Pennsylvania Academy of Family Physicians Foundation & UPMC 43rd Refresher Course in Family Medicine

CME Conference March 10-13, 2016

Fibromyalgia Update Wayne Blount, MD

Disclosures: Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will not include discussion of unapproved or investigational uses of products or devices.

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The Chronic Pain of Fibromyalgia

B. WAYNE BLOUNT, MD, MPHJenCare

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Disclosure

• The speaker has no conflict of interest, financial agreement, or working affiliation with any group or organization.

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Objectives

• Definitions

• Pathophysiology

• Fibromyalgia

• Summary

• Extras : lots

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New Patient

56 yo w female c/o chronic, unrelieved, diffuse pain X 8 years. PMH: Insomnia & migraines

Her last doctor had her on lortabs : 10/650 mg, 1-2 q 4-6 hrs and xanax 1 mg TID.

She just moved to your state & town because “Medicaid is easier to work with here”.

She has brought with her an old (4 yrs ago) CT scan to prove she has real problems.

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What do you do?

• Start from scratch !!

• If the patient is unwilling to do that, that, in itself is a red flag that there might be drug seeking.

• An approach to such a patient

• 1st ? Define what you’re working with

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What is Fibromyalgia?

• A clinical syndrome of widespread muscle pain :

• Chronic,

• Non-inflammatory, with

• Fatigue &

• Tender points

• Extremely common pain phenomenon occurring in a defined pattern

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More on Fibromyalgia

• Prevalence 1-12%

• All ethnic groups

• All nations

• Increases with age

• Women 4-7 X more at risk

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Signs & Symptoms

• Insidious in onset • Diffuse soft tissue pain• Pain increased in A.M., with weather changes,

anxiety, & stress • Pain improved by mild physical activity or

stress reduction• Non-restorative sleep: reduced sleep efficiency

of 75%

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Signs & Symptoms

• Abnormal non-rapid eye movement stage IV sleep **

• Generalized fatigue or tiredness **

• Chronic headache **

• Anxiety

• Irritable bowel syndrome

• A.M. Stiffness

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Signs & Symptoms

• Depression • Reduced physical endurance • Decreased social interaction• Cognitive “fog”• Subjective, non-confirmable :

– Paresthesias– Swollen joints

• All sx may wax & wane 10

Most Common Complaints

# 1 : Sleep problems

# 2 : Fatigue

# 3 : Cognitive dysfunction

# 4 : Pain

Fibromyalgia is much more than a pain disorder

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What Causes FM?

Cause is unknown and is probably multifactorial and may be different in different patients

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Some Causes of FM?

Lower levels of – Serotonin: Related to sleep, pain perception, HAs, &

mood disorders

– Dopamine: Related to pleasure, motivation, & motor control; lower levels in FM patients 2nd-ary to pain stimulus

– Growth hormone 2nd-ary to

sleep disruption;

related to tissue repair13

What Causes FM?

• Abnormally high levels of Substance P in spinal fluid in some patients

• Substance P important in transmission and amplification of pain signals to and from brain

• Areas of brain activated with mild tactile pressure: 2 in controls vs. 12 in FM

• “Volume control” is turned up too high in brain’s pain centers 14

Altered Neuro StructureChronic pain accompanied by cortical

reorganization : Flor, Neurosci Lett, 1997

Chronic back pain is accompanied by brain atrophy : Apkarian, Neurosci, 2004

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Grey Matter Loss in Fibromyalgia

Burgmer M, et al. Psychosom Med. 2009;71:566-573. Kuchinad A, et al. J Neurosci. 2007;27:4004-4007.Wood PB, et al. Eur J Neurosci. 2007;25:3576-3582. All images adapted.

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What Causes FM?

Familial tendency to develop FMS suggests genetic role

Can be triggered by physical, emotional or environmental stressors such as car accidents, repetitive injuries and certain diseases :

– Rheumatoid arthritis and SLE pts. are more likely to develop FMS

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Who Gets FM?

• Affects as many as 1 in 30 Americans

• Most common in middle-aged women

• Men and children also get the disorder

• More likely with :– RA, SLE and Ankylosing spondylitis

– Other family members with FMS

– Lower income & education

• Prevalence increases to age 8018

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Differential for Fibromyalgia

• Hypothyroidism

• Muscle overuse

• Inflammatory disorders:– Myopathies

– Polymyalgia rheumatica

– Temporal arteritis

– Chronic Fatigue

– R.A.

– SLE 19

How is FM diagnosed?

Symptoms of FM

are typically very

non-specific,

common to many

other conditions.

