FIBROMYALGIA
MARILYN LAJOIE, MD, DC, CCSP
Dr. Lajoie is a medical doctor, specializing in Internal Medicine, and a Chiropractic Physician. She has 40 years of experience as a Chiropractor and over 20 years as a medical doctor. As a Diplomate of the Chiropractic Board of Examiners, she is also a Certified Chiropractic Sports Physician. She has worked extensively in the private sector, then for over five years with the Veterans Healthcare System. Integrating traditional with complementary forms of treatment, Dr. Lajoie has specialized in pain management and musculoskeletal disorders. She is licensed to practice in Florida, Massachusetts, and Montana. Additionally, she has two doctorates in theology, a Doctorate in Biblical Studies and a Doctorate in Ministry. Dr. Lajoie is a District Licensed Minister, and combines this in Integrative Holistic Medicine, caring for the body, the mind, and the soul. She and her husband live in Helena, Montana, raising a herd of over 20 llamas.
TOPIC OVERVIEW
Fibromyalgia is a common and chronic disorder characterized by widespread pain, diffuse tenderness, and a number of other symptoms. Diagnosis and treatment of fibromyalgia require clinicians to have an understanding of the risks and causes of the disease. Research indicates pain pathways function abnormally, which leads to an enhanced pain experience in affected individuals. Treatment includes medication and lifestyle changes to reduce the level of pain felt. Pharmacists play a role in educating patients on pharmacological and non-pharmacological treatments for fibromyalgia that may be integrated with a patient’s prescribed medications.
Accreditation Statement:
RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.
Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is
Pharmacist 0669-0000-22-029-H08-P
Pharmacy Technician 0669-0000-22-030-H08-T
Credits: 1 hour of continuing education credit
Type of Activity: Knowledge
Media: Internet Fee Information: $4.99
Estimated time to complete activity: 1 hour, including Course Test and course evaluation
Release Date: September 5, 2022 Expiration Date: September 5, 2025
Target Audience: This educational activity is for pharmacists.
How to Earn Credit: From September 5, 2022, through September 5, 2025, participants must:
Read the “learning objectives” and “author and planning team disclosures;”
Study the section entitled “educational activity;” and
Complete the Post-test and Evaluation form. The Post-test will be graded automatically. Following successful completion of the Post-test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)
Learning Objectives: Upon completion of this educational activity, participants should be able to:
Identify the diffused symptoms that may be associated with fibromyalgia
Describe the role central and peripheral sensitization has in the onset and symptoms of fibromyalgia
Compare the benefits and adverse effects of pharmacological treatments for fibromyalgia
Describe the pharmacist’s role in educating patients on pharmacological and non-pharmacological treatments for fibromyalgia
Disclosures: The following individuals were involved in the development of this activity: Marilyn Lajoie, MD, DC, CCSP, Susan DePasquale, MSN, PMHNP- BC, and Steve Malen, PharmD. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.
ⓒ RxCe.com LLC 2022: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.
Introduction
Fibromyalgia is characterized by chronic, widespread pain and other diverse symptoms. In the past, clinicians labeled this syndrome as a diagnosis of exclusion, but this was largely due to an absence of standardized, diagnostic criteria for fibromyalgia. Advances have been made in understanding the pathophysiology, onset, and manifestations of fibromyalgia. These advances have improved the methodologies for diagnosing this condition; they have also introduced polysomnography, functional magnetic resonance imaging, electroencephalograms, and other tools to evaluate chronic, widespread pain. Additionally, the progress in understanding fibromyalgia has guided treatment options that include pharmacotherapy, complementary and alternative approaches, and patient self-help. Pharmacists have a role to play in educating patients about non-pharmacological treatments that may be integrated with medications. Scientific research into the pathophysiology of chronic pain continues to advance, and a pharmacist can help patients integrate non- pharmacological treatments with their prescription medications through the pharmacist’s education on the potential causes of chronic pain.
Epidemiology of Fibromyalgia
Fibromyalgia (FM) is a condition marked by chronic pain, fatigue, sleep interruption, cerebral dysfunction, and depression that is not accompanied by joint or tissue inflammation. In addition to widespread musculoskeletal pain, FM is attended by non-pain symptoms such as fatigue, sleep, memory, and mood issues. These symptoms can lead to a person’s inability to carry out normal daily activities.1
Prevalence
Fibromyalgia is one of the most common, chronic pain conditions.1-3 According to the Centers for Disease Control and Prevention (CDC), fibromyalgia affects 2% of adults in the United States. This means that about 4 million Americans have this condition.2 Women suffer from FM at a higher
rate than men.1 Fibromyalgia negatively impacts a person’s quality of life and bodily functions.1
While it is most prevalent in women (75-90% of the people with FM are women), it also occurs in men and children of all ethnic groups. The disorder is often seen in families, among siblings or mothers and their children. The diagnosis is usually made between the ages of 20 to 50 years, but the incidence rises with age so that by age 80, approximately eight percent of adults meet the American College of Rheumatology classification of FM.2
Defining Fibromyalgia
Fibromyalgia was preceded by other disorders of the muscle, fascia or fibrous tissues: “Regional pain syndrome” or “chronic pain syndrome,” and fibrositis are precedent, similar or overlapping syndromes to FM.4 The word fibrositis was used to indicate inflammation of the fibrous tissue;4-6 however, these syndromes are not necessarily accompanied by inflammation.4,7 In this regard, fibromyalgia is not regarded as a condition that involves tissue or joint inflammation. A recent study evaluated patients referred to a rheumatologist for FM and chronic pain.7 In this study, none of the patients were diagnosed with inflammatory arthritis or connective tissue disease.7
In 1976, Dr. P.K. Hench composed the term “fibromyalgia” by taking the Latin word “fibro,” which means fibrous tissue, and combining it with the Greek words “mio” and “algia,” which mean muscle and pain.8,9 Fibromyalgia was used to describe pain around or outside the joints, known as non-articular rheumatism.8 Smythe and Moldofsky followed Dr. Hench with their clinical evaluations and description of FM.1,9-11
In 1990, the American College of Rheumatology published diagnostic criteria for FM.12 In 2010, the diagnostic criteria were updated.13 The 2010 criteria broadened the net of patients who could be diagnosed with FM: It included patients who were not previously found to have FM because they had comorbidities that excluded a diagnosis of FM.9 However, in clinical practice,
practitioners do not apply the 2010 diagnostic criteria as they continue to find FM only after excluding other similar diseases.9
Economic Burden of Fibromyalgia
The cost of FM to individuals and society is extensive.1,14,15 A 2016 study found that direct healthcare costs of FM patients over three months were approximately $951 per patient.14 Prominent FM researchers and specialists estimate the costs in the U.S., between $12-14 billion each year and account for a loss of one to two percent of the nation’s overall productivity.15
Earlier reports of the cost burden of FM indicated that the total annual costs for FM claimants were more than twice as high as the costs for the typical insurance beneficiary. The prevalence of disability among employees with FM was twice as high as among all employees.15 For every dollar spent on FM- specific claims, employers spent approximately $50-$100 on additional direct and indirect costs. Work and disability status of 1,668 patients with FM reported that 25% had received disability payments.15
Failure to diagnose a true case of FM has its costs, largely consisting of excess visits to medical providers, assessments and testing, and prescriptions.15 Working adults with FM average almost 17 days of missed work per year compared to six days for persons without FM.16
Onset of Symptoms and Symptom Severity
