The onset of effect for escitalopram and its relevance for the clinical management of depression

Objective: To analyse the significance of 'onset of effect' on clinical outcome in the treatment of depression and the contribution of individual Montgomery-Asberg Depression Rating Scale (MADRS) items to improvements in the MADRS total score. Research design and method: All five published placebo-controlled clinical studies in depression as per January 1, 2005, with escitalopram, were included in this pooled analysis. Results: Of the 1636 patients who were randomised to either escitalopram (882) or placebo (754), 1333 completed 8 weeks of treatment (707 escitalopram and 626 placebo). A statistically significant difference (p < 0.05) between the MADRS total score responses of escitalopram and placebo treatments was observed at week 1. All 10 MADRS single items showed a significant treatment effect at week 8. For items representing core symptoms of depression (apparent sadness, reported sadness, inner tension, concentration difficulties, inability to feel, pessimistic thoughts and suicidal thoughts) the effect was detected early (week 1) and for other items (reduced sleep, reduced appetite and lassitude) the effect was detected later (week 6 -8). Of the patients who showed an onset of effect (>= 20% reduction in MADRS) after 2 weeks, = and who remained on escitalopram until week 8, 63% were in remission at week 8 (mean MADRS score of 6.1). Conclusion: Onset of treatment response at 2 weeks is an important indicator of subsequent remission at 8 weeks. It would therefore be a reasonable clinical recommendation that if patients fail to show a measurable clinical improvement within 2 weeks, a dose increase should be considered at this time.