A woman in her 50s presented for medically managed withdrawal from an ultra-high-dose opioid regimen of 1620 mg MEDD for chronic back pain stemming from a 1983 injury. Over multiple decades, her opioid doses escalated despite providing limited functional benefit and resulting in several hospitalizations. She agreed to an acute inpatient withdrawal managed with buprenorphine, allowing her to discontinue full agonists without functional impairment. The case illustrates the risks of long-term high-dose opioid therapy and the need to regularly re-evaluate risks versus benefits.

1. Copyright 2016 American Medical Association. All rights reserved.
LESS IS MORE
Ultra–High-Dose Opioids With Low Efficacy
and Significant Harm—Time to Make a Change
A Teachable Moment
Story From the Front Lines
A woman in her 50s presented for medically managed
withdrawal from ultra–high-dose opioid therapy for
chronic back pain. Her pain began following a back in-
juryin1983thatresultedinmultipleherniateddiscs.Tar-
geted injections of chymopapain to dissolve her dis-
placeddiscsinsteadleftherwitharachnoiditis.Overthe
nextdecade,sheunderwentmultiplelumbarspinesur-
gicalproceduresandatonepointreturnedtowork,but
anaccidentalfallaggravatedherinjury,renderingherin-
definitely unable to work. Her pain was then managed
with methadone but, concerned about oversedating
effects, she underwent inpatient detoxification. At-
temptsatpaincontrolusingnonopioidmedicationfailed
toprovideadequaterelief,soshewasprescribedoxyco-
done,15mg,4timesaday,or90mgofmorphineequiva-
lent daily dose (MEDD).
By 2000, her dose had escalated nearly 9-fold to
780 mg MEDD. To attempt more localized therapy, she
received an intrathecal pump with baclofen and hydro-
morphone. While it provided the best relief to date, her
doses escalated until she was hospitalized for respira-
tory failure requiring intubation and naloxone. Her in-
trathecal medications were then reduced and supple-
mented with oral hydromorphone. Following a pump
revision in 2008, she acquired a methicillin-resistant
Staphylococus aureus infection, leading to permanent
pump discontinuation. Instead, she was prescribed
oxycodone at 1620 mg MEDD. After a few years taking
this dose, she was admitted for abdominal pain, weight
loss,andearlysatietythoughttobenarcoticbowelsyn-
drome following an extensive workup.
When the patient presented in 2016 to our outpa-
tientpainclinic,shewasstillprescribedoxycodone,1620
mgMEDD,inadditiontocarisoprodol,5600mg,andlor-
azepam, 4 mg daily. Functionally, she remained severely
limited—mostlyhousebound,requiringascooterformo-
bility.Herstatedfunctionalgoalwastobeabletovisither
brother and participate in family celebrations. Agreeing
tolowerheroxycodonedosebutanxiousaboutslowlyta-
pering, she agreed to acutely withdraw. Once admitted,
opioids were abruptly discontinued. She was monitored
using the Clinical Opiate Withdrawal Scale (COWS), and
buprenorphine-naloxonewasstartedroughly12hoursfol-
lowingherlastoxycodonedose(COWS = 18)toavoidpre-
cipitating withdrawal. She responded positively with
enough pain control to continue off full-agonist therapy
without further functional impairment and had an early
benefit of craving food for “the first time in years.”
Teachable Moment
Thiscaseillustratesthedifficultyintreatingchronicnon–
cancer-related pain and the out-of-control opioid dos-
ing that can occur when clinicians exhaust alternative
treatments in someone with unrelenting pain desensi-
tized to opioids. The current guidance—continue opi-
oids only if benefit is outweighing harm—would have
served this patient well. She continued to receive opi-
oidsovermultipledecadesdespitelowefficacyandcom-
plications, including hospital admissions for bowel is-
sues, deconditioning, and respiratory failure.
It is perhaps not surprising that this patient contin-
ued to receive opioids despite her related hospitaliza-
tions and limited functional benefit. A retrospective
study examining the treatment patterns of patients
receiving long-term opioids for chronic non–cancer-
related pain showed that 91% of patients hospitalized
for a nonfatal opioid overdose continued to be pre-
scribed them.1
Patients receiving high-dose therapy
(>100 mg MEDD) had a 17% risk of repeated overdose
within 2 years.
