4th Annual Thoughtful Approach to Chronic Pain“New Horizons, What Clearly Works”

Managing Chronic Pain in the Primary Care Setting:

Advancing Practice in the Post-Opioid Era

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David J. Tauben, MD, FACPChief, UW Division of Pain Medicine

Hughes M & Katherine G Blake Endowed ProfessorClinical Associate Professor

Depts of Medicine and Anesthesia & Pain MedicineUniversity of Washington, Seattle WA

DISCLOSURES

CME grant support from:

ER/LA Opioid Analgesics REMS Program Companies

NIH Pain Consortium Center of Excellence in Pain Education

Off-label use of many drugs is recommended in the management of pain and so will be

discussed

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objectives

1. Evaluate the risks and benefits of drug and non-drug treatments used for pain.

2. Discuss new standards for use of opioids in chronic non-cancer pain.

3. Discuss the emerging models of primary care based pain assessment and treatment tracking

4. Make more informed pain drug treatment decisions in the outpatient setting

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Understanding pain

“In order to treat something, we must first learn to recognize it.” -William Osler

1. Chronic pain, a complex condition, when understood, assessed, and then treated following a structured approach, improves outcomes

2. Thorough assessment of the common biopsychosocial domains of pain adds important diagnoses also requiring treatment

Pain is NOT nociception, even if it feels that way…

“Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (IASP 1979)

Nociceptors selectively respond to noxious stimulation

What we observe during exam of our patients

Response to the experience of diminishment of one’s capacity

The “Loeser Onion”

Predictors of Abnormal Pain Response

History and examination: Demonstration of “non-

anatomic” territory of pain

Depression or other preexisting mood disorder

Distressed socioeconomic status

Overall poor life coping status and satisfaction

Preexisting pain processing disorders: Like fibromyalgia Prior persistent pain

problems

Active emotional distress Particularly anxiety and

fear (of the consequences or significance of an injury.)

Prior surgical complications or failure to resolve pain after previous surgery

Van Susante J, Acta Orthop Belg. 1998.Von Korff M, Pain. 2005 Carroll LJ, Pain 2004Carragee EJ, Spine J 2005

History shapes beliefs, behaviors, & outcomes: Adverse Childhood Events (ACE)

• Recurrent physical/emotional abuse

• Contact sexual abuse• An alcohol and/or drug

abuser in the household• An incarcerated household

member• Someone who is chronically

depressed, mentally ill, institutionalized, or suicidal

• Mother is treated violently• Emotional or physical neglect

Significant Events: Robust Correlation: Depressed affect, suicide

attempts Multiple sexual partners,

sexually transmitted diseases

Smoking & alcoholism Social, emotional,

cognitive impairment Disease, disability &

social problems Chronic Pain

Anda R., www.acestudy.org

Centralized Pain Syndromes

Irritable bowel

Tension headache

Temporo-mandibular disorder

Myofascial pain syndrome

Pelvic pain

Interstitial cystitis

Yunus 2007

Pain and the Primary Care Provider• 30% of adult PCP visits/week

involve chronic pain; but,1. Scant pain education and training2. “Haven’t got time for the pain”3. Limited or no access to

multidisciplinary pain care 4. Long-term opioids has become

the “de facto” pain treatment

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Daubresse 2010; Dosa & Teno 2010; Giordano 2009; Mezei & Murinson 2011; Schatman 2006; Von Korff 2008

Pain care sites of delivery

20-52% of chronic pain presents and is managed in the primary care setting

• 30% of adult PCP visits/week involve chronic pain

40% receive care by chiropractors 7% by acupuncturists 20% care delivered in the ED

Only 2% by Pain Physicians10

Breuer 2010; Daubresse 2010; Giordano 2009; Krueger & Stone 2008; Marcus 2009; Von Korff 2008

“The Under treatment of Pain” American Medical Association

"In the past several years, there has been growing recognition on the part of health care providers, government regulators, and the public that the under treatment of pain is a major societal problem.”

“Physicians' fears of using opioid therapy, and the fears of other health professionals, contribute to the barriers to effective pain management.”

