Clinical Contributions
A
Review of Advances in Treating Fibromyalgia Syndrome (FMS) Using a Multidisciplinary
Approach. | to
pdf >>
By Elizabeth Oyekan, PharmD,
FCSHP; Jimmie S. Kung, MD, PhD, FABPM
Fibromyalgia syndrome (FMS) is a chronic, nonmalignant condition that
affects three to six million people in the US. The etiology of FMS is
unknown, although many theories have attempted to explain this syndrome.
Because of the complexity of fibromyalgia, a trend is developing toward
use of a multidisciplinary treatment approach, especially in patients
for whom FMS has substantially diminished the quality of life. To maximize
its effectiveness, the treatment plan would assign for each patient
the degree of multidisciplinary involvement appropriate for that patient's
symptoms. Categorizing patients and using a stepwise approach to treating
FMS provides high-quality treatment that is efficient as well as cost-effective.
The most effective treatment for FMS includes a combination of patient
education, medication, regular exercise, physical modalities, stress
reduction, and acquisition of coping skills; patients respond less well
to use of a single treatment modality alone. Patient education should
help patients understand that the goal of therapy for FMS is not necessarily
to completely eliminate pain but to decrease intensity of the pain and
to improve physical function. The choice of therapeutic agents used
in treatment of FMS is guided by the symptoms the patient is experiencing,
past medication history, and the profile of action of the individual
medication. A review of these different treatment modalities and their
importance in the treatment of FMS are discussed.
Introduction
Fibromyalgia syndrome (FMS; also known as fibrositis) is a nonarticular
rheumatic disease that affects three to six million people in the US.1
The etiology of FMS is unknown, although many associations and theories
have been suggested to explain this syndrome.1,2 Such theories
have included disturbance of rapid eye movement (REM) sleep, change
in immune system function, interplay of mechanical stresses in the cervical
and lumbar spine, viral infection, psychological disorders, abnormality
in neurotransmitter function, and metabolic muscle defects. However,
none of these theories explain the diverse symptoms seen in FMS.2-4
FMS is seen most commonly in women between the ages of 25 years to
50 years, and incidence of FMS is highest among family members of affected
people; however, no genetic patterns have been identified.5
FMS is usually primary and occurs in the absence of other medical conditions,
but secondary FMS occurs in some patients. These patients have other
medical disorders (usually hypothyroidism and rheumatoid arthritis)
in conjunction with fibromyalgia.6 Primary fibromyalgia causes
chronic pain and fatigue that can persist for years if left untreated
but which by itself is not degenerative or deforming and is seldom associated
with mortality. Fibromyalgia must be recognized because it accounts
for 20% to 30% of all referrals to rheumatologists, consumes a large
amount of resources, and can cause painful symptoms that lead to substantial
disability.6,7 When extensive diagnostic tests fail to identify
a visible source for the reported pain, practitioners may think patients
have a psychological problem and may refer them to a clinical specialist
or to a behavioral medicine specialist.1 Because they have
constant pain and little relief for extended periods of time, patients
with FMS tend to "shop" from practitioner to practitioner--a
practice that extensively consumes expensive health care resources while
often achieving poor outcomes and inadequate solutions for pain.6
By the time patients are diagnosed correctly, they may have already
seen several specialists and may be taking medications inappropriate
for their condition. Other patients are led to believe that they are
drug addicts looking for a way to legitimize their habits. These circumstances
and conditions are demoralizing to patients and can cause them to feel
angry, frustrated, and depressed.
FMS continues to be undertreated and unrecognized by many health care
professionals because of its complex and diffuse nature. This situation
produces substantial disability for patients and increases costs to
the health care system.
