There are no data on the comparative efficacy of venlafaxine to other SSRI's in severe MDD.

In a post hoc analysis, data were pooled from 8 double-blind active controlled studies in outpatients with a diagnosis of MDD. Patients randomly assigned to venlafaxine (dose range 75-225 mg) or SSRI (fluoxetine (20–80 mg/day), fluvoxamine (100 mg/day), or paroxetine (20 mg/day)) were included in the analysis. Severe MDD was defined as baseline HAM-D17 >24 and alternatively as baseline MADRS≥ 31. Treatment groups were compared by mean improvement in the 17-item Hamilton Rating Scale for Depression (HAM-D17) (and alternatively MADRS) scores from baseline to last observation carried forward (LOCF). Secondary outcomes included HAM-D17 response (≥50% reduction in HAM-D17) and remission (HAM-D17 ≤7) rates, MADRS response (≥50% reduction in MADRS) and remission (MADRS≤10). Changes from baseline for the primary end point were evaluated using analysis of covariance with treatment, study, and baseline in the model.

A total of 1503 patients were included in the analysis (venlafaxine n = 805; SSRI, n = 698); 649/1503 (43%) patients had severe depression (HAM-D17 >24) at baseline. Venlafaxine improved HAM-D17 scores vs. SSRI in patients with severe MDD (venlafaxine, −15.26 [0.73]; SSRI, −12.91 [0.81]; P = 0.003). Response and remission were significantly higher in venlafaxine compared with SSRI (Response: Venlafaxine = 63% vs SSRI= 53% (p = 0.004); Remission: 41% vs. 31% (p = 0.005)). The results of the analyses were similar when baseline severity was defined by MADRS scores.

In this retrospective pooled analysis, venlafaxine was superior to SSRI's in treating severe MDD.