94302 • Fibromyalgia

Table of Contents

94302 • Fibromyalgia

How to Receive Credit

Course Overview

Audience

Accreditations & Approvals

Designations of Credit

Individual State Nursing Approvals

Special Approvals

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

Director of Development and Academic Affairs

Director Disclosure Statement

About the Sponsor

Disclosure Statement

Implicit Bias in Health Care

1. INTRODUCTION

2. EPIDEMIOLOGY

3. PATHOGENESIS

4. POTENTIAL ENVIRONMENTAL RISK FACTORS

5. ASSOCIATION WITH AUTOIMMUNE DISEASES

6. CLINICAL MANIFESTATIONS

7. DIAGNOSTIC EVALUATION

RANGE AND VARIATION IN SYMPTOMS

ASSESSMENT OF FIBROMYALGIA-RELATED SYMPTOMS

DIAGNOSTIC CRITERIA

COMORBIDITIES AND COMPLEX DIFFERENTIAL DIAGNOSIS

8. TREATMENT

NONPHARMACOLOGIC TREATMENT

PHARMACOLOGIC TREATMENT

9. FOLLOW-UP

10. CONCLUSION

Works Cited

Evidence-Based Practice Recommendations Citations

94302 • Fibromyalgia

Lori L. Alexander, MTPW, ELS, MWC

John M. Leonard, MD

www.netce.com

Copyright © 2026 NetCE, All rights reserved.

This course provides an overview of the current understanding of the pathogenesis of and evidence-based approaches to the diagnosis, treatment, and follow-up for fibromyalgia. Fibromyalgia is found in a substantial proportion of individuals with an autoimmune disease and can be difficult to diagnose and treat. The discussion of diagnosis emphasizes differentiating characteristics and the need to evaluate patients for signs of other diseases that are frequently found concurrently. Throughout, evidence-based approaches are described, when available, and patient education is highlighted, as self-management is an essential component in the treatment of this chronic disorder.

94302 • Fibromyalgia

Education Category. Infection Control / Internal Medicine

Release Date. 08/01/2026

Expiration Date. 07/31/2029

How to Receive Credit

To complete this course for continuing education credit please go to http://www.netce.com/course/3639 in your browser.

For assistance with receiving continuing education credit, please contact us at help@netce.com.

Course Overview

This course provides an overview of the current understanding of the pathogenesis of and evidence-based approaches to the diagnosis, treatment, and follow-up for fibromyalgia. Fibromyalgia is found in a substantial proportion of individuals with an autoimmune disease and can be difficult to diagnose and treat. The discussion of diagnosis emphasizes differentiating characteristics and the need to evaluate patients for signs of other diseases that are frequently found concurrently. Throughout, evidence-based approaches are described, when available, and patient education is highlighted, as self-management is an essential component in the treatment of this chronic disorder.

Audience

This course is designed for physicians, physician assistants, nurses, and other healthcare professionals involved in the diagnosis, treatment, and care of patients with fibromyalgia.

Accreditations & Approvals

In support of improving patient care, TRC Healthcare/NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. NetCE is accredited by the International Accreditors for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.

Designations of Credit

This activity was planned by and for the healthcare team, and learners will receive 3 Interprofessional Continuing Education (IPCE) credit(s) for learning and change. NetCE designates this enduring material for a maximum of 3 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 3 ANCC contact hour(s). NetCE designates this continuing education activity for 1 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 3.6 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 3 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and/or Self-Assessment requirements of the American Board of Surgery's Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. This activity has been approved for the American Board of Anesthesiology’s® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program® (MOCA®), known as MOCA 2.0®. Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program® and MOCA® are registered certification marks of the American Board of Anesthesiology®. MOCA 2.0® is a trademark of the American Board of Anesthesiology®. Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 3 MOC points in the American Board of Pediatrics' (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. This activity has been designated for 3 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME's "CME in Support of MOC" program in Section 3 of the Royal College's MOC Program. NetCE is authorized by IACET to offer 0.3 CEU(s) for this program. AACN Synergy CERP Category A.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353 (valid through July 30, 2029); Arkansas, Provider #50-2405; California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; District of Columbia, Provider #50-2405; Florida, Provider #50-2405; Georgia, Provider #50-2405; Kentucky, Provider #7-0054 through 12/31/2027; South Carolina, Provider #50-2405; West Virginia RN and APRN, Provider #50-2405.

Special Approvals

This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.

Course Objective

The purpose of this course is to provide healthcare professionals with the information necessary to diagnose and treat fibromyalgia according to evidence-based or guideline-endorsed recommendations in order to improve patient quality of life.

Learning Objectives

Upon completion of this course, you should be able to:

1. Outline the assessment and diagnostic criteria established for fibromyalgia and discuss potential difficulties in establishing a diagnosis.

2. Identify appropriate treatment modalities for patients with fibromyalgia, including patient education and follow-up needs.

Faculty

Lori L. Alexander, MTPW, ELS, MWC, is President of Editorial Rx, Inc., which provides medical writing and editing services on a wide variety of clinical topics and in a range of media. A medical writer and editor for more than 30 years, Ms. Alexander has written for both professional and lay audiences, with a focus on continuing education materials, medical meeting coverage, and educational resources for patients. She is the Editor Emeritus of the American Medical Writers Association (AMWA) Journal, the peer-review journal representing the largest association of medical communicators in the United States. Ms. Alexander earned a Master’s degree in technical and professional writing, with a concentration in medical writing, at Northeastern University, Boston. She has also earned certification as a life sciences editor and as a medical writer.

John M. Leonard, MD, Professor of Medicine Emeritus, Vanderbilt University School of Medicine, completed his post-graduate clinical training at the Yale and Vanderbilt University Medical Centers before joining the Vanderbilt faculty in 1974. He is a clinician-educator and for many years served as director of residency training and student educational programs for the Vanderbilt University Department of Medicine. Over a career span of 40 years, Dr. Leonard conducted an active practice of general internal medicine and an inpatient consulting practice of infectious diseases.

Faculty Disclosure

Contributing faculty, Lori L. Alexander, MTPW, ELS, MWC, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Contributing faculty, John M. Leonard, MD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John V. Jurica, MD, MPH

Mary Franks, MSN, APRN, FNP-C

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Director of Development and Academic Affairs

Sarah Campbell

Director Disclosure Statement

The Director of Development and Academic Affairs has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Implicit Bias in Health Care

The role of implicit biases on healthcare outcomes has become a concern, as there is some evidence that implicit biases contribute to health disparities, professionals' attitudes toward and interactions with patients, quality of care, diagnoses, and treatment decisions. This may produce differences in help-seeking, diagnoses, and ultimately treatments and interventions. Implicit biases may also unwittingly produce professional behaviors, attitudes, and interactions that reduce patients' trust and comfort with their provider, leading to earlier termination of visits and/or reduced adherence and follow-up. Disadvantaged groups are marginalized in the healthcare system and vulnerable on multiple levels; health professionals' implicit biases can further exacerbate these existing disadvantages.

