U P D A T E S I N

SIDNEY ERWIN T. MANAHAN, MD, FPCP, FPRA

FIBROMYALGIA

CHRONIC WIDESPREAD PAIN

• Rheumatoid Arthritis

• Spondyloarthritis

• SLE

• Vasculitic syndromes

• Infections

• Osteoarthritis

• Multiple soft tissue rheumatism

• Hypothyroidism

• Cervical myelopathy

• Spinal stenosis

• Major depression

• Drug-related

• FIBROMYALGIA

Burckhardt K, Goldenberg D. American Pain Society Clinical Practice Guideline for the Management of

Fibromyalgia Syndrome Pain in Adults and Children, 2005.

FIBROMYALGIA

“Fibromyalgia is a chronic rheumatologic condition

characterized by widespread pain and the presence

of soft tissue tenderness.”

“Fibromyalgia is a syndrome characterized by

diffuse body pain associated with fatigue,

sleep disturbance, cognitive changes, mood

disturbance and other variable somatic

symptoms.”

Epidemiology

Prevalence 0.5-5%

• Females 3.5%

• Males 0.5%

Age

• Common 30-55 years*

• Pediatric 1.2 – 1.4%

Fibromyalgia in Males

• Fewer pain sites

• Fewer tender points

• Less fatigue

• Less somatic symptoms

Fitzcharles MA, Yunnus M. Pain Research and Treatment 2012. doi: 10.1155/2012/184835

FM Clinical Features

PAIN

Fatigue

Sleep disorders

Cognitive problems

Mood disorders

Anxiety disorders

100%

90%

90%

60%

50%

40%

The Company FM Keeps Functional Somatic Syndromes

DIAGNOSIS OF EXCLUSION?

5% 17% 22%

1990 ACR

• Widespread Pain of at

least 3 months duration

– Left and right side

– Above and below the

waist

– Axial pain

• 11/ 18 Tender points

Limitations of the ACR 1990

• Fails to capture other clinical features, i.e.

fatigue and sleep disturbance

• Tender points

• No. of tender points = severity; not for monitoring

• Correlates poorly with measures of disease activity

• Differences in performing the tender point

examination

• Not all meet TP criteria (e.q. those who were treated)

“25% of patients would no longer satisfy criteria

for Fibromyalgia on subsequent visits”

Other FM Criteria (Non-TP) SYMPTOM INTENSITY SCORE

• Pain in any of the following in the last 7 days

• Fatigue Visual Analogue Score (0-10 cm)

• FMS: Pain >8 Areas AND Fatigue >6cm

R/L Jaw

Neck

R/L Shoulder

R/L Upper Arm

R/L Forearm

Upper Back

Chest

Abdomen

Lower Back

R/L Hip

R/L Thighs

R/L Calves

Other FM Criteria (Non-TP)

Modified SYMPTOM INTENSITY SCORE

• SIS =

2

• mSIS >5.75

Fatigue VAS + Regional Pain Score

---------------------------------------------------

2

Detects Fibromyalgia

Assesses for co-morbid

depression

Over-all measure of health

2010 ACR Diagnostic Criteria

Widespread Pain Index (WPI)

Symptom Severity Score (SS)

• Fatigue

• Waking Unrefreshed

• Cognitive symptoms

• Somatic symptoms

2010 ACR Diagnostic Criteria

WIDESPREAD PAIN INDEX

• Pain in any of the ff areas in the last 7 days

R/L Jaw

Neck

R/L Shoulder

R/L Upper Arm

R/L Forearm

Upper Back

Chest

Abdomen

Lower Back

R/L Hip

R/L Thighs

R/L Calves

2010 ACR Diagnostic Criteria

SYMPTOM SEVERITY Score

How severe were the following in the past 7 days

• Fatigue

• Waking unrefreshed

• Cognitive symptoms

0 – No problems

1 – Slight or mild problems; intermittent

2 – Moderate or considerable problems; often present

3 – Severe, pervasive, continuous or life-disturbing

problems

2010 ACR Diagnostic Criteria

SYMPTOM SEVERITY Score

• Somatic Symptoms – Have you had any of the following in

the last 6 months

Blurred vision

Dry eyes

Tinnitus

Hearing difficulties

Mouth sores

Dry mouth

Dysgeusia

Headache

Dizziness

Fever

Chest pains

Dyspnea

Wheezing

Anorexia

Nausea

Heart burn

Diarrhea

Constipation

Itching

Hives/ welts

Vomiting

Easy bruising

Hair loss

Urinary symptoms

2010 ACR Diagnostic Criteria

Widespread Pain

Index (WPI)

Symptom Severity

Score (SS)

Fatigue

Waking unrefreshed

Cognitive symptoms

Somatic Symptoms

WPI > 7 and SS Score > 5

WPI 3-6 and SS Score > 9

* Symptoms present for at least 3 months

12?

