Analysis Gives Venlafaxine Slender Edge Over SSRIs

By Charles Bankhead
ATLANTA, Feb. 27 -- For achieving major depression remission, a dual neurotransmitter reuptake inhibitor has a thin advantage over selective serotonin reuptake inhibitors, found a meta-analysis. Slightly more patients with major depression went into remission with venlafaxine (Effexor), the dual neurotransmitter reuptake inhibitor, than did those taking SSRIs. But the clinical significance of the difference remained unclear. Venlafaxine demonstrated a 5.9% advantage in remission rates in direct clinical comparisons with SSRIs, Charles Nemeroff, M.D., Ph.D., of Emory University, and colleagues, reported in the Feb. 15 issue of Biological Psychiatry. In a small number of trials that included a placebo arm, venlafaxine achieved a 13% difference in remission rates compared with a 6% difference between SSRIs and placebo.
"One would expect to treat approximately 17 patients with venlafaxine to see one more success than if all had been treated with another SSRI," the authors said. "Although this difference was reliable and would be important if applied to populations of depressed patients, it is also true that it is modest and might not e noticed by clinicians in everyday practice."
"Nonetheless, a number needed to treat of 17 may be of public health relevance given the large number of patients treated for depression and the significant burden of illness associated with this disorder," they added.
The approved antidepressants are widely perceived as having similar efficacy, the authors said. However, few individual studies of newer antidepressants have had sufficient statistical power to demonstrate a difference in efficacy between effective therapies.
A meta-analytical approach offers the potential to reveal meaningful differences that individual randomized controlled trials could not, the authors continued. Previous meta-analyses have suggested that venlafaxine, which inhibits reuptake of serotonin and norepinephrine, has an efficacy advantage over SSRIs.
The current study, funded by Wyeth, continued the meta-analytical approach and involved two strategies for analyzing the data. One meta-analysis included all double-blind Wyeth-sponsored trials comparing venlafaxine and SSRIs. The authors said the limited analysis was undertaken to ensure access to individual patient data.
For the second analysis, the investigators used a funnel plot analysis to extend the primary dataset by including data from all studies in the public domain. The funnel plot analysis was based on 48 studies, including 14 additional studies, 11 of which were not funded by Wyeth. No evidence of statistically significant selection bias was observed in the updated analysis of 48 studies, suggesting to the authors that study sponsorship did not significantly influence outcomes.
The study included 34 randomized, double-blind studies of 4,191patients treated with venlafaxine or 3,621 given an SSRI. Nine studies with 932 patients also included a placebo control arm. The primary outcome was intent-to-treat remission rates at week eight, as defined by a Hamilton Rating Scale score of ≤7.
The overall difference between venlafaxine and the SSRIs as a class was statistically significant (P<0.001). When the SSRIs were considered separately, venlafaxine had a statistically significant advantage only versus fluoxetine (6.6%, 95% CI 0.030 to 0.095). Significantly more patients withdrew because of adverse events with venlafaxine than with SSRIs (11% versus 9%, P=0.0011).
Acknowledging limitations of the study, the authors said the generalizability of the findings to clinical practice is unknown as patients with more complex conditions were excluded from the trials. The trials involved short-term treatment, and the possibility of SSRI "catch up" with longer treatment could not be ruled out. They also acknowledged potential questions about the validity of combining all the SSRIs into a single group for the analysis.
Dr. Nemeroff had a lengthy list of financial disclosures that included relationships with Wyeth, which sponsored the study.
Primary source: Biological PsychiatrySource reference:Nemeroff CB, et al "Comprehensive analysis of remission (COMPARE) with venlafaxine versus SSRIs" Biol Psychiatry 2008; 63: 424-434.