As with autoimmune diseases, the prevalence of fibromyalgia is higher among women than men, although data are conflicting. A female-to-male ratio of 6:1 to 9:1 has been reported in some studies [5,12,16]. However, estimates that use newer, symptom-based diagnostic criteria show a female-to-male ratio of 2:1 [13,14].

Genetics is thought to be a factor in the susceptibility of fibromyalgia. Family clustering has been reported, and the risk for fibromyalgia is eight times higher for first-degree relatives of individuals with the syndrome [25]. Abnormalities in the serotonin transporter gene and the catecholamine-O-methyltransferase gene have been identified[5,9,26]. 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 [5].

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 [6,8]. 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 [27].

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) [1,3,27,31,32,33,34]. 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 [27]. Nearly all individuals with fibromyalgia are polysymptomatic [27].

Most individuals with fibromyalgia describe pain as arising from muscles and joints and also have tender skin [3]. Pain is typically axial in distribution, and pain/stiffness usually occurs in the morning and evening [3]. Patients may note a feeling of swelling in the soft tissues, primarily around the joints, but there is no objective evidence of swelling [3,28]. The American Pain Society recommends using self-reports as the primary source for pain assessment, focusing on such details as [4]:

A systematic review to compare the effectiveness of the three antidepressants demonstrated several differences [81]:

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 [41,72,82]. The effect of the drug has lasted for as long as six months [41]. The drug was well tolerated, with the common side effects being dizziness and sedation, which tended to resolve with time of treatment [41].

Anticonvulsants have been evaluated in several trials, and the American Pain Society found level II evidence for this class of drug, whereas the later EULAR guidelines note level I evidence for pregabalin specifically [4,46,49]. Another anticonvulsant drug, gabapentin, has also demonstrated efficacy with respect to pain, patient global assessment, function, and sleep [41,70,72]. Gabapentin has not been approved by the FDA to treat fibromyalgia, and the drug is not specifically noted in treatment guidelines [4,46]. Approximately one-third of the respondents in the NFA survey said they had "ever used" gabapentin, and 46% who had used it considered the drug helpful [27]. The side effect profile of gabapentin is similar to that of pregabalin, but the pharmacokinetic and pharmacodynamic profile is not as favorable [41]. An overview of systematic reviews of anticonvulsants showed that both drugs had a modest effect on pain reduction, and it was not possible to conclude if one drug was better than the other [72]. 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 [72].

Strong evidence has also been documented for cyclobenzaprine, which has both muscle relaxant and tricyclic antidepressant properties [26,58,83]. A 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, than controls [83]. Among the NFA survey respondents, 64% had ever used cyclobenzaprine and 58% of these patients considered the drug to be helpful [27].

The authors of one review of nonpharmacologic treatment suggest that clinicians use the acronym ExPRESS to follow principles of nonpharmacologic pain management [47]: