Escitalopram (S-Enantiomer of citalopram): Clinical efficacy and onset of action predicted from a rat model

Escitalopram is the active S-enantiomer of citalopram. In a chronic mild st ress model of depression in rats, treatments with both escitalopram and cit alopram were effective; however, a faster time to onset of efficacy compare d to vehicle treatment was observed for escitalopram-treated (5 mg/kg/day) than for citalopram-treated (10 mg/kg/day) rats at Week 1. To study the pre dictability of this observation in the clinic, we analysed 4-week data from an 8-week, double-blind, randomised, placebo-controlled, flexible-dose stu dy that compared escitalopram and citalopram to placebo in primary care pat ients with major depressive disorder (baseline Montgomery and Asberg Depres sion Rating Scale (MADRS) scores greater than or equal to 22 and less than or equal to 40). Since the flexible dosing started after Week 1, analysis o f 4-week data ensured that the patients received fixed doses of 10 mg/day e scitalopram (155 patients), 20 mg/day citalopram (160 patients), or placebo (154 patients). The efficacy analysis showed a significantly superior ther apeutic effect for escitalopram versus placebo from Week 1 onwards (observe d cases) with an adjusted mean change in MADRS at Week 4 (last observation carried forward) of 2.7 points (P=0.002). By comparison, 20 mg/day citalopr am did not demonstrate a statistically significant effect compared to place bo. Escitalopram was well tolerated with an adverse event profile similar t o that of citalopram. The preclinical observation that escitalopram possess es a Faster time to onset of efficacy than citalopram was also seen in prim ary care patients with major depressive disorder. Thus, escitalopram is eff icacious in depression and the effect occurs earlier than for citalopram.