cme information cme accreditation this activity has been planned and implemented in accordance with...

CME Information

CME AccreditationThis activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the University of Wisconsin School of Medicine and Public Health and Academic Alliances in Medical Education Inc. The University of Wisconsin School of Medicine and Public Health is accredited by the ACCME to provide continuing medical education for physicians.Credit DesignationCME CreditThe University of Wisconsin School of Medicine and Public Health designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.Continuing Education UnitsUniversity of Wisconsin-Madison, as a member of the University Continuing Education Association (UCEA), authorizes this program for 0.1 Continuing Education Unit (CEU) or 1.0 hour.

AAFP EB CME Credit

This activity has been reviewed and is acceptable for up to 2.0 prescribed credit(s) by the American Academy of Family Physicians. Of these credits, 1.0 conforms to the AAFP criteria for evidence-based CME clinical content. CME credit has been increased to reflect 2 for 1 credit for only the EB CME portion. When reporting AAFP credit, report total Prescribed and Elective credit for this activity. It is not necessary to label credit as evidence-based CME for reporting purposes.

The EB CME credit awarded for this activity was based on practice recommendations that were the most current with the strongest level of evidence available at the time this activity was approved. Since clinical research is ongoing, AAFP recommends that learners verify sources and review these and other recommendations prior to implementing them into practice.

Intended Audience and Scope of Practice

This activity is intended for primary care physicians, nurses, nurse practitioners, physician assistants, and other interested health professionals who diagnose, treat, and manage fibromyalgia and related disorders in diverse populations.

This educational activity has been designed to meet the needs of clinicians and other health care professionals who manage patients with fibromyalgia.

Faculty Disclosure Statement

As a sponsor accredited by the ACCME, it is the policy of the University of Wisconsin School of Medicine and Public Health to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with either the commercial supporter(s) of this activity or the manufacturer(s) of any commercial product(s) discussed in an educational presentation. Disclosure information for each speaker will appear on the slides.

NOTICE: The University of Wisconsin School of Medicine and Public Health advises the audience that one or more presentations in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices. Speakers are asked to notify the audience when discussing unlabeled or unapproved uses of drugs during their presentation. Disclosure information will appear on the slides.

Educational ReviewerSusan Hylland, MDClinical Assistant ProfessorDepartment of Medicine, Section of RheumatologyUniversity of Wisconsin School of Medicine and Public HealthMadison, Wisconsin

The following faculty have made the following disclosures, and all potential conflicts of interest have been resolved

Faculty Corporate Organization

Content Development Bill McCarberg, MD

Speaker Honoraria: Alpharma, Cephalon, Endo, King, Lilly, Merck, Pfizer Inc

Speaker Patrick B. Wood, MD

Speaker Honoraria: Jazz Pharmaceuticals

CME ReviewerSusan Hylland, MD

Dr Hylland has no relevant financial relationships to disclose

The following have documented that they have no relevant financial relationships to disclose and no conflicts of interest to resolve

Andrew Urban, MD, University of Wisconsin School of Medicine and Public Health, Office of Continuing Professional Development (OCPD) in Medicine and Public Health

Danielle R. Hepting, University of Wisconsin School of Medicine and Public Health, Office of Continuing Professional Development (OCPD) in Medicine and Public Health

Barbara Kaszuba, Academic Alliances in Medical Education Inc

Financial Support

The University of Wisconsin School of Medicine and Public Health and Academic Alliances in

Medical Education Inc gratefully acknowledge the unrestricted educational grant provided

by Pfizer Inc.

