Thirty-four RCTs compared venlafaxine with SSRIs (n=7,155). Eighteen RCTs compared venlafaxine with tricyclic antidepressants (n=2,769). Seven RCTs compared venlafaxine with other antidepressants (n=1,338), but only four (n not reported) provided data. Five RCTs compared venlafaxine with other antidepressants in treatment resistant depression (n=4,754). Three RCTs compared venlafaxine with placebo in the prevention of relapse or recurrence after major depressive episode (n=973). Most studies were double blinded. None reported allocation concealment.
Compared to SSRIs, venlafaxine was associated with a significant increase in response (OR1.15, 95% CI 1.02 to 1.29; 29 studies) and remission (OR 1.19, 95% CI 1.06 to 1.34; 23 studies). There was no significant difference between venlafaxine and SSRIs in overall drop-outs. There was no significant heterogeneity for response and some evidence of heterogeneity for remission (p=0.03, I2=38%).
Compared to TCAs, venlafaxine was associated with a significant increase in response using the exact method (OR 1.21, 95% CI 1.03 to 1.43; 16 studies), but there was no significant difference in response using a full random-effects model and no significant difference in remission rates. TCAs were associated with higher overall drop-out rates compared to venlafaxine (OR 0.77, 95% CI 0.65 to 0.90; 15 studies). There was some evidence of heterogeneity for response (p=0.06, I2=37%), but no evidence of heterogeneity for remission.
Compared to alternative antidepressants in patients with treatment resistant depression, venlafaxine was associated with a significant increase in response (OR 1.35, 95% CI 1.19 to 1.54; four studies) and remission (OR 1.35, 95% CI 1.20 to 1.52; five studies).There was no significant heterogeneity for either analysis.
Compared to placebo, venlafaxine was associated with a significant increase in relapse prevention (OR 0.37, 95% CI 0.27 to 0.51; three studies).