Is escitalopram really relevantly superior to citalopram in treatment of major depressive disorder? A meta-analysis of head-to-head randomized trials.
OBJECTIVE
To evaluate clinical relevance of differences between escitalopram and citalopram (equimolar) for major depressive disorder.


METHODS
Review and meta-analysis of comparative randomized controlled trials (RCT). Comparisons were in relation to Montgomery-Asberg depression rating scale (MADRS) score reduction at weeks 1 (5 RCTs), 4 (5 RCTs), 6 (4 RCTs), 8 (5 RCTs), and 24 (1 RCT); proportion of responders at weeks 2, 4, 6 (2 RCTs for each time point), 8 (5 RCTs), and 24 (1 RCT); clinical global impression-severity (CGI-S) reduction at weeks 6 (1 RCT), 8 (5 RCTs), and 24 (1 RCT), and discontinuation due to adverse events or inefficacy during short-term (up to 8 weeks) and medium-term (24 weeks) treatment.


RESULTS
MADRS reduction was greater with escitalopram, but 95% confidence intervals (CI) around the mean difference were entirely or largely below 2 scale points (minimally important difference) and CI around the effect size (ES) was below 0.32 ("small") at all time points. Risk of response was higher with escitalopram at week 8 (relative risk, 1.14; 95% CI, 1.04 to 1.26) but number needed to treat was 14 (95% CI, 7 to 111). All 95% CIs around the mean difference and ES of CGI-S reduction at week 8 were below 0.32 points and the limit of "small," respectively. Data for severe patients (MADRS> or =30) are scarce (only 1 RCT), indicating somewhat greater efficacy (response rate and MADRS reduction at week 8, but not CGI-S reduction) of escitalopram, but without compelling evidence of clinically relevant differences. Discontinuations due to adverse events or inefficacy up to 8 weeks of treatment were comparable. Data for the period up to 24 weeks are scarce and inconclusive.


CONCLUSIONS
Presently, the claims about clinically relevant superiority of escitalopram over citalopram in short-to-medium term treatment of major depressive disorder are not supported by evidence.
Trkulja
Vladimir
V
Vladimir Trkulja, Department of Pharmacology, Medical School, University of Zagreb, Salata 11, 10000 Zagreb, Croatia. vtrkulja@mef.hr
D000293:Adolescent; D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use*; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram