Updates in Complex Chronic Pain Soraya Azari, MD Associate - - PDF document

2/26/2019 1

Updates in Complex Chronic Pain

Soraya Azari, MD Associate Professor of Medicine

Disclosures



None

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Objectives



To be familiar with all the new, exciting medical evidence related to chronic pain management and the use of opioids.



To be able to describe the level of evidence for

• pioid tapers & best practices



To review the management of patients with opioid use disorder and chronic pain.



To give you resources for patient education and support for chronic pain.

Case



MW is a 35yo F with a prior motor vehicle accident (~ 10 years ago) s/ p surgery with resultant chronic pain syndrome, GAD, PTSD, depression, and she is taking chronic opioid therapy. She has been on these medications for ~ 10 years.



Her meds include:

 Oxycodone ER 20mg 1-2 tabs QID  Oxycodone IR 20mg 1 tab tid  MME= 290mg  Duloxetine 60mg BID  Tizanidine 4mg tid prn spasm pain  Diclofenac 1% gel TID prn pain  Lidocaine 5% cream applied tid prn pain  APAP 500mg q6hr prn pain

2/26/2019 3

Case Continued



The patients is seen by primary care, pain management clinic,

• rthopedics (recommending no surgical intervention)



The pain management clinic does not prescribe opioids (only provides recs on non-opioid analgesics). There is a cognitive behavioral therapist that sees the patients when she goes to clinic (which is every 1-2 mos).



The patient is very fixated on her opioid analgesics. She is splitting the oxycodone IR tabs so she can take some every 3 hours exactly (she watches the clock). She feels like the

• xycodone is the only thing she can use for her pain. She

feels minimal benefit from her duloxetine, tizanidine, and topical agents.



She is seen in the clinic with her daughter

 She is diaphoretic, anxious-appearing and with pressured

speech talking about the ways she takes her pills. Her daughter is very active in the exam room, and the patient seems to have poor recognition of the child’s need for attention.

Case Continued



Her pain

 Pain scores shown



Her function

 She is not working  She has a spouse and

a 2 year old child

 She attends ~ 65% of

her appointments



Concerning behaviors

 Utox pos oxy, THC  Denies any substance

use

 Admits that she uses

her opioids to help manage her anxiety Dose increases

Pain Level

1 2 3 4 5 6 7 8 9 Mar-14 Mar-15 Mar-16 Mar-17 Mar-18

80mg 180mg 290mg

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Her Perspective



I don’t have a problem with my medications. I need these to get through my day and function. These are allowing me to function. I keep feeling pressured by everyone to change my dose of the medication or to do something different.

Question



Which of the following summarizes the best treatment for this patient?

 1) Taper medication due to 2016 CDC guideline

recommendations

 2) Opioid rotation based on prospective RCTs

demonstrating benefit of this technique

 3) Continue same medications and amplify

psychological interventions

 4) Transition to buprenorphine-naloxone or

methadone maintenance

 5) Taper medication due to abnormal urine tox

screen

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Question



Which of the following summarizes the best treatment for this patient?

 1) Taper medication due to 2016 CDC guideline

recommendations

 2) Opioid rotation based on prospective RCTs

demonstrating benefit of this technique

 3) Continue same medications and amplify

psychological interventions

 4) Transition to buprenorphine-naloxone or

methadone maintenance

 5) Taper medication due to abnormal urine tox

screen

Let’s Go Through These:

• 1. Tapers



Tapers of chronic opioid therapy

 Evidence-base

 New, systematic review looking at opioid tapers in

patients on chronic opioid thearpy

• KEY: We have 20 studies looking at this. NONE are

prospective, RCTs of opioid tapers

• 81% of trials shows statistically significant reduction in

pain

• 65% of trials done in multi-disciplinary pain clinics
• 55% of trials did partial reductions (not to off)
• WHAT THI S MEANS:

– Voluntary tapers with support likely do not cause worsening of pain, and may be associated with improvement Fishbain and Pulikal. Pain Medicine 2018

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Tapers Cont’d



Unilateral tapers of chronic opioid therapy (based

• n dose)