Pathophysiology and Etiology of FMS
FMS is characterized by widespread musculoskeletal pain and tenderness
at 11 or more of 18 specific tender points at characteristic locations
(Fig. 1) according to criteria published
by the American College of Rheumatology.2 According to these
criteria, at least 11 of these 18 tender points (located primarily at
the junctions) become extremely painful when a force of approximately
4 kg/cm2 (ie, moderate pressure) is applied to them.1,2
The tenderness is focal (ie, not diffuse) and is present on both sides
of the body (paired), above and below the waist, and at the midline.1
Although pain is the predominant symptom, most patients have additional
symptoms: irritable bowel syndrome, general weakness and fatigue, chronic
headache, sleep disturbance, nocturnal myoclonus, numbness and tingling,
morning stiffness, generalized muscloskeletal pain not accompanied by
tissue inflammation, female urethral syndrome, abnormal function of
neurotransmitters (serotonin and norepinephrine), depression, and Raynaud's
phenomenon. FMS is further aggravated by fatigue, tension, excessive
work, immobilization, and change in weather.2,6,8
Diagnosis of FMS
Like low back pain, FMS is a clinical syndrome that cannot be explained
using current theories of pathophysiology.1 FMS is not definitively
diagnosed by any laboratory test or characterized by any typical x-ray
abnormality, and laboratory tests (erythrocyte sedimentation rate, complete
blood count, and thyroid function tests) administered to patients with
primary FMS usually give normal results; physical examination and laboratory
tests should therefore be used to rule out conditions that may mimic
FMS--conditions such as lupus erythematosus, rheumatoid arthritis, hypothyroidism,
and infection.6 Any abnormal results of the above-mentioned
tests warrant further search for an underlying disorder other than FMS.6
Physical examination is done also to confirm the presumptive diagnosis
of FMS by locating the tender points.
FMS should be considered in any patient with some or all of the signs
or symptoms listed in Table 1.1,2,9
Clinicians who suspect FMS on the basis of symptoms listed in Table
1 should begin treatment as soon as possible and should not take
too much time to diagnose FMS in a patient that exhibits classic symptoms:
doing so may lead to unnecessary use of health care resources.1,6
Principles of Treatment
FMS has no known cure. However, the condition can be managed successfully
if relevant biological, psychological, and social factors are addressed.1,6
FMS is a chronic condition whose mean duration of symptoms before diagnosis
is approximately five years.7
On average, patients with FMS visit outpatient health care facilities
13 times annually.10 At these visits, patients have countless
laboratory tests done, see several health care practitioners, and receive
numerous prescription medications that provide minimal benefit.
The multiple components and complexity of fibromyalgia have led to
a growing trend toward use of a multidisciplinary approach.4
Such an approach may be a cost-effective way to treat fibromyalgia,
especially in highly dysfunctional patients, because almost all issues
affecting patients with FMS can be addressed decisively by experts in
various disciplines, leading to better outcomes. The multidisciplinary
team caring for patients with FMS usually consists of practitioners
from internal medicine, anesthesiology, behavioral medicine, nursing,
physical medicine, and pharmacy.
Goals of therapy should include patient education and involvement in
the treatment plans, decreased pain intensity, increased physical activity,
decreased reliance on narcotic pain medications, use of the most appropriate
and least amount of medication to treat the pain, improved psychosocial
functioning, return to work if possible, and reduced utilization of
health care services. To achieve these goals, treatment plans must include
all the following components to varying degrees: patient education,
medication therapy, regular exercise, and physical, behavioral, and
psychological modalities (stress reduction and coping skills). This
multifaceted approach is necessary because studies have shown that patients
respond little to any treatment modality given by itself.4,6,11
The degree of multidisciplinary involvement required by an effective
treatment plan depends on each patient's symptoms. Categorizing patients
with FMS and using a stepwise approach to its treatment may provide
high-quality treatment that is efficient as well as cost-effective (Fig.