Patrick B. Wood, MD Angler Biomedical Technologies,

LLCJonestown, Texas

Program Agenda

5 minutes: Welcome and Introduction

40 minutes:

Illuminating the Evidence: Management of Fibromyalgia in a Primary Care Setting

15 minutes:

Q & A and Self-assessment

Learning Objectives

At the conclusion of this activity, participants should be able to apply evidence

based medicine to

• Evaluate and diagnose patients with fibromyalgia using available techniques and tools

• Explain fibromyalgia to patients and their families, communicating the benefits and importance of physical activity, patient education, and stress management

• Based on symptoms and clinical evidence, implement realistic strategies for fibromyalgia management with stepwise drug therapy and individualized physical activity plans

• Identify and treat common comorbid conditions

• Determine when specialty care, counseling, and/or referrals for complementary care are appropriate

Elements of Competence

This activity has been designed to address the general competencies of patient care

and medical knowledge.

Housekeeping

• Please complete the Activity Evaluation and Self-assessment and return to staff at the end of the program

• Your feedback will help- Assess the educational value of this program- Gauge the level of interest that you have in

this topic for future programs

Which One of the Following Statements Describes Your Current Knowledge of Fibromyalgia (FM)?

A. Strong — it gives me confidence in diagnosis and management

B. Adequate — it serves as a basic framework for diagnosis and management

C. Deficient — it does not give me confidence in diagnosis and management

The Case of Mrs. D

• A 42-year-old female with continuous pain following an automobile collision 18 months ago

• Has seen multiple doctors and tried acupuncture and chiropractic

• Is disabled, irritable

• Has hand-carried records showing an extensive workup including x-rays and MRI studies of C and LS spine

• Has tried multiple failed drug trials; only acetaminophen + hydrocodone helps “a little”

• “No one is doing anything to help me”C=cervical; LS=lumbosacral.

Mrs. D’s Current Symptoms

• Sleep disturbance

• “Pain all over”

• Fatigue

• Persistent diarrhea

• Morning stiffness

• Dry, itchy eyes

• Muscle tenderness

• Joint pain

• Tension headaches

• Depression

Mrs. D’s Medications and Physical Examination Findings

• 17/18 tender points

• Remainder of the exam is noncontributory

• Current medications– Nighttime acetaminophen for sleep– Ibuprofen for pain– Loperamide for diarrhea

Which Piece of Evidence Is Most Relevant to Mrs. D’s Diagnosis?

A. Findings on her past x-ray and MRI studies

B. Her history of pain, sleep disturbance, and depression developing over 18 months

C. The finding of widespread pain plus tenderness at specific anatomic sites

D. A history of multiple failed drug trials for pain

E. No finding of inflammation

American College of Rheumatology: Criteria for the Classification of FM

• Widespread pain– Above and below the waist– On right and left side of the body– In axial skeleton

• Present for 3 months or more

• 11 or more tender points (out of 18 possible)

• The combination of widespread pain and specific tender points has a sensitivity of 88% and specificity of 81% for differentiating FM from other chronic musculoskeletal conditions

Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.

American College of Rheumatology: Tender Point Locations

Tender point locations are established via manual palpation using moderate pressure

(about 4 kg) with the thumb of the dominant hand.

American College of Rheumatology: Tender Point Locations

• Tender point sites (all are bilateral)– Occiput: at suboccipital muscle insertions– Low cervical: at anterior aspects of the intertransverse spaces at C5-

C7– Trapezius: at midpoint of the upper border– Supraspinatus: at origins, above scapula spine near medial border– Second rib: at second costochondral junctions, just lateral to

junctions on upper surfaces– Lateral epicondyle: 2 cm distal to epicondyles– Gluteal: in upper outer quadrants of buttocks in anterior fold of

muscle– Greater trochanter: posterior to the trochanteric prominence– Knee: at medial fat pad proximal to joint line

• Axial skeleton locations are the cervical spine, anterior chest, thoracic spine, or low back

Tenderness Is Important (but Tender Points Are Misleading)

• Tender points are highly correlated with psychological factors, especially distress1

• Give inappropriate impression about the nature of the problem in FM (ie, in the muscle)

• Account for artifactual association of distressed females with FM2

• Women are 11 times more likely than men to have >11 tender points, though they are only 1.5 times more likely to have tenderness3

1. Wolfe F. Ann Rheum Dis. 1997;56:268-271. 2. Dadabhoy D, Clauw DJ. Nat Clin Pract. 2006;2:364-372.3. Wolfe F, et al. J Rheumatol. 1995;22:151-156.

