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Bupropion was first synthesized by Burroughs Research in 1966, and patented by Burroughs-Wellcome (later Glaxo-Wellcome, and, as of 2000, GlaxoSmithKline) in 1974. It was approved by the Food and Drug Administration (FDA) as an antidepressant in 1984 and marketed under the name Wellbutrin. However, a significant incidence of seizures at the originally recommended dosage (400-600 mg) caused in 1986 the removal of the drug from the market. It was shown that the risk of seizures increases from 0.1% at 100-300 mg/day to 0.3-0.4% at 450 mg/day to 2% at 600 mg/day. Reflecting this experience, bupropion was re-introduced to the market in 1989 with the maximum dose of 450 mg/day.
In 1996 the FDA approved sustained-release (SR) and in 2003 extended release (XL) formulations of Wellbutrin that release bupropion at a slower rate. Wellbutrin SR is taken twice a day and Wellbutrin XL once a day, as compared to three times a day for the immediate release bupropion. Wellbutrin SR and XL are now available in generic form. In 1997, bupropion was approved by the FDA for use as a smoking cessation aid under the name Zyban. In late 2006, Wellbutrin XL was approved for use by the FDA as treatment for seasonal affective disorder.
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