Many sx cannot

be objectively

evaluated. 20

How is FM diagnosed?

• 2 sets of criteria:

• 1990 & 2010

• ?research vs. clinical?

• 1990 considered the “Gold” standard

• Can use either one

• Choose the one better for you & your clinic

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2010 Fibromyalgia Criteria

• Contains 2 scoring subsets

• Widespread Pain Index (WPI)

• Symptom Severity Score (SSS)

• Uses floating combinations of these 2 scores– E.G. WPI >7 & SSS>5 or

– WPI 3-6 & SSS >9

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2010 ACR Diagnostic Criteria for FM and Measurement of Symptom Severity

• Widespread pain index (WPI) and symptom severity (SS) scale score

• Symptoms have been present at similar level for > 3 months

• Patient does not have another disorder that would otherwise explain the pain

No physical examination necessaryCan be self-administered

Probably more sensitive to change than ACR criteria

No physical examination necessaryCan be self-administered

Probably more sensitive to change than ACR criteria

Wolfe F, et al. Arthritis Care Res. 2010;62:600-610. 23

How is FM diagnosed? (1990)

• Diagnosis made by evaluation of symptoms & presence of tender points

• Not a diagnosis of exclusion

• Widespread pain for at least 3 months and

pain in 11 out of 18 tender point sites on digital palpation

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ACR Diagnostic criteria

Both criteria must be satisfied

– History of widespread pain for more than 3 months, on both sides of the body, above and below the waist, and axial skeleton (cervical spine, anterior chest, thoracic pain, or low back)

– Pain in 11 of 18 tender point sites on digital palpation with approximate force of 4 kg.

Presence of second clinical disorder does not exclude diagnosis of fibromyalgia.

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Fibromyalgia Impact Questionnaire

• Assesses functional abilities in daily life &

• Measures patient progress & outcomes

• Self-administered, 10 item questionnaire

• 10 Minutes to complete

• Good Validity

• www.myalgia.com/FIQ/fiq.pdf

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ACR Diagnostic Criteria

• ACR diagnostic criteria● History of chronic

widespread pain ≥3 months

● Patients must exhibit ≥11 of 18 tender points

• FM can be identified from among other rheumatologic conditions with use of ACR criteria with good sensitivity (88.4%) and specificity (81.1%)

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Physical Exam Requirement• Systematic palpation of the 18 tender point sites.

Palpation force is 4 kg

• Equal to the force needed to just blanch your thumbnail

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How is FM Diagnosed?

X-rays, blood tests, specialized scans such as nuclear medicine and CT, muscle biopsies are all normal

Objective “markers of inflammation” such as ESR are normal

Distinguish from other common diffuse pain conditions; e.g. RA, SLE, Hypothyroidism and Polymyalgia Rheumatica

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LABS to Get

• ESR

• CBC, ANA

• TSH, CPK

• If any abnormality,

work it up. Probably not fibromyalgia

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How is FM treated?

Fibromyalgia is a chronic condition managed with both medications and physical modalities

Medication therapy is largely symptomatic, as there is no definitive treatment nor cure for fibromyalgia

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From Mechanism to Treatment

Central neural factors play a critical role

This is a polygenic disorder

There is a deficiency of noradrenergic-serotonergic activity

Lack of sleep or exercise increases pain and other somatic sx, even in normals

How FM patients think about their pain may directly influence pain levels

Treatments at the periphery (drugs, injections) are not efficacious

There will be sub-groups of FM needing different treatments

Drugs that raise norepinephrine and serotonin will be efficacious in some

Exercise, “sleep hygiene,” and other behavioral interventions are effective therapies for biological reasons

Cognitive therapies are effective in FM 32

Medications in FM

Strong evidence : ‘A’ Rec

●Amitriptyline, 25-50 mg at bedtime●Cyclobenzaprine, 10-30 mgs at bedtime●Pregabalin, 450 mg/day●Gabepentin, 1600-2400 mg/day●Duloxetine, 60-120 mg/day●Milnacipran, 100-200 mg/day

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Medications in FM

Modest evidence : ‘B’ Rec●Tramadol, 200-300 mg/day●SSRIs (fluoxetine, sertraline)

• Weak evidence: pramipexole, gamma hydroxybutyrate, growth hormone, 5-hydroxytryptamine, tropisetron, s-adenosyl-methionine

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No Evidence:•Opioids, NSAIDS, benzodiazepene

and nonbenzodiazepene

Hypnotics, melatonin, magnesium,

DHEA, thyroid hormone, OTCs

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Only 3 Meds are FDA Approved for FM

Duloxetine (Cymbalta)