Evidence for long-term opioid therapy in chronic
non–cancer-relatedpainisweakatbest.2
Asopioidover-
usehasbecomeamajorpublichealthissue,cliniciansare
urged to identify patients who may benefit from dose
reduction or discontinuation, for example, patients for
whomopioidshavediminishinganalgesiceffectsorare
associated with significant harm.
Guidelines for tapering opioids are still being
developed.3
As in this case, patients may have anxiety
in anticipation of discomfort related to a lengthy taper.
Significant risks for failing the attempt to taper include
depression,highstartingdoses,andhighbaselinepain.3
For such patients, detoxification can offer a faster
transition.
Opioid detoxification is typically either outpatient
or inpatient, the latter in hospitals or residential facili-
ties. Hospitals are generally reserved for patients with
comorbidmedicalorpsychiatricillnesses,whileresiden-
tial facilities are preferred for patients who may require
24-hour supervision but not daily physician contact.
While health insurance plans may cover inpatient ad-
missionsforopioiddetoxification,thesearegenerallyap-
provedforalimitedtimeandwithspecificcriteria,some-
times requiring a failed outpatient trial.
Buprenorphine’s role in chronic pain following full-
agonist therapy remains to be established, although
findings from observational studies are encouraging.4
Given this patient’s lengthy history of opioid use, we
TEACHABLE
MOMENT
Paul Guillod, BS
Yale University School
of Medicine, New
Haven, Connecticut.
Ellen L. Edens, MD,
MPE
Yale University School
of Medicine, New
Haven, Connecticut;
and VA Connecticut
Healthcare System,
West Haven.
William C. Becker, MD
Yale University School
of Medicine, New
Haven, Connecticut;
and VA Connecticut
Healthcare System,
West Haven.
Corresponding
Author: Paul Guillod,
BS, Yale University
School of Medicine,
200 College St,
Apt 343, New Haven,
CT 06510 (paul.guillod
@yale.edu).
Opinion
jamainternalmedicine.com (Reprinted) JAMA Internal Medicine Published online November 28, 2016 E1
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2. Copyright 2016 American Medical Association. All rights reserved.
hypothesize that buprenorphine offers additional benefits of
suppressing opioid craving and treating prolonged withdrawal
syndrome.
The optimal strategy for managing chronic pain seems to be
through interdisciplinary teams addressing pain on a biopsychoso-
cial level.5
Programs that support the patient’s full experience are
more likely to provide benefits in pain control and disability reduc-
tion than medication or intervention alone. To this end, our patient
will be treated with cognitive behavioral and physical therapies as
part of our routine outpatient practice.
Published Online: November 28, 2016.
doi:10.1001/jamainternmed.2016.7344
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient for
granting permission to publish this information.
1. Larochelle MR, Liebschutz JM, Zhang F,
Ross-Degnan D, Wharam JF. Opioid prescribing
after nonfatal overdose and association with
repeated overdose: a cohort study. Ann Intern Med.
2016;164(1):1-9.
2. Noble M, Treadwell JR, Tregear SJ, et al. Long-term
opioid management for chronic noncancer pain.
Cochrane Database Syst Rev. 2010;(1):CD006605.
3. Berna C, Kulich RJ, Rathmell JP. Tapering
long-term opioid therapy in chronic noncancer pain:
evidence and recommendations for everyday
practice. Mayo Clin Proc. 2015;90(6):828-842.
4. Berland DW, Malinoff HL, Weiner MA, Przybylski
R. When opioids fail in chronic pain management:
the role for buprenorphine and hospitalization. Am
J Ther. 2013;20(4):316-321.
5. Kamper SJ, Apeldoorn AT, Chiarotto A, et al.
Multidisciplinary biopsychosocial rehabilitation for
chronic low back pain: Cochrane systematic review
and meta-analysis. BMJ. 2015;350:h444.
Opinion Teachable Moment
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Copyright 2016 American Medical Association. All rights reserved.
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