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AMA 2004

The Allure of Opioids

1. They make patients happy, …at least

initially.2. They are very available in even the

most remote sites.3. Insurance covers them better than any

other pain treatment.4. The signed prescription closes the visit.

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TOTAL OUTPATIENT PRESCRIPTIONS OF ER OPIOIDS1991-2008

SDI, Vector One: Nationale. Extracted 12/2009

Opioid Rx Choices

SHORT-ACTING Codeine Fentanyl

lozenge/buccal Hydrocodone Hydromorphone Morphine Oxycodone Oxymorphone

ER/LA Extended release

(“ER”) Morphine Oxycodone

▪ Oxymorphone Transdermal fentanyl Transdermal

buprenorphine*

Long Acting (“LA”) Methadone Levorphanol

www.cope-rems.org

“REMS”: Risk Evaluation and Mitigation Strategies

Long or Short Acting Opioid?CONVENTIONAL WISDOM:

Long-acting for Long-term use Stable and scheduled

dosing Fewer pills Trend toward worse

outcomes: More deaths and misuse

Short-acting taken regularly Activity/function

dependent dosing Lower levels while

asleep

CURRENT APPROACH:

Best patient function Least non-compliance Lowest “Morphine

Equivalent Dose” Risk/harm reduction

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Sipress D. New Yorker 4/6/2015HOW WE MEASURE PAIN

HOW PAIN should be MEASURED

1. Pain intensity*

2. Interference with Enjoyment/Quality of Life*

3. Interference with Function*

4. Impact on Mood*

Anxiety, Depression, PTSD5. Interference with Sleep6. Treatment Risks

Medical: ie. Sleep Apnea Behavioral & Addictions

*From Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. J of Pain 2008:9:105-121

3-item “PEG” Tool

18Krebs et al. 2009

Identifying co-occurring MOOD diagnoses

Anxiety GAD-7 (or PHQ-4) Depression

PHQ-9 (or PHQ-4) PTSD

PC-PTSD ScreenIn your life, have you ever had any experience that was so

frightening, horrible, or upsetting, that in the past month you:

1. Have had nightmares or thought about it when you did not want to?2. Tried hard not to think about it or went out of your way to avoid

situations that reminded you of it?3. Were constantly on guard, watchful, or easily startled?4. Felt numb or detached from others, activities, or your

surroundings?

PHQ-4

“When your brain is on fire I can’t help your pain…”

Non-Drug Multimodal Analgesia

• Cognitive: • Identify distressing negative cognitions and beliefs

• Behavioral approaches: • Mindfulness, relaxation, biofeedback

• Physical: • Activity coaching, graded exercise land & aquatic

with PT, class, trainer, and/or solo• Spiritual:

• Identify and seek meaningfulness and purpose of one’s life

• Education (patient and family): • Promote patient efforts aimed at increased

functional capabilities

21Argoff CE, et al. Pain Medicine 2009;10(S2):53–S66.

Health professionals involved in Pain Management

1. Medical specialties2. Nursing3. Pharmacy4. Physical therapy5. Occupational therapy6. Behavioral health7. Social work8. Chaplain9. Addiction

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PAIN MEASUREMENT BASED STEPPED CARE

Tauben, IASP Clinical Update, 12/2012

Measure and Track:• Function• Mood• Sleep• Risks• Treatment

adherence• Opioid MED

Get inter-professional help

when need identified!

Pain intensity alone is inadequate and in chronic pain a very

poor indicator of successful treatment

Chronic Pain Treatment “Comparing” Effectiveness

Opioids: ≤ 30% Tricyclics/SNRIs: 30% Anticonvulsants: 30% Acupuncture: ≥ 10+% Cannabis: 10-30% CBT/Mindfulness: ≥ 30-50% Graded Exercise Therapy: variable Sleep restoration: ≥ 40% Hypnosis, Manipulations, Yoga: “+ effect”

Extrapolated averages of reduction in Pain Intensity

Turk, D. et al. Lancet 2011; Davies KA, et al. Rheum. 2008; Kroenke K. et al. Gen Hosp Psych. 2009; Morley S Pain 2011; Moore R, et al. Cochrane 2012; Elkins G, et al. Int J Clin Exp Hypnosis 2007.

