Is escitalopram efficacious in severe depression?

Escitalopram efficacy in severe depression, defined as MADRS ≥30, has been demonstrated in meta-analyses (Kennedy 2009; Kilts 2009) and, more importantly, in randomised, controlled trials versus citalopram, paroxetine, venlafaxine XR, and duloxetine.

The most recent meta-analysis by Kennedy et al. (2009) showed a significantly higher mean change in MADRS score (p=0.0004) after  8 weeks of escitalopram treatment versus comparator SSRIs (citalopram, fluoxetine, paroxetine, or sertraline) in severely depressed patients (MADRS ≥30 at baseline).

Escitalopram also produced a significantly higher response rate (defined as ≥50% reduction in baseline MADRS total score; p=0.0015) than other SSRI comparators in these patients, with an odds ratio for response of 1.44.

A similar advantage was seen with escitalopram versus comparator SNRIs (venlafaxine XR and duloxetine), with a significantly higher mean change in MADRS score (p=0.0001), and significantly higher response (odds ratio 2.14, p<0.0001) and remission (odds ratio 1.96, p=0.0003) rates.

The mean difference in MADRS total score for escitalopram versus all comparators was 1.8 (95% CI: 1.1, 2.5), p<0.0001. Further, the more severely depressed the patients were at baseline, the larger the mean treatment differences between escitalopram and the comparator.

Another recent meta-analysis by Kilts et al. (2009) had similar findings. Based upon data from 15 randomised double-blind clinical studies, it was found that the difference in response to escitalopram versus the pooled comparators (citalopram, duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine XR) at week 8 increased with increasing baseline disease severity.

The response versus disease severity ‘slope’ being a 0.13 MADRS point difference between groups (in favour of escitalopram) per 1 MADRS point increase in baseline severity (p=0.0208).

This difference was due to the response to escitalopram remaining stable regardless of baseline disease severity, while the response to comparators decreased with greater baseline severity. Between-group differences in mean MADRS total score reduction from baseline to week 8 supported these findings.

References:

Boulenger J-P et al. CMRO 2006; 22 (7): 1331–1341

Kennedy et al. Curr Med Res Opin 2009;25(1):161-175

Kilts et al. Expert Opin Pharmacother 2009;10(6):927-936

Lancon C et al. Int J Psychiatry Clin Pract 2006; 10(2): 131-137

Wade A et al. CMRO 2007; 23(7): 1605-1614