Pregabalin (Lyrica)

Milnacipran (Savella)

These meds differ in the Sx of FM they relieve36

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Strong Evidence : ‘A’ RecExercise : Must be > moderate (> 50% max HR)

Physical and psychological benefits2-3 X per week for 4-6 weeks to see effectEfficacy not maintained if exercise stops

Cognitive-behavioral therapy : A RecImprovements in pain, fatigue, mood, and physical functionImprovement often sustained for months

Patient education/self-managementImproves pain, sleep, fatigue, and quality of life

Combination (multidisciplinary therapy) : A Rec

Nonpharmacologic Strategies

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Nonpharmacologic Strategies:

Strong Evidence:Sleep restoration

Modest EvidenceStrength trainingAcupunctureHypnotherapyEMG biofeedbackBalneotherapyWgt loss

Weak EvidenceChiropracticManual and massage

therapy ??UltrasoundVitamin DDiets

No EvidenceTender-point

injectionsFlexibility exercise

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Outcomes in FM

Most patients have chronic, persistent symptomsMost patients continue to work, but 10-15% are disabledDuration of time without a diagnosis adversely affects outcomeSubsets of patients important in outcome

Mode of onset:(a) Infection(b) Trauma

Work settingMedicolegal settingConcurrent medical and psychiatric illnessLevels of coping, catastrophizingPrimary vs tertiary referral patients

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Prognosis

With resolution of sleep disturbance, may resolve totally

Aggressive physical therapy is critical in those who do not respond

Approximately 5% do not respond to any form of therapeutic intervention.

Hypnosis may be attempted in that group.

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As a first-line approach for patients with moderate to severe pain, trial with evidence-based medications, e.g.

Trial with low-dose tricyclic antidepressants, SSRI, SNRI, antiseizure medication

Initial Treatment of Fibromyalgia

Provide additional treatment for comorbid conditions

Encourage exercise according to fitness level

Stress management techniques

.

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Polypharmacy; for example, trial of SSRI in AM and tricyclic in PM (‘A’ Rec) SNRI in AM and anti-seizure drug in PM

Further Treatment

Trial of additional analgesics such as tramadol

Comprehensive pain management program

Structured rehabilitation program;Formal mental health program, such as

CBT for patients with prominent psychosocial stressors, and/or difficulty coping, and/or

difficulty functioning

.

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Patients Benefit From:• Regular psychosocial support

• Education about her disease

• Patient support group

• Structured exercise program

• Improved sleep hygiene

• Supportive family environment

• Pacing

• Healthy lifestyles– Address smoking, alcohol, sleep

• Appropriate medication 43

FM and Mood Disorders

• At the time of FM diagnosis, mood disorders are present in 30-50%, primarily depression.

• Increased prevalence of mood disorders is primarily in tertiary-referral patients.

• Increased lifetime and family history of mood disorders in FM vs RA (Odds = 2.0).

• Fibromyalgia co-aggregates with major mood disorder in families (OR 1.8 [95% CI 1.1, 2.9), p=0.01).

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Patient Follow-up

Routine, regular follow-up

Monitor patient’s progress

Assess:Pain

Sleep

Daily functioning

Global well-being

Mood disorders

Can use the FIQR (free)45

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“Art” of FM TherapyIndividualize therapyExhaustion, mood dominate: start with SNRIPain, sleep dominate: start with anti-seizure drugTCA in low dose at bedtime (hs) still can be effectiveFor any drug: start low, go slow

Amitriptyline: 10 mgs hsDuloxetine: 20-30 mgs AM with foodPregabalin: 50 mgs hsGabepentin 100 mg hs

Often will not achieve recommended dose because of adverse side effectsMay be better to add 2nd drug rather than switch but polypharmacy trialsnot yet publishedNon-pharamacologic therapy is as important as drugsMost patients require multi-component therapy

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Principles of Treatment

• Reduction of Pain:– Behavioral, Meds, Blocks, Surgery,

Complementary

– There is no magic bullet, no single cure

• Rehabilitation:– Reconditioning & Prevention

• Coping:– Management of Residual Pain

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Treatment Objectives(Negotiated)

• Decrease the frequency and / or severity of the pain

• General sense of feeling better

• Increased level of activity

• Return to work

• Decreased health care utilization

• Elimination or reduction in medication usage

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Explaining the Typical Outcome

• FM does not herald a systemic disease• No progressive, structural or organ damage• Most patients in specialty practice have chronic,

persistent symptoms• Primary care patients more commonly report

complete remission of symptoms• Most patients continue to work, but 10-15% are

disabled• Most patients’ quality of life improves with medical

management

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Fibromyalgia Conclusions

FM is a recognized disorder

Pathophysiology not completely elucidated

Choosing optimal treatment has recommendations, but may still be a trial-and-error process

Duloxetine, Pregabalin & Milnacipran are the only FDA-approved meds

Treat the whole patient, including co-morbidities

Best non-pharmacologic modalities are Exercise & CBT»

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Bibliography

• Wolfe F et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160-72

• Okifuji A et al. A standardized manual tender point survey. 1. Development & determination of a threshold point for the identification of positive tender points in fibromyalgia syndrome. J Rheum 1997;24:377-83.

