Is escitalopram efficacious in severe depression?

Escitalopram efficacy in severe depression, defined as MADRS ≥30, has consistently been demonstrated in meta-analyses (Kennedy et al., 2009; Korotzer et al., 2007; Kilts et al., 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.

Making a specific comparison with the SNRIs, a pooled analysis of four studies of escitalopram versus either venlafaxine XR or duloxetine (Korotzer et al., 2007), found that the escitalopram treated group had a significantly lower MADRS total score from week 1 to week 8 in patients with severe depression (MADRS ≥30; p<0.001, LOCF).

References:

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

Korotzer et al. poster at ACNP 2007

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