence of long-term data regarding the efficacy of opioid therapy for chronic noncancer pain,
clinicians must rely on empirical evidence and
employ an “N-of-1” trial paradigm to gauge treatment success in the individual patient.
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Disclosures
Dr. Fine discloses that he has held advisory board positions
for pharmaceutical companies involved in the development and/or marketing of opioid analgesics, including
Cephalon, King, Ortho-McNeil/Pricara, and Purdue
Pharma. He has served as a medical-legal expert for
Johnson & Johnson.
Dr. Mahajan has no disclosures to report.
Dr. McPherson has no disclosures to report.
This supplement has been sponsored by an unrestricted
grant from King Pharmaceuticals®, Inc. Editorial support
was provided by Megan Fink, Ariel Buda-Levin MS, John
Lapolla MS, Maggie Van Doren PhD, Jim Kappler PhD,
as well as Innovex Medical Communications.
References
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