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The efficacy of bupropion for the treatment of major depressive disorder is supported by many clinical trials. All three forms have proven to be equally useful in the treatment of depression. In 1983, Fabre et al. published results of a multicenter trial showing that bupropion IR at dosages of 300–600 mg/day was significantly better than placebo in reducing symptoms of depression. This was followed by a 6-week double-blind, placebo-controlled five-center trial by Lineberry et al. (1990), which supported the conclusion that bupropion IR 300 mg/day was more efficacious than placebo in treating major depressive disorder. In evaluations against TCAs such as doxepin, amitriptyline, and imipramine in several clinical trials, bupropion was demonstrated to be equally efficacious (Branconnier et al. 1983; Feighner et al. 1986; Mendels et al. 1983). These studies also noted the more benign side-effect profile and improved tolerability of bupropion IR in comparison with TCAs. In 1991, Feighner et al. examined the efficacy of bupropion and fluoxetine in treating depressed outpatients and found it to be comparable. In addition, similar effectiveness in treating depression was also found between trazodone and bupropion IR (Weisler et al. 1994).

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