The Foundation for Medical Excellence 27th Annual Pain & Suffering Symposium http://tfme.org

1. Medication Management for
Patients with Persistent Pain
Launette Rieb, MSc, MD, CCFP, CCSAM, FCFP, dip ABAM
Clinical Associate Professor, Dept. of Family Practice, UBC
Director, St. Paul’s Hospital Goldcorp Addiction Medicine Fellowship
FME March 7-8, 2014 - Vancouver, BC, Canada

2. Faculty/Presenter Disclosure
 Faculty: Launette Rieb
 Relationship with commercial interests:
 Grants/research support:
 UBC Clinical Scholar’s Program
 UBC Special Populations Grant
 Speaker’s bureau Honoraria: SPH-CME this talk
 FME (Oregon College of Physicans), CPSBC, UBC-
CPD, various health authorities, Olympic bid
committee Qatar.
 Consulting fees: OrionHealth, Orchard Recovery
 Other: Providence Health (St. Paul’s Hosp)

3. Disclosure of Commercial Support
 No financial support or in-kind support for
this program
 No potential conflicts of interest for Dr. Rieb

4. Mitigating Potential Bias
 There is no bias to mitigate

5. Learning Objectives
 Review medications used to treat persistent
pain, and common interactions
 Increase awareness of what to order on
urine drug screen
 Gain knowledge of titration and tapering

6. 35 year old carpenter with right shoulder
tendinopathy on nortriptyline 30 mg hs and
tramadol 50 mg bid presents with elevated
blood pressure, slight fever and twitching. The
addition of which medication in the last month
is likely responsible?
1. Acetominophen 1000 mg q6h
2. Ibuprofen 600 mg q8h
3. Pregabalin 75 mg bid
4. Duloxetine 60 mg od

7. Acetaminophen
 Often forgotten
 Max dose 3.2 – 4.0 gms/d divided q6-8h
 One preparation may be tolerated better
 Lower dose if impaired liver, ETOH, elder
 Occasional GI upset – about 10%
 Can get rebound headaches

8. NSAIDS
 No clear evidence that one is superior
 Analgesic potency equal to opiates (2-3/10)
 Ibuprofen is least expensive
 Ibuprofen max dose is 2400 mg/d div. q8h
 Fluid retention, HTN, renal failure, asthma
 Beware if CVD, HTN, liver or kidney dis.
 Risk of GI bleed lowered with cox 2 inh., PPI
 Misoprostol not as protective, can give diarrhea

9. Antidepressants - TCAs
 High dose treats depression (2-300 mg/d)
 Low dose treats sleep cycle disturbance
(10-150 mg), consolidates stage IV sleep
 Lessens neuropathic pain & fibromyalgia
 I start with nortriptyline 10 mg hs titrate up
q4-7d, once sleep helped hold 3-6 weeks
 If not sedating enough switch to amitriptyline
 Also can try desipramine or imipramine

10. TCAs and Benzos
 TCAs
 S/Es: Dry mouth, postural hypotension,
weight gain, sedation, urinary retention, sexual
dysfunction, HTN – beware with CVD
 Beware with SNRIs, SSRIs, - serotonin syndr.
 Benzodiazepines have no effect on pain,
do not consolidate sleep, can lead to falls,
depression, anxiety, & addiction: Avoid
 N.B. This includes the “Z” drugs

11. Tetracyclic and NRI
 Trazodone and mirtazapine help sleep
cycle restoration, but no evidence for pain.
 They block 5HT2 receptors & decrease sleep
fragmentation induced by SSRIs, SNRIs,
TCAs – so add in low dose
 Trazodone
 lower side effects than TCAs
 Little erectile dysfunction, can cause priapism

12. Antidepressants - SNRIs
 Serotonin-noradrenalin re-uptake inhibitors
(SNRIs) reduce pain in non-depressed pts
 Further benefits in depressed patients
 Venlafaxine is an SSRI at 37.5 mg/d and
becomes an SNRI at 225 mg/d
 Duloxetine is an SNRI at low dose 30mg
 approved for diabetic neuropathy and fibromyalgia
 Caution: CVD, HTN, TCAs, and tramadol
 Withdrawal syndromes can be significant

