Fib Fib romyalgia - Balance Women's Health
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Repeated pain
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in amplified and
prolonged signals
traveling to
the brain
For mass reproduction, content licensing and permissions contact Dowden Health Media.
36_CPSY0309 36 2/13/09 10:56:44 AM
Web audio at CurrentPsychiatry.com ONLINE
“Is it fibromyalgia or somatization disorder?” ONLY
b romyalgia
Psychiatric drugs target
CNS-linked symptoms
atients with fibromyalgia are a heterogeneous group, yet
many describe a common experience: seeing multiple
Sharon B. (Shay) physicians who seem unable or unwilling to provide a
Stanford, MD diagnosis or treat their symptoms. This situation may be changing
Assistant professor of psychiatry with the recent FDA approval of an anticonvulsant and 2 antide-
and family medicine pressants for managing fibromyalgia symptoms.
Assistant director, Women’s These medications—pregabalin, duloxetine, and milnacipran—re-
Health Research Program
flect a revised understanding of fibromyalgia as a CNS condition,
University of Cincinnati
College of Medicine rather than an inflammatory process in the muscles or connective tis-
Cincinnati, OH sue. As a result, psychiatrists—because of our experience with CNS
phenomena and managing antidepressant and anticonvulsant medi-
cations—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 acci-
dent left her “very sore the next day.”
KEN ORVIDAS FOR CURRENT PSYCHIATRY
“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 diar-
rhea, debilitating fatigue, and sleep disturbance.
continued
Current Psychiatry
Vol. 8, No. 3 37
37_CPSY0309 37 2/17/09 11:21:25 AMTable 1 Ms. D reports she is depressed because
she feels “just too tired” after work to keep up
Medical and cognitive
with social activities or housework. Her phy-
symptoms related to sician’s referral notes a normal physical exam
fibromyalgia except for tenderness over her upper back
Neurologic and hips. Laboratory testing is negative.
Tension/migraine headache
Fibromyalgia Psychiatric
Memory and cognitive difficulties Making the diagnosis
Mood disturbance American College of Rheumatology (ACR)
Anxiety disorders
criteria for fibromyalgia require wide-
Ear, nose, throat spread pain for at least 3 months. “Wide-
Sicca symptoms
spread” is defined as pain in the axial
Vasomotor rhinitis
Vestibular complaints skeleton, left and right sides of the body,
and above and below the waist. Pain must
Cardiovascular
Neurally mediated hypotension be found in at least 11 of 18 tender point
Clinical Point Mitral valve prolapse sites on digital palpation using a force of
Noncardiac chest pain approximately 4 kg/cm2.1 For many fibro-
Musculoskeletal
Gastrointestinal myalgia patients, however, musculosk-
pain is not the Esophageal dysmotility eletal pain is not their most problematic
most problematic Irritable bowel syndrome symptom (Table 1). They may suffer:
symptom for many Urological • migraine and tension headaches (10%
Interstitial cystitis to 80% of patients)
patients with
Gynecological • irritable bowel syndrome (32% to
fibromyalgia Vulvodynia 80%)2
Chronic pelvic pain • mood disorders (major depressive dis-
Oral/dental order [62%], bipolar disorder [11%])
Temporomandibular joint syndrome • anxiety disorders (panic disorder
Other (general) [29%], posttraumatic stress disorder
Chronic fatigue syndrome [21%], social phobia [19%]).3
Sleep disturbances
ACR criteria are useful in research but
Idiopathic low back pain
Multiple chemical sensitivity lack many common symptoms and comor-
bidities. A structured interview that follows
the DSM-IV-TR format incorporates other
Table 2
symptoms into the diagnosis (Table 2).4
Fibromyalgia: Structured Because patients with fibromyalgia
interview for diagnosis often meet criteria for somatization or
somatoform disorders, how to classify
A. Generalized pain affecting the axial, plus
upper and lower segments, plus left and
them—as medically or psychiatrically
rights sides of the body ill—is controversial. Some patients believe
their mood or anxiety problem stems from
Either B or C:
the difficulty they experience dealing with
B. At least 11 of 18 reproducible tender
their physical symptoms, and if they could
ONLINE points
ONLY feel better physically they would not be
C. At least 4 of the following symptoms: depressed or anxious. Others believe their
Download a form • Generalized fatigue
• Headaches
psychiatric symptoms impede their ability
for patients to report
• Sleep disturbance to help themselves feel better.
fibromyalgia symptoms.