Interventions or strategies designed to reduce implicit bias may be categorized as change-based or control-based. Change-based interventions focus on reducing or changing cognitive associations underlying implicit biases. These interventions might include challenging stereotypes. Conversely, control-based interventions involve reducing the effects of the implicit bias on the individual's behaviors. These strategies include increasing awareness of biased thoughts and responses. The two types of interventions are not mutually exclusive and may be used synergistically.

1. INTRODUCTION

Fibromyalgia is a chronic, complex centralized pain syndrome characterized by disordered processing of painful stimuli resulting in widespread musculoskeletal pain and often accompanied by fatigue, sleep disturbances, and cognitive symptoms [1,2]. Acceptance of fibromyalgia as a distinct clinical entity (not associated with an apparent organic disease) has been slow but is gaining recognition [3; 4; 5]. A 2024 study found that 84% of physicians considered fibromyalgia a distinct clinical entity, and 51% considered the condition psychosocial in nature [6]. While long considered a rheumatic disorder, fibromyalgia has been more accurately reclassified as a central pain syndrome or neurological disorder, although it is often diagnosed with other rheumatic diseases [4]. The onset of fibromyalgia is insidious, symptoms wax and wane in intensity, and the course is variable [1].

Fibromyalgia has a substantial negative effect on physical, psychological, and social well-being, and the syndrome is associated with a significant burden in terms of both disability and healthcare costs. Fibromyalgia has been found to have a greater negative impact on quality of life than many other diseases, including osteoarthritis, chronic obstructive pulmonary disease, and permanent ostomies [7]. Activities of daily living and work within the home are often substantially limited. In a large survey of women 31 to 78 years of age, more than 25% had difficulty taking care of personal needs and bathing and more than 60% had difficulty doing light housework, going up/down one flight of stairs, walking one-half mile, or lifting/carrying 10 pounds [9]. The average survey respondent was assessed as having less functional ability than a typical woman in her 80s [9]. Approximately 20% to 50% of individuals with fibromyalgia are able to work few or no days; 36% are absent from work two or more days each month; 31% have lost employment; and 26% to 55% receive disability or Social Security payments [10].

The economic burden is also high. According to a study published in 2022, the total direct cost of fibromyalgia was estimated to be between $1,750 and $35,920 per patient [11]. Healthcare costs of fibromyalgia are two to three times higher (compared with controls) as a result of more visits to the physician's office or emergency department and a higher number of prescription medications [11]. Healthcare utilization and costs are often higher in the years preceding as well as following the initial diagnosis of fibromyalgia [11,12].

2. EPIDEMIOLOGY

According to prevalence and population estimates, fibromyalgia affects approximately 4 million people in the United States. Determining the true prevalence is difficult because of the problems associated with defining its diagnosis according to the available criteria. The prevalence is estimated to be 2% to 8% of the population and increases with age [1,13].

As with autoimmune diseases, the prevalence of fibromyalgia is higher among women than men, although data are conflicting. Studies have found that women are diagnosed between 2 to 14 times as often as men, depending on the criteria used [1]. Fibromyalgia is usually diagnosed between the ages of 20 and 55 years, but can affect individuals of all ages, including children [1,13].

The prevalence of fibromyalgia according to race/ethnicity in older studies has been inconclusive, as studies have either included a predominantly White population or have not specified the race/ethnicity of the subjects [14,15]. In general, fibromyalgia is reported to be more prevalent among White adults than Black, Hispanic, Asian, or American Indian individuals. However, studies have shown that, compared to White individuals, non-Hispanic Black individuals experience a lower rate of fibromyalgia diagnosis and lower rates of pain control. While no known etiological differences explain this disparity, some scholars have cited factors within the healthcare system related to differential treatment of pain and pain-related diagnoses between Black and White adult patients [14,15]. There is no evidence of a higher prevalence of fibromyalgia in industrialized countries and cultures.

3. PATHOGENESIS

Several etiologies for fibromyalgia have been postulated and explored; the syndrome has been thought to be an inflammatory condition, an autoimmune disease, a rheumatic disease, an unexplained medical syndrome, or a psychiatric condition [3,4,16,17]. However, research has provided little or no evidence to support these bases [1,5].

Pioneering sleep studies in the 1970s demonstrated that people with fibromyalgia had abnormal sleep physiology, suggesting a central pathology [18]. Since then, substantial evidence has supported a mechanism of central sensitization, or the amplification of pain in the spinal cord through spontaneous nerve activity, expanded receptive fields, and augmented stimulus responses. Studies have also shown that, compared with healthy individuals, people with fibromyalgia experience pain differently and have physiologically lower pain thresholds. Research has also indicated significant dysregulation of the hypothalamic-pituitary-adrenal axis is found in fibromyalgia. In addition, there may be abnormalities of descending inhibitory pathways, neurotransmitters, or neurohumoral responses; low levels of serotonin and norepinephrine metabolites have been found in the cerebrospinal fluid of individuals with fibromyalgia [1].

Genetics is thought to be a factor in the susceptibility of fibromyalgia. Family clustering has been reported, and the risk for fibromyalgia is up to nine times higher for first-degree relatives of individuals with the syndrome [1,19]. Abnormalities in the serotonin transporter gene, dopamine receptor gene, and the catecholamine-O-methyltransferase gene have been identified [19]. These abnormalities affect the metabolism or transport of serotonin and norepinephrine, which decrease the sensitivity of pain-processing systems through the descending central nervous system pain pathways [1,19]. Additional suggested etiologies include diffuse inflammation, glial cell activation, and small fiber neuropathy [1].

4. POTENTIAL ENVIRONMENTAL RISK FACTORS

As with autoimmune diseases, several environmental risk factors have been thought to act as triggers for the development of fibromyalgia. Because research on the etiology of fibromyalgia is lacking, individuals' perceptions of triggers have been the source of some of the available information [20]. Perhaps as a result, data on the frequency of environmental triggers are conflicting, with some studies showing that half of all cases have a distinct physical or emotional trigger and other studies indicating that three-quarters of cases or more had no triggering event [4,20].

Psychiatric conditions have long been associated with fibromyalgia, and research suggests that such conditions may precede fibromyalgia and act as a trigger for the disease. In one study, when individuals were asked what they perceived to be a trigger for fibromyalgia, 73% attributed the development of the disease to emotional trauma or chronic stress; 24% noted emotional/physical abuse as an adult or child as a perceived trigger [20].