 NOT a recommendation in the 2016 CDC Guidelines Clinicians should evaluate benefits and

harms of continued therapy with patients every 3 months or more frequently. If benefits do not outweigh harms of continued opioid therapy, clinicians should optimize other therapies and work with patients to taper opioids to lower dosages or to taper and discontinue opioids.

https://www.cdc.gov/drugoverdose/pdf/guidelines_factsheet-a.pdf

Tapers Cont’d



Health Systems Interventions

 VA (Clin Practice Guidelines 2017)

• Opioids + BZD  tapering one or both
• > 90mg MME  evaluation for taper

 Kaiser

 Strongly encourage taper if any are

present:

• Concurrent use of sleeping pills,

alcohol, muscle relaxers, THC, illicit drugs, sedating antihistamines

• Uncontrolled psych issues
• 65 or older
• COPD, CHF, cognitive concerns, CKD
• Osteoporosis
• Severe obesity
• OSA
• Pregnancy

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Outcomes?



Kaiser

 40% reduction in high dose patients  No change in patient satisfaction scores



VA

 From 2012 to 2016 (Opioid Safety Initiative):

 decrease in opioid prescriptions 25% across VA clinics

(baseline 25% COT)

 47% dec opioid+ BZD  Dec rate OD in pts on COT from 0.16 to 0.08% 

CMS, Medicare Part D

 Sponsor may put in “hard safety edits” > 200MME Sharp et al. Am Journal Of Managed Care 2018. Gellad W JAMA IM. 2017;177:611.

Legislation

Available at: www.ncsl.org

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Public Health Benefits? Dose Cap State

https://agportal-s3bucket.s3.amazonaws.com/uploadedfiles/Another/News/Press_Releases/ OpioidSummitReport.pdf

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Will There Be Harm From Tapers?



50 deaths



Drop in life expectancy

CDC report: Available at: https://www.cdc.gov/nchs/data/hus/hus17.pdf

Tapering Cont’d



How to do it: Voluntary Taper

 Education & Support

 Counsel the patient in advance about the possibility of an OUD

and the need to transition to a different treatment

 Team -based care: IPMP?, Behavioral health?, RNs?, PharmD?  Alternative agents for pain management

 Schedule

 10% per week cited by many guidelines (* * no strong evidence

base)

 CDC Taper Guide:

https: / / www.cdc.gov/ drugoverdose/ pdf/ clinical_pocket_guide_ta pering-a.pdf

 On-line schedule generator:

http: / / www.hca.wa.gov/ medicaid/ pharmacy/ documents/ taperschedule.xls

Berna et al. Mayo Clinic Proceedings 2015;90(6):828-842

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VA Opioid Taper Decision Tool. See references for URL.

Advice to Clinicians on Tapers



• 1. Identify the Social, Emotional, and Health Factors

that will impact the Taper



• 2. Address Fears about Tapering, INCLUDING Fear
• f Abandonment

 Separate fear of pain from anticipation of pain  Talk about withdrawal



• 3. Only Propose Tapering When You Believe It is in

the Patient’s Best Interest

 Don’t just cite guidelines. Risks and benefits.



• 4. Tell them What To Expect and Make a Plan. Be

OK with Adjustments

 Pause, temporarily reverse taper during flares Henry et al 2018 J of Pain

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Henry et al 2018 J of Pain Henry et al 2018 J of Pain

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Education for Patients



Tapering handouts:

 Vancouver DPH:

https: / / vch.eduhealth.ca/ PDFs/ EA/ EA.835.O86.pdf

 Pain and Ways To Manage I t:

https: / / vch.eduhealth.ca/ PDFs/ FM/ FM.850.M311.PHC.pdf

 McMaster Univ:

http: / / nationalpaincentre.mcmaster.ca/ documents/ Opioid% 20Tape ring% 20Patient% 20Information% 20(english).pdf



Tapering Videos

 UC Davis: patient testimonials (13min):

https: / / www.youtube.com/ watch?v= bdAdkcpxXdw

 Laura’s Story: Stanford:

https: / / www.youtube.com/ watch?v= 75PEivn1I Ok&index= 3&list= P LT73E4yXLvEWr5VZ9q6UM_Ctmx_fh5SXz&t= 0s

 TED Talk by patient (14min):

https: / / www.youtube.com/ watch?v= WhpAYw9kCt8

Take-Home Points on Tapers



Low quality medical evidence suggests the feasibility of opioid tapering and possible reductions in pain.