Saves time, structures • Neuropsychiatric complaints Consider fibromyalgia in any patient
• Numbness, tingling sensations with widespread pain of unknown cause.
office visits.
• Irritable bowel symptoms
CurrentPsychiatry.com Before making the diagnosis, rule out oth-
D. It cannot be established that disturbance er illnesses that present with similar symp-
was due to another systematic condition
toms (Table 3). Because many patients
Current Psychiatry
Source: Reference 4
38 March 2009 newly diagnosed with fibromyalgia worry
38_CPSY0309 38 2/17/09 11:21:35 AMTable 3
Differentiating fibromyalgia from illnesses with similar symptoms
Illness Tests to differentiate from primary fibromyalgia
Rheumatic diseases
Osteoarthritis Radiographs
Spondyloarthropathies, Rheumatic markers (antinuclear antibody,
rheumatoid arthritis rheumatoid factor, antibodies)
Systemic lupus erythematosus, Inflammatory markers (ESR, C-reactive protein)
polymyalgia rheumatica
Osteomalacia Vitamin D level
Myopathy CPK
Neurologic
Multiple sclerosis, Chiari’s MRI
malformation, spinal stenosis,
radiculopathy
Clinical Point
Neuropathy EMG
Endocrine
Fibromyalgia
Hypothyroidism TSH patients show lower
Diabetes Basic chemistry panel with fasting glucose levels of serotonin,
Other norepinephrine,
Infectious CBC and dopamine
Lyme disease Lyme titer
metabolites in
Hepatitis Hepatitis antibody panel, liver function tests
cerebrospinal fluid
Anemia Hemoglobin/hematocrit
Cancers 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
that something “more serious” may be go- Fibromyalgia affects 3.5% of women and
ing on, confirm the diagnosis with appro- 0.5% of men.5 It runs in families with his-
priate testing and physical examination, tories of fibromyalgia and major mood
usually by a rheumatologist or primary and anxiety disorders, suggesting ge-
care physician. netic links.6 Defects in genes controlling
serotonin and norepinephrine have been
CASE CONTINUED implicated.7-9
Central pain sensitization Fibromyalgia patients show lower lev-
As you elicit more details about Ms. D’s mood, els of serotonin, norepinephrine, and do-
she continues to focus on her physical symp- pamine metabolites in cerebrospinal fluid
toms. She states that some days she wishes (CSF), compared with controls.10 These
to die because her pain gets so bad, but she neurotransmitters may inhibit descending
denies any plan or intent to harm herself. She pain pathways in the CNS, and low levels
worries that her symptoms will worsen and in the brain and spinal cord may inhibit
that she will become completely disabled. CNS regulation of pain impulses from the
Her primary physician attempted to relieve periphery.11
Ms. D’s pain with multiple trials of nonsteroidal Although many patients describe mus-
anti-inflammatory drugs (NSAIDs) and cyclo- cle pain, evidence suggests central pain
benzaprine. She says she gained no benefit augmentation rather than an abnormality
from the NSAIDs and discontinued the muscle of muscle or connective tissue.12 Some stud-
Current Psychiatry
relaxant because it made her too sleepy. ies have found evidence of “windup,” in Vol. 8, No. 3 39
continued on page 46
39_CPSY0309 39 2/13/09 10:56:59 AMcontinued from page 39
Box
Managing unrealistic expectations of fibromyalgia patients
BELIEF: ‘A magic pill exists that will resolve BELIEF: ‘You (the psychiatrist) can make
all my symptoms and have no side effects’ me feel better’
Clinical evidence: Most medications that Clinical evidence: Psychiatrists can
have been studied were effective in 30% to help by prescribing appropriate medications,
50% of patients and reduced pain scores by but much of the burden falls on the patient
Fibromyalgia 30% to 50%. to maintain a healthy, active lifestyle and to
Patient education: Explain to the patient manage stressors in an adaptive manner.
with a pain rating of 7 at the first visit that Patient education: A fibromyalgia
achieving a pain level of 3 to 4 may be patient may find relief with a medication, but
possible with treatment. Even with successful symptoms may flare if they ‘overdo’ and take
treatment, symptoms may flare intermittently. on too many physical or emotional stressors.
