Philip J. Mease, Kelly Dundon, Piercarlo Sarzi-Puttini,
There have been substantial advances in the pharmacotherapy of fibromyalgia (FM), which have occurred in parallel with advances in our understanding of the pathophysiology of FM in the past several years. Consortia of researchers have established a core set of symptom domains, which constitute the condition of FM, including pain, fatigue, sleep and mood disturbance and cognitive dysfunction, which significantly impact a patient’s overall well-being and ability to function. Outcome measures, which assess these domains, both singly and in composite format, are showing increasing reliability to discriminate between the treatment and placebo arms in clinical trials of emerging therapies, which are targeting the pathophysiologic mechanisms of FM. Several different medications, including the serotonin and norepinephrine reuptake inhibitors, duloxetine and milnacipran, and the α2δ modulator, pregabalin, have been approved by the Food and Drug Administration (FDA) for the management of FM, based on their clinically meaningful and durable effect on pain in monotherapy trials. They also have been shown to beneficially effect patient global impression of change, function and variably other key symptom domains, such as fatigue, sleep disturbance and cognition. Other medicines, although they have not gone through the formal approval process, have also shown efficacy in multiple domains of FM. Although combination trials have generally not yet been performed, the combined use of medicines with complementary mechanisms of action is rational, and, when done with appropriate caution, will likely be shown to be safe and well tolerated. Adjunctive therapy with medicines targeted at specific symptom domains, such as sleep, as well as treatments aimed at common co-morbid conditions, such as irritable bowel syndrome, or disease states, such as rheumatoid arthritis, should be considered for the purpose of reducing the patient’s overall symptom burden. Current therapies neither completely treat FM symptoms nor benefit all patients; thus, further research on new therapies with different mechanisms and side-effect profiles is needed.