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Evidence-Based Reviews

Fibromyalgia: Psychiatric drugs target CNS-linked symptoms

Repeated pain signals in the periphery may sensitize spinal cord neurons, resulting in amplified and prolonged signals traveling to the brain

Vol. 8, No. 3 / March 2009

Listen to Dr. Stanford discuss,
"Is fibromyalgia a somatoform disorder?

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Patients with fibromyalgia are a heterogeneous group, yet many describe a common experience: seeing multiple physicians who seem unable or unwilling to provide a diagnosis or treat their symptoms. This situation may be changing with the recent FDA approval of an anticonvulsant and 2 antidepressants for managing fibromyalgia symptoms.

These medications—pregabalin, duloxetine, and milnacipran—reflect a revised understanding of fibromyalgia as a CNS condition, rather than an inflammatory process in the muscles or connective tissue. As a result, psychiatrists—because of our experience with CNS phenomena and managing antidepressant and anticonvulsant medications—are likely to play a larger role in treating fibromyalgia.

CASE REPORT: ‘Just too tired’

Ms. D, age 50, has a history of migraine headaches and is referred by her primary physician for evaluation of depression and anxiety. She reports deteriorating mood over 6 months, beginning when a minor car accident left her “very sore the next day.”

“Nothing helps” the persistent pain in her back, shoulders, and thighs, which she rates as 7 to 8 on a 0-to-10 pain scale. She describes an intense ache, “like having the flu,” that worsens with activity and in stressful situations. She also experiences nausea and intermittent diarrhea, debilitating fatigue, and sleep disturbance.

Ms. D reports she is depressed because she feels “just too tired” after work to keep up with social activities or housework. Her physician’s referral notes a normal physical exam except for tenderness over her upper back and hips. Laboratory testing is negative.

Making the diagnosis

American College of Rheumatology (ACR) criteria for fibromyalgia require widespread pain for at least 3 months. “Widespread” is defined as pain in the axial skeleton, left and right sides of the body, and above and below the waist. Pain must be found in at least 11 of 18 tender point sites on digital palpation using a force of approximately 4 kg/cm2.1 For many fibromyalgia patients, however, musculoskeletal pain is not their most problematic symptom (Table 1). They may suffer:

  • migraine and tension headaches (10% to 80% of patients)
  • irritable bowel syndrome (32% to 80%)2
  • mood disorders (major depressive disorder [62%], bipolar disorder [11%])
  • anxiety disorders (panic disorder [29%], posttraumatic stress disorder [21%], social phobia [19%]).3

ACR criteria are useful in research but lack many common symptoms and comorbidities. A structured interview that follows the DSM-IV-TR format incorporates other symptoms into the diagnosis (Table 2).4

Because patients with fibromyalgia often meet criteria for somatization or somatoform disorders, how to classify them—as medically or psychiatrically ill—is controversial. Some patients believe their mood or anxiety problem stems from the difficulty they experience dealing with their physical symptoms, and if they could feel better physically they would not be depressed or anxious. Others believe their psychiatric symptoms impede their ability to help themselves feel better.

Consider fibromyalgia in any patient with widespread pain of unknown cause. Before making the diagnosis, rule out other illnesses that present with similar symptoms (Table 3). Because many patients newly diagnosed with fibromyalgia worry that something “more serious” may be going on, confirm the diagnosis with appropriate testing and physical examination, usually by a rheumatologist or primary care physician.

Table 1

Medical and cognitive symptoms related to fibromyalgia

Tension/migraine headache

Memory and cognitive difficulties
Mood disturbance
Anxiety disorders

Ear, nose, throat
Sicca symptoms
Vasomotor rhinitis
Vestibular complaints

Neurally mediated hypotension
Mitral valve prolapse
Noncardiac chest pain

Esophageal dysmotility
Irritable bowel syndrome

Interstitial cystitis

Chronic pelvic pain

Temporomandibular joint syndrome

Other (general)
Chronic fatigue syndrome
Sleep disturbances
Idiopathic low back pain
Multiple chemical sensitivity

Table 2

Fibromyalgia: Structured interview for diagnosis

A. Generalized pain affecting the axial, plus upper and lower segments, plus left and rights sides of the body

Either B or C:

B. At least 11 of 18 reproducible tender points

C. At least 4 of the following symptoms:

  • Generalized fatigue
  • Headaches
  • Sleep disturbance
  • Neuropsychiatric complaints
  • Numbness, tingling sensations
  • Irritable bowel symptoms

D. It cannot be established that disturbance was due to another systematic condition

Source: Reference 4

Table 3

Differentiating fibromyalgia from illnesses with similar symptoms


Tests to differentiate from primary fibromyalgia

Rheumatic diseases
Spondyloarthropathies, rheumatoid arthritis
Systemic lupus erythematosus, polymyalgia rheumatica

Rheumatic markers (antinuclear antibody, rheumatoid factor, antibodies)
Inflammatory markers (ESR, C-reactive protein)
Vitamin D level

Multiple sclerosis, Chiari’s malformation, spinal stenosis, radiculopathy



Basic chemistry panel with fasting glucose

  Lyme disease

Lyme titer
Hepatitis antibody panel, liver function tests
Routine cancer screening tests, bone scan, blood chemistries specific for suspected primary cancer

ESR: erythrocyte sedimentation rate; CPK: creatine phosphokinase; EMG: electromyography; TSH: thyroid-stimulating hormone; CBC: complete blood count

CASE CONTINUED: Central pain sensitization

As you elicit more details about Ms. D’s mood, she continues to focus on her physical symptoms. She states that some days she wishes to die because her pain gets so bad, but she denies any plan or intent to harm herself. She worries that her symptoms will worsen and that she will become completely disabled.