How to use criteria

AT BASELINE

• 1990/ 2010 ACR Criteria, SIS, Other Criteria

• SS Score to document baseline severity

SUBSEQUENT VISIT

• SS Score to reassess severity

Managing Fibromyalgia 2007 (EULAR)

Carville SF, Arendt-Nielsen S, et al. Ann Rheum Dis 2007; doi:10.1136

2009 (S3) Hauser W, Eich W, et al. Dtsch Arztebl Int 2009; 106 (23): 383-91.

2010 (Spain) Alegre de Miguel C, Garcia Campayo J, et al. Actas Esp Pqiguiatr 2010; 38 (2): 108-20

2012 (Canada) Fitzcharles MA, Ste-Marie PA, et al.

What?

How?

For whom?

What Works (2007)

Intervention LoE / SoR Pain Function

Pharmacologic

Tramadol IB / A

Antidepressants

• Amitriptyline, Fluoxetine,

Duloxetine, Milnacipran,

Moclobemide and

Pirlindole

IB / A

Pregabalin

Pramipexole

Tropisetron

IB / A

What Works (UPDATED) Drugs LoE Dose Comments

Amitriptyline 1A 10-50 mg Frequent side effects

PREGABALIN 1A 150-450 mg FDA-approved, Long-term

efficacy

Duloxetine 1A 30-60 mg FDA-approved, Long-term

efficacy

Milnacipran 1A 25-200 mg FDA-approved

Gabapentin 1B 1200-2400 mg One large RCT

Fluoxetine 2A 20-60 mg Three small RCT

Paroxetine 2B 20 mg One large RCT

Tramadol 2B 50-300 mg Two RCT Tramadol 150 mg +

Paracetamol 1300 mg

IASP Pain: Clinical Updates Vol XVIII Issue 4 June 2010

What Works (2007)