2). Patients can be categorized into three groups on the basis of
type of symptoms and degree of functional impairment.12
Group 1 Patients
Patients in this group have had FMS for less than two years and function
almost normally: they experience only low levels of fatigue or sleep
disturbance and little interference with activities of daily living,
work performance, or interpersonal relationships.12 If these
patients cannot be adequately treated by their primary care physician,
referral to the multidisciplinary program may be necessary for thorough
evaluation and for development of a treatment plan that incorporates
education, self-help strategies, unsupervised cardiovascular fitness,
sleep health, psychotherapeutic intervention, and minimal medication
use. After recommendations are made, the patient returns to the primary
care physician for further follow-up. The multidisciplinary team continues
to act as an effective bridge between the primary care physician and
the patient to maximize the effectiveness of subsequent clinician-patient
interactions.4
Group 2 Patients
Patients in this group experience moderate interference with normal
everyday functions: they have more pain and fatigue and more disruption
of functioning than patients in Group 1.12 Patients in group
2 have decreased work performance (absenteeism) and increased stress
with interpersonal relationships.12 For these patients, a
multidisciplinary program provides a comprehensive treatment plan that
incorporates education, a supervised cardiovascular fitness regimen,
promotion of sleep health, psychotherapeutic intervention, and a more
comprehensive medication regimen.12 Patients who show signs
of depression should be treated with full doses of the newer, selective
serotonin reuptake inhibitors (eg, fluoxetine).12 Analgesic
agents and trigger-point injections may also be beneficial for these
patients and should be used to treat pain not controlled by tricyclic
antidepressant agents used alone.12
Group 3 Patients
Patients in this group have the highest level of dysfunction, manifested
as disintegration of family life, drastically reduced job performance,
and substantial overall disruption to daily life.12 These
patients mustbe enrolled for an extended period of time in a multidisciplinary
pain management program that incorporates intensive patient education,
medication therapy, a regular exercise program, physical modalities,
stress reduction skills, and coping skills.12 To improve
continuity and long-term outcome treatment, primary care physicians
must remain involved during the multidisciplinary process.11
Structure of the Pain Management Program for Patients
with FMS at Kaiser Permanente Medical Center, Los Angeles
The Chronic Pain Management Program (CPMP) at Kaiser Permanente Medical
Center, Los Angeles is a multidisciplinary service whose core members
are the pain management coordinator, interventional anesthesiologist,
physical therapist, physiatrist, psychologist, pharmacy specialist,
clinical pain specialist, and administrative liaison (Fig.
3). The purpose of the CPMP is to serve as a consultative source
for treating patients who have unresolved or difficult pain and to provide
comprehensive care and service to patients with chronically painful
medical conditions such as fibromyalgia.
The Triage Process
Patients are referred to the CPMP by their primary care physician, other
health care practitioner, or both. Referred patients are triaged by
the pain management coordinator. Patients' charts are then ordered and
reviewed by several members of the CPMP team to obtain and confirm medical
diagnoses, past and current pharmacological and nonpharmacological therapies
received, and other important pertinent information. The team then determines
whether the patient should be further evaluated by the team or referred
back to their health care practitioner. Patients who are to be evaluated
by the CPMP team are so notified by the administrative assistant, an
appointment is made, and a comprehensive questionnaire is mailed to
the patient.
Evaluation of Patients and Referral to Other Departments
The CPMP team's evaluation is extensive and comprehensive: the physician
examines the patient and asks pertinent medical questions, the psychologist
asks questions designed to evaluate the psychological status of the
patient, the physical therapist obtains information on past physical
therapy treatment, and the pharmacist reviews all past drug therapy
(especially as administered for pain), duration of past therapy, reasons
for discontinuing past therapy, allergy profile, and current therapy.
Laboratory test results and other pertinent information are also reviewed.
After this comprehensive evaluation, patients are either admitted to
the eight-week CPMP or are triaged to other services or disciplines
as recommended by the team. Patients not admitted to the eight-week
CPMP are given a detailed treatment plan and are referred to one or
more of the following:
- Their health care practitioner, who is given specific treatment
recommendations from the CPMP team;
- The anesthesiology department for procedures, shots, epidural injections,
and highly technical interventional techniques;
- The physiatrist for individualized treatment which may include trigger-point
injections and other modalities;
- The physical therapist for individualized treatment which is monitored
by the CPMP physician, the patient's health care practitioner, or
both;
- The psychologist for complete psychological examination as well
as instruction on coping skills and biofeedback techniques--all monitored
by the CPMP physician, the patient's health care provider, or both;
- The pharmacist for monitoring and adjusting each patient's drug
therapy as needed (in consultation with the CPMP physician) and for
reinforcing the importance of compliance with the medication regimen.
