Duloxetine was first synthesized in the 1980s and subsequently patented in 1991. The U.S. Food and Drug Administration (FDA) did not approve this drug for the treatment of major depressive disorder and diabetic neuropathy, however, until the third quarter of 2004. This long delay occurred because the drug was initially tested in depressed patients at low dosages of 5–20 mg/day, which were not efficacious. Duloxetine has received approval in most countries worldwide since then but became available in Canada only in 2008. It is also approved in the United States for generalized anxiety disorder and fibromyalgia. Milnacipran was approved in France for the treatment of depression in 1996 but only recently was approved for use in North America for patients with fibromyalgia.