ACR Fibromyalgia Diagnostic Criteria

Fibromyalgia Syndrome Diagnostic Criteria

Fibromyalgia is a distinctive syndrome which can be diagnosed with clinical precision. It may occur in
the absence (primary fibromyalgia) or presence of other conditions such as rheumatoid arthritis or
systemic lupus erythematosus (concomitant fibromyalgia). It is rarely secondary to another disease, in
the sense that alleviation of the associated disease also cures the fibromyalgia. It may be confidently
diagnosed in patients with widespread musculo-skeletal pain and multiple tender points.
The American College of Rheumatology
1990 Criteria for the Classification of Fibromyalgia
History of widespread pain has been present for at least three months
Definition: Pain is considered widespread when all of the following are present:

Pain in both sides of the body

Pain above and below the waist In addition, axial skeletal pain (cervical spine, anterior chest,
thoracic spine or low back pain) must be present. Low back pain is considered lower segment
pain.

Pain in 11 of 18 tender point sites on digital palpation

Definition: Pain, on digital palpation, must be present in at least 11 of the following 18 tender point sites:

Occiput (2) - at the suboccipital muscle insertions.

Low cervical (2) - at the anterior aspects of the intertransverse spaces at C5-C7.
Trapezius (2) - at the midpoint of the upper border.
Supraspinatus (2) - at origins, above the scapula spine near the medial border.
Second rib (2) - upper lateral to the second costochondral junction.
Lateral epicondyle (2) - 2 cm distal to the epicondyles.
Gluteal (2) - in upper outer quadrants of buttocks in anterior fold of muscle.
Greater trochanter (2) - posterior to the trochanteric prominence.
Knee (2) - at the medial fat pad proximal to the joint line.

Digital palpation should be performed with an approximate force of 4 kg. A tender point has to be painful
at palpation, not just "tender."

Illustration of Tender Points

Fibromyalgia Syndrome Symptoms

Arthritis and Rheumatism, Vol. 33, No. 2, Feb 1990, F. Wolfe, et al.
Condition
Muscular Pain

% of FMS Symptoms
100

Fatigue

96

Insomnia

86

Joint Pains

72

Headaches

60

Restless Legs

56

Numbness and Tingling

52

Impaired Memory

46

Leg Cramps

42

Impaired Concentration

41

Nervousness

32

Depression (Major Depression)

20

New and Old Medications Being Developed for Fibromylgia

A randomized, double-blind, placebo-controlled trial of pramipexole, a

dopamine agonist, in patients with fibromyalgia receiving concomitant
medications.
Andrew J. Holman and Robin R. Myers.
OBJECTIVE: To assess the efficacy and safety of pramipexole, a dopamine 3 receptor agonist, in
patients with fibromyalgia. METHODS: In this 14-week, single-center, double-blind, placebo-controlled,
parallel-group, escalating-dose trial, 60 patients with fibromyalgia were randomized 2:1
pramipexole:placebo) to receive 4.5 mg of pramipexole or placebo orally every evening. The primary
outcome was improvement in the pain score (10-cm visual analog scale [VAS] at 14 weeks. Secondary
outcome measures were the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Health
Assessment Questionnaire (MDHAQ), the pain improvement scale, the tender point score, the 17question Hamilton Depression Inventory (HAM-d), and the Beck Anxiety Index (BAI). Patients with
comorbidities and disability were not excluded. Stable dosages of concomitant medications, including
analgesics, were allowed. RESULTS: Compared with the placebo group, patients receiving pramipexole
experienced gradual and more significant improvement in measures of pain, fatigue, function, and global
status. At 14 weeks, the VAS pain score decreased 36% in the pramipexole arm and 9% in the placebo
arm (treatment difference 1.77 cm). Forty-two percent of patients receiving pramipexole and 14% of
those receiving placebo achieved >50% decrease in pain. Secondary outcomes favoring pramipexole
over placebo included the total FIQ score (treatment difference 9.57) and the percentages of
improvement in function (22% versus 0%), fatigue (29% versus 7%), and global (38% versus 3%)
scores on the MDHAQ. Compared with baseline, some outcomes showed a better trend for pramipexole
treatment than for placebo, but failed to reach statistical significance, including improvement in the
tender point score (51% versus 36%) and decreases in the MDHAQ psychiatric score (37% versus
28%), and BAI score (39% versus 27%), and the HAM-d score (29% versus 9%). No end points showed
a better trend for the placebo arm. The most common adverse events associated with pramipexole were
transient anxiety and weight loss. No patient withdrew from the study because of inefficacy or an
adverse event related to pramipexole. CONCLUSION: In a subset of patients with fibromyalgia, ~50% of
whom required narcotic analgesia and/or were disabled, treatment with pramipexole improved scores on
assessments of pain, fatigue, function, and global status, and was safe and well-tolerated. Arth and
Rheum, vol. 52, No. 8, Aug 2005, pp 2495-2505