National guidelines for chronic opioid therapy DO NOT recommend involuntary tapers.



Most patients have thought about or are interested in tapering their dose.



Major, large health-care institutions have successfully decreased opioid prescribing, but have utilized ancillary supports for behavioral health and pain management.



For opioid tapers: go slow, provide choice, cheerlead, and pause, if needed.



If a patient has an OUD, do NOT taper. Treat OUD.

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Question



Which of the following summarizes the best treatment for this patient?

 1) Taper medication due to 2016 CDC guideline

recommendations

 2) Opioid rotation based on prospective RCTs

demonstrating benefit of this technique

 3) Continue same medications and amplify

psychological interventions

 4) Transition to buprenorphine-naloxone or

methadone maintenance

 5) Taper medication due to abnormal urine tox

screen

• 2. Opioid Rotation



Bottom Line, Evidence-base:

 No proven benefit in prospective, RCTs.  Low quality evidence (case reports, retrospective,

uncontrolled studies)

Quigley C. Cochrane Database Syst Rev 2004;CD004847

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Question



Which of the following summarizes the best treatment for this patient?

 1) Taper medication due to 2016 CDC guideline

recommendations

 2) Opioid rotation based on prospective RCTs

demonstrating benefit of this technique

 3) Continue same medications and amplify

psychological interventions

 4) Transition to buprenorphine-naloxone or

methadone maintenance

 5) Taper medication due to abnormal urine tox

screen

• 3. Psychosocial Interventions in Pain



Evidence for Non- Pharm, Non-Invasive Tx of Pain from AHRQ review in 2018:

AHRQ review available in references.

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Group Visits for Chronic Pain



PCORI-funded pros RCT study in Alabama of safety-net patients with chronic pain

 290 patients: 71% F, 67% AA,

72% at/ below poverty level, 83% disabled, 50% LBP, 68%

• n opioids, > 15yr pain

 Exclude: cancer pain, self-

reported substance abuse

 Primary outcome:

 Pain, function, depression

 Tx: 90min CBT class q wk x10

• v. education 90min/ wk v. UC

 Outcome: https://pmt.ua.edu/uploads/1/3/9/9/13995339/lamp_cbt_client_workbook.pdf. Thorn et al. Ann Intern Med 2018;168:471

CBT Group

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Take-Home Points



Many psychosocial interventions are successful for the treatment of pain.



Cognitive behavioral therapy delivered through a group class for safety-net patients is associated with improvements in pain, function, and depression scores.

Question



Which of the following summarizes the best treatment for this patient?

 1) Taper medication due to 2016 CDC guideline

recommendations

 2) Opioid rotation based on prospective RCTs

demonstrating benefit of this technique

 3) Continue same medications and amplify

psychological interventions

 4) Transition to buprenorphine-naloxone or

methadone maintenance

 5) Taper medication due to abnormal urine tox

screen

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 4Rs

 Risk of bodily

harm

 Relationship

trouble

 Role Failure  Repeated attempts

to cut back

 Tolerance*  Withdrawal*  4Cs

 Loss of Control  Consequences  Compulsion  Craving

• 4. Does this patient have

an opioid use disorder?

* Don’t count if pt on COT for pain

DSM-5 Criteria for Substance Use Disorders Recommendations and Rationale



Source: Am J Psychiatry. 2013;170(8):834-851.

a One or more abuse criteria within a 12-month period and no dependence diagnosis; applicable to all substances

except nicotine, for which DSM-IV abuse criteria were not given.

b Three or more dependence criteria within a 12-month period. c Two or more substance use disorder criteria within a 12-month period. d Withdrawal not included for cannabis, inhalant, and hallucinogen disorders in DSM-IV. Cannabis withdrawal added

in DSM-5.