The onset of symptoms in FM is highly variable. It may be acutely precipitated by physical trauma, surgery, infection, or significant psychological stress. In other cases, symptoms gradually accumulate over time with no single triggering event.19 Many people who have FM also have tension headaches, temporomandibular joint (TMJ) disorders, irritable bowel syndrome, anxiety, and depression.18,20 Symptoms may flare and subside but usually do not disappear completely.19
There is no cure for FM but a variety of medications can help control its symptoms. Exercise, relaxation, and stress-reduction measures also may help. A review was performed spanning fourteen years to assess if FM patients were physically able to engage in strength training exercises without exacerbating their pain. The results of the review found that not only could an FM patient participate in strength training but the exercise improved the patient’s muscle strength while lessening self-reports of pain.14
Fortunately, FM is not progressive or life-threatening and does not lead to joint, muscle, or nerve damage. People who have FM sometimes worry that continued symptoms mean the condition is getting worse. Although pain and other chronic symptoms can decrease a person’s quality of life and functioning, this is not regarded as disease progression.20
Fibromyalgia can be frustrating as well as exhausting. It can drain an individual’s energy and may interfere with work, school and family responsibilities, emotional health, and personal relationships. Fortunately, there are ways to manage FM and regain control of one’s life.20
Pathophysiology of Fibromyalgia
The pathophysiology of chronic pain from FM is not well defined. Studies have led scientists to believe that central sensitization causes a person to have a hypersensitivity to pain.1 More recent studies have also connected peripheral sensitization to a person experiencing hypersensitivity to pain. Additionally, dysfunction of descending inhibitory pain pathways (that limit pain) has been implicated in FM patients, and neurotransmitter abnormalities.1 Autoimmunity, neuroinflammation, and small fiber neuropathy are also thought to play a role in the pathogenesis of FM.18
Central and Peripheral Sensitization
With respect to central and peripheral sensitization, functional magnetic resonance imaging has identified alteration of central and peripheral neuronal function in nociceptive processes.1 Imaging is performed on patients when
they are at rest and during activity to study connections between various parts of the brain.1
Some researchers believe that FM amplifies painful sensations by affecting the way the brain processes pain signals; that is, FM seems to be caused by a hypersensitivity to pain due to the brain not processing pain correctly or because of psychological problems.1 Hypersensitivity to pain is referred to as central sensitization. Central sensitization is “a neuronal signal amplification mechanism within the central nervous system that leads to a greater perception of pain.”1
The sensitivity of central nervous system (CNS) neurons to painful stimuli is inherent to normal pain transmission. In FM, the CNS neurons become hypersensitive, which exaggerates and prolongs pain sensation from an acute protective mechanism to one that is chronic and pathologic. Additionally, the negative feedback loop that physiologically initiates the cessation of pain sensation is inhibited, causing the already amplified pain sensation to continue indefinitely.1
Siracusa, et al. (2021), point out that even though “FM is thought to be a central pain disorder, many studies have shown peripheral nerve changes in patients with FM.”1 Peripheral sensitization may also lead to a hypersensitivity to pain. This could be due to abnormalities in the peripheral nervous system that may cause an increase in nociceptive tonic supply within the spinal cord.1 This may cause enhanced pain perception. When mild tactile stimulation is transmitted as pain from the periphery to the brain, regions in the brain send CNS signals, which in turn result in the perception of musculoskeletal pain.1
Dysfunctional Pain Inhibitory Mechanisms
Pain associated with FM may not be limited to hypersensitivity in the brain regions. It may be due to dysfunctional pain inhibitory mechanisms within certain regions of the brain. An example of this would be hypo- connectivity between the anti-nociceptive areas in the brain stem. These brain
functions that inhibit pain - the descending inhibitory systems - may be dysfunctional in patients with FM.1
Neurotransmitters
As for the neurotransmitters, research shows abnormalities of both dopamine and serotonin are involved in FM.1 Plasma and cerebrospinal fluid serotonin have been found to be lower in patients with FM when compared with patients that do not exhibit this pain syndrome. Serotonin is partly responsible for the inhibition of pain pathways; therefore, the lack of this neurotransmitter in patients with FM adds to the problem of stopping the pain response. Dopamine levels in FM patients are also decreased when compared with patients that do not exhibit a pain syndrome. In times of acute stress, an increase in dopamine levels is the natural physiologic response for enhanced analgesic effects; however, in times of continual stress, dopamine will become decreased as the body overcompensates in an attempt to restore homeostasis (similar to cortisol). This dopamine deficiency then contributes to increased pain perception. The result of this dopamine deficiency in FM patients also creates an additional risk factor for depression.1
Endocrine Dysfunctions
Sleep disruptions associated with FM may be a direct manifestation of endocrine dysfunctions in the hypothalamic-pituitary-adrenal (HPA) axis. During times of chronic stress, the body experiences continual increases in cortisol secretion. Over time, the body attempts to restore homeostasis and overcompensates the cortisol elevation by intensifying the normal physiological negative feedback loop initiated by glucocorticoids, resulting in a cortisol deficiency. Rather than having a continuously increasing level of cortisol, which naturally exists during stress and the early phases of FM, cortisol secretion becomes diminished later in the course of the condition, resulting in disrupted sleep.1
Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy
The pathogenesis of FM may have an autoimmune component. Events that may trigger autoimmunity - trauma or infection - are commonly seen in FM patients just prior to the onset of the disease.18 Conditions that reportedly may contribute to FM symptoms include autoimmune Epstein‒Barr, Herpes simplex virus, and Hepatitis-C.18
Mast cells, monocytes, and neutrophils act as mediators of the inflammation processes in the body. They may lead to inflammation in patients with FM.1,18 “Pro-inflammatory cytokines could play a role in the generation of chronic muscle pain, including FM.”1
Small fiber neuropathy is characterized by abnormalities in the structure of small nerve fibers resulting in distal terminals of nerve endings degenerating.18 This condition has been seen in a large number of FM patients.18
Symptoms of Fibromyalgia
Chronic, widespread body pain is the primary symptom of FM. Most people with FM experience moderate to extreme fatigue, sleep disturbances, sensitivity to touch, light, sound, and cognitive difficulties. Many individuals also experience a number of other symptoms and overlapping conditions. This diffuse nature of FM’s many symptoms muddies the diagnostic waters making it difficult to describe FM as a distinct disease entity.4 Because of this, it may be helpful to look at FM as a continuum disorder, similar to others such as diabetes or depression, rather than a “discrete disorder that could be present or absent at a particular time point.”21 This would help to explain the multiple symptoms which can be present. Fibromyalgia “constitutes the end of a continuous spectrum of polysymptomatic distress (somatic and psychological symptom burden) within the population.”21
The main FM symptoms have been outlined “using the FIBRO mnemonic and include Fatigue and Fog (cognitive dysfunction), Insomnia (difficulties with all aspects of sleep including initiation, maintenance, and restorative), Blues (depression and anxiety), Rigidity (stiffness in muscles and joints) and Ow! (widespread pain and tenderness).”22
Pain
The pain of FM is profound, chronic, and widespread. It can migrate to all parts of the body and vary in intensity.23 Pain associated with FM has been classified as nociplastic pain.24 This classification of pain is relatively new. It was proposed by Kosek, et al. (2016).25 Previously, pain associated with FM was either nociceptive or neuropathic pain. These traditional classifications often excluded FM patients whose clinical assessment did not appear to involve activation of nociceptors, nor widespread pain from a nervous system disease.26 As a result, nociplastic pain has gained fairly broad acceptance. The International Association for the Study of Pain defines nociplastic pain as follows: “Pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.”27 The note following the definition states that a patient may “have a combination of nociceptive and nociplastic pain.”27
