Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) for Treatment of Fibromyalgia: A Comprehensive Clinical Review

Fibromyalgia is a complex clinical entity characterized by a broad range of symptoms including chronic widespread musculoskeletal pain, profound fatigue, impaired cognition, and mood disturbances. Current understanding of disease pathogenesis assumes neurotransmitter dysregulation and central pain sensitization play a key role resulting in heightened pain sensitivity. Genetic predisposition as well as alterations in endocrine and immune function have been implicated. Accurate diagnosis requires a comprehensive evaluation, and a personalized treatment approach is needed to address the biopsychosocial components of the disease process. Among pharmacologic treatment options, serotonin norepinephrine reuptake inhibitors (SNRIs) have demonstrated analgesic effects in addition to mood stabilizing properties. Currently, duloxetine and milnacipran are approved by the Food and Drug Administration although other agents in this drug class including venlafaxine and desvenlafaxine have been studied in the management of fibromyalgia. In addition, selective norepinephrine reuptake inhibitors, esreboxetine and reboxetine, as well as tramadol, a weak opioid mu-receptor agonist with SNRI activity have shown potential utility. Although some studies have demonstrated SNRIs to be effective and well tolerated in patients with fibromyalgia, individual response may vary. There remains a continued need for large scale clinical trials to establish the safety and clinical effectiveness of these agents in this patient population. Further information is needed to optimize patient selection and dosing regimens as well as elucidate the clinical factors associated with poor response. Moreover, pharmacologic agents may be combined with lifestyle changes and non-drug-based treatments to address the complex interactions of biological and psychosocial factors that facilitate disease development and persistence of symptoms.