Injury/trauma and physical illness may also be triggers. Approximately one-third of individuals who attributed fibromyalgia to an environmental trigger noted physical injury (including those from a motor vehicle accident) as the perceived trigger [20]. Acute illness was perceived as a trigger in 27% of individuals in the same survey [20]. Viral infections have been associated with the development of fibromyalgia, and hepatitis C, Epstein-Barr virus, human immunodeficiency virus (HIV), parvovirus, and Lyme disease are thought to be viral triggers, but no causality has been established. Other pain conditions, hyperprolactinemia, and autoimmune diseases have also been reported to be factors [4,21].

5. ASSOCIATION WITH AUTOIMMUNE DISEASES

Several autoimmune diseases have been found in conjunction with fibromyalgia. In a retrospective study of 2,595 cases of fibromyalgia in a nationwide claims database, the likelihood of systemic lupus or rheumatoid arthritis was two to seven times greater than that for controls [22]. Other studies have confirmed an association between fibromyalgia and systemic lupus and rheumatoid arthritis, with reported rates of up to 65% and 57%, respectively [23]. High rates of Sjögren syndrome (up to 50%), and thyroiditis (up to 31%) have also been reported among individuals with fibromyalgia [1,7,24]. A small study has suggested that Hashimoto disease and/or subclinical hypothyroidism may be a predisposition to fibromyalgia; signs and symptoms of fibromyalgia were found in nearly one-third of individuals [24].

6. CLINICAL MANIFESTATIONS

Chronic, widespread musculoskeletal pain (pain in at least four out of five regions for at least three months) is the defining feature of fibromyalgia [1,25]. This pain is often associated with muscle tenderness (to palpation) adjacent to areas of tendon insertion. In addition, a constellation of other symptoms is common and varies across patients. Most patients complain of stiffness (especially in the morning), fatigue, sleep abnormalities, and difficulties of cognition, such as mental torpor, maintaining attention, and performing tasks that require rapid thought [1,25].

The likelihood of depression is high among individuals with fibromyalgia. Depression has been identified in more than 50% of individuals with the syndrome. Factors associated with major depression have included younger age, female gender, being unmarried, number of chronic conditions, and limitations in activities [1,26].

Cognitive dysfunction (often referred to as "fibrofog") affects approximately 50% to 80% of individuals with fibromyalgia [26]. The primary effect is on memory (working, episodic, and semantic), especially when tasks are complex and the individual's attention is divided [26]. Although memory impairment is not as common as many other symptoms, patients have considered them to be among the most troublesome, which is not surprising given that the impairment is equivalent to about 20 years of aging [27]. Attentional control/function is also commonly impaired in individuals with fibromyalgia. Studies have indicated that cognitive dysfunction cannot be attributed solely to symptoms such as depression, anxiety, and sleep problems, but it does seem to be related to the level of pain [28,29].

7. DIAGNOSTIC EVALUATION

Fibromyalgia cannot be diagnosed on the basis of laboratory tests, imaging studies, or pathologic results. As a result, the diagnosis relies on a clinical diagnosis after careful review of medical history and comprehensive physical examination. The current challenge in diagnosing fibromyalgia stems from many factors, including a wide range and variation in symptoms and a complex differential diagnosis. As such, it often takes more than two years to receive a diagnosis of fibromyalgia, with patients seeing an average of 3.7 different physicians during that time [30].

RANGE AND VARIATION IN SYMPTOMS

There is a wide range of symptoms and comorbidities associated with fibromyalgia, and they occur in a variety of combinations and differ in terms of severity. After the three primary manifestations (fatigue, stiffness, and sleep abnormalities), the most common symptoms are headaches (usually migraine), dry mouth, low back pain, and paresthesias (Table 1) [17,20,21,25,31]. In an online survey conducted by the National Fibromyalgia Association (NFA), 19 symptoms, affecting virtually all body systems, were noted by at least 25% of the respondents [20]. Nearly all individuals with fibromyalgia are polysymptomatic [20].

Table 1: COMMON SYMPTOMS OF FIBROMYALGIA

Symptom

Reported Prevalence

Stiffness

76% to 91%

Fatigue

24% to 90%

Sleep abnormalities

76%

Headaches

47% to 75%

Dry mouth

18% to 71%

Low back pain

67%

Paresthesias

44% to 67%

Restless legs syndrome

32% to 64%

Depression

20% to 62%

Irritable bowel syndrome

36% to 60%

Anxiety

30% to 56%

Raynaud phenomenon

9% to 53%

Muscle spasms

46%

Balance problems

45%

Cognitive dysfunction (impaired memory and/or concentration)

40%

Bloating

40%

Sinus problems

37%

Tooth disorders

32%

Jaw pain

29%

Bladder problems

26%

Source: [17,20,21,25,31]

ASSESSMENT OF FIBROMYALGIA-RELATED SYMPTOMS

Most individuals with fibromyalgia describe pain as arising from muscles and joints and also have tender skin. Pain is typically axial in distribution, and pain/stiffness usually occurs in the morning and evening. Patients may note a feeling of swelling in the soft tissues, primarily around the joints, but there is no objective evidence of swelling. Self-reports are often used as the primary source for pain assessment, focusing on such details as [1,21]:

- Type and quality of pain

- Source

- Location

- Duration

- Time course

- Pain affect

- Effects on quality of life

Patient assessment must include evaluation of the severity of symptoms most often associated with fibromyalgia, as well as overall quality of life and functional assessment [1,7,17]. Assessment tools specific to fibromyalgia and associated symptoms have been developed, including an initial screening tool, the Fibromyalgia Rapid Screening Tool (FiRST), a self-administered questionnaire developed in 2010. The tool was developed by a group of rheumatologists and pain experts and consists of six questions that can be answered with a yes/no response [32]. A score of five "yes" responses gave the highest rate of correct identification of fibromyalgia patients (87.9%), with a sensitivity of 90.5% and a specificity of 85.7% [32]. FiRST is meant to be used as an initial screening tool, with established diagnostic criteria used to subsequently confirm the diagnosis [1,32].

In addition, the Patient-Reported Outcomes Measurement Information System (PROMIS) tools for fatigue, sleep, and global health developed in 2016 may assist in assessing symptoms of fibromyalgia. The Fibromyalgia Impact Questionnaire (FIQR) is also a useful tool to assess the impact of fibromyalgia on quality of life. As part of a general health review, healthcare professionals should ask patients about how their symptoms affect their ability to work, as physical limitations and cognitive dysfunction may result in an inability to maintain normal employment [1,7,33].

Several pain assessment tools are available that may be useful in the setting of fibromyalgia (Table 2) [1,7,17].

Table 2: INSTRUMENTS FOR ASSESSMENT OF FIBROMYALGIA-RELATED SYMPTOMS

Symptom

Assessment Tool

Pain

Visual analog scale

Brief Pain Inventory

Short Form–McGill Pain Questionnaire-2

Widespread Pain Index (WPI)

Fatigue

Multidimensional Assessment of Fatigue Instrument

Multidimensional Fatigue Inventory

Fatigue Severity Scale

Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue

Sleep

Insomnia Severity Index

Medical Outcomes Study Sleep Scale

Pittsburgh Sleep Quality Index

Sleep Assessment Questionnaire

PROMIS Sleep Disturbance and Sleep Related Impairment

Depression/anxiety

Beck Depression Inventory

Patient Health Questionnaire

Beck Anxiety Inventory

Hospital Anxiety and Depression Scale

Generalized Anxiety Disorder

Quality of life/functional assessment

Fibromyalgia Impact Questionnaire-Revised

Short Form–36 Health Survey

Fibromyalgia Severity Scale (combined WPI and SSS)

PROMIS Global Health

Source: [1,7,17]

Healthcare professionals should also ask about factors that may exacerbate musculoskeletal symptoms, as these symptoms are modulated in approximately 60% to 79% of individuals [8]. Emotional distress has been the most commonly reported exacerbating factor (83%), followed by changes in the weather (80%), sleeping problems (79%), and strenuous activity (70%) [20]. Many other factors are perceived to worsen symptoms, including fatigue, physical inactivity, mental stress, soft-tissue injuries, travel in a car or plane, and work-related conflict [1,20].

In relating their history, individuals will often focus on the symptoms that are of most concern or that are most troublesome. According to the NFA survey, the most troublesome symptoms were (in descending order): morning stiffness, fatigue, nonrestorative sleep, pain, forgetfulness, poor concentration, difficulty falling asleep, muscle spasms, anxiety, and depression [20]. In another study, 100 individuals with fibromyalgia ranked symptoms slightly differently, but the top five symptoms were similar: pain or physical discomfort, joint pain/aching, fatigue or lack of energy, poor sleep, and cognitive dysfunction [34].

Because of the predominance of fibromyalgia among women, there are few data on the clinical profile for men with the syndrome. The available research points to differences in the clinical presentation according to gender. Women tend to report more symptoms, to describe more symptoms as major problems, and to report greater life interference from pain [15,35]. Men have noted significantly lower health perceptions and more physical limitations [15]. With regard to specific symptoms, fatigue and sleep disorders are more common among women, with some studies showing a threefold higher rate [35]. "Pain all over" is also more frequently reported by women than men. The most powerful discriminator between women and men with fibromyalgia is the number of tender points [35].

DIAGNOSTIC CRITERIA

In 1990, the American College of Rheumatology (ACR) designed the classification criteria for fibromyalgia for epidemiologic classification noting that the criteria would also be useful for diagnosis [8]. However, the criteria were used by only about half of rheumatologists in routine practice and were seldom used in the primary care setting. The classification system consisted of two criteria: a history of widespread pain and pain in 11 of 18 tender point sites on digital palpation. These criteria showed a sensitivity of 88%, a specificity of 81%, and an accuracy of 85%, but several important problems were identified [25,35].

The primary problem with the 1990 classification criteria for the purpose of diagnosis was found to be the focus on the tender point evaluation, which proved difficult for clinicians, especially primary care providers, to perform correctly. Perhaps equally as problematic was that widespread pain as the only criterion for diagnosis did not seem sufficient, given the broad range of symptoms associated with the syndrome. A third major problem was the lack of a severity scale, which means that an individual with fibromyalgia may not satisfy the diagnostic criteria for the syndrome if symptoms or pain at tender points improve. As a result of these drawbacks, the diagnosis of fibromyalgia was often symptom-based [1,25].

To address the problems inherent in its classification system, the ACR published diagnostic criteria for fibromyalgia in 2010/2011, which eliminated the physical examination of tender points and added the Symptom Severity Score (SSS) and the Widespread Pain Index (WPI). In 2016, the ACR further revised these criteria to construct a new case definition of fibromyalgia: a WPI score of 7 or greater and an SSS of 5 or more OR a WPI score of 4–6 and a SSS of 9 or greater. The WPI has been found to correlate well with findings of the tender point examination, eliminating the need for that examination [25]. The symptoms evaluated by the SSS are fatigue, cognitive dysfunction, and waking unrefreshed (Table 3) [25]. In addition, the updated criteria minimizes misclassification of regional pain disorders and eliminates the confusing recommendation regarding diagnostic exclusion. Another advantage is that the criteria can demonstrate change in the individual's health status and allows for fibromyalgia to be seen as part of a continuum [25].

Table 3: 2016 AMERICAN COLLEGE OF RHEUMATOLOGY (ACR) DIAGNOSTIC CRITERIA FOR FIBROMYALGIA

Criteria

A patient satisfies diagnostic criteria for fibromyalgia if the following conditions are met:

- WPI ≥7 and SSS score ≥5 or WPI 4–6 and SSS score ≥9.

- Generalized pain is present, defined as pain in at least 4 of 5 regions (left upper, right upper, left lower, right lower, axial). Jaw, chest, and abdominal pain are excluded from the generalized pain definition.

- Symptoms have been generally present at a similar level for at least three months.

- A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses.

Ascertainment

Widespread Pain Index (WPI)

Note the number of areas in which the patient has had pain over the past week. In how many of the following areas has the patient had pain? Total score will be between 0 and 19. (Number of regions will determine generalized pain definition).

Region 1: Left upper region

- Jaw, left

- Shoulder girdle, left

- Upper arm, left

- Lower arm, left

Region 2: Right upper region

- Jaw, right

- Shoulder girdle, right

- Upper arm, right

- Lower arm, right

Region 3: Left lower region

- Hip (buttock, trochanter), left

- Upper leg, left

- Lower leg, left

Region 4: Right lower region

- Hip (buttock, trochanter), right

- Upper leg, right

- Lower leg, right

Region 5: Axial region

- Neck

- Upper back

- Lower back

- Chest

- Abdomen

Symptom Severity Score (SSS)

For each of the following symptoms, 1) fatigue; 2) waking unrefreshed; and 3) cognitive symptoms, indicate the level of severity over the past week using the following scale. Combine the number ratings for each symptom. Score will be between 0 and 9.

