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To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined.The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period.After 12 weeks of treatment, the mean (SD) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P = 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P = 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P = 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P = 0.001). The ASEX score and CGI-SF score were correlated (P = 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age.Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.