The Differential Diagnosis of FM Includes Which One of the Following?

A. Chronic fatigue syndrome

B. Myofascial pain syndrome

C. Hypothyroidism

D. Polymyalgia rheumatica

E. All of the above

F. None of the above

Other Diagnoses to Consider in Evaluating FM

• Numerous illnesses may mimic, complicate, or coexist with FM, including– Hypothyroidism– Ankylosing spondylitis– Chronic fatigue syndrome– Myofascial pain syndrome– Systemic lupus erythematosus– Rheumatoid arthritis or osteoarthritis

Paradigm Shift in FM

• Discrete illness

• Pain, focal areas of tenderness

• Psychological and behavioral factors nearly always present

• Part of a larger continuum

• Many somatic symptoms, diffuse tenderness

• Psychological and behavioral factors play a role in some cases

FM Isn’t Just FM

Affective disordersTension/migraine headache

Temporomandibular joint syndrome

Cognitive difficulties

Vestibular complaints

ENT complaints (sicca sx, vasomotor rhinitis, accommodation problems)

Multiple chemical sensitivity, “allergic” symptomsEsophageal dysmotility

Noncardiac chest pain, dyspnea due to respiratory dysfunction

Neurally mediated hypotension, mitral valve prolapse

Constitutional symptomsWeight fluctuationsNight sweatsWeaknessSleep disturbances

Irritable bowel syndromeNondermatomal paresthesias

Interstitial cystitis, female urethral syndrome, vulvar vestibulitis, vulvodynia

Which One of the Following Actions Is Not Recommended in Further Assessment of FM?

A. Evaluate the severity of comorbid conditions

B. Measure ability to perform daily tasks and job functions

C. Obtain routine laboratory tests: CBC, thyroid, ESR, liver function, muscle enzymes

D. Obtain additional MRI scans of brain and spinal cord

Further Assessments in the FM Workup

• Evaluate severity of comorbid symptoms including sleep problems, fatigue, and depression (may require referral for psychological testing)

• Limit laboratory testing – CBC, metabolic panel, thyroid function, ESR, muscle

enzymes, liver function in new patient with probable FM

• Measure functional ability (eg, Fibromyalgia Impact Questionnaire) at initial and subsequent patient visits

Burckhardt CS, et al. American Pain Society; 2005. Chakrabarty S, Zoorob R. Am Fam Physician. 2007;76:247-254.

Fibromyalgia Impact Questionnaire (FIQ)

• The FIQ is a self-reported assessment of1

– Functional abilities in daily life: shopping, driving, meal prep, stair climbing, etc, over previous 7 days

– Impact of FM symptoms on work

– Degrees of pain, fatigue, sleep quality, stiffness, anxiety, depression

– May underestimate FM impact/progress in pts with mild symptoms2

Were you able to:

• Do shopping? 0 1 2 3

• Prepare meals? 0 1 2 3

• Vacuum a rug? 0 1 2 3

• Make beds? 0 1 2 3

• Walk several blocks? 0 1 2 3

• Visit friends or relatives? 0 1 2 3

• Do yard work? 0 1 2 3

• Drive a car? 0 1 2 3

• Climb stairs? 0 1 2 3

1. Burckhardt CS, et al. J Rheumatol.1991;18:728-733. 2. Mease PJ, et al. J Rheumatol. 2005;32:2270-2277.

Section of FIQ shown below

Having Arrived at a Diagnosis of FM: Which One of the Following Statements Is Appropriate to Tell Mrs. D?