In the clinical setting, FM pain has been described as stabbing and shooting pain, and deep muscular aching, throbbing, and twitching. Neurological complaints such as numbness, tingling, and burning are often present and add to the discomfort of the patient. The severity of the pain and stiffness is often worse in the morning. Aggravating factors that affect pain include cold or humid weather, non-restorative sleep, physical and mental fatigue, excessive physical activity, physical inactivity, anxiety, and stress.23
The pain associated with FM often is described as a constant dull ache that lasts for at least three months. To be considered widespread, the pain must occur on both sides of the body and above and below the waist. However, the pain may initially be localized, often in the neck and shoulders. Patients
typically describe pain predominantly throughout the muscles but often state that their joints hurt, and sometimes describe joint swelling as well.23
Fatigue
In today's world, many people complain of fatigue; however, the fatigue of FM is much more than being tired after a particularly busy day or after a sleepless night. The fatigue of FM is an all-encompassing exhaustion that can interfere with occupational, personal, social, or educational activities. Symptoms include profound exhaustion and poor stamina.23
The fatigue is often especially notable when arising from sleep but is also marked in the mid-afternoon. Seemingly minor activities aggravate the pain and fatigue, although prolonged inactivity also heightens symptoms. Patients are stiff in the morning and feel unrefreshed, even if they have slept eight to ten hours. Patients with FM characteristically sleep lightly. This causes them to awaken frequently during the early morning, and they have difficulty getting back to sleep.23
Sleep Problems
People with FM often awaken tired, even though they report sleeping for long periods of time. Sleep is often disrupted by pain, and many patients with FM have other sleep disorders, such as restless legs syndrome and sleep apnea.23,28
Many FM patients have an associated sleep disorder that prevents them from getting deep, restful, and restorative sleep. Medical researchers have documented specific and distinctive abnormalities in stage four, deep sleep, of FM patients. During sleep, individuals with FM are constantly interrupted by bursts of awake-like brain activity, limiting the amount of time they spend in deep sleep. Such sleep disturbances contribute to the symptom of fatigue.28 A study by Fallon, et al. (2018) investigated resting brain wave activity via electroencephalographic (EEG) in patients with FM and concluded that there is enhanced theta activity in the regions of the brain which are related to the
endogenous inhibition of pain impulses as well as how people perceive and are attentive to pain impulses.28 These sites, being localized as demonstrated by EEG, show promise for the treatment of FM patients.28
Psychiatric Symptoms
Depression is found in approximately 25% of patients diagnosed with FM.23 This is 2–3 times higher than individuals without FM.23 Moreover, depression or anxiety can be present in up to 60% of patients within certain demographic groups.1,29
Clinicians need to ask whether depression is a primary disorder or whether it is secondary to FM. A patient suffering from chronic pain will almost certainly develop anxiety or depression, especially if the pain lasts for years.23 Depression appears to be more significant when pain is intense. In addition, depressed fibromyalgia patients tend to be young, with greater pain and sleep disorders, associated with less social satisfaction and well-being. These patients tend to need more assistance.23
Cognitive Dysfunction
A patient with FM may also be symptomatic of cognitive impairment. The patient may have difficulty with memory, concentration, or thought organization (sometimes called “fibro fog”).30 Fibro fog has been described as a subjective, cognitive dysfunction associated with FM.31,32 It involves a loss of mental clarity or mental fog, attention deficits, and memory impairment.31 Although it is important, it has not been adequately studied.32
Other Symptoms or Overlapping Conditions
Additional symptoms may include headache, irritable bowel and interstitial cystitis/painful bladder syndromes, headaches and migraines, restless legs syndrome, ringing in the ears, dizziness, vision problems, impaired memory and concentration, skin sensitivities and rashes, dry eyes and mouth, and impaired coordination.23,33 Many of these additional
symptoms for FM overlap with other syndromes. In addition to the syndromes that may be represented by the symptoms listed above, FM may present with symptoms of lupus and arthritis,34,35 anxiety, depression, Raynaud's Syndrome, neurological symptoms, painful menstrual periods, and endometriosis.30
In addition to those already listed, other reported symptoms include facial pain, chest wall pain, heightened sensitivity to odors, noises, bright lights and touch, stiffness, numbness or tingling in the arms and legs, and dizziness.4,23,36-38
Fibromyalgia Risk Factors and Contributing Conditions
Risk factors for FM are multifactorial and involve a person’s gender, age, family history, and history of rheumatic disease. Female gender is associated with a higher rate of FM.1 Onset of FM is typically between the ages of 30 and
35.1 However, it can occur in the teen years and old age. Younger children can also develop widespread body pain and fatigue.39
As mentioned above, conditions that reportedly may contribute to FM symptoms include autoimmune Epstein‒Barr, Herpes simplex virus, and Hepatitis-C.18,40 Vaccination, silicone breast implants, or mineral oil injections have also been seen in patients diagnosed with FM.18
Genetic factors appear to raise the risk that a person will have fibromyalgia. A person may be more likely to develop FM if a relative also has the condition.1 Another risk factor is rheumatic disease. A person with osteoarthritis, rheumatoid arthritis, or lupus may be more likely to develop FM;1 however, the presence of these conditions may be the basis for a differential diagnosis of a disease other than fibromyalgia.23
Diagnosis of Fibromyalgia
No specific test can confirm FM; the diagnosis was previously made based on exclusion, which means that health care providers first rule out other
diseases or conditions that may be causing pain and other symptoms, but this has changed. It is now a diagnosis that requires a positive diagnosis.41 This condition remains undiagnosed in up to 75% of cases.41
Research shows that people with FM typically see many health care providers before receiving the diagnosis. One reason for this may be that pain and fatigue, the main symptoms of FM, overlap with those of many other conditions. Therefore, healthcare providers often must rule out other potential causes of these symptoms before making a diagnosis of FM. This has led some clinicians to doubt the existence of the disorder. “The root cause of the FM controversy is that reasonable people can argue that FM is more a mind/brain disease than a musculoskeletal disease.”42 Another reason is that there are currently no diagnostic laboratory tests for FM; standard laboratory tests fail to reveal a physiologic reason for pain.41,42 Because there is no generally accepted, objective test for FM, some health care providers unfortunately may conclude a patient’s pain is not real, or they may tell the patient there is little they can do. This is a valid cause of frustration and concern for those with FM.21
After reviewing the medical history and performing a physical exam, health care providers may recommend blood tests, X-rays, or other tests to help rule out other conditions that can cause similar symptoms (for example, rheumatoid arthritis, lupus, low thyroid hormone production, and multiple sclerosis).16
American College of Rheumatology (ACR) in 1990 brought some “official recognition” by establishing the fibromyalgia classification criteria. It included a history of widespread pain in all four quadrants of the body for a minimum duration of three months, and pain in at least 11 of the 18 designated tender points when a specified amount of pressure is applied.9,12
It did not consider other factors, such as the difficulty of applying standardized pressure algometry in the primary care setting, which was necessary for meeting the threshold of pain in the sites of designated trigger points. The criteria also made for an “all or none” diagnosis, instead of a
