BackgroundIn individual studies and limited meta-analyses venlafaxine has been reported to be more effective than comparator antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs).AimsTo perform a systematic review of all such studies.MethodWe conducted a systematic review of double-blind, randomised trials comparing venlafaxine with alternative antidepressants in the treatment of depression. The primary outcome was the difference in final depression rating scale value, expressed as a standardised effect size. Secondary outcomes were response rate, remission rate and tolerability.ResultsA total of 32 randomised trials were included. Venlafaxine was more effective than other antidepressants (standardised effect size was −0.14, 95% Cl −0.07 to −0.22). A similar significant advantage was found against SSRIs (20 studies) but nottricyclic antidepressants (7 studies).ConclusionsVenlafaxine has greater efficacy than SSRIs although there is uncertainty in comparison with other antidepressants. Further studies are required to determine the clinical importance of this finding.