SSRIs significantly increase the risk of both serious and non-serious adverse events .
The potential small beneficial effects seem to be outweighed by harmful effects .
Background The evidence on selective serotonin reuptake inhibitors ( SSRIs ) for major depressive disorder is unclear .
Methods Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo , ‘ active ’ placebo , or no intervention in adult participants with major depressive disorder .
Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study*
ABSTRACT Objective : The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment1 . The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine ( a dual serotonin and norepinephrine reuptake inhibitor ) and escitalopram ( a selective serotonin reuptake inhibitor ) . Research design and methods : This was a r and omized , double-blind , placebo- and active comparator-controlled study , in which patients ( ≥ 18 years ) meeting DSM‑IV criteria for Major Depressive Disorder ( MDD ) received duloxetine 60 mg once daily ( QD ; N = 273 ) , escitalopram 10 mg QD ( N = 274 ) , or placebo ( N = 137 ) for 8 weeks . The primary objective was to compare the onset of antidepressant efficacy , by testing the hypothesis that the percentage of duloxetine-treated patients achieving onset criteria at Week 2 was not inferior to that in the escitalopram group . Main outcome measures : Onset of efficacy was defined as a 20 % decrease from baseline on the 17‑item Hamilton Rating Scale for Depression ( HAMD17 ) Maier subscale that was maintained or exceeded at all subsequent visits . Results : Probabilities of meeting onset criteria at Week 2 for duloxetine- and escitalopram-treated patients were 42.6 % versus 35.2 % , respectively ( treatment difference = 7.4 % ; 95 % confidence interval , –1.3 % to 16.2 % ; p = 0.097 ) . Both drugs showed significant improvement compared with placebo ( p ≤ 0.05 ) on the primary efficacy measure ( Maier subscale ) at Week 1 and endpoint ( Week 8) . No differences were found between duloxetine , escitalopram , and placebo rates of remission or response at 8 weeks . Adverse events that occurred significantly more frequently among duloxetine-treated patients when compared with those receiving escitalopram were nausea , dry mouth , vomiting , yawning , and irritability . The rate of discontinuation due to adverse events did not differ significantly between treatment groups . Limitations : Given the difficulties in constructing appropriate dose comparisons , the results of this study should be interpreted specific to the doses tested and not extrapolated to the drug as a whole . This study employed a fixed-dose design ; flexible-dose design s are more likely to find a difference between antidepressants and placebo . Conclusion : In this study , both duloxetine and escitalopram showed significantly greater improvement on the primary efficacy measure than placebo over the 8‑week acute treatment period , while no differences were observed between drugs or between drugs and placebo on response and remission rates at 8 weeks . Escitalopram at a starting dose of 10 mg QD was better tolerated  than duloxetine at a starting dose of 60 mg QD . This study met its pre-defined primary objective of assessing if duloxetine was non-inferior to escitalopram  in antidepressant onset efficacy , and the results show that duloxetine is at least as fast as ( non-inferior to ) escitalopram . Trial registration : Clinical Trials.gov identifier : NCT00073411
SSRIs significantly increase the risk of both serious and non-serious adverse events .
The potential small beneficial effects seem to be outweighed by harmful effects .
Background The evidence on selective serotonin reuptake inhibitors ( SSRIs ) for major depressive disorder is unclear .
Methods Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo , ‘ active ’ placebo , or no intervention in adult participants with major depressive disorder .