The methods of assessing the clinical relevance of a significant difference between antidepressants and placebo are discussed. The commonly used criteria of treatment effect and responder rates, as well as the percentage difference in responders between antidepressant and placebo, are critically reviewed and applied to assess the clinical relevance of the significant advantages reported in double-blind, randomized, controlled studies of escitalopram compared with other antidepressants. A significant advantage for escitalopram has been reported in randomized, double-blind, short-term studies compared with citalopram, paroxetine and duloxetine. The reported significant differences are clinically relevant based on a treatment effect difference of at least 2 points on the Montgomery and Asberg Depression Rating Scale as well as a significant advantage in the protocolled responder or remission analysis. The mean unadjusted treatment effect advantage for escitalopram compared with the antidepressants studied is 2.42 points on the Montgomery and Asberg Depression Rating Scale in the short-term treatment. Excluding one study that did not report short-term responder rates, there were significantly more responders on escitalopram (74%) than comparators (63%). Both of these measures demonstrate a clinically relevant difference in favour of escitalopram.