Post-hoc pooled analysis of data from two 6-month randomised controlled trials in patients with major depressive disorder (MDD) revealed superior efficacy and tolerability of escitalopram when compared with paroxetine. Escitalopram (n=394) produced a significantly (p<0.01) greater mean treatment difference of 2.0 points in primary endpoints, judged using the Montgomery-Asberg Depression Rating Scale (MADRS) total score, compared with paroxetine (n=383). Significant differences were also observed in Clinical Global Impression (CGI)--severity (escitalopram, 2.1; paroxetine, 2.4; p<0.01) and CGI--improvement (escitalopram, 1.8; paroxetine, 2.0: p<0.01). In the sub-group of severely depressed patients (baseline MADRS> or = 30), escitalopram showed further improved efficacy compared with paroxetine in all scores. This analysis supports previous observations of superior efficacy and tolerability of long-term escitalopram treatment (10 to 20 mg/day) compared with paroxetine (20 to 40 mg/day). Escitalopram is a good therapeutic option for the long-term treatment of MDD, particularly in severely depressed patients.