Her primary physician attempted to relieve Ms. D’s pain with multiple trials of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclobenzaprine. She says she gained no benefit from the NSAIDs and discontinued the muscle relaxant because it made her too sleepy. Fibromyalgia affects 3.5% of women and 0.5% of men.5 It runs in families with histories of fibromyalgia and major mood and anxiety disorders, suggesting genetic links.6 Defects in genes controlling serotonin and norepinephrine have been implicated.7-9

Fibromyalgia patients show lower levels of serotonin, norepinephrine, and dopamine metabolites in cerebrospinal fluid (CSF), compared with controls.10 These neurotransmitters may inhibit descending pain pathways in the CNS, and low levels in the brain and spinal cord may inhibit CNS regulation of pain impulses from the periphery.11

Although many patients describe muscle pain, evidence suggests central pain augmentation rather than an abnormality of muscle or connective tissue.12 Some studies have found evidence of “windup,” in which second-order neurons in the spinal cord become sensitized by repeated signals from first-order neurons in the periphery, resulting in amplified and prolonged pain signals traveling to the brain.13

Levels of substance P—a primary transmitter of pain impulses—are significantly higher in CSF of fibromyalgia patients compared with controls.14 This finding, in addition to low levels of serotonin and norepinephrine, indicates that pain signals are ascending unchecked to be processed by the brain.

Neuroimaging studies confirm this observation. In a study using functional magnetic resonance imaging (fMRI), researchers applied pressure to the thumbnails of fibromyalgia patients and controls until each subject reported pain:

  • Twice as much pressure was required before controls rated their pain at a level similar to that of fibromyalgia patients.
  • When controls and fibromyalgia patients reported similar pain, a very high degree of overlap was seen in brain areas responsible for pain processing. This indicates that fibromyalgia patients and controls were experiencing the pain they reported in the same way.15

Treating the whole patient

As a clinician who specializes in fibromyalgia, I counteract my patients’ and my own frustration with this condition by structuring office visits, determining realistic treatment goals, and treating all symptoms as part of a common syndrome rather than individual illnesses.

Structure office visits. Before every visit, have patients rate each symptom domain and write their top 2 or 3 concerns for that day (Click here for a sample form). Focusing on the patient’s most troublesome symptoms can help both of you feel greater satisfaction with treatment.

Educate patients. Ask them to discuss their beliefs about fibromyalgia; many know others with this condition or have researched diagnosis and treatment. Before developing a treatment plan, explain that their symptoms are chronic and all part of the same syndrome. Describe their pain as a complex phenomenon with possible peripheral and CNS components. Guide them to reputable Web sites and resources (see Related Resources).

Set realistic expectations. Many patients expect to resume an energetic and pain-free life, which usually is not the case with fibromyalgia (Box). Most medications are considered successful if they reduce pain by 30% to 50%, and side effects can be problematic. Discuss side effects before treatment begins to reduce patients’ anxiety and improve compliance in the first weeks.

Cognitive-behavioral therapy (CBT) for fibromyalgia incorporates relaxation techniques, helping patients view symptoms as manageable, reinforcing adaptive coping skills, and teaching them how to monitor thoughts, feelings, and behavior to change the view that they are helpless victims. A modest course of 6 weekly group CBT sessions significantly improved physical functioning in 25% of fibromyalgia patients (n=76) compared with 12% in a standard-care group (n=69), even though patients’ pain severity did not improve.16

Recommend exercise, lifestyle changes. Aerobic exercise can significantly improve well-being and physical functioning in fibromyalgia patients.17 Low-impact aerobics, such as done in warm water, usually are well tolerated, although any low-impact exercise can help. Because fibromyalgia symptoms often increase with physical activity, counsel patients to begin with a few minutes daily and increase very slowly each week.

Lifestyle changes are as important as medications in controlling fibromyalgia symptoms. In addition to exercise, recommend that patients:

  • follow a daily routine
  • pace activity to avoid exacerbating symptoms
  • reduce stress.

Sometimes, I use the analogy of diabetes: treating fibromyalgia with medication but without changing lifestyle is like prescribing medication for a diabetic patient without changing diet. Follow up on this “homework” at each visit to reinforce that patients helping themselves is an important part of treatment.


Managing unrealistic expectations of fibromyalgia patients

BELIEF: ‘A magic pill exists that will resolve all my symptoms and have no side effects’

Clinical evidence: Most medications that have been studied were effective in 30% to 50% of patients and reduced pain scores by 30% to 50%.

Patient education: Explain to the patient with a pain rating of 7 at the first visit that achieving a pain level of 3 to 4 may be possible with treatment. Even with successful treatment, symptoms may flare intermittently. As with any treatment, adverse effects may occur. Discuss these, so the patient is not surprised.

BELIEF: ‘I can’t exercise’

Clinical evidence: Most patients experience more fatigue and pain with physical activity, but exercise is important to maintain physical function.

Patient education: When discussing an exercise program, focus on what the patient can do. Most patients attempt too much, too soon; advise them to start at a tolerable level (such as 2 to 3 minutes of aerobic activity daily for the first week) and gradually increase as tolerated.

BELIEF: ‘You (the psychiatrist) can make me feel better’

Clinical evidence:

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