0 = No problem

1 = Slight or mild problems, generally mild or intermittent

2 = Moderate, considerable problems, often present and/or at a moderate level

3 = Severe: pervasive, continuous, life-disturbing problems

Add 1 point to the previous symptom score (0–9) for each additional symptom that has occurred within the previous 6 months. Total score will be between 0 and 12.

Headaches (+1)

Pain or cramps in lower abdomen (+1)

Depression (+1)

Source: [25]

COMORBIDITIES AND COMPLEX DIFFERENTIAL DIAGNOSIS

Given the broad range of symptoms and conditions found in association with fibromyalgia, it is difficult to differentiate true comorbidities from manifestations of the syndrome itself [36]. For example, irritable bowel syndrome and restless legs syndrome are traditionally thought of as comorbidities but may be part of the overall clinical syndrome [8,36,25]. This is true for many autoimmune diseases but particularly for fibromyalgia, which has been described as overlapping with virtually every other unexplained syndrome [1,3]. In a study in which current and lifetime comorbidities associated with fibromyalgia, rheumatoid arthritis, and systemic lupus were evaluated, fibromyalgia was associated with significantly higher rates of depression and psychiatric conditions, gastrointestinal problems, and severe allergies (Table 4) [36].

Table 4: COMORBIDITIES ASSOCIATED WITH FIBROMYALGIA

Comorbidity

Prevalence

Lifetime

Current

Any gastrointestinal problem

72%

34%

Any psychiatric problem

68%

39%

Depression

68%

39%

Hypertension

49%

35%

Any genitourinary problem

48%

5%

Severe allergies

41%

21%

Any endocrine problem

40%

28%

Any lung problem

37%

19%

Source: [36]

The multitude of symptoms and comorbidities associated with fibromyalgia add to the complexity of making a differential diagnosis. Many other conditions can mimic widespread pain, and these conditions must be considered in the differential diagnosis (Table 5). Although most objective testing cannot confirm a diagnosis of fibromyalgia, it can play an important role in ruling out other possible diagnoses. A CBC, ESR, muscle enzymes, liver function studies, and thyroid function tests can help identify other conditions. However, given the high rate of conditions that occur concurrently with fibromyalgia, clinicians must remember that finding another diagnosis does not automatically rule out a diagnosis of fibromyalgia, and fibromyalgia may be diagnosed concurrently with other diseases. Differentiating fibromyalgia from other rheumatic diseases and conditions involving widespread pain is especially difficult. Individuals who have widespread pain and fibromyalgia are typically more symptomatic, dysfunctional, and depressed than people who have widespread pain without fibromyalgia [1,25].

Table 5: DIFFERENTIAL DIAGNOSIS OF FIBROMYALGIA

Diagnoses to Consider

Shared Manifestations

Distinguishing Features

Myofascial pain syndrome

Painful, tender areas in the muscles, commonly affecting the axial muscles

Pain arising from trigger points in individual muscles during examination

Chronic fatigue syndrome

Chronic pain and fatigue

Low-grade fever, enlargement of lymph glands, continuous subclinical inflammatory process, and acute onset of illness

Rheumatoid arthritis

Joint pain/stiffness

Involvement of hands and feet, positive rheumatoid factor (in 80% to 90% of cases), radiographic evidence of joint erosion

Systemic lupus erythematosus

Involvement of multiple systems, joint pain

Malar rash, positive antinuclear antibody test

Hypothyroidism

Profound fatigue, muscle weakness, mental slowing

Weight gain, hair loss, increased TSH level

Polymyalgia rheumatica

Pain/stiffness in sacrohumeral and pelvic girdle

Increased ESR (in 80% to 90% of cases), age older than 65 years, treatment with glucocorticoids resolves symptoms

Spondyloarthropathy

Pain in neck, mid-thoracic, anterior chest wall, or lumbar regions

Pain localized to specific spinal areas, radiographic evidence of sacroiliitis, or radiographic changes in vertebral bodies

Polyarticular osteoarthritis

Pain in multiple joints

Radiographic evidence of joint degeneration

Polymyositis or other myopathies

Muscle weakness

Proximal, symmetrical muscles affected, increased serum levels of muscle enzymes, abnormal findings on EMG testing and on evaluation of biopsy samples

Neuropathic pain syndromes

Tingling, numbness

Burning, shooting pain

EMG = electromyography; ESR = erythrocyte sedimentation rate; TSH = thyroid-stimulating hormone.

Source: [1,21]

One test that may be of use in the diagnosis of fibromyalgia is a cytokine array–based blood test, known as the FM/a Test. This test has the potential to help confirm the diagnosis of fibromyalgia, as patients with fibromyalgia demonstrate higher cytokine production in stimulated immune cells than in the general population. The FM/a Test demonstrated 93% sensitivity and 89% specificity in 160 patients with fibromyalgia. Compared with people who have rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) without fibromyalgia, the specificity of the FM/a Test was 70%, making this test useful in differentiating patients with fibromyalgia from those with RA or SLE or from healthy control patients. It should be noted that this test has not been shown to distinguish fibromyalgia from non-fibromyalgia in previously undiagnosed patients with several typical fibromyalgia symptoms. Other limitations of this test are a high cost compared with using standard criteria for diagnosis and the need to discontinue all immune suppressing medication for at least 14 days prior to testing [1,37].

8. TREATMENT

As with all chronic illnesses, the goal of treatment in fibromyalgia is to reduce symptoms, improve function, and engage the patient's involvement in self-care. Studies have shown that treatment is most effective when it includes the combination of patient education, lifestyle changes (including exercise), cognitive-behavioral therapy, and/or selective pharmacotherapy for persistent symptoms or comorbidities [1,2].

Management guidelines for fibromyalgia were published in 2016 by the European League Against Rheumatism (EULAR), with subsequent systematic reviews and meta-analyses continuing to support a combination of pharmacologic and nonpharmacologic treatment [2]. It should be noted that the American Pain Society (APS) originally published the first fibromyalgia management guidelines in 2005, which were widely used and cited in literature, and foundational for the current EULAR guidelines. However, the organization permanently closed in 2019, and the APS guidelines are now considered archived and historical [38].

Familiarity with current guidelines and recommended treatments, especially among primary care providers, is low, and adherence is suboptimal. A meta-analysis published in 2024 that included nearly 9,000 physician participants found that knowledge of formal diagnostic criteria for fibromyalgia was more likely among rheumatologists (69%) versus general practitioners (38%). In regard to treatment, symptom relief was endorsed as the primary management goal by most physicians (73%). Exercise, physiotherapy, antidepressants, nonsteroidal anti-inflammatory drugs, and non-opioid analgesics were the most endorsed management therapies for fibromyalgia. Opioids and most complementary and alternative interventions (e.g., homeopathy, chiropractic, and massage) received limited endorsement [6].

NONPHARMACOLOGIC TREATMENT

Nonpharmacologic measures are important components of an effective fibromyalgia treatment plan. Strong evidence has been documented for physical activity (including aerobic and/or muscle-strength training), cognitive-behavioral therapy, and patient education, and the combination of the three components is recommended as the initial management approach [1,2].

Patient Education

The goal of patient education is to effect a change in the patient's perception of his or her role in managing and coping with symptoms. Patients benefit from an explanation of the disease and reassurance regarding symptoms and prognosis; other topics for discussion are treatment options, sleep hygiene, the importance of conditioning and exercise, and the role of pharmacotherapy for pain and comorbidities. There is good evidence that patient education is an essential component of effective treatment and can improvement symptoms of pain, fatigue, morning tiredness, stiffness, anxiety, and depression. Education in a variety of formats has been found to be useful, including lectures, written materials, group discussions, demonstrations, and Internet-based programs and support groups. Healthcare professionals should encourage their patients to take advantage of many free reliable online educational resources [1,2].

Language, cultural competency, and health literacy are significant issues, given the growing percentages of racial/ethnic populations. According to U.S. Census Bureau data from 2024, more than 50.2 million Americans are foreign-born, 74 million Americans (23% of the population) speak a language other than English at home, and more than 28.9 million (9% of the population) report that they speak English less than "very well" [39]. Clinicians should ask their patients what language they prefer for their medical care information, as some individuals prefer their native language even though they have said they can understand and discuss symptoms in English [40].

Most important, perhaps, is the fact that clinical consequences are more likely with ad hoc interpreters than with professional interpreters [41]. A systematic review of the literature showed that the use of professional interpreters facilitates a broader understanding and leads to better clinical care than the use of ad hoc interpreters, and many studies have demonstrated that the lack of an interpreter for patients with limited English proficiency compromises the quality of care. The use of professional interpreters improves communication (errors and comprehension), utilization, clinical outcomes, and patient satisfaction with care [42,43].

Exercise

The EULAR guidelines strongly recommend exercise as part of treatment for fibromyalgia, as it is effective for pain management and physical function and well-being and is cost-effective, readily available, and poses a low safety concern. Evidence did not distinguish between benefits of aerobic versus strength-training exercises and additionally found that both land and aquatic exercises appear equally effective [2].

Exercise not only helps to alleviate many fibromyalgia symptoms but also helps to reverse the effects of deconditioning and improve physical fitness [35,44,45,46,50]. In a study of 207 women who were actively treated with medication for confirmed fibromyalgia, progressive walking, simple strength-training exercises, and stretching activities led to several improvements, including higher scores for functional status, reduced fatigue, better mental health, reduced depression, and greater self-efficacy [44]. The benefits of exercise are enhanced when combined with targeted self-management education [21,44].

A meta-analysis showed that supervised aerobic exercise training has beneficial effects on physical capacity and symptoms related to fibromyalgia and that strength training may also have benefits on some fibromyalgia symptoms [47]. Another meta-analysis published in 2010 showed that aerobic exercise has a significant positive effect on a variety of disease-related symptoms, with reductions in pain, fatigue, depressed mood, and limitations of health-related quality of life, as well as improved physical fitness [46]. A 2013 Cochrane review found low-quality evidence that resistance training (moderate-to-high intensity) improves functioning, muscle strength, pain, and tenderness in women with fibromyalgia [48]. Other low-quality evidence suggests that aerobic exercise is superior to resistance training for improving pain, but resistance training is superior to flexibility exercise training in women with fibromyalgia for improvements in pain and multidimensional function. Moderate-to-high resistance training is safe for women with fibromyalgia [48].

A 2018 report provides evidence that a mind-body treatment approach, specifically a tai-chi program, is of equal or greater benefit than standard care aerobic exercise alone [49]. In this blinded, prospective study, 226 adults with fibromyalgia (WPI ≥7 and SSS ≥5) were randomly assigned either to supervised aerobic exercise (24 weeks, twice weekly) or to one of four classic Yang-style tai chi interventions (12 or 24 weeks, once or twice a week). Participants were followed for 52 weeks; the primary outcome was change in the fibromyalgia impact questionnaire scores at 24 weeks compared with baseline. The results showed that improvement in symptom scores was greater for subjects in each of the tai chi groups than for those receiving aerobic exercise. A clinically significant difference was only observed when comparing the highest-intensity tai chi program (twice weekly for 24 weeks) with aerobic exercise. Benefit with respect to secondary outcomes (assessment scores for anxiety, depression, coping strategies, functional limitations, sleep, and quality of life) also favored the tai chi interventions. At 52 weeks the combined tai chi groups continued to show more improvement in primary and most secondary outcomes than the aerobic exercise group [49].

EULAR notes that exercises should be tailored to the individual patient, and modifications should be made according to the severity of symptoms [2]. For example, a sedentary individual with moderate-to-severe fibromyalgia should begin with breathing, posture, and relaxation training, move to flexibility exercises, then to strength and balance exercise, and finally, to aerobic exercise [45].

Cognitive-Behavioral Therapy

The goal of cognitive-behavioral therapy is to move patients toward more adaptive beliefs about their ability to cope with symptoms, which in turn increases self-management [50]. Cognitive-behavioral therapy is designed to help individuals improve the way they think about fibromyalgia and cope with the overall effects of its symptoms [35]. It is most effective when it focuses on a specific outcome, especially one that is the subject of the patient's maladaptive thoughts and expectations [35,50].

A systematic review of 23 studies showed that of 30 psychological treatments for fibromyalgia, cognitive-behavioral therapy was associated with the greatest effect sizes, especially for short-term reduction in pain [51]. Cognitive-behavioral therapy has been shown to lead to improvements in short-term and medium-term reductions in pain and disability [1]. Benefit is typically achieved in 10 to 20 sessions [21]. Despite recommendations for cognitive-behavioral therapy, it may be underutilized [20].

Cognitive-behavioral therapy has been significantly beneficial in many individuals with psychiatric illnesses, such as depression and anxiety disorders, and so may be most useful for individuals with fibromyalgia who have these symptoms. The individuals most likely to respond are probably those who have greater emotional distress, fewer coping skills, or less social support [1,21].

Other Approaches

Relaxation techniques are often part of cognitive-behavioral therapy for fibromyalgia, and their effectiveness is generally accepted, even though direct evidence is lacking. Mindfulness-based stress reduction therapy has also been evaluated; however, only weak evidence exists for benefit in fibromyalgia [2,50,52].

The EULAR guidelines include a "weak for" evidence-based recommendation (level Ia) for hydrotherapy (e.g., spa, heated pool) or acupuncture on the basis of studies showing improvement in pain and function, although a review of 10 randomized controlled trials demonstrated moderate evidence that hydrotherapy has short-term beneficial effects on pain and health-related quality of life [2].

The lack of fully effective treatments has led patients—and sometimes their healthcare providers—to explore other options to help manage symptoms. Some of these options have no or weak evidence of effectiveness, and the approaches most commonly used by patients are often not recommended practices. For example, the three interventions used most often by the NFA survey respondents were resting (86%); distraction, such as reading or watching television (80%); and heat modalities, such as warm water or hot packs (74%) [20]. The issue is not that these methods are not helpful, rather that the use rates for these approaches are much higher than for many evidence-based recommended strategies [20].

Among the other approaches patients often try are complementary and alternative medicine; between 40% and 90% of individuals with fibromyalgia have tried at least one such method [20,53,54]. However, evidence indicates that most of these methods are ineffective. There is limited evidence to support spinal manipulation. Evidence is also lacking on the effectiveness of herbal, nutritional, and dietary supplements (including St. John's wort, ginseng, valerian, melatonin, and botanical oil) for the symptomatic treatment of fibromyalgia [2,50]. Despite this, approximately 43% to 68% of people with fibromyalgia use such supplements, although they give low ratings for their effectiveness [20,53]. Given the high rate of individuals with fibromyalgia who seek symptomatic relief from complementary and alternative methods, it is important that clinicians ask their patients about their use of such practices and educate them about their effectiveness and possible negative interactions.

Methods with greater evidence of benefit include acupuncture and massage therapy. A 2013 Cochrane review found low-to-moderate level evidence that acupuncture (particularly electro-acupuncture) is effective for the treatment of fibromyalgia symptoms compared with no treatment or standard therapy [55]. Acupuncture in general may relieve pain and stiffness, and electro-acupuncture may improve overall well-being, fatigue, and sleep quality. A 2014 meta-analysis of nine randomized controlled trials found that massage therapy (for at least five weeks) has beneficial immediate effects on improving pain, anxiety, and depression in fibromyalgia patients [56]. However, no follow-up data are available to show long-term benefit. Long-term data are similarly unavailable for qigong, a somewhat popular Chinese medical exercise, but low-quality evidence exists for the short-term improvement of pain, quality of life, and sleep quality and very low-quality evidence exists for improvement of fatigue [57]. Increased psychological well-being is often reported by qigong practitioners.

PHARMACOLOGIC TREATMENT

No single drug has been found to manage all fibromyalgia symptoms, and a combination approach is often used [20,2]. Antidepressants were the first medications used to treat fibromyalgia; drugs in this class include tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). In general, antidepressants reduce pain through a direct effect rather than an indirect effect mediated by an effect on depression. Other drugs that have been shown to be effective include anticonvulsant drugs, some analgesics/muscle relaxants, and nonbenzodiazepines (Table 6) [2,58,59,60].

Table 6: PHARMACOLOGIC TREATMENTS USED IN FIBROMYALGIA

Drug

Dose

Common Adverse Events

Comments

Antidepressants

Amitriptyline

25–50 mg PO at bedtime

Nausea, vomiting, dry mouth, dizziness, drowsiness, headache

Recommended "weak for" by EULAR; found effective at low dose 6 to 8 weeks; high dose did not demonstrate efficacy

Duloxetine

60 mg PO daily

Nausea, dry mouth, constipation, drowsiness, decreased appetite

Approved by FDA for fibromyalgia in 2008

Milnacipran

50–100 mg PO twice daily

Nausea, headache, constipation, dizziness, hot flush, dry mouth

Approved by FDA for fibromyalgia in 2009

Anticonvulsants

Pregabalin

300–450 mg PO daily

Diarrhea, dizziness, blurred vision, dry mouth, vomiting

Approved by FDA for fibromyalgia in 2010

Gabapentin

1,200–2,400 mg PO daily

Viral infections (in children), dizziness, somnolence, ataxia

Limited data on effectiveness; Recommended "weak for" by EULAR

Analgesics/Muscle Relaxants

Cyclobenzaprine

5.6 mg PO daily at bedtime

Drowsiness, xerostomia, dizziness

Approved by FDA for fibromyalgia in 2025

NSAIDs

—

—

No evidence to support use, but may be of benefit in treating comorbidities

Glucocorticoids

—

—

No evidence to support use, but may be of benefit in treating comorbidities

Opioids

Low-dose (tramadol)

200–300 mg PO daily

Hot flush, dizziness, headache, constipation, nausea

Recommended "weak for" by EULAR

Potent

—

—

Not recommended; should be used only if all other approaches have been exhausted

Sedative Hypnotics

Zolpidem

5–10 mg PO at bedtime

Headache, somnolence, dizziness

Improves sleep; no effect on pain

Benzodiazepines and sedatives

—

—

Evidence of effectiveness is lacking

Source: [2,58,59,60]

Antidepressants

Evidence Based Practice Recommendation

The European League Against Rheumatism recommends low-dose amitriptyline for the treatment of patients with fibromyalgia.

https://ard.bmj.com/content/76/2/318

Last Accessed: August 27, 2026

Level of Evidence: A (Weak for)

The EULAR found weak evidence for the use of a tricyclic antidepressant (amitriptyline) for the treatment of fibromyalgia, based on high-quality data concluding that 25 mg/day amitriptyline improved pain, sleep and fatigue at 6 to 8 weeks of treatment but not at 12 weeks, while 50 mg/day did not demonstrate efficacy [2]. Use for the management of short-term sleep and pain symptoms may be considered but is considered off-label for treatment of fibromyalgia [58].

Two of the four drugs approved by the FDA are SNRIs: duloxetine and milnacipran [2,58]. Duloxetine was approved on the basis of two trials. In the first study, duloxetine led to a clinically significant treatment response (at least a 30% reduction in pain severity on the Brief Pain Inventory) in more than half of the study participants [61]. Two doses were evaluated: 60 mg once daily and 60 mg twice daily; both doses were associated with significantly higher response rates than that for the placebo group [61]. Duloxetine also significantly improved function and quality of life. Similar results were achieved with the same doses of the drug in the other study [62]. Neither study showed improvement in sleep; however, duloxetine did not interfere with sleep [2,61,62]. The drug was also well tolerated, and nausea was the most common side effect. Given the similarity in response with the two doses of duloxetine, the approval is based on the once-daily dose. A 2014 Cochrane review indicated that there is a lack of efficacy data, but that 60–120 mg daily doses were associated with a greater improvement in mental symptoms than in somatic physical pain [63].