continuum as discussed earlier. There were other issues with the criteria, however by 1992, two important decisions were made, providing even more legitimacy to the disorder. Fibromyalgia was officially given a diagnostic code and was thereby included in the International Classification of Diseases. This made FM a disorder for which research could be funded, and it gained recognition within the academic community. The second event in 1992 was when the World Health Organization recognized FM as a disease, labeling it as a type of rheumatism that did not involve the joints.9
Although the 1990 ACR criteria are no longer in use for the diagnosis of FM, the criteria helped to establish the validity of the disorder. In 2010, the ACR revised its classification system and used two scales to reach a diagnosis. The Widespread Pain Index (WPI) had a list of 19 points that the patient would report on as to whether pain was absent or present. The second was the Symptom Severity Scale, which was further divided as having two parts. In the first part, the patient would use a scale of 0-3 to assess the “severity of fatigue, waking unrefreshed, and cognitive symptoms.”9 The second part has a checklist of 41 symptoms, to which the patient had to acknowledge the absence or presence of each. A rating system based on the results would then be reviewed by the physician, who would then be able to make the diagnosis of FM or some other condition. As with the 1990 ACR criteria, the findings had to have been present for a minimum of three months to complete the diagnosis. There have been two other, more recent proposals made for the diagnosis of FM, one in 2011, and the other in 2016; however, neither has been formally accepted, and the criteria now in use are the 2010 ACR criteria.9
After a thorough medical evaluation has ruled out serious underlying causes for the condition, managing symptoms effectively may be more helpful than additional tests. However, it is only by receiving a diagnosis that patients will be able to learn about the condition and receive appropriate advice on managing their symptoms.
Treatment of Fibromyalgia
Fibromyalgia can be difficult to treat because of the diffused symptoms often associated with it, and the overlap these symptoms have with other medical conditions and diseases. Clinical practice guidelines for patients with FM set forth a variety of treatments. They include pharmacological treatments and non-pharmacological treatments.
Pharmacological Treatments
Only three medications, duloxetine (CymbaltaⓇ), milnacipran (SavellaⓇ), and pregabalin (LyricaⓇ), are approved by the U.S. Food and Drug Administration (FDA) for the treatment of FM.43 Duloxetine was originally developed for and is still used to treat depression. Milnacipran is similar to a drug used to treat depression but is FDA-approved only for FM. Pregabalin is a medication developed to treat neuropathic pain (chronic pain caused by damage to the nervous system) or seizures.44 Other medications to treat FM are currently in development and may be approved for use by the FDA in the future.41
Duloxetine (Cymbalta!)
Duloxetine is a serotonin-noradrenaline reuptake inhibitor (SNRI). Rodrigues-Amorim, et al. (2020) examined a number of studies that used duloxetine in doses that ranged from 60–120 mg daily.44 Earlier studies showed 30mg/day, with a maximum of 60 mg/day, also referencing 120 mg/day in clinical trials.30 The studies reviewed showed that duloxetine was safe, effective, and well-tolerated in patients, including elderly patients.44
The most common side effects of duloxetine treatment are nausea, dry mouth, headache, somnolence, and fatigue.44,45 Duloxetine, as an SNRI, increases the levels of serotonin and norepinephrine. As such, adverse events from duloxetine may include tachycardia (increased heart rate) and hypertension but these are rare. Adverse events connected to duloxetine were
reportedly mild to moderate and tended to cease or subside with continued use of the drug.44
Rodrigues-Amorim, et al., added that “duloxetine is a monotherapy” that may be used to treat disorders such as major depressive disorder and neuropathic pain. This could be an advantage for FM patients with psychological disorders such as depression. These patients may take duloxetine to treat FM and avoid the issues (e.g., adverse events caused by taking multiple drugs), and the costs associated with polytherapy.44
Milnacipran (Savella!)
Milnacipran is an SNRI.46,47 Welsch, et al. (2018) reported on the use of milnacipran in a number of studies that used fixed dosages of 100 mg a day,
200 mg a day, and 100 mg or 200 mg a day.47 Earlier studies showed 12.5mg/day, with a maximum of 50 mg twice daily (FDA indicated at 50mg- 100mg twice daily).30 Milnacipran has been studied and found effective as a monotherapy.47 Milnacipran has been shown to be effective in treating FM and other symptoms such as fatigue.43
The most common adverse reactions from treatments with milnacipran were nausea, headache, constipation, dizziness, insomnia, hot flush, hyperhidrosis, vomiting, palpitations, tachycardia, dry mouth, and hypertension.46 Studies showed that these adverse reactions occurred in 5% or more of participants when compared to participants receiving a placebo.46
Pregabalin (Lyrica!)
Pregabalin is a gabapentinoid. Gabapentinoids “act by binding to the alpha2delta subunit of voltage-gated calcium channels in the CNS.”43 Studies showed that pregabalin is effective in treating FM, and the pain, fatigue, and sleep disturbances that accompany FM.43 Dosing for pregabalin was fixed at 450 mg a day in a clinical study.47 Dosing has also been reported at 75mg two times per day (total 150 mg/day).30
However, other studies did not find pregabalin to be more effective than placebo for improving fatigue. None of the trials indicated any improvement in depression. In animal trials, lacosamide was more effective than pregabalin at reducing muscular hyperalgesia.43 Adverse effects associated with pregabalin included nausea, dizziness, somnolence, insomnia, and peripheral edema.47,48
Off-label Medications
Health care providers also treat FM with a variety of medications developed and approved for other indications. All medications can have side effects. Some side effects may be more severe than others. Patients should be informed of these potential side effects and be instructed to report them to their health care providers.
Amitriptyline
Amitriptyline (Elavil!) is a tricyclic antidepressant. It may be used for
pain, fatigue, and problems with sleep.30 Research on its use for treating fibromyalgia is not as conclusive as the FDA-approved drugs listed above.30,49 (The same is true of cyclobenzaprine, a skeletal muscle relaxant.30) However, amitriptyline has been used as a first-line treatment for FM for many years, and this use is expected to continue.49,50 One reason why amitriptyline may work so well in practice is it treats not only pain but depression associated with FM, and sleep issues.50
Opioids
Analgesics, or “painkillers,” range from OTC products to prescription medicines. For a subset of people with FM, opioid medications are prescribed for severe muscle pain. There is some evidence showing that opioids may be used to treat the chronic pain of FM.51,52 However, health care providers must be cautious and vigilant when prescribing opioids because of the risk that a patient taking them will become physically or psychologically dependent on them.52,53
Nonsteroidal Anti-inflammatory Drugs
As their name implies, nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, and naproxen, are used to treat inflammation. Although inflammation is not a symptom of FM, NSAIDs also relieve pain. The mechanism of action is through inhibiting substances in the body called prostaglandins, which play a role in pain and inflammation. These medications, some of which are available without a prescription, may help ease the muscle aches of FM. They may also relieve menstrual cramps and the headaches often associated with FM.16
Non-Pharmacological Treatments
Clinical practice guidelines for patients with FM set forth a variety of treatments.54 In addition to pharmacological treatments discussed above, non-pharmacological treatments can include patient education, physical therapy, and psychiatric interventions.54,55 In addition, alternative therapies such as yoga, tai chi, or acupuncture are also accepted treatments.54,55 In most cases, patients will have better outcomes when using a multidisciplinary approach to FM treatment that combines drug therapy and nonpharmacological treatments.55 Many of the nonpharmacological approaches to treating FM focus on the need for the patient to make lifestyle changes.