Loss of Control Compulsion

Consequences

Craving Compulsion Risk bodily harm

Rel’ship trouble Role Failure

Repeated try cut back

2/26/2019 18

Why It’s Hard to Make this Diagnosis



Consequences hard to detect with lack of scarcity



Provider and patient are emotionally incentivized to not think/ look/ consider an OUD

 Provider sees no problem  patient loves me, don’t

want to be “duped” or culpable

 Patient sees no problem  I am suffering in pain. I

am not one of “those people”.



Lack of collateral



Stigma



Transitions in care

This patient …



Source: Am J Psychiatry. 2013;170(8):834-851.

a One or more abuse criteria within a 12-month period and no dependence diagnosis; applicable to all substances

except nicotine, for which DSM-IV abuse criteria were not given.

b Three or more dependence criteria within a 12-month period. c Two or more substance use disorder criteria within a 12-month period. d Withdrawal not included for cannabis, inhalant, and hallucinogen disorders in DSM-IV. Cannabis withdrawal added

in DSM-5.



Loss of Control Compulsion

Consequences

Craving Compulsion Risk bodily harm

Rel’ship trouble Role Failure

Repeated try cut back

2/26/2019 19

From Washington State Kaiser Permanente Opioid Guidelines Risk factors misuse Young age Hx SUD MDE Use of psychotropics

Other Strategies



COMM



Consultation



Increased monitoring

 Pill counts  Decreased

refill interval

 Urine

toxicology screening

Available at: http://mytopcare.org/wp-content/uploads/2013/05/COMM.pdf

2/26/2019 20

Treatment of OUD & Chronic Pain

 Methadone

 Higher level of

care

 Other SUD,

especially etoh & BZDs

 Active psychiatric

illness

 Need for

monitoring

 Daily, observed

dosing liquid med (lifestyle)

 Buprenorphine-

naloxone

 Office-based

treatment from primary care

 Dissolvable tab or

film used sublingually

 Provider must

have waiver to prescribe

 Safe

storage

Question



Which of the following summarizes the best treatment for this patient?

 1) Taper medication due to 2016 CDC guideline

recommendations

 2) Opioid rotation based on prospective RCTs

demonstrating benefit of this technique

 3) Continue same medications and amplify

psychological interventions

 4) Transition to buprenorphine-naloxone or

methadone maintenance

 5) Taper medication due to abnormal urine tox

screen

2/26/2019 21

• 5. Marijuana and Opioids



Common – estimate ~ 18% of patients



Urine toxicology testing positive for marijuana is not by itself considered reason to discontinue

• pioids



Positive urine toxicology for THC in COT patients

 Risk factor for future aberrancy  Increase monitoring



Urine toxicology testing is not perfect

 Use of other medications can cause false positives

(dronabinol, pantoprazole, NSAIDs)

 More frequent use can cause prolonged positive

results

 4d/ week  may be pos 5-7 days  Daily use  may be pos 10-15 days

DiBenedetto DJ et al. Pain Med 2018;19:1997. Standridge J Am Fam Physician 2010;81(5):635 Nugent SM et al. Gen Hosp Psychiatry. 2018;50:104.

Marijuana & Opioids



Is it the answer?

 Dec opioid-related deaths in states with

medical marijuana compared to those without (2014)

 Observational data of decreased opioid-

related deaths in states with legalization (Colorado), 2017

 High quality studies still lacking

 What “dose” of marijuana? What active

ingredient is most important? Who benefits?

Livingston MD et al. Am J Public Health 2017;107:1827. Bachhuber MA et al. JAMA IM 2014

2/26/2019 22

Case Continued



The patient’s case was very complicated.

 Some members of her care team felt she had a

prescription opioid use disorder.

 Others disagreed.  Everyone agreed that her level of pain control was

poor.

 She has begun a taper due to lack of benefit from

• pioid analgesics for pain control or significant

functional improvement.

 She has been counseled about the option of switching

to bupe-naloxone for pain+ OUD, should that need arise.

Take-Home Points, Case 1



We are all frequently encountering the question of

• pioid tapers in our patients. Ultimately it is a

question of risk v. benefit.



Use your MI skills to elicit patient thoughts and concerns about their dose.