As with any treatment, adverse effects may A consistent, healthy routine is ideal.
occur. Discuss these, so the patient is not
BELIEF: ‘I will eventually become disabled
surprised.
by fibromyalgia’
Clinical Point BELIEF: ‘I can’t exercise’ Clinical evidence: Despite little long-
Clinical evidence: Most patients term research on fibromyalgia patients, most
Many patients experience more fatigue and pain with evidence points to a chronic, fluctuating
expect to resume an physical activity, but exercise is important to syndrome that does not worsen with age.
maintain physical function. Factors that may worsen symptoms include
energetic, pain-free Patient education: When discussing an uncontrolled comorbid conditions, chronic
life, which usually exercise program, focus on what the patient opiate use, inactivity, and deconditioning.
can do. Most patients attempt too much, too Patient education: Discourage long-term
is not the case soon; advise them to start at a tolerable level physical disability; exercise and maintaining
with fibromyalgia (such as 2 to 3 minutes of aerobic activity an active daily routine helps patients avoid
daily for the first week) and gradually increase focusing in a nonadaptive manner on their
as tolerated. dysfunction and symptoms.
Source: Sharon B. (Shay) Stanford, MD
which second-order neurons in the spinal degree of overlap was seen in brain ar-
cord become sensitized by repeated signals eas responsible for pain processing. This
from first-order neurons in the periphery, indicates that fibromyalgia patients and
resulting in amplified and prolonged pain controls were experiencing the pain they
signals traveling to the brain.13 reported in the same way.15
Levels of substance P—a primary trans-
mitter of pain impulses—are significantly
higher in CSF of fibromyalgia patients Treating the whole patient
compared with controls.14 This finding, As a clinician who specializes in fibromyal-
in addition to low levels of serotonin and gia, I counteract my patients’ and my own
norepinephrine, indicates that pain signals frustration with this condition by structur-
are ascending unchecked to be processed ing office visits, determining realistic treat-
by the brain. ment goals, and treating all symptoms as
Neuroimaging studies confirm this part of a common syndrome rather than
observation. In a study using functional individual illnesses.
magnetic resonance imaging (fMRI), re-
searchers applied pressure to the thumb- Structure office visits. Before every visit,
nails of fibromyalgia patients and controls have patients rate each symptom domain
until each subject reported pain: and write their top 2 or 3 concerns for that
• Twice as much pressure was required day (for a sample form, see this article at
before controls rated their pain at a level CurrentPsychiatry.com). Focusing on the
similar to that of fibromyalgia patients. patient’s most troublesome symptoms can
• When controls and fibromyalgia pa- help both of you feel greater satisfaction
Current Psychiatry
46 March 2009 tients reported similar pain, a very high with treatment.
46_CPSY0309 46 2/17/09 11:21:40 AMEducate patients. Ask them to discuss their
beliefs about fibromyalgia; many know oth-
ers with this condition or have researched di-
agnosis 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 resourc-
es (see Related Resources, page 50).
Set realistic expectations. Many patients ex-
pect to resume an energetic and pain-free life,
which usually is not the case with fibromyalgia
Your search is over!
(Box). Most medications are considered success- DISCOVER CURRENT PSYCHIATRY’S
ful if they reduce pain by 30% to 50%, and side
effects can be problematic. Discuss side effects
before treatment begins to reduce patients’ anxi-
ety and improve compliance in the first weeks.
Ñ PSYCHIATRYFindit.com defined:
Cognitive-behavioral therapy (CBT) for fi- PSYCHIATRYFindit.com is a custom vertical search tool
bromyalgia incorporates relaxation techniques, that allows visitors to perform targeted searches of Web
sites most relevant to psychiatrists and related clinicians.
helping patients view symptoms as manage-
PSYCHIATRYFindit.com covers hundreds of carefully
able, reinforcing adaptive coping skills, and
selected Web sites containing information directly related
teaching them how to monitor thoughts, feel- to psychiatric practice.
