Baseline Anxiety Effect on Outcome of SSRI Treatment in Patients with Severe Depression: Escitalopram Vs Paroxetine

Objective: To investigate if treatment outcome for severely depressed patients depends on their baseline level of anxiety.

Research Design And Methods: Patients with a primary diagnosis of severe major depressive disorder (n = 459) were randomised to 24 weeks of double-blind treatment with escitalopram (20 mg) or paroxetine (40 mg). Post hoc analyses of efficacy in patients with a baseline HAM-A total score < or =20 (n = 171) or >20 (n = 280) were based on analysis of covariance (ANCOVA) (ITT, LOCF).

Results: At week 24, the mean change from baseline in MADRS total scores was -24.2 for escitalopram-treated patients (n = 141) and -21.5 for paroxetine-treated patients (n = 139) (p < 0.05) in high baseline anxiety patients and the mean change from baseline in HAM-A total score was -17.4 (escitalopram) and -15.1 (paroxetine) (p < 0.05). When examining the proportion of complete remitters (CGI-S = 1) after 24 weeks of treatment, there was an increasing treatment difference as a function of baseline HAM-A total score in favour of escitalopram (ITT, LOCF). There was no treatment difference in the low baseline anxiety group. Significantly more patients (p < 0.01) withdrew from the paroxetine group (31%) than from the escitalopram group (17%), partly as the result of significantly more withdrawals due to AEs (p < 0.05). Incidence of AEs and withdrawals were not related to baseline anxiety and there were no significant differences in the incidence of individual AEs with escitalopram compared to paroxetine.

Limitations: The post hoc nature of these analyses, the absence of placebo control group, and the requirement that patients should be suffering from severe depression, limit the generalisability of the results.

Conclusion: Patients with severe depression together with comorbid anxiety symptoms responded significantly better to treatment with escitalopram 20 mg compared with paroxetine 40 mg. Contrary to paroxetine, escitalopram maintained its efficacy with increasing baseline anxiety levels.