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Biol Psychiatry. 2002 Dec 15;52(12):1166-74.

Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression.

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  • 1The Neuroscience Education Institute, Carlsbad, California 92009, USA.



Serotonergic and adrenergic enhancement may be synergistic and more effective than serotonergic enhancement alone in treating depression. The dual serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine is a dual reuptake inhibitor that may therefore offer greater efficacy than selective serotonin reuptake inhibitors (SSRIs).


Data from eight randomized, double-blind, controlled studies were pooled to compare efficacy in depressed patients receiving venlafaxine/venlafaxine extended release (XR), SSRIs, or placebo for </=8 weeks. The mean changes from baseline in the 21-item Hamilton Rating Scale for Depression (HAM-D(21)), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impressions-Global Improvement (CGI-I) and CGI-Severity of Illness (CGI-S) item scores were compared, as were response rates derived from these scales.


Statistically significant differences in mean HAM-D(21) score decrease between venlafaxine (14.5) and SSRIs (12.6) and between the active treatments and placebo (11.3) were observed. Venlafaxine significantly decreased the mean MADRS scores more than SSRIs (17.8 vs. 15.9), and both treatments were significantly better than placebo (12.9). The same pattern of significance for CGI-I, HAM-D(21), and MADRS response rates between venlafaxine (71%, 64%, and 67%, respectively), SSRIs (64%, 57%, and 59%, respectively), and placebo (50%, 42%, and 41%, respectively) was observed.


Venlafaxine was significantly more effective than SSRIs in improving depression, perhaps due to enhancing both serotonin and norepinephrine.

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