ings, and behavior to change the view that
they are helpless victims. A modest course of Ñ PSYCHIATRYFindit.com delivers results from:
6 weekly group CBT sessions significantly im- •Peer-reviewed psychiatric journals
proved physical functioning in 25% of fibro- •Psychiatric professional associations
myalgia patients (n=76) compared with 12% •Government agencies
•Patient advocacy sites
in a standard-care group (n=69), even though
patients’ pain severity did not improve.16 Ñ Benefits to psychiatrists are:
• Targeted and relevant searches
Recommend exercise, lifestyle changes. • Time-saving tool
Aerobic exercise can significantly improve • Trusted source: CURRENT PSYCHIATRY
well-being and physical functioning in fibro- Ñ PSYCHIATRYFindit.com provides 3 convenient
myalgia patients.17 Low-impact aerobics, such search options:
as done in warm water, usually are well tol- • “CURRENT PSYCHIATRY” allows searches of current and
erated, although any low-impact exercise can archived issues.
help. Because fibromyalgia symptoms often • “Psychiatry sites” includes hundreds of the most
increase with physical activity, counsel pa- relevant sites selected by CURRENT PSYCHIATRY’s editors
tients to begin with a few minutes daily and and Editorial Board.
increase very slowly each week. • “PubMed” includes 18 million citations from life science
journals.
Lifestyle changes are as important as medica-
tions in controlling fibromyalgia symptoms. In
Visit us online at www.PSYCHIATRYFindit.com today!
addition to exercise, recommend that patients:
• follow a daily routine
• pace activity to avoid exacerbating
symptoms
• reduce stress. SYCH IATRY CURRENTPSYCHIATRY.com
Sometimes, I use the analogy of diabetes:
treating fibromyalgia with medication but
47_CPSY0309 47 2/17/09 12:04:49 PMTable 4
Off-label medications shown to benefit patients with fibromyalgia
Drug Comment
Amitriptyline27,28 Considered first-line because of studies supporting its use, low cost,
and wide availability; may be associated with more side effects than
newer medications
Fibromyalgia Gabapentin29 Possible alternative to pregabalin but may not be as well tolerated
30
Tramadol May help with breakthrough pain; use with extreme caution in patients
taking antidepressants because of serotonin syndrome risk
Fluoxetine31 Dosages of 40 to 60 mg/d may help patients who do not tolerate SNRIs
32
Venlafaxine Dosages of 150 to 225 mg/d may be an alternative to other SNRIs
SNRIs: serotonin/norepinephrine reuptake inhibitors
without changing lifestyle is like pre- brain and spinal cord. This SNRI was
Clinical Point scribing medication for a diabetic patient first FDA-approved for diabetic periph-
Pregabalin may be without changing diet. Follow up on this eral neuropathic pain and major depres-
“homework” at each visit to reinforce that sive disorder. Approval for fibromyalgia
a beneficial first
patients helping themselves is an impor- at 60 mg/d in June 2008 was based on 2
choice for patients tant part of treatment. placebo-controlled, double-blind, 12-week
who report pain and trials comprising 874 patients.23,24 For de-
sleep as major issues tailed findings of these studies and a 6-
New direction with medications month fixed-dose trial,25 see this article at
Pregabalin is an anticonvulsant that binds CurrentPsychiatry.com.
to the alpha-2-delta subunits of neurons’ In clinical trials, duloxetine dosages of
voltage-gated calcium channels. This ac- 60 mg/d and 120 mg/d were significantly
tivity reduces calcium influx at nerve ter- more effective than placebo. The most com-
minals and inhibits release of excitatory mon side effects were nausea, constipation,
neurotransmitters, such as substance P excessive sweating, and somnolence.23-25
and glutamate.18 In June 2007, pregabalin
was the first medication FDA-approved Milnacipran is an SNRI that was approved
for fibromyalgia. for treating fibromyalgia in January 2009
Two placebo-controlled trials19,20 showed at dosages of 50 mg bid and 100 mg bid.
that pregabalin at 150 mg bid, 225 mg bid, Like other SNRIs, milnacipran is thought
or 300 mg bid significantly reduced weekly to work by inhibiting pain signals through
mean pain scores in fibromyalgia patients. increasing serotonin and norepinephrine
For details of these trials, see this article at in the brain and spinal cord. Milnacipran
CurrentPsychiatry.com. The most common has a higher selectivity for norepineph-
side effects—dizziness, somnolence, pe- rine reuptake compared with duloxetine,
ripheral edema, blurred vision, and weight which may mean these medications will
gain—were regarded as mild to moderate have different effects in different patients.