• www.fmnetnews.com

• Chakrabarty S & Zoorob R. Fibromyalgia. Am Fam Physician 2007;76:247-54

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Bibliography• AMA. Module 1 Pain Management: Pathophysiology of Pain & Pain Assessment.

Feb 2010. @ www.ama-cmeonline.com/pain

• Dworkin RH et al. Recommendations for the pharmacological management of neuropathic pain. Mayo Clin Proc. 2010;85:S3-S13.

• Moriarty O, et al. The effect of Pain on cognitive function. Prog Neurobiol. 2011;93:385-404.

• Traynor LM, et al. Pharmacotherapy of Fibromyalgia. Am J Health-System Pharmacy. 2011;68:1307-19.

Cochrane Review : www.cochrane.org/reviews

For the FIQR, see www.myalgia.com/FIQ/FIQ_B

• Medication Use Agreement : www.aafp.org/fpm/20011100/47atoo_box_a.html

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Bibliography

• Cochrane Database : www.cochrane.org/reviews/en/

• www.medscape.com/viewarticle/707578

• Rooks DS. Fibromyalgia Treatment Update. Curr opin Rheumatol. 2007;19:111-7.

• Carville SF et al. EULAR evidence based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008;67:536-41.

• Buckner WJ. Fibromyalgia. Medscape reference. Feb 2011.

• Maizesl M & McCarberg B. Antidepressants & Antiepileptic Drugs for Chronic Non-cancer Pain. AFP 2005;71:483-90.

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You made it through another presentation!!

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Extra Slides

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You may have heard something about using antipsychotics in

fibromyalgia• Quetiapine 25 – 100 mg/day

• Ziprasidone 20 mg/day

• Each has 1 study done

• Both used as add-on to inadequate other therapy

• Both showed some parameter improvement, but …

• Both have significant side effects56

What about a dopamine agonist?

• Pramipexole, in 1 study, did show significant improvement in several parameters, but …

• Again : Significant side effects

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Who Should Treat Fibromyalgia?

• More than 50% of visits are to primary care physicians

• Currently, 16% of FM visits are to rheumatologists

• The American College of Rheumatology suggest that rheumatologists serve as consultants (tertiary care)

• Other specialists should include mental health professionals, physiatrists and pain management experts

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What about Diet for Fibromyalgia?

• No “magic” diet

• No controlled studies, but …

• May suggest avoidance of foods associated with fatigue :– High fat “Junk” food

– Refined sugar Caffeine

– White flour Salt

– Fried foods Alcohol59

The Fibromyalgia Headache

• In the category of the Chronic Daily Headache

• More resembles a tension-type HA

• Involves neck muscles leading to pressure on occipital nerve

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Tricylics in Fibromyalgia

AMITRIPTYLINE

• Four placebo-controlled trials● Goldenberg,1985● Carette,1986● Carette,1994

• Dose 25 – 50 mg

• Duration 6-26 weeks

• All showed modest efficacy

CYCLOBENZAPRINE• Four placebo-controlled

trials

● Quimby, 1989

● Carette, 1994

● Reynolds,1991

• Dose 10 – 40 mg

• Duration 4 – 12 weeks

• 2 showed efficacy

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Number – 1196PL controlled, double blind, Randomized

Pain composite – VAS - 30% + very much or much impr on PGICFM composite – pain composite + 6 pt impr on PCS of SF36 Secondary – PGIC, SF36 (PCS and MCS) and FIQ total

Baseline observation carried forward (BOCF) at 3 mnths39,46% achieved Pain composite, v 25% PL (0.011, 0.015) 25,26% achieved FM composite, v 13% PL (0.025, 0.004)

Generally well tolerated (discontinuations 34,35% v 28% PL)Common AEs – nausea M – 37%, PL -20%(both studies) headache M – 18%, PL -14%

constipation M – 16%, PL -4%hyperhidrosis M – 9%, PL - 2%

NB – no sig hypertension or wt gain

Milnacipran

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