Yet In spite of Overwhelming evidence…

Efficacy of Behavioral Management/ CBT:

Astin, et al (2002); Keefe & Caldwell (1997); Bradley (2003); Brox et al. (2003); Burns, et al (2003); Chen et al (2004); Cutler et al. (1994); McCracken & Turk (2002); McGrath & Holahan (2003); Morley et al (1999); Okifuji et al (2007); Pincus et al (2002); Roberts et al (1980);Spinhoven et al. (2004); Turner et al (2006); Vlaeyen & Morley (2005); Weydert, et al. (2003)

Efficacy of Multidisciplinary Chronic Pain Programs

Aronoff 1983; Becker et al (2000); Deschner & Polatin (2000); Feuerstein & Zostowny (1996); Flor et al (1992); Gatchel &Turk (1999); Gatchel et al (2007); Guzman et al (2001); Lande & Kulich (); Lang et al (2003); Linton et al (2005); Loeser 1991; McAllister et al (2005); Okifuji (2003); Okifuji et al (1999); Robbins et al (2003); Sanders et al (2005); Skouen et al (2002); Turk (2002) Wright & Gatchel (2002).

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“This review clearly demonstrates that CPPs offer the most efficacious and cost effective, evidence-based treatment for persons with chronic pain.”

“Unfortunately, such programs arenot being taken advantage of because of short-sighted cost-containment policies of third-party payers.”

Gatchel & Okifuji (2006)

Opioid sales, Ods, and addictions

Opioid Overdose Risk

Non-user 1-19 mg. 20-49 mg. 50-99 mg. 100+ mg.0

1

2

3

4

5

6

7

8

9

101.79%

0.68%

0.26%0.16%

0.04%

9-fold increasein risk relative

to low-dosepatients

Dunn et al., Annal Intern Med 2010

**

**

** Significant increment in risk p<0.05

Rela

tive R

isk

by Average Daily Dose of Prescribed Opioids (Morphine Equivalent Dose)

BENZOdiazepines

Lack of evidence for sustained benefits Rebound insomnia Risk of over-sedation especially when

combined with opioids Complicating development of tolerance,

dependency, and addiction.

Use of benzodiazepines for sleep & anxiety are not recommended

in chronic pain 28

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“Bending the curve”WA State First in NATION with decline in opioid related adverse events

30Source: Jennifer Sabel PhD Epidemiologist, WA State Department of Health, April 18, 2014

METHADONE ods >> other opioids

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Source: SAMHSA Drug Abuse Warning Network Medical Examiner Component, 2009.

Methadone

For Pain Treatment Effective analgesic Chronic Opioid Therapy Long acting Inexpensive

For Addiction Treatment Requires special DEA

licensing and treatment support

Once daily liquid dosing eases administration

Reduces mortality among heroin users

Significant accumulation with

repeat dosing

• Initial T½ 13-47 hrs up to 48-72 hrs

• 100% hepatic cleared• CYPs: 1A2, 2D6,

3A4

Inhibits its own CYP metabolism

Drug overdosesWashington State 1999-2013

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Source: C. Banta-Green WA State Department of Health

OpioidsThe Clinical conundrum

OpioidsThe Clinical Challenge

• Not all patients with pain are suitable candidates for chronic opioid therapy (COT).

• Short-term opioid therapy has different goals and purposes and should not progress to COT without reconsideration of goals and purposes.

• Opioid dependence develops in all patients receiving COT, may have a strong psychological component, and is not always easily reversible.

• COT should be goal oriented and discontinued if goals are not met.

• There are significant safety issues that need consideration during COT.

From Ballantyne J, Rehab Clin NA. in press 2015

Opioids are part of plan, not The plan

“Avoid … primary reliance on opioid prescribing, which, when applied alone or in a non-coordinated fashion, may be inadequate to effectively address persistent pain as a disease process and, when employed as the “sole” treatment, is associated with significant societal expense and treatment failure.”