13. Antidepressants – SSRI, DNRI
 SSRIs/DNRIs - no pain relieving benefit
 Use if the patient has a Major Depressive
Disorder and an SNRI can’t be used
 Paroxetine and citalopram are options
 The DNRI bupropion – least weight gain
 Containd: Seizure or eating disorders, cocaine

14. Neuromodulators
Gabapentin – class action suit
Reduces pain 1/10 beyond placebo effect
With placebo effect about 1/3 get pain relief
NNT = 6-8, NNH= 8, no role in acute pain
Max 3600 mg/d div. q6h, but if no benefit by 2400
mg/d then taper off
Start at 100 mg hs, increase by 100 mg q3-4d until
300 mg tid, then can incr. by 300 q3-4d – slow down
titration if side effects

15. New(er) Neuromodulators
 Pregabalin
 Benefits/harms like gabapentin, more expensive
 Max 300-600 mg/d divided q 12h
 Easier and faster to titrate than gabapentin
 Start with just 25mg qhs, increasing q 3-4d
 Side effects (like those of gabapentin):
 Dizziness, edema, somnolence, and memory
impairment, word finding difficulty. Beware of
use with kidney problems.

16. New(er) Opioids
 Tramadol
 Weak opioid plus weak serotonin-noradrenalin
re-uptake inhibitor (SNRI) effects
 Can get a serotonin syndrome with use,
especially in combination with SSRIs or SNRIs
 Can get serotonergic withdrawal symptoms
 Metabolized via Cytochrome P450 2D6 - so
10% can’t metabolize (similar to codeine).
Beware converting to and from other opioids
 UDS –Ask for by name: won’t show as “opioid”

17. New(er) Opioids
 Oxycodone + naloxone
 Decreases gut immobilizing opioid effect
 NNT around 9 to decrease constipation
 Modest effect in those with results
 Tapentadol
 Opioid plus weak noradrenalin re-uptake inhibitor
(NRI), may have serotonergic (5HT) effects??
 Not much clinical experience as yet
 UDS: Ask for tapentadol (GCMS)

18. Opioid with issues
 Long acting oxycodone – old formulation
 Fast high peak – highly addicting
 Easily crushed – snorted, injected for rapid high
 High street value - prime diversion drug
 Pharmaceutical maker marketed it as less
addicting – Class action suit in US won against
company and executives, pending suit in Canada
 UDS – Ask oxycodone by name (does not show
as “opioid”)

19. New(er) opioids
 New long acting oxycodone
 Crush resistant – can’t crush even with a hammer
 Forms gelatinous substance in fluid “Jelly-nose”
 Pushing IV users back to heroin if done before
 Lowers risk of converting to IV use in those
never used IV before starting oral opioids
 Recipes on internet for grinding, microwaving
and baking to make a snortable/injectable powder
 UDS: Ask for oxycodone by name (does not
show up as “opioid”)

20. More Opioids
 Methadone blocks the NMDA receptor
 Lessens tolerance & opioid induced hyperalgesia
 Good for neuropathic pain, indicated in SUD
 Dosed q6-8h for pain (daily for addiction)
 You must have an exemption to prescribe this
controlled substance for pain – read instructions
and articles online on the CPSBC website and
speak with the registrar for your exemption
PLEASE! If prescribed for addiction do 1d course
 UDS – Ask for methadone metabolites, not opioid

21. New(er) Opioid
 Buprenorphine
 Is a partial mu opioid agonist with a ceiling effect
that displaces other opioids from the receptors
 Is a kappa antagonist so is less dysphoric than other
opioids, and may improve mood
 Patches (BuTrans): UDS-Can NO SHOW!
 Indicated for moderate chronic pain
 May be opioid naive or in mild withdrawal
 5, 10, 20 microgram/hr patch changed weekly –
convenient, even, low sedation, low OD risk