Dose reduction is possible. Be flexible and understanding during the taper process.



If a patient has both an opioid use disorder and chronic pain, offer bupe-nx or methadone.



Use of marijuana in patients taking chronic opioid therapy is generally not considered a reason for automatic discontinuation.

2/26/2019 23

Evidence Updates as Told Through Another Case: Case 1



Your 55yo M patient has a history of obesity, COPD, chronic low back pain and HTN is presenting for f/ u. He is complaining of ongoing pain in his low back with pain that “shoots down” the leg. The pain is 9/ 10, severe, and has been constant for several weeks now. No other neuro sxs. Exam is non-focal.



He is taking:

 Gabapentin 300mg po tid  Benaz-HCTZ 10-12.5mg daily  Lidocaine cream topically  Tiotropium 1 cap inhaled daily



Which of the following will be your best next step to address his current pain complaint?

 A) Refer for urgent neurosurgical evaluation – non

focal exam

 B) Arrange ESI as soon as possible  C) Raise dose of his gabapentin to 600mg tid  D) Trial of opioid therapy  E) Trial of amitriptyline  F) Something else

2/26/2019 24

Epidural Steroid Injections (ESI)



Evidence-Base

 Systematic review

 30 trials of ESI for radiculopathy  8 trials of ESI for spinal stenosis  5 trials good quality  Outcome:

• ESI : dec pain 7 pts* * (0-100 scale) which was below

the threshold for a predefined clinically important

• difference. No long-term benefit.
• No change function
• SS – no sig benefit

Chou R et al. Ann Intern Med 2015.

ESI and Back Pain



ESI

 On the rise given the opioid epidemic (inc 13% from

2012 to 2016; VA 17% increase)

 Medicare reimbursement for procedure increased in

2016 (opioid epidemic)

 Safety concerns with Depo-Medrol

 Complaints of injuries and complications from the shots

– Pfizer asked DEA to ban tx 5yrs ago, but they did not

 Warning label:

• “Serious neurologic events, some resulting in death, have

been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke.”

https://www.nytimes.com/2018/07/31/health/opioids-spinal-injections.html

2/26/2019 25



Which of the following will be your best next step to address his current pain complaint?

 A) Refer for urgent neurosurgical evaluation  B) Arrange ESI as soon as possible  C) Raise dose of his gabapentin to 600mg tid  D) Trial of opioid therapy  E) Trial of amitriptyline  F) Something else

Gabapentin for Low Back Pain



Recent systematic review of gabapentin and pregabilin for LBP + / - radicular symptoms

 9 placebo-controlled RCTs  High-quality evidence  NO EFFECT on pain or disability in short- or

intermediate-term



Anticonvulsants for back pain prescribing

 Increases 535% in past 10 years Landefeld NEJM 2009. Shanthanna et al. PLOS 2017

2/26/2019 26

Gabepentin/Pregabilin for Back Pain



Harms Related to Gabapentin & pregabilin

 Nested case-control study from Canada (1997-2013)

 Cases: died of opioid-related causes  Controls: living, also taking opioids  Matching: age, sex, yr start opioids, CKD, disease risk

index

 Exposure: gabapentin in 120d before death  Result: gabapentin associated with 4 9 % increased

risk of opioid-related death com pared to opioids alone

 Pregabilin study

 Nested case-control study from Canada (1997-2016)

• Result: pregabilin exposure associated with 6 8 %

increase risk of opioid-related death compared to those on opioids alone

Gomes et al. PLOS 2017. Gomes T et al. Ann Intern Med 2018;169:732.

Is it addictive?



What do we know?

 # 5 rx drug in US (goodrx)  Anecdotal reports of its ability to

potentiate “opioid high”

 Estimated misuse in ~ 2 0 % of pts using

• pioids

 Use of gabapentin and opioids – 4-fold inc

risk resp depression

 Schedule 5 in Kentucky; pend Ten  Rescheduled in England Smith RV et al. Addiction 2016;111(7):1160. Peckham AM et al. 2018 Risk Man and Healthcare Policy, vol 11.

2/26/2019 27



Which of the following will be your best next step to address his current pain complaint?