Impact of fibromyalgia pain on health-related quality of life before and

after treatment with tramadol/acetaminophen.
Robert M Bennett, Jeff Schein, Mark R. Kosinski, David J. Hewitt, Donna M. Jordan and Norman R.
Rosenthal
OBJECTIVE: To assess health-related quality of life (HRQOL) in patients with moderate-to-severe
fibromyalgia pain compared with the general population, and to assess the relationship between pain
severity and HRQOL before and after treatment with an analgesic. METHODS: Data were obtained from
a randomized, double-blind study of patients with moderate-to-severe fibromyalgia pain. Patients
received either tramadol/acetaminophen or placebo 4 times/day as needed for 91days. HRQOL was
measured with the Short Form 36 Health Survey 9SF-36) and the Fibromyalgia Impact Questionnaire
(FIQ). Baseline HRQOL sores were compared with HRQOL due to congestive heart failure. Patients
with fibromyalgia were divided into tertiles by change in pain severity, and SF-e6 scores were compared
across the tertiles. Mean changes in SF-36 and FIQ scores were compared between treatment groups.
RESULTS: Patients with fibromyalgia scored lower than the US norm on all SF-36 scales (P< 0.0001)
and lower than patients with congestive heart failure on most scales. More severe pain was associated
with greater impairment of HRQOL compared with less severe pain (P< 0.0001). Patients in the highest
tertile for improved pain severity had greater improvement in HRQOL scores than patients in the lower
tertiles. Compared with patients who received placebo (n=157), patients treated with

tramadol/acetaminophen (n=156) showed greater improvement on SF-36 Physical functioning, role

physical, bodily pain, and physical summary scales, as well as FIQ scales for ability to do job, pain, and
stiffness (P< 0.01). CONCLUSION: Moderate-to-severe fibromyalgia pain significantly impairs HRQOL,
and effective pain relief in these patients significantly increases HRQOL.
Arth & Rheum (Arthritis Care and Research), Vol. 53, No.4 Aug 15, 2005, pp 519-527

The effects of sodium oxybate on clinical symptoms and sleep patterns

in fibromyalgia.
Martin B. Scharf, PhD, Margaret Baumann, David V. Berkowitz, MD
BACKGROUND: Fibromyalgia is associated with the sleep phenomenon of alpha intrusion, and with low
growth hormone secretion. Sodium oxybate has been shown to increase both slow-wave sleep and
growth hormone levels. This double-blind, randomized, placebo-controlled, crossover trial was
conducted to evaluate the effects of sodium oxybate on the subjective symptoms of pain, fatigue, and
sleep quality and the objective polysomnographic (PSC) sleep parameters of alpha intrusion, slow-wave
(Stage 3, 4 sleep), and sleep efficiency ciency in fibromyalgia patients. METHODS: Patients received
either 6.0 g/d sodium oxybate or placebo for 1 month, with an intervening 2-week washout period.
Efficacy measures included PSG evaluations, tender point index (TPI), and subjective measurements
from daily diary entries. Safety measures included clinical laboratory values, vital signs and adverse
events. RESULTS: Twenty-fourfemales patients were included in the study; 18 completed the trial. TPI
was decreased from baseline by 8.5, compared with an increase of 0.4 for placebo (p=0.0079). Six of
the 7 pain/fatigue scores (overall pain, pain at rest, pain during movement, end of day fatigue, overall
fatigue, and morning fatigue) were relieved by 29% to 33% with sodium oxybate, compared with 6% to
10% relief with placebo (p<0.005). Alpha intrusion, sleep latency, and REM sleep were significantly
decreased, with slow-wave (Stage 3, 4) sleep was increased significantly, compared with placebo
(p<0.005). Two of the 5 subjective sleep-related variables were significantly different from placebo
morning alertness ((improved by 18% with sodium oxybate, compared with 2% for placebo; p=0.0033)
and quality of sleep (improved by 33% and 10% respectively; p=0.0003). CONCLUSIONS: In this study,
sodium oxybate effectively reduced the symptoms of pain and fatigue in fibromyalgia, and dramatically
reduced the sleep abnormalities (alpha intrusion and decreased slow-wave sleep) associated with the
non-restorative sleep characteristic of this disorder.
J Rheum; 2003:30:1070-4