Comprehensive Eight-Week Program for Patients with Chronic Pain
and FMS
At the first session, a physician, physical therapist, psychologist,
and pharmacist each discuss the goals of the CPMP and the responsibilities
of each specialty during the eight weeks of the program. The physician
evaluates each patient, educates patients about their disease, and provides
the following modalities as needed: trigger-point injections, "spray
and stretch" (the skin is sprayed with a local anesthetic and the
muscles in that area stretched), joint mobilization and manipulation,
peripheral nerve blocks, epidural nerve blocks, and medication for sympathetic
blocks. The physical therapist uses gentle muscle rehabilitation, education,
muscle stretching, progressive training, and endurance training to help
patients resume normal or nearly normal activity. The psychologist uses
cognitive behavioral therapy (CBT) as well as relaxation training to
help patients cope with pain and to assist patients in developing an
active, resourceful, self-management approach to coping with FMS. The
pharmacist assesses each patient's drug therapy weekly and makes any
needed dosage adjustment and titration (in consultation with the CPMP
physician). For patients whose therapy proves ineffective after an adequate
trial, alternative treatment plans are developed. The pharmacist also
educates and reinforces the importance of adherence to medication regimens,
works with patients to prevent adverse drug effects and potential drug
interactions, and expedites all refill prescriptions for CPMP patients
during and after the eight-week CPMP. The pain management coordinator
coordinates patients' overall care with practitioners in designated
departments (referring, primary care, or both) across the continuum,
conducts follow-up telephone calls on care efficacy, ensures appropriate
patient management, and manages quality assurance activities. The administrative
assistant provides support to the coordinator and to other members of
the multidisciplinary team.
After patients have successfully completed the eight-week program,
the CPMP team gives each patient an individual discharge plan that contains
a set of instructions to help the patient follow recommendations of
the team. Patients are requested to bring this plan with them to their
next physician visit. A copy of the discharge plan is also sent to the
patient's health care practitioner for inclusion in the patient's medical
record.
Nonpharmacologic Therapy
Patient Education
Patient education about FMS is vital because patients need to know that
their symptoms are not "all in their head" but that distinct
recognizable symptoms distinguish FMS from other medical conditions.6
Patients also need reassurance that although a painful and sometimes
debilitating syndrome, FMS does not permanently damage tissues or muscle
and can be managed successfully. Emphasizing this point is particularly
important because some patients have been led to believe that they might
have more serious conditions, eg lupus erythematosus or multiple sclerosis.7
Patients also must be helped to understand that the goal of therapy
in treating FMS is not to completely eliminate pain but to decrease
the intensity of the pain and to improve coping skills. Patients should
understand that current therapy used to treat FMS is palliative and
not curative.
Sleep Health
Nonrestorative sleep--deep sleep that is interrupted, leaving a patient
tired and feeling worse the next day--is prevalent in FMS patients.
Abstaining from caffeine-containing products such as caffeinated coffee,
tea, sodas, and sports drinks, is therefore important. Daytime naps
and short naps at the end of the workday should also be avoided because
they may interfere with nighttime sleep.12 Patients should
be encouraged to create a soothing atmosphere in the bedroom by not
watching television, paying bills, settling family disputes, or trying
to overcome stressful situations there. These practical considerations
may effectively restore a modicum of normal sleep and should be considered
before resorting to enrollment
in expensive sleep studies.12
Physical Therapy and Cardiovascular Training
Some patients with FMS suffer from motor dysfunction caused by chronic
muscle misuse (as occurs in inactivity, abnormal postural stress, or
overuse) that must be corrected if patients are to resume normal activity.13
Gentle muscle rehabilitation should be used to treat this dysfunction.4,7
The long-term goal of physical therapy must incorporate muscle stretching,
progressive training, and endurance training. Symptoms of FMS can be
further relieved by incorporating exercise into the lifestyles of patients
with FMS. Aerobic exercise is particularly beneficial because it decreases
pain perception, increases duration of deep sleep, and affects symptoms
of FMS by activating beta-endorphins.7,14,15 Studies have
also shown that cardiovascular training and flexibility exercises can
substantially raise a patient's pain threshold as measured at FMS tender
points; increase level of physical activity; and improve psychological
well-being.7,14,15
FMS patients need a home-based program of muscle stretching, gentle
strengthening, active range-of-motion exercises, and aerobic conditioning.4,13
Regular exercise should become a part of lifestyle and not merely
a temporary solution. Patients are advised to begin any exercise program
slowly so that an overambitious start does not cause injury and frustration
and lead patients to abandon the exercise program entirely.4 Moreover,
incremental improvement in exercise capacity and stretching provides
positive physiological feedback. Application of hot packs combined with
high-frequency, high-intensity transcutaneous electric nerve stimulation
(TENS) and deep massage are sometimes helpful when used in combination
with an exercise program.
Behavioral and Psychological Therapy
Cognitive behavioral therapy and relaxation training are forms of behavioral
and psychological therapy that can help patients cope with some of their
FMS symptoms.
Cognitive Behavioral Therapy (CBT)
Most patients with FMS experience psychological distress as a consequence
of chronic pain.4 Most commonly, these patients experience
dysthymia, depression, anxiety disorders, and maladaptive pain behavior.
Cognitive behavioral therapy for chronic pain has proved beneficial
in managing patients' pain, stress, anxiety, depression, and anger.12
The goal of CBT is to help patients to develop an active, resourceful,
self-management approach to coping with their FMS.12 Cognitive
therapy in FMS patients has led to improved functional ability such
as spending time out of bed and increasing activity level.16
A sense of control and mastery over life circumstances are also enhanced.17,18
Cognitive behavioral therapy is most beneficial when used in conjunction
with aerobic exercise, physiotherapy, biofeedback training, and relaxation
therapy.10
Relaxation Training
A relaxation training program uses biofeedback-assisted relaxation training,
autogenesis, progressive muscle relaxation, imagery, breathing exercises,
distraction, and self-hypnosis techniques to help patients to reduce
the overall level of stress in their lives. Relaxation techniques have
also been effective in decreasing pain levels.12
Support Groups
Support groups are an important resource for patients with FMS. During
the past five years, support groups and seminars on FMS around the country
have been formed to offer information to educate patients about FMS.8
A list of support groups is given in Table 2.
Pharmacologic Therapy
Drug regimens should be individually tailored to each patient's needs
after an extensive drug history has been obtained. This history includes
all over-the-counter and prescription medications the patient has used
for pain, dosages, directions for use, and duration of therapy. This
information is important, because most patients who complain about treatment
failure have received the wrong therapy, subtherapeutic doses of medication,
or have not received therapy long enough for the medication to be effective.15
Medications used to treat FMS are listed in Table
3.
Antidepressants and Sleep Therapy
Studies have shown that tricyclic antidepressant drugs and trazodone
are beneficial in the treatment of FMS.3,6,9,15,19,20 These
drugs promote deep sleep by blocking reuptake of serotonin, a neurotransmitter
which has been shown to be important in stage 4 deep sleep15
and which has been implicated in the pathogenesis of FMS.3
Patients with fibromyalgia have shown increased serotonin receptor density
on their circulating platelets as well as lower serum levels of serotonin
than found in the general population.21 In addition to improving
a patient's overall mood, TCAs and trazodone also have analgesic effects22
and may reduce the symptoms of irritable bowel syndrome12
because of anticholinergic side effects that lead to decreased intestinal
motility. These effects address symptoms reported by FMS patients.
Improved sleep is particularly important for patients with FMS because
when these patients increase the amount of deep sleep they get, other
symptoms improve substantially. Tricyclic antidepressant drugs and trazodone
seem to relieve muscle pain and spasms by altering pain perception in
the brain. These drugs increase both the intensity of effect as well
as the duration of activity of other analgesic medications when taken
concurrently with these medications and may be used to reduce the need
for narcotic pain medications.
Tricyclic antidepressant drugs and trazodone are usually first-line
therapy for treatment of FMS. A trial of tricyclic antidepressant therapy
should be considered for all patients with FMS unless this approach
is contraindicated (eg, by major cardiac arrhythmia, prostatic hypertrophy,
or narrow-angle glaucoma).23 Initially, patients should be
given the lowest possible dose (Table 3)
at bedtime; this dose should be increased incrementally every few days
until the patient obtains maximum relief without experiencing unacceptable
side effects.
