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CME Information
CME Accreditation
This 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 Designation
CME Credit
The 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 Units
University 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 evidencebased 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 Reviewer
Susan Hylland, MD
Clinical Assistant Professor
Department of Medicine, Section of Rheumatology
University of Wisconsin School of Medicine and Public Health
Madison, 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 Reviewer
Susan 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, LLC
Jonestown, 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
• Dry, itchy eyes
• “Pain all over”
• Muscle tenderness
• Fatigue
• Joint pain
• Persistent diarrhea
• Tension headaches
• Morning stiffness
• 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 disorders
Tension/migraine headache
Cognitive difficulties
Temporomandibular joint
syndrome
ENT complaints (sicca sx, vasomotor
rhinitis, accommodation problems)
Interstitial cystitis, female
urethral syndrome, vulvar
vestibulitis, vulvodynia
Vestibular complaints
Multiple chemical sensitivity,
“allergic” symptoms
Esophageal dysmotility
Constitutional symptoms
Weight fluctuations
Night sweats
Weakness
Sleep disturbances
Irritable bowel syndrome
Nondermatomal paresthesias
Noncardiac chest pain, dyspnea due to
respiratory dysfunction
Neurally mediated hypotension, mitral
valve prolapse
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)
Section of FIQ shown below
• 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
1. Burckhardt CS, et al. J Rheumatol.1991;18:728-733.
2. Mease PJ, et al. J Rheumatol. 2005;32:2270-2277.
Were you able to:
•
Do shopping?
0123
•
Prepare meals?
0123
•
Vacuum a rug?
0123
•
Make beds?
0123
•
Walk several blocks?
0123
•
Visit friends or relatives?
0123
•
Do yard work?
0123
•
Drive a car?
0123
•
Climb stairs?
0123
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 men1
1. 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
Widespread Pain
Males
Females
Regional Pain
Fatigue
Irritable Bowel
Migraine
Tension HA
0%
20%
40%
60%
80%
Chey WD, et al. Am J Gastroenterol. 2002;97:2803-2811. Jason LA, et al. Lancet. 1999;354:20792080. 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.
Functional MRI: Pain Processing
14
Pain Intensity
12
10
8
Fibromyalgia (n=16)
Stimulus Pressure Control (n=16)
6
4
Subjective Pain Control (n=16)
2
0
1.5
2.5
3.5
Stimulus Intensity (kg/cm2)
Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343.
4.5
Stimuli and Responses During Pain Scans
14
SI
Pain Intensity
12
SI (decrease)
10
8
6
Fibromyalgia
4
Subjective Pain Control
2
Stimulus Pressure Control
0
1.5
2.5
3.5
4.5
Stimulus Intensity (kg/cm2)
IPL
SII
STG, Insula, Putamen
Cerebellum
Which One of the Following Statements
Is False?
A. Monotherapy with corticosteroids or nonsteroidal antiinflammatory 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.
Evidence of Benefit From FM Treatments:
APS Guidelines
• 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.
Evidence of Benefit From FM Treatments:
APS Guidelines
• Strongest — cardiovascular exercise, CBT, patient
education, multidisciplinary therapy, amitriptyline,
cyclobenzaprine, duloxetine, pregabalin,
milnacipran, and gabapentin
• 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.
Evidence of Benefit From FM Treatments:
APS Guidelines
• Strongest — cardiovascular exercise, CBT, patient
education, multidisciplinary therapy, amitriptyline,
cyclobenzaprine, duloxetine, pregabalin,
milnacipran, and gabapentin
• Moderate — strength training, hypnotherapy,
biofeedback, massage, balneotherapy, tramadol,
SSRIs, SNRIs, anticonvulsants
• Weak — chiropractic, tender point injections, SAMe,
growth hormone, malic acid
SAMe=S-adenosylmethionine.
Burckhardt CS, et al. American Pain Society; 2005. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
Evidence of Benefit From FM Treatments:
APS Guidelines
• Strongest — cardiovascular exercise, CBT, patient education,
multidisciplinary therapy, amitriptyline, cyclobenzaprine,
duloxetine, pregabalin, milnacipran, and gabapentin
• Moderate — strength training, hypnotherapy, biofeedback,
massage, balneotherapy, tramadol, SSRIs, SNRIs,
anticonvulsants
• 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.
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.
Change From Baseline in LS Mean Pain Score
Pregabalin: Improvement in
Mean Pain Scores
Placebo (n=374)
Pregabalin 300 mg/day (n=368)
Pregabalin 450 mg/day (n=373)
Pregabalin 600 mg/day (n=378)
0
-1
-2
§
§
§
§
§
§
§
§
§
-3
1
2
3
†
§
§
‡
§
§
§
§
§
‡
§
§
‡
§
§
†
‡
§
†
§
§
*
§
§
§
‡
§
§
4
5
6
7
8
9
10
11
12
13
Treatment Week
*P<.05. †P<.01. ‡P<.001. §P.0001. LS=least squares.
Arnold LM, et al. Ann Rheum Dis. 2007;66(suppl II):62.
§
§
‡
§
§
EP
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
60
% of Patients
50
*
Gabapentin
Placebo
40
30
20
10
0
*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
LS Mean Change From Baseline
BPI Average Pain
0
Duloxetine (n=325)
Placebo (n=211)
-0.5
-1
-1.5
*
-2
*
*
-2.5
*
*
*
*
-3
-3.5
0
1
2
4
6
8
10
12
*P.001 vs placebo.
Weeks on Treatment
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
No Current MDD
(n=371)
Current MDD
(n=156)
No Current MDD
(n=365)
0
Current MDD
(n=156)
0
Mean Change
Mean Change
-5
-1
-2
-10
-15
**
**
-3
BPI Average Pain Score
-20
**
Duloxetine
Placebo
*
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.
Duloxetine: Adverse Events
40
***
Duloxetine (N=326)
% of Patients
30
Placebo (N=212)
***
20
***
10
*
**
**
***
0
Nausea
Dry Mouth
Constipation Somnolence
Decreased
Appetite
Increased
Sweating
Anorexia
*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
40
50% Reduction at End Point
ITT Response Rate (%)
35
*
30
25
20
15
10
5
0
Placebo
(n=28)
MIL QD
(n=46)
MIL BID
(n=51)
*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
Stepwise Management of FM
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
Stepwise Management of FM
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 With
Chronic 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, not
what 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://arthritisresearch.com/content/8/4/212
• Strength of Evidence: A (based on consistent findings from
good-quality randomized controlled studies)
Clinical Practice Recommendation
• 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
Clinical Practice Recommendation
• 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)