22. New(er) Opioid
 Buprenorphine/naloxone pill (Suboxone)
 In Canada only used in those with substance
dependence (Substance Use Disorder) +/- pain
 BC: MD must have a methadone exemption 1st,
then take online training course (not in Ont.)
 In the US it can be used in those not addicted
 Never 1st line, patient must be opioid tolerant
 Put into withdrawal (can use COWS score)
 Test dose of 1-2 mg 1st, then titrate up…
 UDS: Ask for buprenorphine – does show

23. New(er) Opioid
 Fentanyl patch
 Pure mu opioid agonist, fairly even blood levels
 12, 25, 50, 100 micrograms per hour
 Change every 3 days, put over hairless muscled area
 Can be cut up and sucked, or heated and smoked
 So have patients return all used patches to pharmacist
 UDS – ask for fentanyl by name -not shown as “opioid”,
and very low dose patch may not show at all
 Fentanyl sublingual tablet – for cancer only
 Fentanyl liquid, ampules - caution

24.  High opioid doses are commonly
given to high risk patients
 Escalation is an easy short-term solution that
can create difficult long-term problems when
patients are demanding or present with
overwhelming suffering and disability
Adverse Selection

25. Help when prescribing opioids
 Do a complete hx + px, have a contract, UDS
 Establish realistic expectations
 Only 1 in 4 pts with CNCP get relief from opioids
 2/10 drop is a successful result – do not chase up
the dose past one or 2 increases without benefit
 Function must change for prescribing to continue
 Use the Opioid Manager – Cnd Guidelines
 Watchful dose = 200 mg equivalent morphine
 Pt to use non-medication active pain strategies

26. Opioids
 Physician conducts opioid trial (2-3/10 relief)
 Select opioid – stepped potency approach
 Start low and titrate to optimal dose
 usually < 200mg/d of morphine equivalent
 MD reassesses risks/benefits, function, side
effects, mood, substance use disorders
 Beware of conversions between opioids
 Eg. morphine to methadone conversion
 For other meds – convert and give 50-80% only

27. Opioid Dose Adjustments
 Physician adjusts dose as required:
 Increase or decrease by 5-10% at a time
 The earliest dose change should be after 5 half
lives of that particular drug
 Morphine (1/2 life 3 hr) daily adjust in hospital
 Methadone (1/2 life 24-36h) adjust q5+ days
 If unsuccessful (no change pain + function)
 taper off, might try a diff opioid, or not
 Go slower at the end of a taper – last 20%

28. Opioid Short > Long Conversion
 Long acting can provide smoother control
 But beware of high peak of some long acting
formulations which can produce euphoria
 Change 50-75% of the total dose over to the
long acting formulation – provide the rest in
short acting with a warning for sedation
 Review in 1 week and convert more to long
 Ideally very little to no breakthrough

29. Opioid Issues
 Generally avoid caffeinated products
 Use short acting formulations dosed on the
half life, or long acting formulations with
some caution about peak serum levels
 Suppression of testosterone
 decreased sex drive and performance
 treatable: vitamin V, or testosterone
 Cognitive impairment, drowsiness, and
respiratory depression can all adapt

30. Cannabinoids
 Try all other medication categories 1st
 Analgesia less than NSAID or codeine
(1/10 reduction) in meta-analysis. May be a
bit better for neuropathic pain, anti-emetic
 Contraindicated: Psychotic disorders,
Substance Use Disorders, CVD
 Side effects
 Hypotension, tachycardia, arrhythmias,
dizziness, depersonalization, drymouth,
hyperphagia, depression, anxiety, memory,
perception, impulse/motor control, paranoia,
psychosis, COPD, cancer elevated risk