▪ ABPM Pain Medicine Position Paper, Pain Medicine 2009:987-988.

Anti-Spasm drugs

• Antispasm drugs have limited evidence for effectiveness, are predominantly sedative, and add polypharmacy to chronic pain management with little benefit.

• Carisoprodol should never be used because of no benefit and high risk.

• When true spasticity is present, as in spinal cord injury and multiple sclerosis, baclofen and tizanidine may be useful.

• Avoid abrupt withdrawal off baclofen because of the potential for severe rhabdomyolysis and fever.

37van Tulder MW et al. Cochrane Library 2008

antidepressant analgesia

Principal neurotransmitters in “descending inhibitory systems”

Multimodal benefits: PAIN, SLEEP, &

MOOD

DESCENDING INHIBITORY NOXIOUS CONTROL SYSTEMS“Gate Theory”

Ascending pain pathways

Descending pain pathways

Proposed Mechanisms of Antidepressant analgesic effect

39Verdu B. Drugs 2008

CLINICAL KEY Points

Antidepressant Analgesia

• Antidepressants that elevate synaptic norepinephrine (TCAs > SNRIs) are effective analgesics

• Sedating antidepressants are useful agents to improve both sleep initiation and maintenance

• Anticholinergic side-effects are most common with TCAs

• Nausea is common with SNRIs• Dose related QTc prolongation occurs with TCAs

>SNRIs• Warn patient and family about risks of suicidality

when any antidepressant is prescribed• Mania may be precipitated by any category of

antidepressant

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Tricyclic Antidepressant Effectiveness:

Post Herpetic NeuralgiaNNT* 2.1-2.7

Diabetic Peripheral NeuropathyNNT 1.2-1.5

Atypical Facial PainNNT 2.8-3.4

Fibromyalgia/Central PainNNT 1.7

Saarto T, Wiffen PJ. Cochrane Database of Systematic Reviews 2007

*NNT = Number needed to treat

“Gabapentinoids” for PainPrototypic Ca++ current inhibitors

Gabapentin Pregabalin

• Well studied• Fewer side effects than

other anticonvulsants• Limited drug-drug side

effects• 100% excreted in the urine• Gabapentin absorption via

active transport; not so pregabalin

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Side-effects:Weight GainEdemaCognitive slowingDizziness/AtaxiaTwitchingSuicidality

Pharmacodynamics (“mechanism”):Selective inhibitory effect on voltage-gated calcium channels containing the α2δ-1 subunit.

Larsen MS, et al. Res. Pharm Res. 2014

Gabapentinoids efficacy: diabetic Pn and fibromyalgia

Pregabalin600 mg: NNT 4300 mg: NNT 6

Diabetic Peripheral Neuropathy

FibromyalgiaGabapentin

1200-2400mg

Pregabalin 300-600mg

NNT

>30% improvement: 5-9

>50% improvement: 8-12

NNH: 6-14

Freeman R. et al Diabetes Care 2008 Hauser 2009

Benefit/risks of Na+ channel Anticonvulsants

Risks of ACDs• SIADH• Increased LFTs• Sedation/Weight gain• Suicidality• Neutropenia1

• Hyperammonemia2

• Rash/Stevens Johnson Syndrome3

• Metabolic acidosis4

• Glaucoma4

• Kidney stones4

Carbemazepine1 & Oxcarbazepine

Valproic Acid2

Lamotrigine3

Topiramate4

Lacosamide

Variable effectiveness in different disease states

• Carbamazepine: Trigeminal neuropathy (TN)

• Oxcarbazepine: TN, Multiple Sclerosis

• Lamotrigine: TN, HIV PN, ± Diabetic PN

• Topiramate: MigraineCummins TR et al. Pharmacology of Pain. IASP Press; 2010

Other “off-label” use of anticonvulsants in pain*

1. Headache disorders:Migraine, Chronic Daily Headaches, Tension-type

2. Visceral “hyperalgesia” syndromes:(gabapentinoids)

Chronic Pelvic Pain Chronic Abdominal Pain

3. Peri-operative hyperalgesia prevention:(gabapentinoids)

Thoracotomy, abdominal and pelvic surgeries

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*Variable levels of quality of evidence to support use

Key Points

Anticonvulsant Drugs for Pain

• Anticonvulsant drugs with both sodium and calcium channel modulating effects are effective in a variety of neuropathic pain disorders, fibromyalgia, and headache.