 A) Refer for urgent neurosurgical evaluation  B) Arrange ESI as soon as possible  C) Raise dose of his gabapentin to 600mg tid  D) Trial of opioid therapy  E) Trial of amitriptyline  F) Something else

Opioids and LBP: SPACE Trial



240 VA patients 2013-15 with moderate to severe chronic back or hip or knee OA pain despite analgesic use

 Excluded: patients on LT opioids or SUD  Included: severe depression (~ 20% ), PTSD (~ 20% )  13% F, 88% white, 65% LBP, 35% hip/ knee OA, 25%

current smokers, 3% Etoh, 10% illicit drugs



Randomized to either:

 Opioids: IR  LA  fentanyl (to max 100ME)  Non-opioids: APAP/ NSAIDs  TCA, gaba, top lido 

pregabilin, dulox, tramadol (11% )

 Monthly visit w/ pharm., BPI (1˚ ), pain intensity (2˚ )



Outcome (1 yr):

 BPI: no difference, pain intensity (better in non-opioid),

more side effects (opioid)

JAMA 2018. 319(6):872-82

2/26/2019 28



Which of the following will be your best next step to address his current pain complaint?

 A) Refer for urgent neurosurgical evaluation  B) Arrange ESI as soon as possible  C) Raise dose of his gabapentin to 600mg tid  D) Trial of opioid therapy  E) Trial of amitriptyline  F) Something else

2/26/2019 29

TCAs and Low Back Pain



Amitriptyline and LBP

 N= 146 Aust patients with nonspecific chronic LBP

(61% M, depressed, NOT on opioids)

 Design: randomized, double-blind, pros RTC  Tx: amitriptyline (25mg/ d) v. benztropine (1mg/ d)

x6mo

 Outcome:

• Amitriptyline: 12 point reduction on VAS scale (0-100) v.

4.8 (benztropine), less disability at 3mos

• No differences pain, disability, work at 6mos.
• Support for a larger trial

Answer



Which of the following will be your best next step to address his current pain complaint?

 A) Refer for urgent neurosurgical evaluation  B) Arrange ESI as soon as possible  C) Raise dose of his gabapentin to 600mg tid  D) Trial of opioid therapy  E) Trial of amitriptyline  F) Som ething else

2/26/2019 30

Take-Home Points



Systematic reviews do NOT suggest benefit for gabapentin or pregabilin in patients with low back pain.



Gabapentin and pregabilin have been observed to be associated with increased risk of opioid-related death when co-prescribed, and have some addictive properties.



Pooled data does not show benefit to epidural steroid injections (ESI) for radicular low back pain

• r spinal stenosis.



Opioids are not superior to non-opioids for treatment of low back pain.

Summary



Voluntary opioid tapers are achievable and may be associated with reductions in pain.



Chronic opioid therapy treatment is about risks versus benefits. When the risks outweigh the benefits, that is an indication to taper.



If a patient has pain and an opioid use disorder, they need to be offered medication treatment including buprenorphine-naloxone or methadone.



New data is making us question some of our medication and intervention choices – including use

• f gabapentin and pregabilin and epidural steroid

injections.



Non-pharmacologic treatments for chronic pain are effective and beneficial for our patients. We need to adapt our clinical systems to meet our patients’ needs.

2/26/2019 31

Resources



Patients:

 Pain Toolkit:

 http: / / www.change-pain.com/ cmsdata/ change-pain-

portal/ en_EN/ pdf/ pain_toolkit_cp_en.pdf

 Chronic Pain Facebook Groups  You tube videos to educate patients about pain:

 Chronic pain in 5 minutes:

https: / / www.youtube.com/ watch?v= C_3phB93rvI

 Treatment options: https: / / vimeo.com/ 74825810 

Providers:

 Washington Agency Medical Directors Guidelines:

http: / / www.agencymeddirectors.wa.gov/ Files/ 2015AMDGOpio idGuideline.pdf

 SFHP patient/ provider resources:

http: / / www.sfhp.org/ providers/ pain-management/ resource- tools/

 CDC: https: / / www.cdc.gov/ drugoverdose/ pdf/ guidelines_at-

a-glance-a.pdf

With permission from Peter Moore.