Development of milnaciprin, a dual reuptake inhibitor for treatment of

chronic pain associated with fibromyalgia.
Jay D. Kranzler, MD, PhD, Cypress Bioscience, Inc., San Diego, CA
Milnacipran is a chemically novel, dual acting reuptake inhibitor, distinguished from other SNRIs
(Serotonin Norepinephrin Reuptake Inhibitors) by its preference for norepinephrine (NE) reuptake
inhibition over serotonin (5-HT). This profile most closely mimics that seen with tricyclic antidepressants
(TCAs) such as amitriptyline. While mimicking the NE preference seen with TCAs, milnacipran lacks the
other receptor interactions that underlie the side effects of the TCAs, and limit their use. While new
antidepressants have displaced TCAs for most psychiatric indications, the TCAs remain in clinical use in
chronic pain states, where they have consistently demonstrated superior efficacy to SSRIs, NSAIDs and
non-opiate pain medications. Such applications include the so-called Functional Somatic Syndromes
(FSS), such as fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS),and tension headaches
(TH), which share a similar spectrum of symptoms, including pain, disturbed sleep, fatigue, and
depressed mood; b) a level of distress, as reported by the patient, that can not be readily explained by
the physical and laboratory findings of the physician; and c) high levels of comorbidity. These syndromes
are common, accounting for up to 60% of all primary care visits in the United States, by some estimates.
We hypothesize that the NE reuptake inhibition preference of agents such as amitriptyline may account
for their superior efficacy relative to SSRIs in chronic pain states, and set out to test this hypothesis by
studying the efficacy of milnacipran in FMS, a prototypical FSS. A rigorous Phase II randomized, doubleblind, placebo-controlled, flexible dose escalation monotherapy trial was conducted to evaluate

milnacipran in patients with a diagnosis of FMS. Following washout of any centrally-acting agents
including antidepressants, patients began a two week baseline period, followed by dosing at 25 mg daily
(active or placebo pill), provided either QD or BID in a blinded fashion. Patients were then escalated
weekly to 50, 100 and finally 200mg daily, or until dose-limiting toxicity became evident. The four weeks
of dose escalation was followed by eight weeks of stable dosing. During the 14-week study, participants
were asked to carry an electronic diary and record pain, fatigue, sleep and quality of life information. The
custom designed diary captured spontaneous pain data in several ways including: (a) random daily
prompts (the device notified the patient to record their current level of pain 4-5 times per day), (b) a daily
prompt in the morning querying about the previous 24-hours pain and (c) a weekly report asking about
the patients average pain for the past seven days. The electronic assessments were supplemented with
traditional recording of weekly average pain during clinic visits at baseline and weeks 10 and 14. Since
pain amplification as a result of central sensitization has been reported in FMS, as well as in other FSS
a novel Applied Pain Threshold Tester (APT2) apparatus was developed, and patients evoked pain to
pressure stimuli were monitored at baseline, and after 4 and 8 weeks of treatment. This study of
milnacipran as a new therapy for the treatment of the pain associated with FMS represents the first in a
series of studies within the FSS spectrum of disorders. Additional studies are planned to assess the
efficacy of milnacipran on depressed mood within the context of FMS and related chronic pain states.
National Fibromyalgia Research Association
Neurology and New Treatment Modalities in Fibromyalgia
Sympossium Portland, Oregon October 2002

