Introduction
A reexamination of the clinical principles involved in the initiation,
continuation, and discontinuation of long-term opioid therapy (LTOT) for
chronic pain is long overdue, especially in the context of an
unrelenting opioid overdose crisis in United States (US) that is
believed to have originated partly from excessive LTOT prescribing. LTOT
reestablished itself as a prevalent treatment of non-cancer chronic pain
in the late 1980s and the subsequent decades after the success of
opioids in hospice care among cancer patients.1 This
resurgence of popularity of LTOT was based on few clinical assumptions:
1) regular repeated use of opioids – powerful short-term analgesics
–would provide sustained pain reduction for people with chronic pain,
which would in turn provide sustained improvement in individual
suffering and function, 2) opioid dependence and tolerance are expected
physiological effects of LTOT that are benign in the absence of opioid
use disorder (OUD) or addiction, 3) LTOT is largely safe and serious
adverse effects like overdose, respiratory failure and addiction are
rare and avoidable, and 4) opioid describing is safe and easy when
indicated. Our clinical experience with LTOT over the past decades has
suggested that none of these assumptions are valid.
By the 2010s, anecdotal clinical evidence started to emerge that many
patients on LTOT develop a paradoxical pain syndrome whereby both
continuation and discontinuation of LTOT was associated worsening pain
and function instead of the commonly expected improved pain control and
function. 2-4 Consistent with this clinical
observation and contrary to the clinical assumptions justifying the
therapeutic use of LTOT in chronic pain, up to two-thirds of patients on
LTOT reported poor pain control, function and overall
health,5,6 and LTOT was associated with declining pain
control and function over 2 years of follow up in large observational
studies.7 Recent clinical trials reported that while
LTOT may have modest short-term benefits, it is not associated with
clinically meaningful longer term benefits.8-10Contrary to previous assumptions, more recent clinical trial data have
also suggested that opioids are not superior to placebo or non-steroidal
anti-inflammatory agents in providing effective pain control or improved
function even with common acute or sub-acute painful conditions like
kidney stones or low back and neck pain.11-13 It is
now well recognized that LTOT is not as safe as previously assumed and
is associated with significant adverse effects including overdose and
all-cause mortality.10,14-17 Although OUD or opioid
addiction is uncommon among those on LTOT, it is not rare, with about
5% on LTOT in pain clinics developing OUD. 18,19Thus, the available clinical experience and data suggest that LTOT does
not seem to provide consistent analgesia or improvement in function for
most patients and may be associated with increased risk and a
paradoxical worsening of pain and function among many.
It is well accepted that physiological opioid dependence without
addiction/OUD is unavoidable after a few months on LTOT. It is commonly
assumed that opioid deprescribing, the presumed primary option in
treatment of ineffective and unsafe LTOT, is an easy option for many
dependent on LTOT 10,20; however, qualitative studies
report that opioid tapering is incredibly challenging for many such
patients due to worsening pain and suffering from
withdrawal.21-23 Consistent with this, results of
observational studies have suggested that many patients dependent on
LTOT do not want to come off opioids even when reporting worsening pain
or even when faced with life threatening complications like
overdose.6,24 In one study, 90% of people who
suffered opioid related non-fatal overdose were restarted on opioids in
the next year, demonstrating the difficulty in
deprescribing.24 It is also commonly presumed that
LTOT deprescribing is associated with significant benefits and a
reduction of opioid related risks.10,20 However,
systematic reviews have failed to reveal any substantial evidence
demonstrating significant benefits or reduced risks associated with LTOT
deprescribing.25,26 In fact, over a dozen recent
observational studies have shown that opioid deprescribing is associated
with an escalation of several types of opioid related risks including
overdose, suicides, illicit opioid use, mental health destabilization,
disruption of care relationships with provider, hospitalizations and
even all-cause mortality.27-39 These risks appear to
persist for months to years and risk does not appear to be diminished
even with a slower taper, a commonly suggested solution to the harms of
opioid deprescribing. 27-39 Thus, clinical experience
and empirical data suggest that opioid dependence associated with LTOT
is often not a benign state and opioid deprescribing is often difficult,
ineffective, and risky among those with physiological dependence from
LTOT and these adverse effects can persist for several years.
Despite all these limitations, LTOT is still often trialed among
patients with debilitating chronic pain after other options have failed
because of a shared hope among patients and providers that the
short-term benefit will persist. In the absence of effective alternative
short-term “pain medications,” opioids will continue to be used for
the foreseeable future in several clinical situations where pain control
is essential for clinical stabilization, treatment participation and
acute functional recovery (e.g. recovery from severe physical trauma or
extensive surgeries). Many of these patients could require LTOT to
maintain their recovery journey. In addition, millions of patients who
are already prescribed LTOT (i.e., “legacy” patients) need continued
care as de-prescribing LTOT could be ineffective and risky. This
opioid-induced pain crisis is a significant problem in US and often
eclipsed by or confabulated with the opioid addiction crisis. About 14
million US adults were estimated to receive LTOT in 2014, declining to
about 7 million by 2019 after the rise in popularity of opioid tapering
following the 2016 CDC guidelines on opioid prescribing for chronic
pain. 40-42 As a result, millions of US adults were
left to cope with the adverse effects of opioid deprescribing that is
often not recognized or treated as a valid clinical
entity.43-45 In short, we cannot deprescribe our way
out of the enormous clinical problem created by excessive LTOT
prescribing over several decades.
The current conceptualization of LTOT as a long-term analgesic therapy
with occasional side effects of overdose, misuse, and addiction and
inevitable but benign and easily resolvable physiological opioid
dependence appears to be an unjustifiable framework. The enormous opioid
pain crisis that leaves millions of US adults in severe pain and
disability– whether they are continued on LTOT or deprescribed–
raises the need for a more scientific conceptualization of the role of
opioids and LTOT to guide safe and effective LTOT use and deprescribing.
To address this urgent need, we first provide a comprehensive review of
the neurobehavioral mechanisms involved in opioid pain relief,
explanations for the paradoxical worsening of pain and disability in
LTOT continuation and persistent clinical worsening with deprescribing.
We further suggest a detailed clinical approach to safe and effective
LTOT use and treatment of ineffective or unsafe LTOT based on the above
theoretical explanations for short- and long-term effects of opioids
pertinent to pain treatment. We hope such a reexamination of clinical
principles in LTOT will improve collaboration with patients facing the
LTOT clinical conundrum or considering LTOT as an option and will help
them move forward in the path to functional recovery.
A plain language description of common terminologies used in the next
section is provided in Box 1.
———————–Start
Box————————