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

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)

Disclosure of Commercial Support

No financial support or in-kind support for this program

No potential conflicts of interest for Dr. Rieb

Mitigating Potential Bias

There is no bias to mitigate

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

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 q6h2. Ibuprofen 600 mg q8h3. Pregabalin 75 mg bid4. Duloxetine 60 mg od

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

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

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

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

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

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

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

Neuromodulators

Gabapentin – class action suitReduces pain 1/10 beyond placebo effectWith placebo effect about 1/3 get pain relief NNT = 6-8, NNH= 8, no role in acute painMax 3600 mg/d div. q6h, but if no benefit by 2400 mg/d then taper offStart 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

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.

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”

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)

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”)

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”)

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

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

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

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

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

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

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

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%

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

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

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

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

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

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

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

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

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)

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

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

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

Ms. Z – PxPleasant 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

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

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

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

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

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

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

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”

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

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

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

Harmony

Sunyata

Your cases?

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