Pregabalin for the treatment of fibromyalgia syndrome: Results of a

randomized, double-blind, placebo-controlled trial.
Crofford LJ, Rowbotham MC, Mease PJ, Russell IJ, Dworkin RH, Corbin AE, Young JP, LaMoreaux LK,
Martin SA, Sharma U and the pregabalin 1008-105 study group.
OBJECTIVE: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal lowered
pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an
estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy
and safety of pregabalin, a novel alpha 2- ligand, for treatment of symptoms associated with FMS.
METHODS: This multicenter, double-blind, 8 week, randomized clinical trial compared the effects of
placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related
quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point
mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin
treatment groups and the placebo group. RESULTS: Pregabalin at 450 mg/day significantly reduced the
average severity of pain in the primary analysis compared with placebo (-0.93 on a 0-10 scale)
(P<=0.001), and significantly more patients in this group had >50% improvement in pain at the end point
(29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated
with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at
450 mg/day improveproved several domains of health-related quality of life. Dizziness and somnolence
were the most frequent adverse events. Rates of discontinuation due to adverse events were similar
across all 4 treatment groups. CONCLUSION: Pregabalin at 450 mg/day was efficacious for the
treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo.
Pregabalin was well tolerated and improved global measures and health-related quality of life.
Arthritis Rheum (2005 Apr) 52(4):pp 1264-1273

Duloxetine with placebo in the treatment of fibromyalgia patients with or

without major depressive disorder.
Lesley M. Arnold, Yili Lu, Leslie J. Crofford, Madeleine Wohlreich, Michael J. Detke, Smiriti Iyengar, and
David J. Goldstein, for the Duloxetine Fibromyalgia Trial Group.
OBJECTIVE: To assess the efficacy and safety of duloxetine, a serotonin and norepinephrine reuptake
inhibitor, in subjects with primary fibromyalgia, with or without current major depressive disorder.
METHODS: This study was a randomized, double-blind, placebo controlled trial conducted in 18

outpatient research centers in the US. A total of 207 subjects meeting the American College of
Rheumatology criteria for primary fibromyalgia were enrolled (89% female, 87% white, mean age 49
years, 38% with current major depressive disorder). After single-blind placebo treatment for 1 week,
subjects were randomly assigned to receive duloxetine 60 mg twice a day (n=104) or placebo (n=103)
for 12 weeks. Co-primary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ) total
score (score range 0-80, with 0 indicating no impact) and FIQ pain score (score range 0-10). Secondary
outcome measures included mean tender point pain threshold, number of tender points, FIQ fatigue,
tiredness on awakening, and stiffness scores, Clinical Global Impression of Severity (CGI-Severity)
scale, Patient Global Impression of Improvement (PGI-Improvement) scale, Brief Pain Inventory (short
form), Medical Outcomes Study Short Form 36, Quality of Life in Depression Scale, and Sheehan
Disability Scale. RESULTS: Compared with placebo-treated subjects, duloxetine-treated subjects
improved significantly more (P=0.027) on the FIQ total score, with a treatment difference of -5.53 (95%
confidence interval -10.43, -0.63), but not significantly more on the FIQ pain score (P=0.130). Compared
with placebo-treated subjects, duloxetine-treated subjects had significantly greater reductions in Brief
Pain Inventory average pain severity score (P=0.008), Brief pain Inventory average interference from
pain score (P=0.004), number of tender points (p=0.002), and FIQ stiffness score (P=0.048), and had
significantly greater improvement in mean tender point pain threshold (P=0.002), CGI-Severity
(P=0.048), PGI-Improvement (P=0.033), and several quality-of-life measures. Duloxetine treatment
improved fibromyalgia symptoms and pain severity regardless of baseline status of major depressive
disorder. Compared with placebo-treated female subjects (n=92), duloxetine-treated female subjects
(n=92) demonstrated significantly greater improvement on most efficacy measures, while duloxetinetreated male subjects (n=12) failed to improve significantly on any efficacy measure. The treatment
effect on significant pain reduction in female subjects was independent of the effect on mood or anxiety.
Duloxetine was safely administered and well tolerated. CONCLUSION: In this randomized, controlled,
12-week trial (with a 1-week placebo lead-in phase), duloxetine was an effective and safe treatment for
many of the symptoms associated with fibromyalgia in subjects with or without major depressive
disorder, particularly for women, who had significant improvement across most outcome measures.
Arthritis & Rheum, Vol. 50. No. 9, Sept 2004, pp 29742984