Intervention LoE / SoR

Non-Pharmacologic

Heated pool treatment IIA / B

Aerobic exercise and

strength training IIB / C

Cognitive behavioral

therapy IV / D

Relaxation, rehabilitation,

physiotherapy and

psychological support

IIB / C

The Impact of Aerobic Exercise

Parameter Effect Size P-value

Pain -0.31 (-0.46, 0.17) <0.001

Fatigue -0.22 (-0.38, -0.05) 0.006

Depressed Mood -0.32 (-0.53, -0.12) 0.002

HRQoL -0.40 (-0.60, -0.20) <0.001

Physical Fitness 0.65 (0.38, 0.93) <0.001

Sleep 0.01 (-0.19, 0.21) 0.92

Hauser et al. Arth Res Ther 2010: 12: R79

* compared vs. Placebo

Aerobic Ex Prescription

Parameter # Studies # Patients Effect Size P-value

TYPE OF EXERCISE

Land based 22 463 -0.29 (-0.46, -0.13) 0.0005

Water based 3 61 -0.67 (-1.04, -0.29) 0.0005

Mixed 4 43 -0.03 (-0.45, 0.39) 0.89

TYPE OF EXERCISE

AE only 12 273 -0.35 (-0.61, -0.09) 0.0008

Combined 17 294 -0.28 (-0.45, -0.15) 0.001

INTENSITY OF AEROBIC EXERCISE

<50% Max HR 1 37 -0.09 (-0.54, 0.36) NA

>50% Max HR 21 367 -0.26 (-0.42, -0.11) 0.02

Up to Patient 2 79 -0.42 (-0.77, -0.07) 0.0007

Hauser et al. Arth Res Ther 2010: 12: R79

Aerobic Ex Prescription

Parameter # Studies # Patients Effect Size P-value

DURATION OF STUDY

< 7 weeks 2 32 -1.16 (-1.86, -0.48) 0.001

7 – 12 weeks 13 194 -0.24 (-0.50, -0.02) 0.03

> 12 weeks 12 338 -0.24 (-0.40, -0.08) 0.004

FREQUENCY OF TRAINING

1/ week 2 37 -0.07 (-0.52, 03.9) 0.48

2/ week 5 127 -0.69 (-0.95, -0.27) 0.0004

3/ week 16 241 -0.35 (-0.62, -0.09) 0.009

>3/ week 4 142 -0.13 (-0.38, 0.13) 0.33

Hauser et al. Arth Res Ther 2010: 12: R79

Educating the FM Patient

• Symptoms do not lead to invalidism or shorten

life span

• Complete relief is not possible in all patients

• Goal is ADAPTATION

• Regular physical activity leads to adaptation

1

2

3

How to Use: S3 Guidelines

• Cognitive behavioral therapy (1A)

• Aerobic endurance training (1A)

• Pool-based exercises (1A)

• Spa therapy (1A)

• Amitriptyline (1A)

• Diagnosis and management of comorbids (5)

• Multimodal Therapy (1A)

• Short term pharmacotherapy (1A)

• Short term non-pharma

interventions (2A)

• Multimodal booster therapy (5)

• Complementary med (2B)

Start Level I

Interventions

Improvement

at 6 months?

Start Level 2

Interventions

Improvement

at 6months?

Start Level 3

Interventions

Improvement

12 months?

Improvement

at 6months?

Sufficient

functioning in

daily activities/

ADAPTATION

Yes

Yes

Yes

No

No

No

Yes

PATIENT TAILORED Approach

Multi-modal treatment

Multi-component treatment

Self-management strategies

Symptom based approach

Fibromyalgia Subgroups by Giesecke

• DEPRESSION

Center for Epidemiologic Studies Depression Scale

• ANXIETY

State-Trait Personality Inventory

• CATASTOPHISM

Coping Strategies Questionnaire

• HYPERALGESIA

Pain scale/ Painful Pressure

Group 1 Group 2 Group 3

ANXIETY / DEPRESSION

Moderate High Normal

CATASTROPHISM/ COPING

Moderate High Low

HYPERALGESIA/ TENDER POINTS

Low High High

Giesecke Group 1

• Education

• Exercise program

• For depression

– SNRI (Duloxetine, Milnacipran)

and tricyclic antidepressants

• For anxiety

– Pregabalin, SSRI, SNRI

• For hyperalgesia

– Pregabalin, gabapentin

Giesecke Group 2

• Education

• Exercise program

• For depression

– SNRI (Duloxetine, Milnacipran)

and tricyclic antidepressants

• For anxiety

– Pregabalin, SSRI, SNRI

• For hyperalgesia

– Pregabalin, gabapentin

• Cognitive Behavior Therapy

Giesecke Group 3

• Education

• Exercise program

• For hyperalgesia

– Pregabalin, gabapentin

• Do not give SNRI, SSRI, TCA

• No Cognitive Behavioral Tx

Dosage of Pregabalin Used (n=1,134)

48

97 97 98

274

68 65

243

88

56

0

50

100

150

200

250

300

25 mg 50 mg 75 mg 100 mg 150 mg 200 mg 225 mg 300 mg 450 mg 600 mg

Dosages of Duloxetine Used (n=1,377)

73

239

23

714

2

125

194

0

100

200

300

400

500

600

700

800

20 mg 30 mg 40 mg 60 mg 80 mg 90 mg 120 mg

Efficacy

15

34

26

16

10

20

37

22

13

7

0

5

10

15

20

25

30

35

40

Major Moderate Slight None Unsure

Duloxetine (n=316) Pregabalin (n=319)

Adverse Events

19

26 28

26

29 30

25

16

0

5

10

15

20

25

30

35

Severe Moderate Mild None

Duloxetine (n=432) Pregabalin (n=418)

Most Common AEs: Pregabalin

164

102

95

92

81

76

0 20 40 60 80 100 120 140 160 180

Weight gain

Brain fog

AM Sleepiness

Dizziness

Lack of concentration

Blurry vision

Most Common AEs: Duloxetine

97

90

89

76

72

57

0 20 40 60 80 100 120

Decreased libido

Increased sweating

Nausea

Dizziness

Brain cloud

Insomnia

Summary

• Described the clinical features of fibromyalgia

• Compared the utility of the 1990 vs 2010 ACR Diagnostic Criteria

• Synthesized recommendations of different practice guidelines

• Reported patient experience on the use of two FDA-approved fibromyalgia treatments