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 .
Results From 2 Randomized, Double-Blind, Placebo-Controlled Studies of the Novel NK1 Receptor Antagonist Casopitant in Patients With Major Depressive Disorder
Clinical study results for neurokinin ( NK ) receptor antagonists in the treatment of depression have been mixed , with Phase III studies failing to fulfill the early promise demonstrated in Phase II studies . Casopitant , a selective NK1 antagonist that achieves nearly complete receptor occupancy was studied in 2 r and omized , placebo-controlled , double-blind , Phase II trials in depressed out patients to test the hypothesis that nearly complete NK1 receptor occupancy is required to achieve antidepressant efficacy . Study 092 used an interactive voice response system to recruit depressed patients with baseline Hamilton Depression ( 17-item , HAMD17 ) total scores higher than 24 who were r and omized to fixed-dose casopitant 30 mg/d , 80 mg/d , or placebo for 8 weeks ( n = 356 ) . Study 096 required Carroll Depression Scale-Revised self- assessment scores of higher than 24 for r and omization to casopitant 120 mg/d , paroxetine 30 mg/d ( both reached via forced titration ) , or placebo for 8 weeks ( n = 362 ) . In study 092 , casopitant 80 mg but not 30 mg achieved statistically significant improvement versus placebo on the primary outcome measure , week 8 last observation carried forward change from baseline HAMD17 ( difference = −2.7 ; 95 % confidence interval , −5.1 to −0.4 , P = 0.023 ) . In study 096 , neither casopitant nor paroxetine achieved statistical separation from placebo at end point on HAMD17 ( casopitant difference = −1.7 ; 95 % CI , −3.8 to 0.4 , P = 0.282 ) . Casopitant and paroxetine were generally well tolerated in most patients . These studies suggest that NK1 antagonists that have nearly complete receptor occupancy may be effective in the treatment of depression
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 .