Journal: Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. Authors and Affiliation: Leo RJ, Brooks VL; Department of Psychiatry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Erie County Medical Center, NY 14215, USA. Rleomd@aol.com PMID: 16869117 Milnacipran is a serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor currently available for use as an antidepressant in several countries. Phase III clinical trials are currently underway to assess its potential role in the treatment of fibromyalgia syndrome, and in pursuit of US Food and Drug Administration approval for this indication. Evidence has accumulated suggesting that in animal models, milnacipran may exert pain-mitigating influences involving NE- and 5-HT-related processes at supraspinal, spinal and peripheral levels of pain transmission. Preliminary evidence suggests that milnacipran may be useful in mitigating pain and fatigue associated with fibromyalgia. However, its role in addressing comorbidities associated with fibromyalgia, including visceral pain and migraine, has yet to be investigated.