Double-Blind Comparison of Escitalopram and Duloxetine in the Acute Treatment of Major Depressive Disorder

Arif Khan; Anjana Bose; George S. Alexopoulos; Carl Gommoll; Dayong Li; Chetan Gandhi


Clin Drug Invest. 2007;27(7):481-492. 

In This Article

Abstract and Introduction


Background and Objective: Escitalopram is the most selective serotonin reuptake inhibitor antidepressant; in contrast, duloxetine inhibits both serotonin and norepinephrine reuptake. Double-blind comparison studies may help guide treatment decisions by revealing the relative benefits of different therapeutic approaches. This study evaluated the efficacy and safety of escitalopram versus duloxetine in the acute treatment of patients with moderate to severe major depressive disorder.
Methods: A 1-week, single-blind, placebo lead-in period followed by an 8-week, randomised, double-blind, multicentre, parallel-group comparison was conducted from 20 April 2005 to 10 March 2006 in independent psychiatric research facilities with principal investigators who were board certified in psychiatry. A total of 278 outpatients of 382 patients screened with Diagnostic and Statistical Manual of Mental Disorders (4th edition)-diagnosed major depressive disorder (Montgomery-Åsberg Depression Rating Scale [MADRS] total score =26) were randomised to the two treatment groups. Eight patients received no medication and were excluded from the safety group. Patients were treated with either escitalopram 10--20 mg/day (fixed at 10 mg/day for the first 4 weeks) or duloxetine 60 mg/day. The primary efficacy variable was change from baseline at week 8 in MADRS total score using the last observation carried forward (LOCF) approach. Efficacy, safety and tolerability measures were prospectively defined in the statistical analysis plan prior to study initiation unless otherwise specifically noted as conducted post hoc.
Results: A significantly greater proportion of escitalopram-treated patients completed the 8-week study compared with duloxetine-treated patients (87% vs 69%, respectively; p < 0.01). Mean baseline MADRS total scores were 31.0 for the escitalopram group and 31.6 for the duloxetine group. At week 8, escitalopram treatment resulted in significantly greater improvement compared with duloxetine on the prospectively defined primary efficacy endpoint of mean change from baseline in MADRS total score using the LOCF approach (least-squares mean difference [LSMD] -2.42; 95% CI -4.73, -0.11; p < 0.05). There was no difference between treatment groups in the observed cases (OC) analysis (LSMD -0.32; 95% CI -2.71, 2.07; p = 0.79). Significantly fewer escitalopram-treated patients discontinued because of adverse events compared with duloxetine (2% vs 13%, respectively; p < 0.01).
Conclusion: These findings suggest that escitalopram is better tolerated and at least as effective as the serotonin-norepinephrine reuptake inhibitor duloxetine in the treatment of major depressive disorder.


Major depressive disorder (MDD) is a recurrent and protracted illness contributing to functional impairment, morbidity and mortality.[1,2,3] According to the National Comorbidity Survey Replication (NCS-R), the 12-month prevalence of MDD in the US is 6.7%, with at least 80% of respondents categorised as moderate or severe cases (50% and 30%, respectively).[4] Despite the burden of MDD, a great many patients remain untreated or inadequately treated when correctly diagnosed.[5] Among respondents from the NCS-R with a 12-month diagnosis of MDD, only 51.7% used any healthcare services in the prior year; more problematic is that minimally adequate treatment was received by only 38% of these respondents.[6]

Treatment adherence over time is a critical factor in achieving successful outcomes with pharmacotherapy in MDD patients.[7,8] Furthermore, adverse effects are a major medication-specific determinant of patient adherence to pharmacotherapy.[9] Several community-based surveys suggest that adverse events are the most frequent reason for prematurely discontinuing antidepressant medication, particularly early on in treatment (i.e. =30 days).[10,11] Substantial evidence also suggests that patients who prematurely discontinue treatment may be at greater risk for depression relapse and recurrence, as well as poor long-term outcomes.[12,13,14] The safety and tolerability of serotonin reuptake inhibitors (SRIs) can vary considerably across individual agents,[15,16] and, therefore, it is not surprising that differences in tolerability profiles between antide-pressant medications represent a primary consideration for physicians and patients when selecting initial pharmacotherapy.[17,18]

The present study compared the efficacy and tolerability of the selective serotonin reuptake inhibitor (SSRI) escitalopram (10--20 mg/day; dose fixed at 10 mg/day for the first 4 weeks) versus the dual serotonin and norepinephrine reuptake inhibitor (SNRI) duloxetine (60 mg/day) in the treatment of moderate to severe MDD. Dosing was consistent with information in the US FDA-approved package insert of both drugs. The recommended starting dose of escitalopram, the most selective SRI studied to date,[19] is 10 mg/day, with efficacy and tolerability having been demonstrated in several placebo-controlled MDD studies;[20,21] the therapeutic dose range of escitalopram is 10--20 mg/day.[22] Duloxetine is an SNRI with a recommended starting and therapeutic dose of 60 mg/day.[23,24,25] In a pair of randomised double-blind clinical studies, escitalopram was shown to be at least as effective and better tolerated than an extended-release (XR) formulation of the SNRI venlafaxine.[26,27] Moreover, in a previous head-to-head study, escitalopram 10 mg/day and duloxetine 60 mg/day were shown to produce comparable improvements on the primary efficacy measure, while escitalopram was better tolerated.[28]