1813 01 REUMA3 Editoriale - ME/CFS Australia

Fibromyalgia syndrome: the pharmacological treatment options 51proving symptoms, and aggressive use of exerciseand cognitive-behavioural approaches to retain orrestore function (4-6). Physicians and patientsshould be educated about current theories regardingthe underlying pathophysiologic mechanismsof FM, and then set realistic goals for all modalitiesof treatment.However, it is not possible to draw definite conclusionsconcerning the best approach to managingFM because results of randomized clinical trialspresent methodological limitations, and therapeuticprograms are consistently heterogeneous, whichrenders them difficult to compare (7,8). However,a variety of pharmacological treatments, includinganalgesics, antidepressants, antiepileptics andmany other drugs have been used to treat symptomsof FM with mixed results (8). In this review, wewill discuss those drugs that have produced themost significant clinical results in treating FM patients.AnalgesicsThe use of steroids and nonsteroidal anti-inflammatorydrugs (NSAIDs) in FM has had disappointingoutcomes (1, 8). NSAIDs, which are commonlyused for arthritic conditions, may be less effectivefor FM because pain associated with FM isnot caused by muscle or joint inflammation. Thereis no scientific evidence that NSAIDs are effectivewhen used alone in FM patients, although they maybe useful adjuncts for analgesia when combinedwith tricyclic medications (1); the combination ofNSAIDs with benzodiazepines, however, gave inconsistentresults (1, 7-9).The central nervous system (CNS) mechanisms forthe disorder, specifically, central sensitization, centraldisinhibition and a dysfunctional hypothalamic-pituitary-adrenalaxis, could justify the relativelyreduced efficacy of NSAIDs and opioids, thelatter being more effective for “peripheral” pain(7). However, NSAIDs can be helpful in reducingpain that flares with excessive physical activity,tendinitis or bursitis; but they should be used onlyas needed to avoid side effects. COX 2inhibitorshave much fewer side effects, but have less efficacyin pain.Acetaminophen acts differently for FM patients; ithas a degree of strength for FM and is safe for useover long periods (9). Wolfe et al. surveyedrheumatic disease patients about their preferencesfor NSAIDs versus acetaminophen in terms of efficacyand side effects (10). There was a considerableand statistically significant preference forNSAIDs among patients; but the authors stress thatif safety and costs are issues, then the recommendationof the American College of Rheumatologythat acetaminophen be the first choice, primarilyfor mild pain, seems appropriate given the long durationof safe use (11).The use of NSAIDs or acetaminophen, with orwithout opioids, is always justified when patientswho already suffer from FM have other peripheralsources of pain (osteoarthritis, inflammatory arthritis,degenerative disk disease) (11).Opioids are meant to improve function in FM patientswho are impaired by pain, even though thereis an open debate about their usefulness and safetyas a “specific” medication for fibromyalgia patients(12-14).Few clinical trials exist that address the use of opioidsto treat persistent pain in FM patients, butthose trials show that these drugs are helpful for relievingFM pain; moreover, opioids can help to reducesleep disturbances, anxiety and depressionand to increase mobility and enjoyment of life (13,15).Potential side effects tend to decline over time, andaddiction has been disproven by the scientific literature.Opioids that are available on the Italian market includecodeine, tramadol, oxycodone, hydromorphon,morphine, buprenorphine and fentanyl.Furlan et al. (15) conducted a meta-analysis of 41randomized trials (6019 patients, 7% affected byFM) to evaluate the efficacy of opioids ranging induration from 1-16 weeks. They found that opioidswere more effective than placebo for both painand functional outcomes; and strong opioids weresignificantly superior to naproxen and nortriptyline,but only for pain relief. Despite the relativebrevity of the trials, more than 1/3 of the participantsabandoned treatment (15).Tramadol, in particular, was beneficial for FM patients(8, 9, 12-14). It is an atypical pain relieverthat differs from other narcotics in its action on thecentral nervous system, specifically, on reuptakeof serotonin and norepinephrine. Its most commonside effects are drowsiness, dizziness, constipationand nausea, and it should not be given in combinationwith tricyclic antidepressants.Tramadol, used alone or in combination with acetaminophen,is commonly prescribed for relief offibromyalgia pain (16-18) in a dose of 200-300mg/d. A small double-blind, placebo-controlled trialinitially suggested that tramadol was effectiveand well-tolerated in patients with FM (16).