Choice of Medication
Appropriate choice of antidepressant drugs depends on the patient's
medical history and clinical symptoms as well as the side effect profile
of the medication. Amitriptyline has been most widely studied and used
for treatment of FMS; however, because of its long half-life and its
tendency to cause sedation, orthostatic hypotension, and anticholinergic
side effects (eg, dry mouth, urinary retention), amytriptyline should
be avoided by elderly patients and by patients who do not have major
sleep disorders. Amitriptyline also causes the most weight gain of all
the tricyclic antidepressant drugs, and this effect can be a source
of noncompliance--especially in patients who are concerned about weight
gain.6 A trial of secondary-amine tricyclic antidepressant
drugs (desipramine and nortryptyline) should be given to patients who
are unable to tolerate the anticholinergic or hypotensive effects of
tertiary-amine tricyclic antidepressant drugs (amitriptyline, doxepin,
imipramine) or who are predisposed to toxicity from these agents. Secondary-amine
tricyclic antidepressant drugs have fewer anticholinergic side effects,
less potential for causing weight gain, and shorter half-lives than
other tricyclic antidepressant drugs.
Doxepin has been effective in patients with coexistent psychogenic
headache. Trazodone, an antidepressant drug that is structurally different
from tricyclic antidepressant drugs, effectively treats FMS when anxiety
is a major component of this syndrome. Trazodone also has few anticholinergic
side effects, a feature which can be beneficial.22
Dosing Recommendations
Except for trazodone and doxepin (which may be given in initial doses
of 25 mg), use of tricyclic antidepressant drugs for treatment of FMS
should begin with 10-mg doses. Doses of tricyclic antidepressant drugs
and trazodone should be increased gradually after a few days in increments
of 10 mg to 25 mg as tolerated, to the maximum doses shown in Table
3. Improvement in symptoms may be observed after about two weeks.3,22
Patients who cannot tolerate the side effects of one tricyclic antidepressant
drug or who obtain no relief from a maximum dose should be considered
for a trial of a different tricyclic depressant drug with or without
additional medications such as skeletal muscle relaxants, analgesic
drugs, and sedatives. Alternatively, these medications may be appropriately
given without tricyclic antidepressant drugs. Clinical experience suggests
that lack of response to one tricyclic antidepressant drug does not
necessarily indicate likelihood of a poor result with another.1
Patients with FMS may require trials of several medications in combination
before finding what will work well,4,15,20,24 and drug dosages
used to treat FMS must be tapered or titrated carefully over time to
achieve optimal outcome with minimal side effects.
In general, tricyclic antidepressant drugs and trazodone cause varying
degrees of drowsiness, lightheadedness, impairment of memory or concentration,
headache, dry mouth, blurred vision, constipation, urinary retention,
and seizure.
Other Considerations
Even when taken correctly, tricyclic antidepressants and trazodone are
effective only in about 25% to 45% of patients3 and therefore
are generally not used alone in treating FMS; other medications (eg,
muscle relaxants, analgesic drugs, and sedatives) are used concomitantly.
Moreover, physical, cognitive, and behavioral therapy must accompany
medication therapy to increase physical activity and to address the
negative thoughts and depression that may increase suffering and anxiety.12
Selective Serotonin Reuptake Inhibitors
Selective serotonin reuptake inhibitors (SSRIs) have been used to treat
the depression associated with FMS when tricyclic antidepressant therapy
has not been effective. However, SSRIs have been no more effective than
placebo in reducing the pain associated with FMS.6 Concomitant
use of fluoxetine in the morning and tricyclic antidepressant drugs
at bedtime has been beneficial because fluoxetine counteracts some of
the side effects of tricyclic antidepressant drugs, particularly weight
gain and daytime drowsiness.10,22,25 This counteractive effect
may help improve compliance for patients who would discontinue use of
tricyclic antidepressant drugs because of weight gain and other side
effects. Possible side effects of fluoxetine include insomnia, drowsiness,
headache, and nausea.
Skeletal Muscle Relaxants
When FMS is not well controlled by using tricyclic antidepressant or
trazodone therapy, causing patients to have substantial morning stiffness,
addition of a skeletal muscle relaxant to the regimen may be beneficial.
Skeletal muscle relaxants effectively treat the discomfort which accompanies
localized skeletal muscle spasm.1,3,6 Because these drugs
can help improve range of movement, they can be especially beneficial
for patients who are just starting physical therapy and an exercise
program.3 Cyclobenzaprine and carisoprodol are the muscle
relaxants most often used for this purpose. Cyclobenzaprine is also
the skeletal muscle relaxant preferred for pregnant women.23
Possible side effects include drowsiness, dizziness, and dry mouth.
