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Sexual side-effects due to antidepressant treatment are an important consideration when selecting a treatment regimen and can influence patient compliance. Sexual function during treatment with the selective noradrenaline reuptake inhibitor reboxetine, the selective serotonin reuptake inhibitor (SSRI) fluoxetine and placebo has been assessed in a multicentre, randomized, 8-week, double-blind study of 450 patients diagnosed with major depressive disorder. Sexual function was measured by the Rush Sexual Inventory completed by male and female patients and administered at baseline, week 4 and week 8. The results indicate that reboxetine was similar to placebo and superior to fluoxetine in its effect on overall sexual function. There was a greater degree of sexual satisfaction in the reboxetine group compared to fluoxetine (P= 0.02). The percentage of female patients able to achieve orgasm increased during the study period for women who received reboxetine and placebo, but decreased for those who received fluoxetine. These results suggest that reboxetine may be of particular benefit for patients at risk for sexual dysfunction with SSRIs.