in 87% of patients.21 Although milnacipran is approved as an
ONLINE
ONLY Although a dosage of 300 mg bid also antidepressant in other countries, the FDA
was studied, the FDA approved pregaba- has not approved it for treating depression
Details of clinical lin at dosages of 150 mg bid and 225 mg in the United States.
trials that supported
bid for fibromyalgia.22 For details of a 15-week, double-blind,
fibromyalgia indications
for 3 CNS medications. placebo-controlled trial of milnacipran in
CurrentPsychiatry.com Duloxetine is a serotonin/norepineph- patients with fibromyalgia, see this article
rine reuptake inhibitor (SNRI) thought at CurrentPsychiatry.com. Side effects in
to inhibit dorsal horn neurons’ response clinical trials were similar to those of du-
to peripheral pain signals by increas- loxetine, with nausea, constipation, and in-
Current Psychiatry
48 March 2009 ing serotonin and norepinephrine in the creased sweating being most prominent.26
48_CPSY0309 48 2/17/09 12:04:57 PMOther medications, such as the first-line CASE CONTINUED
agent amitriptyline, have shown beneficial Not as hopeless
effects in fibromyalgia but are not FDA- Ms. D’s primary care physician confirms your
approved for this indication (Table 4).27-32 presumptive diagnosis of fibromyalgia. He
prescribes a trial of amitriptyline, which she
Choosing medications. When prescribing does not tolerate well because of sedation and
one of the FDA-approved medications to weight gain. At her next psychiatric visit, she
treat fibromyalgia, consider their benefits tells you she remains very frustrated about her
and side effects. physical symptoms and reports that her doc-
Pregabalin may be a beneficial first choice tor “has given up on me.”
for patients who report pain and sleep as You discuss what a fibromyalgia diagnosis
major issues. Although the medication’s means to her and educate her about the syn-
label recommends starting with twice-daily drome. You refer her to a colleague who does
dosing, patients might better tolerate an ini- CBT with chronic pain patients and start her
tial dose of 50 to 75 mg in the evening, with on a low dose of duloxetine (30 mg once daily)
the morning dose added later. Pregabalin to minimize side effects. You discuss possible
can be useful in patients taking multiple side effects and that she may need a higher Clinical Point
medications because of its renal clearance, dose to notice improvement in her pain. She Milnacipran’s more
resulting in low risk of interactions with seems receptive to starting a graded exercise
selective effect on
drugs metabolized by liver enzymes. It also program, and you encourage her to reduce
can be useful in patients who have not toler- physical and emotional stress in her life. norepinephrine
ated antidepressants in the past or in whom When she returns, she reports her pain could be beneficial
antidepressants are contraindicated. is somewhat improved and medication side for patients with
If a patient has a history of depression effects have subsided. She is not as hopeless
excessive fatigue
or discontinuing medications because of and tells you she is up to 10 minutes of walk-
sedating side effects, an antidepressant ing daily. You increase duloxetine to 60 mg/d
such as duloxetine or milnacipran may be and reinforce her ability to exercise and man-
more successful than starting with prega- age her stress.
balin. In general, if a patient does not re-
spond to one of these SNRIs, moving on to References
1. Wolfe F, Smythe HA, Yunus MB, et al. The American College
the other might help. Milnacipran’s more of Rheumatology 1990 criteria for the classification of
fibromyalgia. Report of the Multicenter Criteria Committee.
selective effect on norepinephrine could Arthritis Rheum. 1990;33(2):160-172.
be beneficial for some patients, especially 2. Aaron LA, Buchwald D. Chronic diffuse musculoskeletal pain,
fibromyalgia and co-morbid unexplained clinical conditions.
those with excessive fatigue. Others, es- Best Prac Res Clin Rheumatol. 2003;17(4):563-574.
pecially those with a high level of anxiety, 3. Arnold LM, Hudson JI, Keck PE, et al. Comorbidity of
fibromyalgia and psychiatric disorders. J Clin Psychiatry.
might respond better to a more balanced 2006;67(8):1219-1225.
SNRI such as duloxetine. 4. Pope HG Jr, Hudson JI. A supplemental interview for forms
Bottom Line
Consider fibromyalgia in patients with pain, depression, sleep problems, fatigue,
and cognitive dysfunction beyond what is expected for a primary mood disorder.
