Objective: An antidepressant's tolerability, generally captured as the frequency and severity of adverse events (AEs), is often as important as its efficacy in determining treatment success. This study used a composite outcome - remission of major depressive disorder (MDD) without AEs - to compare the benefit-risk profiles of escitalopram versus the norepinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine extended release (XR).
Methods: Pooled data from three randomized, double-blind, multicenter trials were analyzed, in which patients with MDD were treated for 8 weeks with either escitalopram (n = 462) or an SNRI (n = 467).
Clinical trial registration: clinicaltrials.gov identifiers: NCT00108979; NCT00384436.
Main outcome measures: The composite outcome was defined as remission (Montgomery-Åsberg Depression Rating Scale [MADRS] score ≤10) and concurrent absence of an AE. The proportions of remitted patients free of (1) any AEs, (2) moderate-to-severe AEs, and (3) study drug-related AEs were compared between treatment groups at each study visit and longitudinally across study visits common to all trials during the first 8 weeks of treatment.
Results: At endpoint (week 8), escitalopram-treated patients were more likely than SNRI-treated patients to experience remission free of any AEs (28.4 vs. 21.6%; p = 0.0179) and remission free of study drug-related AEs (45.2 vs. 36.8%; p = 0.0092). Compared to SNRI-treated patients, escitalopram-treated patients had 38% greater odds of remission free of any AEs, 28% greater odds of remission free of moderate-to-severe AEs, and 34% greater odds of remission free of study drug-related AEs (all p < 0.05).
Conclusion: Treatment of adult MDD patients with escitalopram was significantly more likely to result in remission without concurrent AEs compared to treatment with current SNRIs. Study limitations include focus on only the initial 8 weeks of treatment and exclusion of trials for which individual patient data were not obtained.