• Sodium channel ACDs have a wide range of potential serious adverse drug effects, including electrolyte disorders, pancytopenias, and skin rashes, and so require routine laboratory monitoring.

• Gabapentinoids side effects are usually clinically evident: cognitive slowing, weight gain, and edema.

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Tauben D. Phys Med Rehab Clinic NA, in press 7/2015

From Finnerup et al., 2007 and adapted from Sindrup SH, Jensen TS.1999.

Drug Class MAJOR EFFECT ON PAIN NNT1 NNH2

Tricyclic antidepressants

Inhibition NE>5-HT reuptake, blockade sodium & calcium channels and NMDA receptors

1.5-3.7

10-25

5-HT/NA Reuptake inhibitors

Inhibition 5-HT/NE reuptake 3.4-14

Lidocaine Blockade voltage-dependent sodium channels

Carbemazepine/Oxcarbazepine

Blockade voltage-dependent sodium channels 1.6-2.5

13-79

Lamotrigine Blockade voltage-dependent sodium channels/inhibits glutamate release

3.5- 8.1

Gabapentin/Pregabalin

Blockade voltage gated calcium channel 4.0- 5.6 4-30

Tramadol/Tapentadol

Opioid agonist, inhibits 5-HT/NE reuptake 2.7- 6.7 2.7- 6.7

Opioids Mu-receptor agonists, partial agonists, and antagonists

2.0- 3.2 10-663

1NNT (# needed to treat)2NNH (# needed to harm)3Dose related

Key Points:Cannabis Use for Pain• Evidence supports use in neuropathic pain conditions

• >30 published RCTs, positively supporting moderate efficacy: BUT most low quality

• Most clinical trials use combinations of mixed varieties of cannabinoids

• 50% pain reduction in multiple sclerosis patients in a good quality open label long-term one-year follow-up study

• Demonstrated risks of reduced lifetime achievement, motor vehicle accidents and addiction

• May reduce opioid requirements and lower accidental opioid overdose deaths

• Complex regulatory and legal environment

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Koppel BS, et al. Neurology 2014Aggarwal SK. Clin J Pain 2013Volkow ND, et al. N Engl J Med. 2014

OTHer Pain Rx

• Capsaicin• Transient receptor potential vanilloid

(TRPV1) agonist • Transdermal analgesic and is available in

several low-dose products (creams, gels, and lotions).

• Menthol (in combination with methyl salicylate)

• Mechanism of effect is not fully established• Magnesium

• NMDA antagonist, calcium channel blocker, and inhibits catechol release from peripheral nerve endings.

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Anand P et al. Br J Anesth. 2011Topp R et al. Int J Sports Phys Ther. 2011Koinig H et al. Anesth Analg. 1998

Pain Practice 12(7) 2012

…And All Pain Providers!!!

INCREASE ACCESS TO PAIN EXPERTISE

“Telemedicine”: Patient/Provider interaction “Telementoring”: Provider/Provider support

Improving Access To Pain Specialists

UW TelepainContact Information: Cara Towle RN MSN ctowle@u.washington.eduhttp://depts.washington.edu/anesth/care/pain/telepain/index.shtml

or search: uw telepain

Sessions: (Pacific time)Wednesdays noon-1:30

Thursdays7:00-8:00 am

University of Washington

PAIN PROVIDER TOOLKIT

http://depts.washington.edu/anesth/care/pain/index.shtml

Summary

Chronic pain care is NOT:

… just a 5th vital sign… to be conflated with opioids … focused on misuse and addiction

Chronic pain care is: … a chronic multisystem disease… disabling to patients, practices, and communities… complex, so requires a structured assessment

… is challenging to treat, but when managed well is enormously satisfying to patient, provider, community and health care system

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