To determine whether age/gender-based differences in efficacy exist between bupropion and the selective serotonin reuptake inhibitors for major depressive disorder, we pooled the findings of 10 double-blind studies comparing bupropion with a selective serotonin reuptake inhibitor. Men (N=943) and women (N=1179) were divided into three age groups (younger than 40, 40-55, older than 55). Improvement in terms of the 17-item Hamilton Depression Rating Scale, as well as the Bech melancholia, anxiety-somatization, and insomnia factors of the Hamilton Depression Rating Scale was compared between the two treatment groups. Of 64 pair-wise comparisons, only one was statistically significant. Specifically, more women treated with a selective serotonin reuptake inhibitor experienced a 50% or greater decrease in Hamilton Depression Rating Scale Anxiety-Somatization scores (58.8 versus 63.8%, P=0.0394). No difference, however, was seen in the degree of resolution of Hamilton Depression Rating Scale Anxiety-Somatization scores (continuous measure) between women treated with bupropion versus a selective serotonin reuptake inhibitor (P=0.114). Bupropion and the selective serotonin reuptake inhibitors, thus, appear to be equally effective in treating depressive symptoms, as well as anxious/somatic symptoms and insomnia in depression. No gender-related or age-related differences were found except that greater improvement was seen in anxious/somatic symptoms of depression among women during selective serotonin reuptake inhibitor treatment. This finding could, however, not be replicated when improvement in anxious/somatic symptoms was defined as a continuous measure.