Bupropion was invented by Nariman Mehta of Burroughs Wellcome (now GlaxoSmithKline) in 1969, and the US patent for it was granted in 1974. It was approved by the United States Food and Drug
Administration (FDA) as an antidepressant on December 30, 1985, and marketed under the name Wellbutrin. However, a significant incidence of seizures at the originally recommended dosage (400–600 mg) caused the withdrawal
of the drug in 1986. Subsequently, the risk of seizures was found to be highly dose-dependent, and bupropion was re-introduced to the market in 1989 with a maximum recommended dose of 450 mg/day.
In 1996, the FDA approved a sustained-release formulation of bupropion called Wellbutrin SR, intended to be taken twice a day (as compared with three times a day for immediate-release Wellbutrin). In 2003, the FDA approved another sustained-release formulation called Wellbutrin XL, intended for once-daily dosing. Wellbutrin SR and XL are available in generic form in the United States, while in Canada, only the SR formulation is available in generic form. In 1997, bupropion was approved by the FDA for use as a smoking cessation aid under the name Zyban. In 2006, Wellbutrin XL was similarly approved as a treatment for seasonal affective disorder.
In 2012, the U.S. Justice Department announced that GlaxoSmithKline had agreed to plead guilty and pay a $3-billion fine, in part for promoting the unapproved use of Wellbutrin for weight loss and sexual dysfunction.
In April 2008, the FDA approved a formulation of bupropion as a hydrobromide salt instead of a hydrochloride salt, to be sold under the name Aplenzin by Sanofi-Aventis.
On October 11, 2007, two providers of consumer information on nutritional products and supplements, ConsumerLab and The People's Pharmacy, released the results of comparative tests of different brands of bupropion. The People's Pharmacy received multiple reports of increased side effects
and decreased efficacy of generic bupropion, which prompted it to ask the online ConsumerLab blog
to test the products in question. The tests showed that "one of a few generic versions of Wellbutrin XL 300 mg, sold as Budeprion XL 300 mg, didn't perform the same as the brand-name pill in the lab." The FDA investigated these complaints and concluded that the Budeprion XL is equivalent to Wellbutrin XL in regard to bioavailability of bupropion and its main active metabolite hydroxybupropion. The FDA also said that coincidental natural mood variation is the most likely explanation for the apparent worsening of depression after the switch from Wellbutrin XL to Budeprion XL. On October 3, 2012, however, the FDA reversed this opinion, announcing that "Budeprion XL 300 mg fails to demonstrate therapeutic equivalence to Wellbutrin XL 300 mg." The FDA did not test the bioequivalence of any of the other generic versions of Wellbutrin XL 300 mg, but requested that the four manufacturers submit data on this question to the FDA by May, 2013.
In France, marketing authorization was granted for Zyban on August 3, 2001, with a maximum daily dose of 300 mg; only sustained-release bupropion is available, and only as a smoking cessation aid. Bupropion was granted a licence for use in adults with major depression in the Netherlands in early 2007, with GlaxoSmithKline expecting subsequent approval in other European countries.