A. She has FM, a disease that can be managed but does not have a cure

B. She has a generalized pain syndrome of unclear etiology

C. She has a psychiatric condition that will require further evaluation and neurologic testing to establish cause

The FM “Label”

• Some doctors fear that giving a diagnosis of FM creates “illness behavior” – Heightened symptoms, worse function, increased disability,

increased use of health services

• However, a 3-year prospective study of 72 patients given a new diagnosis of FM found1

– A statistically significant improvement in health satisfaction– Fewer FM symptoms including major symptoms– No worsening of clinical status or use of health services– Slight worsening of physical functioning

• Validating the diagnosis and educating the patient and family about FM are considered critical steps in optimal management of FM.2

1. White KP, et al. Arthritis Rheum. 2002;47:260-265.2. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.

Importance of Education in FM

Intensive patient education• Begins upon diagnosis of FM• Includes physician-patient

interaction, written materials, lectures, group discussions, demonstrations, Web sites

• Pain, sleep, fatigue, self-efficacy, walking, anxiety, depression improved in randomized controlled trials

• Changes maintained 3-12 months• Especially effective in

combination with exercise or behavioral therapy

Chakrabarty S, Zoorob R. Am Fam Physician. 2007;76:247-254.Goldenberg DL, et al. JAMA. 2004;292:2388-2395.

Prevalence of FM

• 5-6 million adults in the United States have FM1,2

• Overall prevalence ~2%3

– Third most common rheumatologic disorder in the United States2

• Prevalence increases with age3

– Highest rates between 60 and 79 years of age– Also seen in children, adolescents4

• FM is more common in relatives of patients with FM4

.

1. Lawrence RC, et al. Arthritis Rheum. 2008;58:26-35. 2. Peterson EL. J Am Acad Nurse Pract. 2007;19:341-348. 3. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28. 4. Chakrabarty S, Zoorob R. Am Fam Physician. 2007;76:247-254.

Gender Disproportion in FM

• 9 females to every male1

• Highest prevalence >7% in women, ~1% in men (aged 70-79 years)2,3

• Women have lower pain threshold than men1

• Women are likely to have more FM symptoms than men11. Wolfe F, et al. J Rheumatol. 1995;22:151-156.

2. Lawrence RC, et al. Arthritis Rheum. 2008;58:26-35. 3. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28.

Prevalence of Chronic Somatic Symptoms/Syndromes in the United States

0% 20% 40% 60% 80%

Tension HA

Migraine

Irritable Bowel

Fatigue

Regional Pain

Widespread Pain

Males

Females

Chey WD, et al. Am J Gastroenterol. 2002;97:2803-2811. Jason LA, et al. Lancet. 1999;354:2079-2080. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28.

Socioeconomic Consequences of FM

• Up to $14 billion in medical expenses annually1

• $5945 per claimant annually in direct/indirect costs2

• 30% must change jobs1

• Higher rates of divorce3

1. Wallace DJ, Wallace JB. New York: Oxford University Press; 2002:xi.2. Robinson RL, et al. J Rheumatol. 2003;30:1318-1325.3. Wolfe F, et al. Arthritis Rheum.1995;38:19-28.

Mrs. D’s FM Is Most Likely Caused by Which One of the Following?

A. Sleep disorder

B. Automobile accident

C. The cause of FM is unknown

D. More information is needed from psychiatric evaluation

Perceived Events at FM Onset

• The etiology of FM is not clear

• People with FM frequently site traumatic events and/or chronic stress as “triggers” of FM symptoms

• Potential triggers cited in a survey of people with FM were– Chronic stress (42% of respondents)– Emotional trauma (31%)– Acute illness (27%)– Physical injury not from road accident (17%)– Physical injury from road accident (16%)– Surgery (16%)

Bennett RM, et al. BMC Musculoskelet Disord. 2007;8:27.