Two studies of milnacipran demonstrated the effectiveness of the drug in achieving a composite endpoint of improvement in scores for pain (30% improvement on a visual analog scale), patient global assessment ("very much" or "much" improved), and physical component of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) (six points) [64,65]. The studies also evaluated the effect of the drug on pain only (improvement in pain and patient global assessment but not SF-36). Two doses were used: 50 mg twice daily and 100 mg twice daily. In both studies, milnacipran was associated with significant improvements in pain, fatigue, patient global assessment, and physical function [64,65]. Further follow-up has shown the efficacy to be maintained for 12 months [66]. The drug was well tolerated; the most common side effects were mild-to-moderate nausea and headache, both of which resolved with continued use of the medication [64,65]. The FDA approved milnacipran at both doses.

Anticonvulsants

The third FDA-approved drug for the treatment of fibromyalgia is pregabalin, an anticonvulsant agent. Several studies have shown pregabalin to significantly improve pain, patient global assessment, fatigue, and health-related quality of life, as well as sleep disturbances [66,67,68]. The effect of the drug has lasted for as long as six months [66]. The drug was well tolerated, with the common side effects being dizziness and sedation, which tended to resolve with time of treatment [66].

Anticonvulsants have been evaluated in several trials, and EULAR guidelines note weak evidence for pregabalin specifically [2]. Another anticonvulsant drug, gabapentin, has also demonstrated efficacy with respect to pain, patient global assessment, function, and sleep, although it has not been approved by the FDA to treat fibromyalgia, and the drug is not specifically noted in treatment guidelines [2]. The side effect profile of gabapentin is similar to that of pregabalin, but the pharmacokinetic and pharmacodynamic profile is not as favorable [58]. The long-term safety and efficacy of both drugs is also unknown, and many patients are expected to discontinue therapy due to a high incidence of adverse effects. The overview found no evidence of clinical benefit with any other anticonvulsant, including carbamazepine [67].

Analgesics

With a primary symptom of pain, fibromyalgia has often been treated with analgesics. According to the NFA survey, acetaminophen, ibuprofen, and naproxen were the top three ever-used medications (94%, 87%, and 66%, respectively) [20]. Slightly more than one-third to about one-half of the survey respondents said that these medications were helpful [20]. In another study, nearly 30% of 434 women with fibromyalgia reported taking NSAIDs [53]. However, with no inflammatory mechanism, fibromyalgia is not expected to respond to NSAIDs, and there is no evidence to support the use of NSAIDs or glucocorticoids as a treatment modality [2]. NSAIDs may be of benefit in relieving pain associated with comorbidities, such as osteoarthritis, rheumatoid arthritis, or systemic lupus, which may account for their high rate of use in the NFA survey [20,66].

Strong evidence has also been documented for cyclobenzaprine, which earned the first FDA approval for fibromyalgia in more than 15 years in 2025 [59]. Cyclobenzaprine has both muscle relaxant and tricyclic antidepressant properties and is taken as a sublingual tablet daily at bedtime for management of both sleep disturbances and pain [58,59]. An early systematic review of five randomized controlled trials showed that individuals treated with cyclobenzaprine for fibromyalgia were three times as likely to report overall improvement and to note reductions in symptoms, especially sleep disturbances versus the control group [69].

The EULAR does not recommend the use of potent opioids for the treatment of fibromyalgia, noting that they should be used only if all other pharmacologic and nonpharmacologic options have been exhausted and under strict guidance [1,2]. EULAR documented level Ib weak evidence for tramadol, a mild opioid [2]. Caution should be used when prescribing tramadol because of the risk of dependence and abuse [58].

Sedative Hypnotics

Benzodiazepines and sedatives are not recommended for the treatment of fibromyalgia symptoms [21]. Zolpidem, a short-acting nonbenzodiazepine sedative, has been used to improve sleep in people with fibromyalgia, but because zolpidem does not relieve pain, it is useful only as an adjunct medication, and it has not been included in treatment guidelines for fibromyalgia [2,58]. Approximately 41% of the NFA survey respondents said they had ever used the drug, and 64% of these individuals considered it helpful [20]. In general, prescription sleep medication was the intervention that respondents considered the most effective of all interventions [20].

9. FOLLOW-UP

Individuals with fibromyalgia should be followed up routinely to assess response to treatment. Follow-up visits also offer an opportunity for healthcare professionals to encourage their patients to comply with pharmacologic and nonpharmacologic treatment. Reinforcement for the need to exercise is especially important, as 68% to 83% of people with fibromyalgia have been found to not engage in aerobic exercise [20,45]. Rates of exercise among the general population are below optimum, and people with fibromyalgia need added encouragement because of many symptoms that may be perceived as barriers (e.g., fatigue, pain).

One approach to enhance adherence to an exercise program is to begin pharmacologic treatment targeting the most distressing or severe symptoms and then provide education about exercise as symptoms begin to improve [21,2,45]. It is especially important to address sleep disturbances and fatigue. In contrast to recommendations for the general population, increasing lifestyle activity is not effective as exercise for individuals with fibromyalgia; instead, clinicians should encourage their patients with fibromyalgia to conserve their energy in daily life in order to have the ability to comply with prescribed exercises [45].

The authors of one review of nonpharmacologic treatment suggest that clinicians use the acronym ExPRESS to follow principles of nonpharmacologic pain management [50]:

- Ex: Exercise

- P: Psychiatric (i.e., addressing psychiatric comorbidities to help improve pain and disability)

- R: Regain function (helping patients pace activities to avoid doing too much on days they feel well)

- E: Education (referral to reliable resources)

- S: Sleep hygiene

- S: Stress management (such as cognitive-behavioral therapy and relaxation techniques)

10. CONCLUSION

Fibromyalgia is a chronic, complex centralized pain syndrome characterized by disordered processing of painful stimuli resulting in widespread musculoskeletal pain and often accompanied by fatigue, sleep disturbances, and cognitive symptoms [1,2]. It has a substantial negative effect on physical, psychological, and social well-being, and the syndrome is associated with a significant burden in terms of disability and healthcare costs.

After diagnosis, fibromyalgia symptoms will persist in most individuals, but the majority still report that they feel better overall than at the time of diagnosis. Better outcomes have been associated with greater self-efficacy, help-seeking behavior, increased level of exercise, and pacing of activities [1,21]. Therefore, it is important that healthcare professionals are equipped with the information necessary to diagnose and treat fibromyalgia according to evidence-based or guideline-endorsed recommendations in order to improve patient quality of life.

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