Complementary and alternative therapies offer an approach for accomplishing these changes.55,56 When these therapies are coordinated with conventional healthcare, the combined treatments are referred to as integrated therapies.56
The use of complementary and alternative medicine is extensive in patients with FM.57 Pfalzgraf, et al. (2020) reported that 66% of the respondents to an online survey said that they used complementary and alternative treatments.57 Studies indicate that the type of complementary or alternative therapy used differs considerably based on a patient’s age.56
Most people are resistant to change because it implies adjustment, discomfort, and effort. However, in the case of FM, change can bring about recognizable improvements in function and quality of life. Patient education about FM, and the lifestyle choices that may underlie the disease, may provide the patient with a more positive outcome.55,56
The Pharmacist’s Role in Fibromyalgia Treatments
Pharmacists are well-trained, accessible members of healthcare teams. They can ensure pain management regimens are safe and effective, provide pertinent patient education, and collaborate with other healthcare providers to improve patient outcomes.58,59 Pharmacists should be familiar with federal and state laws that may set parameters for their roles. However, in general terms, pharmacists can provide vital patient and caregiver education and suggest referrals to other health care providers to improve outcomes and the patient experience.58,59 Moreover, pharmacists are able to care for patients with chronic pain in many practice areas, including community, inpatient, long-term care, and specialty clinical settings.58,59
In the management of chronic pain and other FM symptoms, pharmacists may be involved in reviewing a patient’s medication histories (including allergies), consider patient-specific factors to select appropriate pharmacologic and nonpharmacologic therapies, identify potential drug interactions, and monitor therapies for adherence and side effects. The pharmacist may consult with the patient’s primary physician and suggest prescription medications that may improve the patient’s health outcomes.58 For example, a patient may have widespread pain, accompanied by depression and insomnia. Rather than pursuing a treatment plan that includes multiple medications to address each symptom, a pharmacist, in collaboration with the primary physician, may recommend a monotherapy that will treat all three (the widespread pain, depression, and insomnia). This could help decrease the patient’s side effects, cost and improve outcomes.
Pharmacists may be further involved in primary care by utilizing “population management activities.”59 An example of population management could include a pharmacist reviewing a patient population group as a whole in order to identify if that group is at higher risk of opioid misuse or other pain management concerns.59 Greater involvement by pharmacists in a patient’s pain management has resulted in a decreased burden on other primary care professionals, and improved patient outcomes.59 Giannitrapani, et al. (2018) concluded by stating: “Interdisciplinary collaboration and communication between the medicine and pharmacy services will be essential to successful clinical pharmacist role expansion and shared team prioritization.”59
Poor diet, inactivity, and inadequate tools to deal with stress are major factors in the onset and symptoms of FM.60-62 These issues may be addressed effectively using non-pharmacological approaches.60-62 While a pharmacist’s focus is dispensing medications, and providing a patient with information related to medications, patients with persistent and chronic pain may look to their pharmacist for information and help with a more integrated treatment plan.63 This means that a pharmacist may play a vital role in helping patients integrate their treatment plans by studying more fully the causes of chronic pain in an FM patient. Knowledge with respect to the pathophysiology of chronic pain can provide pharmacists confidence when they are counseling patients who are seeking help with FM beyond medication treatments.63 Pharmacists should incorporate empathy and patient-centered care into their interactions with FM patients. This will build rapport and trust with the patient and improve the patient’s outcome.63
Fibromyalgia Research
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) sponsors research that will improve scientists’ understanding of the specific problems that cause or accompany FM, in turn helping them develop better ways to diagnose, treat, and prevent this condition.64 The research on FM supported by the NIAMS covers a broad spectrum, ranging from basic laboratory research to studies of medications and interventions designed to
encourage behaviors that reduce pain and change behaviors that worsen or perpetuate pain.64
Researchers continue to study the activation of immune cells from peripheral and central nervous system sources and how they trigger a cascade of events leading to the activation of nerve cells, chronic pain, and the dysregulation of the effects of analgesic drugs against pain.65-67
An intensive evaluation of twins in which one of the pair has chronic widespread pain, and the other does not, along with twins in which neither of the pair has chronic pain, has helped researchers assess physiological similarities and differences in those with and without chronic pain and whether those differences are caused by genetics or environment.66
The use of cognitive behavioral therapy, or CBT, in patients with pain disorders, has been studied. Researchers have sought to advance their knowledge of the role of psychological factors in chronic pain as well as a new treatment option for FM.68 Cognitive behavioral therapy has been used to help FM patients improve their health through lifestyle changes, such as incorporating exercise into their routines. However, many people with FM associate increased exercise with increased pain. Providers and therapists often have a difficult time getting patients to stick with their exercise program. Also, NIAMS-supported research programs are examining ways to help people maintain helpful exercise programs. This research is looking at patients’ fears that cause them to avoid exercise, and the use of behavioral therapies to reduce these fears and help FM patients maintain their exercise routines.69
The Patient-Reported Outcomes Measurement Information System (PROMIS) is an initiative researching and developing new ways to measure patient-reported outcomes (PROs), such as pain, fatigue, physical functioning, emotional distress, and social role participation that have a major impact on quality of life across a variety of chronic diseases.70 The goal of this initiative is to improve the reporting and quantification of changes in PROs. The NIAMS supports an effort to develop PROMIS specifically for use in patients with FM.70
Other groups of researchers are examining the link between sleep disturbance and chronic pain in FM and are studying whether behavioral therapy for insomnia might improve FM symptoms.71 A study by McCrae, et al. (2019) evaluated the effects of CBT on insomnia and chronic pain associated with FM.71 Cognitive behavioral therapy for insomnia was very effective, and although the reductions in pain were not as significant, about a third of the patients had reductions in both pain and insomnia. The pain relief was immediate, although the results were not as long-lasting as CBT for the treatment of insomnia.71
Summary
Fibromyalgia is a complex condition that can have a serious impact on those affected by it. It is associated with chronic, widespread body pain and fatigue and may involve a variety of other symptoms. While there is no cure, there are effective pharmacological and non-pharmacological treatments.
The pathophysiology of chronic pain from FM is not well defined. It may be due to central sensitization that causes a person to have a hypersensitivity to pain. Peripheral sensitization may also be connected to pain hypersensitivity. Additionally, dysfunction of descending inhibitory pain pathways (that limit pain) has been implicated in FM patients, and neurotransmitter abnormalities. Finally, autoimmunity, neuroinflammation, and small fiber neuropathy are also thought to play a role in the pathogenesis of FM.