Lack of Evidence for Physical Trauma as FM “Trigger”

• Retrospective studies in the 1990s suggested that 25%-50% of FM patients cited physical trauma as event at onset

• Prospective data found that patients with whiplash injury and road accident trauma did not have increased rate of FM symptoms after 14.5 months of follow-up1

• If FM symptoms appear after specific event, likely that genetic or behavioral groundwork already present

Tishler M, et al. J Rheumatol. 2006;33:1183-1185.

Causes of FM: Leading Candidates

Genetics Odds ratio for FM >8 for first-degree relatives. COMT involvement?

Phosphate deposition

Phosphate crystals deposit in muscle tissue; symptoms similar to gout

Chiari type 1 Malformation of cerebellar tonsils

Sleep Alpha-delta wave anomaly

HPA axis Stress disorders include blunted cortisol responses, increased somatostatin, increased CRF

COMT=catecholamine o-methyl transferase; HPA=hypothalamic-pituitary-adrenal; CRF=corticotropin-releasing factor.

Abnormal Central Processing

• Pain threshold lowered

• Poor “volume control” of stimuli

• Noxious threshold lowered (ie, sensitivity not just to pressure but to heat, chemical irritants, electrical stimulation)

• Pain inhibitory pathways less effective due to serotonin-norepinephrine deficiencies

• Muscles are “innocent bystanders” Abeles AM, et al. Ann Intern Med. 2007;146:726-734. Clauw DJ, et al. Spine. 1999;24;2035-2041.Crofford LJ. Curr Opin Rheumatol. 2008;20:246-250. Dadabhoy D, Clauw DJ. Nat Clin Pract. 2006;2:364-372. Goldenberg DL. Bull Rheum Dis. 2004;53.

Stimulus Intensity (kg/cm2)

Functional MRI: Pain Processing

0

2

4

6

8

10

12

14

1.5 2.5 3.5 4.5

Pai

n In

tens

ity

Fibromyalgia (n=16)

Subjective Pain Control (n=16)

Stimulus Pressure Control (n=16)

Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.

SI SI (decrease)

IPL SII STG, Insula, Putamen Cerebellum

Stimuli and Responses During Pain Scans

Which One of the Following Statements Is False?

A. Monotherapy with corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) is a first-line treatment for FM

B. Drugs with actions on brain neurochemicals have been the most successful form of pharmacotherapy for FM

C. Multimodal therapy using drug and nondrug options is widely recommended for FM

D. There is strong evidence to support the use of aerobic exercise in FM

Evidence of Benefit From FM Treatments: APS Guidelines

• Strongest — cardiovascular exercise, CBT, patient education, multidisciplinary therapy, amitriptyline, cyclobenzaprine

APS=American Pain Society. CBT=cognitive behavioral therapy. Burckhardt CS, et al. American Pain Society; 2005. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.


• Strongest — cardiovascular exercise, CBT, patient education, multidisciplinary therapy, amitriptyline, cyclobenzaprine, duloxetine, pregabalin, milnacipran, and gabapentin

Burckhardt CS, et al. American Pain Society; 2005. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.



• Moderate — strength training, hypnotherapy, biofeedback, massage, balneotherapy, tramadol, SSRIs, SNRIs, anticonvulsants

SNRI=selective serotonin and norepinephrine reuptake inhibitors(also called dual reuptake inhibitors).SSRIs=selective serotonin reuptake inhibitors.Burckhardt CS, et al. American Pain Society; 2005. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.




• Weak — chiropractic, tender point injections, SAMe, growth hormone, malic acidSAMe=S-adenosylmethionine.

Burckhardt CS, et al. American Pain Society; 2005. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.




• Weak — chiropractic, tender point injections, SAMe, growth hormone, malic acid

• No evidence — flexibility exercises, nutritional, herbs, other CAM, benzodiazepines, melatonin, guaifenesin, DHEA

CAM=complementary and alternative medicine. DHEA=dehydroepiandrosterone.Burckhardt CS, et al. American Pain Society; 2005. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.