Resources Continued



Tapers Info:

 https: / / www.cdph.ca.gov/ Programs/ CCDPHP/ DCDIC/

SACB/ CDPH% 20Document% 20Library/ OpioidPrescrib ersResources.pdf

 VA Tool:

https: / / www.pbm.va.gov/ AcademicDetailingService/ Documents/ Pain_Opioid_Taper_Tool_IB_10_939_P96 820.pdf



Chronic pain group manuals

 https: / / www.va.gov/ painmanagement/ docs/ cbt-

cp_therapist_manual.pdf



AHRQ review:

 https: / / effectivehealthcare.ahrq.gov/ sites/ default/ file

s/ cer-209-evidence-summary-non-pharma-chronic- pain.pdf

2/26/2019 32

Condition Pharm acologic Treatm ent Non-Pharm acologic Treatm ent Chronic Low Back Pain Pain: NSAI Ds, tram adol, SNRI s ( duloxetine), opioids* * . Function (small effect): duloxetine, tramadol, opioids. (Chou et al. Ann Internal Med 2017) Exercise; CBT; massage; mindfulness based stress reduction; yoga; tai-chi; spinal manipulation therapy (AHRQ Review 2018) Fibromyalgia Pregabalin, duloxetine, milnacipran, and amitriptyline (Hauser et al. Arthritis Res Ther 2014) Exercise; CBT; myofascial release therapy; acupuncture; tai chi; qigong; multidisciplinary rehab (AHRQ Review 2018) Osteoarthritis NSAIDs (topical and oral), APAP , tramadol, intra-articular treatments (Bannuru et al. Annals Int Med 2015; link below) Exercise; ultrasound (AHRQ Review 2018) Diabetic Neuropathy serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine (moderate SOE), the anticonvulsants pregabalin and oxcarbazepine (low SOE), the drug classes tricyclic antidepressants (low SOE) and atypical opioids (low SOE), and botulinum toxin (low SOE) were more effective than placebo (Waldfogel et al Neurology 2017) Percutaneous electrical nerve stimulation; topical agents (capsaicin, lidocaine, isosorbide dinitrite spray) Migraine prophylactic agents: beta-blockers, AED > anti-depressants, muscle relaxants Spinal manipulation therapy (AHRQ Review 2018) Chronic Pelvic Pain Am itriptyline, gabapentin, horm onal tx; dz-specific mgmt (Bonnema et al. Cleve Clin J Med 2018, Cochrane rev 2014) Pelvic physical therapy, trigger point inj

Risks of High Dose



Excess mortality (LA opioids, 60% increased risk all-cause mort)



Unintentional overdose (~ 0.7% / year 20-100MED)



Opioid use disorder (~ 20% )



Secondary Hypogonadism (~ 50% of men)

 Dec bone mineral density & inc. fracture risk



Sleep-disordered breathing (60-70% of patients)



Pneumonia (case-control)



Others

 Opioid-induced hyperalgesia  Cardiac toxicity with methadone  NAS: 5/ 1000 births after hx rx opioids during preg

Miller M, et al. JAMA Intern Med. 2015;175(4):608-15. Rose AR, et al. J Clin Sleep Med. 2014;10(8):847-52. Guilleminault C, et al. Lung 2010;188(6):459-68. Rubinstein AL, et al. Clin J Pain. 2013;29(10):840-5. Dublin Setal. JAGS, 2011;59(10): 1899. Smith HS, Elliott JA. Pain Physician. 2012;15(3 Suppl): ES145-56. Teng Z et al. Plos One. 2015;10(6). Desai et al. BMJ 2015

2/26/2019 33

High dose opioids (> 90MME) Concerning Behaviors?

Yes

Evaluate for opioid use disorder Present? Treat Not Present? Give warning. I f behavior continues, re- eval OUD

No

• 1. Bone Density Scan, 2. EKG if on

methadone, 3. Sleep Study, 4. total AM testosterone Risks Outw eigh Benefits?

No

Continue meds & monitoring. Discuss taper

Yes Imminent Safety risk? Yes Taper quickly No

Encourage Slow Taper