Double-blind randomised controlled trials (RCTs) that compared venlafaxine with tricyclic antidepressants for the treatment of depression were eligible for inclusion; single-blind comparisons were excluded.
The primary outcome was a response rate of 50% or greater based upon a decrease in depression rating scale from baseline using the Hamilton Rating Scale for Depression (HRSD) or Montgomery and Asberg Rating Scale; where more than one scale was used the HRSD took precedent. Tolerability was assessed through 'all-cause' and 'side-effects' withdrawals.
In the included trials, tricyclic antidepressants used included imipramine (range 116 to 176mg/day), clomipramine (range 61.5 to 105mg/day) and amitriptyline (range 75 to 103.1mg/day). The mean daily dose of venlafaxine ranged from 75 to 233mg. Just under half of the trials excluded psychotic-depressed and suicidal patients. The majority of trials were undertaken in an outpatient setting. Trial duration ranged from six to 13 weeks, with an average duration of 7.4 weeks.
Four reviewers independently selected studies for inclusion in the review, with disagreements resolved through discussion.