Most people with FM experience moderate to extreme fatigue, sleep disturbances, sensitivity to touch, light, sound, and cognitive difficulties. Risk factors for FM are multifactorial and involve a person’s gender, age, family history, and history of rheumatic disease. The female gender is associated with a higher rate of FM. The onset of FM is typically between the ages of 30 and 35. The 2010 ACR criteria are currently in use for diagnosing FM. Clinical practice guidelines set forth a variety of pharmacological and non- pharmacological treatments for patients with FM.
Pharmacists are important members of healthcare teams. They can ensure pain management regimens are safe and effective, provide pertinent patient education, and collaborate with other healthcare providers to improve patient outcomes. Pharmacists are able to care for patients with chronic pain in many practice areas, including community, inpatient, long-term care, and specialty clinical settings. In the management of chronic pain and other FM symptoms, pharmacists are well-trained to determine accurate medication histories (including allergies), utilize patient-specific factors to select appropriate pharmacologic and nonpharmacologic therapies, identify potential drug interactions, and monitor therapies for adherence and side effects. Additionally, pharmacists can provide vital patient and caregiver education and suggest referrals to other health care providers to improve outcomes and the patient experience.
Course Test
Fibromyalgia is a condition marked by
permanent joint, muscle, or nerve damage.
chronic pain.
progressive, chronic pain caused by inflammation of the joints.
musculoskeletal pain.
Pain associated with fibromyalgia often does not appear to involve activation of nociceptors or a nervous system disease, and because of this, fibromyalgia has been more recently classified as
nociplastic pain.
nociceptive pain.
neuropathic pain.
musculoskeletal pain.
Which of the following statements about fibromyalgia is true?
The cause of FM is well-understood
There is no cure for FM.
Fibromyalgia affects men more than women
Medications are not an effective treatment for FM.
Risk factors for fibromyalgia include
male gender.
old age.
adolescence.
female gender.
True or False: The onset of fibromyalgia is typically between the ages of 30 and 35.
True
False
is a serotonin-noradrenaline reuptake inhibitor (SNRI) that is FDA approved to treat fibromyalgia.
Amitriptyline
Cyclobenzaprine
Milnacipran
Pregabalin
Major factors that play a role in the onset and symptoms of fibromyalgia include
poor diet.
inactivity.
inadequate tools to deal with stress.
All of the above
In the management of fibromyalgia symptoms, pharmacists may
prescribe treatments under the laws of all 50 states.
monitor patient therapies for adherence and side effects.
only discuss OTC medications and supplements with patients.
modify prescriptions issued by a patient’s primary physician.
A patient with fibromyalgia may have a subjective, cognitive dysfunction, which has been described as
dementia.
Alzheimer’s disease.
fibro fog.
a form of senility.
Amitriptyline is that may be used off- label for the treatment of fibromyalgia.
an antiviral
an SNRI
a tricyclic antidepressant
a skeletal muscle relaxant
References
Siracusa R, Paola RD, Cuzzocrea S, Impellizzeri D. Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update. Int J Mol Sci. 2021;22(8):3891. Published 2021 Apr 9. doi:10.3390/ijms22083891
Centers for Disease Control and Prevention. Arthritis. Fibromyalgia.
CDC. 2020. https://www.cdc.gov/arthritis/basics/fibromyalgia.htm.
Accessed July 31, 2022.
Creed F. A review of the incidence and risk factors for fibromyalgia and chronic widespread pain in population-based studies. Pain. 2020 Jun;161(6):1169-1176. doi: 10.1097/j.pain.0000000000001819. PMID: 32040078.
Pearce JM. Myofascial pain, fibromyalgia or fibrositis? Eur Neurol.
2004;52(2):67-72. doi: 10.1159/000079748. Epub 2004 Jul 13. PMID:
15256826.
Smythe HA, Moldofsky H. Two contributions to understanding of the "fibrositis" syndrome. Bull Rheum Dis. 1977-1978; 28(1):928-31.
Bach F. Fibrositis. Br Med J. 1948;2(4572):399. doi:10.1136/bmj.2.4572.399-b.
Pang HY, Farrer C, Wu W, Gakhal NK. Quality of rheumatology care for patients with fibromyalgia and chronic pain syndromes. BMJ Open Qual. 2021;10(1):e001061. doi:10.1136/bmjoq-2020-001061
Hench P.K. Nonarticular rheumatism, 22nd rheumatism review: Review of the American and English literature for the years 1973 and 1974. Arthritis Rheumatol. 1976;19:1081–1089.
Galvez-Sánchez CM, Reyes Del Paso GA. Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives. J Clin Med. 2020;9(4):1219. Published 2020 Apr 23. doi:10.3390/jcm9041219
Smythe HA, Moldofsky H. Two contributions to understanding of the "fibrositis" syndrome. Bull Rheum Dis. 1977-1978;28(1):928-31. PMID: 199304.
Littlejohn G, Guymer E. Key Milestones Contributing to the Understanding of the Mechanisms Underlying Fibromyalgia. Biomedicines. 2020;8(7):223. Published 2020 Jul 17. doi:10.3390/biomedicines8070223
Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990 Feb;33(2):160-72. doi: 10.1002/art.1780330203. PMID: 2306288.
Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of
Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10. doi: 10.1002/acr.20140. PMID: 20461783.
Nelson M. Muscle strengthening activities and fibromyalgia: A review of pain and strength outcomes. Journal of Bodywork and Movement Therapies. 2014;19(2): 370-376. ISSN 1360-8592. Retrieved at https://www.bodyworkmovementtherapies.com/article/S1360- 8592(14)00138-7/fulltext
Lacasse A, Bourgault P, Choinière M. Fibromyalgia-related costs and loss of productivity: a substantial societal burden. BMC Musculoskelet Disord. 2016 Apr 16;17:168. doi: 10.1186/s12891-016-1027-6. PMID: 27084363; PMCID: PMC4833946.
Ryan S. Care of patients with fibromyalgia: assessment and management. Nurs Stand. 2013 Nov 27-Dec 3;28(13):37-43. doi: 10.7748/ns2013.11.28.13.37.e7722. PMID: 24279570.
Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and Central Sensitization in Chronic and Widespread Pain. Anesthesiology. 2018;129(2):343-366. doi:10.1097/ALN.0000000000002130
Ryabkova VA, Churilov LP, Shoenfeld Y. Neuroimmunology: What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus Vaccination?. Int J Mol Sci. 2019;20(20):5164. Published 2019 Oct 18. doi:10.3390/ijms20205164
Aili K, Campbell P, Michaleff ZA, et al. Long-term trajectories of chronic musculoskeletal pain: a 21-year prospective cohort latent class analysis. Pain. 2021;162(5):1511-1520. doi:10.1097/j.pain.0000000000002137
Jahan F, Nanji K, Qidwai W, Qasim R. Fibromyalgia syndrome: an overview of pathophysiology, diagnosis and management. Oman Med J. 2012;27(3):192-195. doi:10.5001/omj.2012.44
Häuser W, Fitzcharles MA. Facts and myths pertaining to fibromyalgia. Dialogues Clin Neurosci. 2018;20(1):53-62. doi:10.31887/DCNS.2018.20.1/whauser
Boomershine CS. Fibromyalgia: the prototypical central sensitivity syndrome. Curr Rheumatol Rev. 2015;11(2):131-45. doi: 10.2174/1573397111666150619095007. PMID: 26088213.