Evidence of Benefit From FM Treatments:EULAR Recommendations

• Heated pool treatment with or without exercise

• Tramadol

• Antidepressants: amitriptyline, fluoxetine, duloxetine, milnacipran, moclobemide, pirlindole

• Tropisetron, pramipexole, and pregabalin

EULAR=European League Against Rheumatism.Carville SF, et al. Ann Rheum Dis. 2008;67:536-541.EULAR=European League Against Rheumatism.Carville SF, et al. Ann Rheum Dis. 2008;67:536-541.

Mrs. D’s Treatment Plan

• Start amitriptyline 25 mg at bedtime

• Schedule return visit in 4 weeks

Nonpharmacologic Treatments in FM

• CBT– Positive effects on ability to cope with pain1,2

– Six sessions of CBT added to standard medical care improved physical function, but not pain3

• Aerobic exercise– Meta-analysis of exercise studies4

• Short-term improvements in physical function and global well-being• No significant decrease in pain

• Acupuncture– Two randomized controlled studies showed that acupuncture

was not significantly better than sham acupuncture in reduction of pain5,6

1. Vlaeyen JW, et al. J Rheumatol. 1996;23:1237-1245. 2. Nicassio PM, et al. J Rheumatol. 1997;24:2000-2007. 3. Williams DA, et al. J Rheumatol. 2002;29:1280-1286. 4. Busch AJ, et al. Cochrane Database Syst Rev. 2007 Oct 17 (4):CD003786. 5. Harris RE, et al.J Altern Complement Med. 2005;11:663-671. 6. Assefi NP, et al. Ann Intern Med. 2005;143:10-19.

Pharmacologic Treatments in FM

• Tricyclics (eg, amitriptyline)– Increase concentrations of serotonin, norepinephrine, or both by

blocking reuptake – Pain, sleep, fatigue1

• SSRIs (eg, fluoxetine)– More effective on mood than pain – Better side-effect profile than tricyclics

• Tramadol– Analgesic with weak central (µ-opioid) activity; also affects

noradrenergic and serotonergic systems– Often used with acetaminophen2

1. Arnold LM, et al. Psychosomatics. 2000;41:104-113.2. Bennett RM, et al. Am J Med. 2003;114:537-545.

Newer Approaches to Pharmacologic Treatment

• Alpha-2-delta (2) ligands– Pregabalin (FDA approved in 2007 for treatment of FM)– Gabapentin (not FDA approved for FM)– Bind to 2 subunit of voltage-gated calcium channels,

reducing pain-related neurotransmitters (eg, substance P)– Used in diabetic peripheral neuropathy; postherpetic

neuralgia• SNRIs

– Duloxetine (submitted to FDA for FM): major depression, diabetic neuropathy

– Milnacipran (submitted to FDA for FM): approved antidepressant in Europe, Asia

– Balanced norepinephrine and serotonin reuptake inhibition; do not interact with adrenergic, cholinergic, or histaminergic receptors or sodium channels

Arnold LM. Arthritis Res Ther. 2006;8:212.Crofford LJ. Curr Opin Rheumatol. 2008;20:246-250.

§

§

§

Pregabalin: Improvement in Mean Pain Scores

§

§

§§

§

§

†

§

§

‡

§

§

†

‡

§

§

§

§

‡

§

§

‡

§

§

†

§

§

*§

§

§

§

§

‡

§

§

‡

§

§

-3

-2

-1

0

1 2 3 4 5 6 7 8 9 10 11 12 13 EPTreatment Week

Ch

an

ge F

rom

Baselin

e in

LS

Mean

Pain

Score

Placebo (n=374)Pregabalin 300 mg/day (n=368)Pregabalin 450 mg/day (n=373)Pregabalin 600 mg/day (n=378)

*P<.05. †P<.01. ‡P<.001. §P.0001. LS=least squares.Arnold LM, et al. Ann Rheum Dis. 2007;66(suppl II):62.

