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 .
The vasopressin V(1b) receptor antagonist SSR149415 in the treatment of major depressive and generalized anxiety disorders: results from 4 randomized, double-blind, placebo-controlled studies.
OBJECTIVE These studies were design ed to evaluate the efficacy and tolerability of the first nonpeptide vasopressin V(1b ) receptor antagonist , SSR149415 , in the treatment of major depressive disorder ( MDD ) and generalized anxiety disorder ( GAD ) . METHOD Studies were r and omized 8-week , double-blind , placebo-controlled trials evaluating 100- and 250-mg twice daily doses of SSR149415 , placebo , and escitalopram 10 mg/day or paroxetine 20 mg/day , conducted from August 2006 through February 2008 . Participants met the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision criteria for MDD or GAD .  Baseline Montgomery-Asberg Depression Rating Scale ( MADRS ) and Hamilton Depression Rating Scale ( HDRS ) total scores were ≥ 24 and 18 , respectively , and in the GAD trial baseline Hamilton Anxiety Rating Scale ( HARS ) score was ≥ 22 . Primary efficacy variables included changes from baseline in total score on HDRS or HARS and MADRS , and the secondary variable included changes in the Clinical Global Impressions-Severity of Illness score ( CGI-S ) . A 4-week , double-blind , placebo-controlled study evaluating the effect of 100- and 250-mg twice daily doses of SSR149415 on the hypothalamic-pituitary-adrenal ( HPA ) axis in MDD patients was also conducted . RESULTS In the GAD trial , SSR149415 did not separate from placebo on the primary ( HARS-100 mg : P = .29 ; 250 mg : P = .21 ) and secondary ( CGI-S-100 mg : P = .18 ; 250 mg : P = .24 ) outcome measures , while paroxetine  demonstrated efficacy ( HARS : P = .003 ; CGI-S : P = .01 ) . In 2 MDD trials , SSR149415-treated patients did not show significant improvement from baseline on any outcome measure compared with placebo-treated patients ( HDRS-100 mg : P = .21 and .48 , respectively ; 250 mg : P = .22 and P = .46 , respectively ; CGI-S-100 mg : P = .64 and P = .82 , respectively ; 250 mg : P = .33 and P = .08 , respectively ) . In the third MDD study , SSR149415 250 mg ( P = .04 ) , but not escitalopram ( P = .15 ) , demonstrated significant improvement compared to placebo on the HDRS total score at week 8 . SSR149415 had no deleterious effects on the HPA axis . CONCLUSIONS These studies demonstrate that SSR149415 may not be useful for the treatment of GAD and that its antidepressant potential needs to be further evaluated . TRIAL REGISTRATION Clinical Trials.gov identifiers : NCT00374166 ( Sanofi ID number : DFI5880 ) , NCT00361491 ( Sanofi ID number : DFI5879 ) , NCT00358631 ( Sanofi ID number : DFI5878 ) , NCT01606384 ( Sanofi ID number : PDY5467 )
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 .