Benzodiazepines
Alprazolam and clonazepam have been used to obtain short-term relief
of anxiety symptoms, nocturnal myoclonus, and sleep disorders associated
with FMS.3,26 Concomitant use with tricyclic antidepressant
drugs produces an additive sedation effect that is beneficial for patients
with insomnia. Alprazolam and clonazepam are used also to relieve skeletal
muscle spasticity and to treat the anxiety associated with FMS. Clonazepam
is especially useful because it also has anticonvulsant properties that
may counteract the seizure-producing potential of tricyclic antidepressant
drugs when used with these drugs. However, benzodiazepines should only
be used occasionally due to the high potential for addiction. Possible
side effects include drowsiness, fatigue, lightheadedness, and impairment
memory or concentration.
Nonnarcotic Analgesic Drugs
Because an important symptom of FMS is widespread pain, analgesic drugs
may be needed in addition to tricyclic antidepressant drugs.27
Acetaminophen
Acetaminophen is most helpful when taken regularly throughout the day
and night instead of being taken on an as-needed basis. By pairing two
stimuli (administration of medication with resultant momentary reduction
in pain) the nervous system may become conditioned to ongoing pain.12
Tramadol
Tramadol has been effective for treating musculoskeletal pain in patients
with FMS. In one series, tramadol produced a 60% to 70% decline from
the original pain level after about three to four weeks of use.27
Patients also obtained relief from morning stiffness, cold extremities,
and trembling hands.27 Use of tramadol concomitantly with
tricyclic antidepressant drugs requires caution because an additive
seizure effect may occur. Side effects of tramadol include dizziness,
nausea, constipation, and headache.
Narcotic Analgesics
In general, narcotic analgesics should be avoided if possible because
they interfere with deep sleep, leaving patients tired and feeling worse
the next day.1,6 Research has not shown that these medications
are effective on a long-term basis. However, most patients with FMS
who take these medications do so after receiving progressively stronger
medications whose inadequate analgesic effects eventually led to prescription
of narcotic agents. If patients who are correctly diagnosed with FMS
are helped by these medications to manage the pain, then the goal should
be to adjust the medication so that patients receive the lowest effective
dose. If patients do not obtain pain relief while using narcotic medications,
then these should be gradually tapered off and substituted with a combination
of tricyclic antidepressant drugs and skeletal muscle relaxants. Because
they induce a high incidence of dependency, narcotics should be used
only as a last resort. Possible side effects of narcotic drugs include
drowsiness, lightheadedness, nausea, vomiting, and constipation.
Steroidal And Nonsteroidal Anti-Inflammatory Medications
The analgesic effect of anti-inflammatory drugs has been well established
for pain associated with inflammation; however, inflammation is not
evident in FMS.2 Some studies show that combining nonsteroidal
anti-inflammatory drugs (NSAIDs) with tricyclic antidepressant drugs
may provide some relief.28,29 However, use of these anti-inflammatory
medications alone has yielded disappointing results in clinical trials.14,28,
In particular, prednisone, ibuprofen, and naproxen have been found
no more effective than placebo.1,10,28,30,31
Miscellaneous Adjunctive Medications
Zolpidem
This nonbenzodiazepine hypnotic agent has been reported to improve subjective
sleep and can be used instead of benzodiazepines because it has minimal
addictive potential.32 Patients treated with zolpidem required
substantially less time to fall asleep, slept longer, awakened less
frequently, had overall improved quality of sleep, and had more daytime
energy, although use of zolpidem did not affect pain associated with
FMS.33,34
Gabapentin
Gabapentin is an antiepileptic agent that has recently been used in
pain management. Although studies of gabapentin use are small and often
not well reported, gabapentin is being used at the Kaiser Permanente
CPMP to treat patients with FMS only after other proven therapies have
failed to produce the desired outcomes. Depending on the patient's tolerance
to its side effects, the medication is titrated to an effective dose
of about 1800 mg/day over a few days. The standard titrating dose used
is 300 mg on day 1, 300 mg twice per day on day 2, 300 mg three times
per day on day 3, and then is increased as appropriate to 1800 mg per
day unless adverse effects preclude doing so. The side effects of gabapentin
include fatigue, weight gain, indigestion, drowsiness, dizziness, ataxia,
and tremor; therefore, to limit side effects, the first dose should
be administered at bedtime. Patients should be informed that fatigue
and sedation may last as long as two weeks before these side effects
resolve.