Pregabalin: Adverse Events

• Among all pregabalin patients– Pregabalin generally well tolerated– Incidence of treatment-emergent adverse events

tended to increase with pregabalin dosage• Dizziness: 31%-45%• Somnolence: 18%-25%

– 18%, 22%, and 29% of patients treated with 300, 450, and 600 mg/day, respectively, of pregabalin discontinued treatment (vs 11% on placebo)

Arnold LM, et al. Ann Rheum Dis. 2007;66(suppl II):62.

Gabapentin: 30% Reduction in BPI Average Pain Severity Score

0

10

20

30

40

50

60

% o

f P

ati

en

tsGabapentinPlacebo

*P=.014. BPI=Brief Pain Inventory. Arnold LM, et al. Arthritis Rheum. 2007;56:1336-1344. This information concerns a use that has not been approved by the US Food and Drug Administration.

*

Gabapentin: Adverse Events

• Of the 150 randomized patients, 12 in the gabapentin group and 7 in the placebo group discontinued treatment (P=0.34)

• Gabapentin-treated patients reported dizziness, sedation, lightheadedness, and weight gain significantly more often than did placebo-treated patients (although no difference in weight changes between groups as measured in the clinic was reported)

Arnold LM, et al. Arthritis Rheum. 2007;56:1336-1344.This information concerns a use that has not been approved by the US Food and Drug Administration.

Duloxetine: Changes in BPI Average Pain Severity Score

-3.5

-3

-2.5

-2

-1.5

-1

-0.5

0

0 1 2 4 6 8 10 12

Weeks on Treatment

LS

Mea

n C

han

ge

Fro

m B

ase

lin

e B

PI

Ave

rag

e P

ain

Duloxetine (n=325) Placebo (n=211)

*

****

*

*

*P.001 vs placebo.LS=least squares.Arnold LM, et al. J Womens Health. 2007;16:1145-1156.This information concerns a use that has not been approved by the US Food and Drug Administration.

Duloxetine: Changes in BPI and FIQ Scores in FM Patients With and Without MDD

FIQ Total Score

*P<.01 vs placebo. **P<.001 vs placebo. MDD=major depressive disorder. Arnold LM, et al. J Womens Health. 2007;16:1145-1156.This information concerns a use that has not been approved by the US Food and Drug Administration.

-20

-15

-10

-5

0

No Current MDD (n=365)

Current MDD(n=156)

Duloxetine

Placebo

-3

-2

-1

0

No Current MDD(n=371)

Current MDD(n=156)

**

BPI Average Pain Score

**

**

*

Mean

Ch

an

ge

Mean

Ch

an

ge

Duloxetine: Adverse Events

***

* **

***

***

** ***0

10

20

30

40

Nausea Dry MouthConstipationSomnolenceDecreasedAppetite

IncreasedSweating

Anorexia

% o

f P

ati

en

ts

Duloxetine (N=326) Placebo (N=212)

*P<.05 vs placebo. **P<.01 vs placebo. ***P<.001 vs placebo.Arnold LM, et al. J Womens Health. 2007;16:1145-1156. This information concerns a use that has not been approved by the US Food and Drug Administration.

Milnacipran: Improvement in Pain in FM Patients

0

5

10

15

20

25

30

35

40

Placebo (n=28)

MIL QD(n=46)

MIL BID(n=51)

ITT R

esp

on

se R

ate

(%

)

*50% Reduction at End Point

*P=.04 vs placebo. ITT=intention to treat. Gendreau RM, et al. J Rheumatol. 2005;32:1975-1985.Vitton O, et al. Hum Psychopharmacol Clin Exp. 2004;19:S27-S35. This information concerns a use that has not been approved by the US Food and Drug Administration.