31. Cannabinoids
 Nabilone
 synthetic delta-9- tetrahydrocannabinol (THC)
 0.25 - 4mg/d divided
 Does not show up on urine drug screen
 Anti-emetic (HIV wasting, chemotherapy)
 Buccal Cannabinoid
 Whole plant extract
 Delta-9-THC + cannabidiol
 1-12 buccal sprays/d
 CB2 targeted for neuropathy (MS, HIV)
 In theory less central effects – not in practice

32. Cannabiniods, con’t
 Smoked marijuana – addiction/diversion potential
 Typically 0.25 to 3 gm/d for pain (3 puffs-6jnt)
beware above – addiction/diversion?
 Health Canada exemption – grow 5 plants/1gm
 As THC rises, CBD falls – increasing psychosis
 Added risks: COPD, cancer. Use pills/spray instead
 Ingested marijuana – diversion potential
 Usually about 1/3 more than smoked, baked
 Harder to titrate than smoked, but longer lasting
 Use pills/spray instead

33. Topicals – for peripheral pain
 Lidocaine and prilocaine cream
 Nitroglycerine patch – use ¼ of a
NitroDur patch daily over a tendonopathy
 Diclofenac gel 1-10%, patch – MSK
 Capsaicin for post herpetic neuralgia, HIV
 Shotgun: PLO Base + diclofenac 10%,
amitriptyline 2-4%, ketamine 2-5%,
lidocaine 5% applied tid-qid to small area

34. Case 3 - Ms. Z
 55 yr. old care aid injured
 Rt. Shoulder pain, sleep
and mood changes
 MRI – full thickness tear and atrophy in
supraspinatus, a possible tear in subscapularis,
tendonopathy in infraspinatus, fluid in the
subacromial bursa and deltoid bursa
 Ortho suggested conservative management

35. Ms. Z. – cont.
 Tx – cortisone injections some help
 Mood – 2h sleep/night, anxious, tired
 PMH
 Previous shoulder injury, resolved
 Asthma
 HTN
 Hyperlipidemia
 Obesity
 Depression – “treated” for 12 years

36. Case 3 – Ms. Z, cont.
 Meds:
 T#3 – 2 q3h up to12/d, runs out early nb 50 pills given
q2 wk = 3-4 pills a day allowed by perscription
 T#1 – 3 q3h up to 18/d when out of T#3s
 Clonazepam 0.25mg qam, 0.5mg noon, 0.25mg qpm,
1.5mg hs (dosing x 12 yrs)
 Oxazepam 45mg hs (x 12 yrs)
 Methylphenidate (Ritalin) 20mg tid when working, 10mg
bid when off work (x 12yrs)

37. Ms. Z – cont.
 Meds – cont.
 Trazadone 300mg hs
 Chloral hydrate 500mg hs
 Risperidone 1.5 mg hs
 Rabeprazole (Pariet) 20 mg od
 Montelukast (Singulair) 10mg hs
 Salbutamol prn
 Advair 1 puff bid

38. Ms. Z. – cont.
 Meds, cont.
 Diltiazem CD 180mg od
 Fosinopril 10mg od
 Hydrochlorothiazide 25mg od
 “Failed” + antidepressants, TCAs, neuromod.
 So stimulant to wake, opiate and anxiolytic in
day, and sedative-hypnotics and antipsychotic to
sleep

39. Ms. Z – substance use hx
 Caffeine: 1c coffee q3d
 Tobacco: ½ ppd (from 1ppd), enjoyment
 Alcohol: current - 1drink q 1/2 - 2 wks
(understands it is contraindicated), around
30 had 4-5 yrs of problems - once weekly 1
bottle of wine, kids taken in by cousins.
Finally divorced, church, cut back on
ETOH and got kids back
 Drugs: no reported use

40. Ms. Z – Px
Pleasant caucasian woman, slightly sedated
 Ht = 5’0” , wt = 230 lbs
 BP elevated
 Cradling right arm, head tilted to right
 Limited shoulder flex, abd., int. rotation
 Shoulder/arm strength reduced - pain limited
 Diffusely tender whole shoulder girdle