Maugars Y, Berthelot JM, Le Goff B, Darrieutort-Laffite C. Fibromyalgia and Associated Disorders: From Pain to Chronic Suffering, From Subjective Hypersensitivity to Hypersensitivity Syndrome. Front Med (Lausanne). 2021;8:666914. Published 2021 Jul 14. doi:10.3389/fmed.2021.666914
Wolfe F, Rasker JJ. The Evolution of Fibromyalgia, Its Concepts, and Criteria. Cureus. 2021;13(11):e20010. Published 2021 Nov 29. doi:10.7759/cureus.20010.
Kosek, et al. (2016) proposed a third type of pain - nociplastic pain.43 Kosek E, Cohen M, Baron R, Gebhart GF, Mico JA, Rice ASC, Rief W, Sluka AK. Do we need a third mechanistic descriptor for chronic pain states? Pain. 2016 Jul;157(7):1382-1386. doi: 10.1097/j.pain.0000000000000507. PMID: 26835783.
Trouvin AP, Perrot S. New concepts of pain. Best Pract Res Clin Rheumatol. 2019 Jun;33(3): 31703792.
International Association for the Study of Pain. IASP Terminology. IASP. Undated. https://www.iasp- pain.org/resources/terminology/?navItemNumber=576#Pain. Accessed September 5, 2022.
Fallon N, Chiu Y, Nurmikko T, Stancak A. Altered theta oscillations in resting EEG of fibromyalgia syndrome patients. Eur J Pain. 2018 Jan;22(1):49-57. doi: 10.1002/ejp.1076. Epub 2017 Jul 31. PMID: 28758313; PMCID: PMC5763419.
Levine D, Horesh D. Suicidality in Fibromyalgia: A Systematic Review of the Literature. Front Psychiatry. 2020;11:535368. Published 2020 Sep
23. doi:10.3389/fpsyt.2020.535368
Firestone, K. A., Holton, K. F., Wright, C. L., Jones, K. D. Optimizing Fibromyalgia Management. Nurse Practitioner. 2012; 37(4):12-21.
Kravitz HM, Katz RS. Fibrofog and fibromyalgia: a narrative review and implications for clinical practice. Rheumatol Int. 2015 Jul;35(7):1115-
25. doi: 10.1007/s00296-014-3208-7. Epub 2015 Jan 13. PMID:
25583051.
Bernardi L, Bertuccelli M, Formaggio E, et al. Beyond physiotherapy and pharmacological treatment for fibromyalgia syndrome: tailored tACS as a new therapeutic tool. Eur Arch Psychiatry Clin Neurosci. 2021;271(1):199-210. doi:10.1007/s00406-020-01214-y
Nickel JC, Tripp DA, Pontari M, et al. Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. J Urol. 2010;184(4):1358-1363. doi:10.1016/j.juro.2010.06.005
Williams DA. Phenotypic Features of Central Sensitization. J Appl Biobehav Res. 2018;23(2):e12135. doi:10.1111/jabr.12135
Fibromyalgia. Mayo Clinic. 2020. https://www.mayoclinic.org/diseases- conditions/fibromyalgia/symptoms-causes/syc-20354780. Accessed September 5, 2022.
Houghton DC, Uhde TW, Borckardt JJ, Cortese BM. Exploratory Investigation of a Brief Cognitive Behavioral Intervention and Transcranial Direct Current Stimulation on Odor Sensitivity. Psychosom Med. 2019;81(4):389-395. doi:10.1097/PSY.0000000000000679
Gui MS, Pedroni CR, Aquino LM, Pimentel MJ, Alves MC, Rossini S, Reimão R, Berzin F, Marques AP, Rizzatti-Barbosa CM. Facial pain associated with fibromyalgia can be marked by abnormal neuromuscular control: a cross-sectional study. Phys Ther. 2013 Aug;93(8):1092-101. doi: 10.2522/ptj.20120338. Epub 2013 Apr 18. PMID: 23599350.
Wolfe F, Walitt B, Perrot S, Rasker JJ, Häuser W. Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias. PLoS One. 2018;13(9):e0203755. Published 2018 Sep 13.
doi:10.1371/journal.pone.0203755
De Sanctis V, Abbasciano V, Soliman AT, et al. The juvenile fibromyalgia syndrome (JFMS): a poorly defined disorder. Acta Biomed. 2019;90(1):134-148. Published 2019 Jan 23.
doi:10.23750/abm.v90i1.8141
Bellato E, Marini E, Castoldi F, et al. Fibromyalgia syndrome: etiology, pathogenesis, diagnosis, and treatment [published correction appears in Pain Res Treat. 2013;2013:960270]. Pain Res Treat. 2012;2012:426130. doi:10.1155/2012/426130
Maffei ME. Fibromyalgia: Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies. Int J Mol Sci. 2020 Oct 23;21(21):7877. doi: 10.3390/ijms21217877. PMID: 33114203; PMCID: PMC7660651.
Bernstein J. Not the Last Word: Fibromyalgia is Real. Clin Orthop Relat Res. 2016 Feb;474(2):304-9. doi: 10.1007/s11999-015-4670-6. Epub 2015 Dec 16. PMID: 26676117; PMCID: PMC4709307.
Tzadok R, Ablin JN. Current and Emerging Pharmacotherapy for Fibromyalgia. Pain Res Manag. 2020 Feb 11;2020:6541798. doi: 10.1155/2020/6541798. PMID: 32104521; PMCID: PMC7036118.
Rodrigues-Amorim D, Olivares JM, Spuch C, Rivera-Baltanás T. A Systematic Review of Efficacy, Safety, and Tolerability of Duloxetine. Front Psychiatry. 2020;11:554899. Published 2020 Oct 23. doi:10.3389/fpsyt.2020.554899
Cymbalta. HIGHLIGHTS OF PRESCRIBING INFORMATION. 2008.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022516lbl
.pdf. Accessed August 1, 2022.
Savella. HIGHLIGHTS OF PRESCRIBING INFORMATION. 2009.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022256s0 11lbl.pdf. Accessed August 1, 2022.
Welsch P, et al. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia. Cochrane Database Syst Rev. 2018 Feb; 2018(2): CD010292. Published online 2018 Feb 28. doi: 10.1002/14651858.CD010292.pub2 PMCID: PMC5846183. PMID:
29489029.
Lyrica. HIGHLIGHTS OF PRESCRIBING INFORMATION. 2018.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021446s0 35,022488s013lbl.pdf. Accessed August 1, 2022.
Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for fibromyalgia in adults. Cochrane Database Syst Rev. 2019;5(7):CD011824. Published 2019 May 28. doi:10.1002/14651858.CD011824
Farag HM, Yunusa I, Goswami H, Sultan I, Doucette JA, Eguale T. Comparison of Amitriptyline and US Food and Drug Administration- Approved Treatments for Fibromyalgia: A Systematic Review and Network Meta-analysis. JAMA Netw Open. 2022;5(5):e2212939. Published 2022 May 2. doi:10.1001/jamanetworkopen.2022.12939
Martucci KT, MacNiven KH, Borg N, Knutson B, Mackey SC. Apparent Effects of Opioid Use on Neural Responses to Reward in Chronic Pain. Sci Rep. 2019;9(1):9633. Published 2019 Jul 3. doi:10.1038/s41598- 019-45961-y
Finan PH, Remeniuk B, Dunn KE. The risk for problematic opioid use in chronic pain: What can we learn from studies of pain and reward?. Prog Neuropsychopharmacol Biol Psychiatry. 2018;87(Pt B):255-262. doi:10.1016/j.pnpbp.2017.07.029
Young JC, Jonsson Funk M, Dasgupta N. Medical Use of Long-term Extended-release Opioid Analgesics in Commercially Insured Adults in the United States. Pain Med. 2020;21(4):724-735. doi:10.1093/pm/pnz155
Spaeth M, Rizzi M, Sarzi-Puttini P. Fibromyalgia and sleep. Best Pract Res Clin Rheumatol. 2011 Apr;25(2):227-39. doi: 10.1016/j.berh.2011.03.004. PMID: 22094198.
Nadal-Nicolás Y, Rubio-Arias JÁ, Martínez-Olcina M, Reche-García C, Hernández-García M, Martínez-Rodríguez A. Effects of Manual Therapy on Fatigue, Pain, and Psychological Aspects in Women with Fibromyalgia. Int J Environ Res Public Health. 2020;17(12):4611. Published 2020 Jun 26. doi:10.3390/ijerph17124611
Mohabbat AB, Mahapatra S, Jenkins SM, Bauer BA, Vincent A, Wahner- Roedler DL. Use of Complementary and Integrative Therapies by Fibromyalgia Patients: A 14-Year Follow-up Study. Mayo Clin Proc Innov Qual Outcomes. 2019;3(4):418-428. Published 2019 Oct 16. doi:10.1016/j.mayocpiqo.2019.07.003
Pfalzgraf AR, Lobo CP, Giannetti V, Jones KD. Use of Complementary and Alternative Medicine in Fibromyalgia: Results of an Online Survey. Pain Manag Nurs. 2020 Dec;21(6):516-522. doi: 10.1016/j.pmn.2020.07.003. Epub 2020 Sep 4. PMID: 32893131; PMCID: PMC7722066.
Murphy L, Ng K, Isaac P, Swidrovich J, Zhang M, Sproule BA. The Role of the Pharmacist in the Care of Patients with Chronic Pain. Integr
Pharm Res Pract. 2021;10:33-41. Published 2021 Apr 30. doi:10.2147/IPRP.S248699
Giannitrapani KF, Glassman PA, Vang D, et al. Expanding the role of clinical pharmacists on interdisciplinary primary care teams for chronic pain and opioid management. BMC Fam Pract. 2018;19(1):107. Published 2018 Jul 3. doi:10.1186/s12875-018-0783-9
Lowry E, Marley J, McVeigh JG, McSorley E, Allsopp P, Kerr D. Dietary Interventions in the Management of Fibromyalgia: A Systematic Review and Best-Evidence Synthesis. Nutrients. 2020;12(9):2664. Published 2020 Aug 31. doi:10.3390/nu12092664
Pleman B, Park M, Han X, et al. Mindfulness is associated with psychological health and moderates the impact of fibromyalgia. Clin Rheumatol. 2019;38(6):1737-1745. doi:10.1007/s10067-019-04436-1
Sosa-Reina MD, Nunez-Nagy S, Gallego-Izquierdo T, Pecos-Martín D, Monserrat J, Álvarez-Mon M. Effectiveness of Therapeutic Exercise in Fibromyalgia Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Biomed Res Int. 2017;2017:2356346. doi: 10.1155/2017/2356346. Epub 2017 Sep 20. PMID: 29291206; PMCID: PMC5632473.
Lau ET, Tan SH, Antwertinger YJ, Hall T, Nissen LM. Counseling interactions between patients living with persistent pain and pharmacists in Australia: are we on the same page?. J Pain Res. 2019;12:2441-2455. Published 2019 Aug 5. doi:10.2147/JPR.S199017
National Institute of Arthritis and Musculoskeletal and Skin Diseases. https://www.niams.nih.gov/. Accessed August 30, 2022.
Banfi G, Diani M, Pigatto PD, Reali E. T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives. Int J Mol Sci. 2020 Feb 11;21(4):1186. doi: 10.3390/ijms21041186. PMID: 32054062; PMCID: PMC7072736.
Markkula RA, Kalso EA, Kaprio JA. Predictors of fibromyalgia: a population-based twin cohort study. BMC Musculoskelet Disord. 2016 Jan 15;17:29. doi: 10.1186/s12891-016-0873-6. PMID: 26772544; PMCID: PMC4715288.
Littlejohn G, Guymer E. Neurogenic inflammation in fibromyalgia. Semin Immunopathol. 2018 May;40(3):291-300. doi: 10.1007/s00281-018- 0672-2. Epub 2018 Mar 19. PMID: 29556959.
Prados G, Miró E, Martínez MP, Sánchez AI, Lami MJ, Cáliz R. Combined cognitive-behavioral therapy for fibromyalgia: Effects on polysomnographic parameters and perceived sleep quality. Int J Clin Health Psychol. 2020;20(3):232-242. doi:10.1016/j.ijchp.2020.04.002
Husak AJ, Bair MJ. Chronic Pain and Sleep Disturbances: A Pragmatic Review of Their Relationships, Comorbidities, and Treatments. Pain Med. 2020 Jun 1;21(6):1142-1152. doi: 10.1093/pm/pnz343. PMID: 31909797.
Merriwether EN, Rakel BA, Zimmerman MB, Dailey DL, Vance CGT, Darghosian L, Golchha M, Geasland KM, Chimenti R, Crofford LJ, Sluka KA. Reliability and Construct Validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments in Women with Fibromyalgia. Pain Med. 2017 Aug 1;18(8):1485-1495. doi: 10.1093/pm/pnw187. PMID: 27561310; PMCID: PMC6279305.
McCrae CS, Williams J, Roditi D, Anderson R, Mundt JM, Miller MB, Curtis AF, Waxenberg LB, Staud R, Berry RB, Robinson ME. Cognitive behavioral treatments for insomnia and pain in adults with comorbid chronic insomnia and fibromyalgia: clinical outcomes from the SPIN randomized controlled trial. Sleep. 2019 Mar 1;42(3):zsy234. doi: 10.1093/sleep/zsy234. PMID: 30496533; PMCID: PMC6424087.
DISCLAIMER
The information provided in this course is general in nature, and it is solely designed to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.
Healthcare professionals, including pharmacists and pharmacy technicians, must consult with their employer, healthcare facility, hospital, or other organization, for guidelines, protocols, and procedures they are to follow. The information provided in this course does not replace those guidelines, protocols, and procedures but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.
Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses are constantly changing, and any person taking this course understands that such person must make an independent review of medication information prior to any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.
Nothing contained in this course represents the opinions, views, judgments, or conclusions of RxCe.com LLC. RxCe.com LLC is not liable or responsible to any person for any inaccuracy, error, or omission with respect to this course, or course material.