Milnacipran: Adverse Events

• No serious adverse events

• Discontinuation– BID milnacipran: 7 patients (13.7%)– QD milnacipran: 10 patients (21.7%)– Placebo: 1 patient (3.6%)– Most frequent reasons for discontinuation:

headache, GI complaints (chiefly nausea)

Gendreau RM, et al. J Rheumatol. 2005;32:1975-1985.Vitton O, et al. Hum Psychopharmacol Clin Exp. 2004;19:S27-S35.This information concerns a use that has not been approved by the US Food and Drug Administration.

If Mrs. D Reports No Improvement in Pain at Follow-up, Which One of the Following Is NOT a Recommended Option?

A. Combine drugs with strong/moderate support of efficacy, eg, tricyclic + SSRI

B. Prescribe a 3-month trial of opioids

C. Refer patient to a rheumatologist, physiatrist, psychiatrist, or other specialist

D. Continue trying different combinations of nonpharmacologic strategies, eg, aerobic exercise + strength training

Stepwise Management of FM

Step 1

• Confirm the diagnosis

• Explain and educate the patient about FM

• Evaluate/treat comorbid illnesses, including mood, sleep problems; may require referral to a specialist

• Assess psychological stressors, level of fitness, barriers to treatment

• Review treatment options


Step 2

• Trial with low dose of evidence-based medication: tricyclics, 2 ligands, SNRIs, tramadol, SSRIs

• Avoid drugs with potential for abuse or dependence

• Begin cardiovascular exercise program

• Refer patient for CBT or combine CBT with exercise


Step 3

• Consider combination medical regimen if no/partial response to monotherapy 2 ligand + SNRI– SSRI + low-dose tricyclic 2 ligand + SSRI– Tramadol + acetaminophen

• Consider specialty referral, eg, rheumatologist, physiatrist, psychiatrist, pain specialist

Advice for Helping Patients WithChronic Pain

• Accept pain as real

• Protect from excessive invasive testing

• Set realistic goals

• Expect to treat, but not to cure

• Evaluate in terms of what they do, notwhat they say

• Prescribe medication on time-contingent, not prn, basis

Advice for Helping Patients With Chronic Pain (cont)

• Prescribe gradual increase in physical exercise

• Clarify difference between hurt and harm

• Educate family to encourage patient’s increased activity

• Focus on patient’s activities and not pain

• Help patient to get involved in pleasurable activities

Which One of the Following Statements Describes Your Current Knowledge of FM?

A. Strong — it gives me confidence in diagnosis and management

B. Adequate — it serves as basic framework for diagnosis and management

C. Deficient — it does not give me confidence in diagnosis and management

Clinical Practice Recommendation

• Practice Recommendation: A modern treatment approach to fibromyalgia pain and comorbidities incorporates trials of medication and nonpharmacologic therapies in a stepwise fashion, based on individual patient evaluation

• Evidence-Based Source: Arthritis Research & Therapy. 2006;8:212

• Web Site of Supporting Evidence: http://arthritis-research.com/content/8/4/212

• Strength of Evidence: A (based on consistent findings from good-quality randomized controlled studies)


• Practice Recommendation: All patients with a diagnosis of fibromyalgia should be given basic information about the disease and treatment options, and should be educated about pain management and self-management programs as an initial part of treatment

• Evidence-Based Source and Web Site of Supporting Evidence: http://www.guideline.gov/summary/summary.aspx?doc_id=7298

• Strength of Evidence: Major Recommendations: Fibromyalgia Syndrome Diagnosis and Assessment. American Pain Society Clinical Practice Guideline No. 4; Evidence Grade A (strongest evidence): There is evidence of type I or consistent findings from multiple studies of types II, III, or IV


• Practice Recommendation: Assigning the label "fibromyalgia" to the diagnosis does not have a meaningful adverse affect on clinical outcome over the long term

• Evidence-Based Source: Arthritis & Rheumatism. 2002;47:260-265

• Strength of Evidence: Single, prospective, within-group comparison using Fibromyalgia Impact Questionnaire (FIQ) was conducted. Type of Evidence III; The strength of Evidence C (based on patient-oriented evidence)

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