This study sought to compare Bupropion versus Sertraline in the treatment of depressed patients with Binge Eating Disorder (BED) prescribed off-label. Medical records of outpatients with diagnosis of BED and Depression (DSM-IV-TR criteria) were selected: 15 patients were treated with bupropion 150 mg/per day, and 15 with sertraline 200 mg/per day. During the screening and control visits (2°-6°-14°-24° week), the selected patients were first weighed and then evaluated using the following questionnaires: Binge Eating Disorder-Clinical Interview (BEDCI), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory X (STAI-X) and Arizona Sexual Experience Scale (ASEX). Both drugs reduced anxious-depressive symptoms and binge frequency: Bupropion showed a better effectiveness in reducing weight and improving sexual performances; weight loss related to it was proportional to the body mass index. Bupropion may be associated with more weight loss in BED, depressed patients than sertraline.