41. Ms. Z. - Dx
 Rt rotator cuff tear, tendonopathy, atrophy
 Mood changes & meds began when
drinking and divorcing, still low, anxious,
sleep disturbed
 Chronic pain disorder – physical and psych
 Overmedicated
 Substance use disorder – ETOH abuse/dep
in remission with intermittent use

42. Ms. Z. – Dx – cont.
 Tobacco dependence
 Current opioid dependence vs pseudo-add.
 Asthma
 Hypertension
 Hyperlipidemia
 Obesity
 Positive work environment – social support

43. Ms. Z. – Recommendations
 Chronic pain program – guarded prognosis
 Taper methylphenidate to elimination
 Taper chloral hydrate, T#3, T#1
 Consolidate benzos and begin slow taper

44. Ms. Z. - Recommendations, cont.
 Discontinue alcohol,
 Hold or decrease cigarettes
 Physio + general conditioning & wt loss
 Psych support, self regulation training
 Call family MD and Psychiatrist

45. Ms. Z. – After 6 weeks in PMP
 Was able to completely come off
methylphenidate, codeine (T#3, T#1), and
chloral hydrate
 Clonazepam reduced to 1.5 mg hs
 Oxazepam reduced to 30 mg hs
 Same dose of trazadone 300mg hs
 Same dose of risperidone 1.5mg hs
 Off alcohol, nicotine <1/2ppd, +caffeine

46. Ms. Z. – 6 wks, cont.
 Lost 15 lbs
 BP normalized 125/76
 Sleep still 2-3 hrs/night, plus 4 hrs rest
 Activity increased – cardio: 45min from 10
 Improved head, neck & arm posture
 Improved shoulder ROM & strength
 Learned relaxation, breathing, mindfulness

47. Ms. Z. – 6 wks, cont.
 Pain “a little bit better, easier to deal with”
 Mood: “Gosh, a lot better and much clearer. I
am much, much better than before… I am
alive! I have more energy. Thank you…”
 Beck depression scale went from severe range
on intake to mild
 Doing a PMP has “given me my life back”

48. Ms. Z. – Recommendations on d/c
 Return to work (GRTW)
 Continue slow taper of clonazepam by
0.125 mg to 0.25 mg q 1-2 wks
 Then taper oxazepam by 15 mg q1-2 wks
 Then taper risperidone by 0.5mg q1-2 wks
 Leave trazadone 300mg hs for 6-12 months
 May have life long sleep disturbance – so
temper the need to treat with meds
 That said, tryptophan & melatonin yet to try

49. Ms. Z. – Follow up
 Successful completion of a GRTW – fit
without limitations
 Happy to be back in the workplace with
friends
 Continued to do well at home and work upon
review 6 mo. post discharge

50. Ms. Z. - Reflections
 Addiction?
 Pseudo-addiction?
 Opioid induced pain sensitivity?
 Mood induced pain and disability?
 Or instead iatrogenic cause of dysfunction
 Layering meds to offset side effects of the last
one prescribed, and time pressure in office –
trying to fix symptoms

51. Harmony
Sunyata
Your cases?

52. References
 Furlan A. et al. Opioids for chronic non-cancer pain: A new Canadian
guideline. CMAJ, June 15, vol. 182(9) 2010: 923-930
 Martin-Sanchez et al. Systemic review and meta-analysis of cannabis
treatment for chronic pain. Pain Medicine, Vol. 10(8)2009:1353-1368
 Drugs for pain: Treatment guidelines. The Medical Letter, vol. 8 (92) April
2010
 Rieb, L. Spreading pain with neuropathic features may be induced by opioid
medications. This Changed My Practice. UBC CPD, Sept. 13, 2011
http://thischangedmypractice.com/
 Gabapentin for pain: New evidence from hidden data. Therapeutics Initiative,
75, July-Dec., 2009
 One slides generously leant to Dr. Rieb by Dr. J. Bordman