Two antidepressants and an anticonvulsant that target the CNS are FDA-approved
for fibromyalgia, although other medications may help. Encourage patients to share
in symptom management by exercising and making lifestyle changes. Cognitive/
Current Psychiatry
behavioral techniques can help patients manage frustration and hopelessness. Vol. 8, No. 3 49
49_CPSY0309 49 2/17/09 12:05:02 PMof “affective spectrum disorder.” Int J Psychiatry Med. 1991;
21(3):205-232.
5. Wolfe F, Ross K, Anderson J, et al. The prevalence and
Related Resources
characteristics of fibromyalgia in the general population. • Arthritis Foundation. Fibromyalgia. www.arthritis.org/
Arthritis Rheum. 1995;38(1):19-28. disease-center.php?disease_id=10.
6. Arnold LM, Hudson JI, Hess EV, et al. Family study of
• National Fibromyalgia Association. www.fmaware.org.
fibromyalgia. Arthritis Rheum. 2004;50(3):944-952.
7. Bondy B, Spaeth M, Offenbaecher M, et al. The T102C • Self-management program for patients with fibromyalgia,
polymorphism of the 5-HT2A-receptor gene in fibromyalgia. cosponsored by the National Fibromyalgia Association and
Neurobiol Dis. 1999;6(5):433-439. Eli Lilly and Company. www.knowfibro.com.
8. Offenbaecher M, Bondy B, de Jonge S, et al. Possible asso-
Fibromyalgia ciation of fibromyalgia with a polymorphism in the serotonin
Drug Brand Names
transporter gene regulatory region. Arthritis Rheum. 1999; Amitriptyline • Elavil, Endep Milnacipran • Savella
42(11):2482-2488. Cyclobenzaprine • Flexeril Pregabalin • Lyrica
9. Gürsoy S, Erdal E, Herken H, et al. Significance of catechol- Duloxetine • Cymbalta Tramadol • Ultram, Ultracet
O-methyltransferase gene polymorphism in fibromyalgia Fluoxetine • Prozac Venlafaxine • Effexor, Effexor
syndrome. Rheumatol Int. 2003;23(3):104-107. Gabapentin • Neurontin XR
10. Russell IJ, Vaeroy H, Javors M, et al. Cerebrospinal fluid
biogenic amine metabolites in fibromyalgia/fibrositis Disclosure
syndrome and rheumatoid arthritis. Arthritis Rheum. Dr. Stanford receives grant/research support from Eli Lilly and
1992;35(5):550-556. Company, Pfizer Inc., Cypress Bioscience, and Allergan.
11. Fields HL, Basbaum AI. In: Wall PD, Melzack R, eds. Textbook
of pain. 4th ed. New York, NY: Churchill Livingstone; 1999:
309-329.
Clinical Point 12. Clauw DJ, Crofford LJ. Chronic widespread pain and
two randomized, placebo-controlled clinical trials. J Womens
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Health (Larchmt). 2007;16(8):1145-1156.
Other patients may Pract Res Clin Rheumatol. 2003;17(4):685-701.
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13. Staud R, Cannon RC, Mauderli AP, et al. Temporal summation
respond better to a of pain from mechanical stimulation of muscle tissue in
multicenter trial comparing duloxetine with placebo in the
treatment of fibromyalgia patients with or without major
normal controls and subjects with fibromyalgia syndrome.
more balanced SNRI Pain. 2003;102(1-2):87-95.
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18. Field MJ, Cox, PJ, Stott E. Identification of the alpha2-delta-1 randomized, double-blind, placebo-controlled study
subunit of voltage-dependent calcium channels as a molecular of moclobemide and amitriptyline in the treatment of
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gabalin in patients with fibromyalgia. J Pain. 2008;9(9):792- blind, placebo-controlled, multicenter trial. Arthritis Rheum.
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the treatment of patients with fibromyalgia. J Rheumatol. and after treatment with tramadol/acetaminophen. Arthritis
2008;35(3):502-514. Rheum. 2005;53:519-527.
21. Crofford LJ, Mease J, Simpson SL, et al. Fibromyalgia relapse 31. Arnold LM, Hess EV, Hudson JI, et al. Randomized, placebo-
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Current Psychiatry
50 March 2009
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