Trigger-Point Injections
Occasional trigger-point injections are helpful when a few trigger points
are present and the muscle cannot stretch because of excessive pain.34
Local anesthetic agents such as bupivacaine, lidocaine, etidocaine,
or a combination of these can be injected into a trigger-point site,
providing better and longer-lasting pain relief for as long as seven
days after injection.34 Sometimes corticosteroids such as
dexamethasone and betamethasone may be combined with a local anesthetic
agent to help relieve pain. Patients should be informed that corticosteroids
may cause a temporary burning sensation at the injection site within
24 to 48 hours after injection but that the subsequent pain relief lasts
as long as 10 days.35 Trigger-point injections are most effectively
used in conjunction with a comprehensive treatment program that includes
stretching exercises, aerobic exercise, behavioral therapy or cognitive
retraining, and medication.
Other Considerations of Pharmacologic Care
In addition to management of the biological, psychological, and social
factors associated with FMS, patient education and adherence to prescribed
therapy are essential to the overall healing process, whose length depends
on the severity of the condition. Patients' adherence to their medication
regimen must be monitored because nearly 50% of all patients who receive
medications for chronic conditions do not comply with their prescribed
drug regimen.36 To increase compliance with medication regimens
and to prevent discontinuation of treatment at the first occurrence
of a side effect, patients should be informed that some tolerance develops
to these side effects.23 Patients on antidepressant therapies
must also be informed that beneficial effects of therapy may require
as long as two weeks to appear.7 The most common reasons
for nonadherence to therapy used to treat FMS include inadequate patient
education, side effects, drug interactions, social stigma associated
with the therapy, presumed ineffectiveness of therapy, and high cost.
Outcome Measurement
The optimal outcome of therapy for FMS can be measured by decreased
pain relief, use of the most appropriate and least amount of medication
needed to treat the pain, improved function, and reduced need for further
health care services. Decrease in pain can be evaluated using the Fibromyalgia
Impact Questionnaire, a visual analog pain scale, and a physician-conducted
examination of tender points.12 Improvement in function can
be documented by measuring any increase in physical activity, improvement
in patient's overall quality of sleep, improvement in psychosocial functioning,
and ability to return to work.12 Adherence to a therapeutic
regimen can be most effectively monitored by reviewing the patient's
complete medication profile and prescription refill history. This monitoring
is most accurate for patients who fill their prescriptions at a single
location or at a pharmacy linked by computer to a network of pharmacies.
Conclusion
FMS is a complex, chronic, painful condition that can be characterized
by a variety of nonspecific symptoms including palpable tender points;
chronic, poorly defined, diffuse musculoskeletal pain; morning stiffness;
fatigue, weakness; and sleep disturbance.4 Although no laboratory
test results or radiographically visible abnormalities are definitively
diagnostic of FMS, distinctly recognizable symptoms do distinguish FMS
from other medical conditions. Because the cause of FMS is as yet largely
unknown, patients and practitioners must understand that current treatment
is more palliative than curative and focuses on improving function,
not abolishing the pain.4 A multi-disciplinary team approach
to treatment of FMS is the most effective way to address its complex
nature and different components. The most effective treatments include
a combination of patient education, medication therapy, regular exercise,
physical modalities, stress reduction, and coping skills (Table
4), because studies4,6,12 have shown that patients do
not respond as well to any one treatment modality administered alone.
Choice of therapeutic agents used for treating FMS should be guided
by each patient's FMS symptoms and by each drug's profile of action
(ie, sedative drugs should be used for patients with insomnia).10
To improve continuity and long-term outcome of treatment, primary health
care providers should remain involved in the patient's treatment,4,12
and the multidisciplinary team should act as a bridge between
primary care practitioners and patients to maximize the effectiveness
of clinician-patient interactions.4
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