Comprehensive analysis of remission (COMPARE) with venlafaxine versus SSRIs.
BACKGROUND
To compare venlafaxine and selective serotonin reuptake inhibitors (SSRIs; fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram) in the treatment of depression.


METHODS
Meta-analysis of 34 randomized, double-blind studies identified by a worldwide search of all research sponsored by Wyeth Pharmaceuticals through January 2007. Patients were treated with venlafaxine (n = 4191; mean dose 151 mg/day) or SSRIs (n = 3621); nine studies also included a placebo control group (n = 932). The primary outcome measure was intent-to-treat (ITT) remission rates (Hamilton Rating Scale for Depression </=7) at week 8.


RESULTS
The overall difference in ITT remission rates was 5.9% favoring venlafaxine (95% confidence interval [CI]: .038-.081; p < .001). Based on this difference, the number needed to treat (NNT) to benefit is 17 (95% CI: 12-26). In the nine placebo controlled studies, the drug-placebo differences were 6% (.02-.09) for the SSRIs and 13% (.09-.16) for venlafaxine. For the specific SSRIs, the difference versus fluoxetine (mean dose = 37 mg/day; 20 studies) was significant (6.6% [95% CI: .030-.095]); smaller differences versus paroxetine (mean dose = 25 mg/day; eight studies; 5%), sertraline (mean dose = 127 mg/day; three studies; 3%), and citalopram (mean dose = 38 mg/day; two studies; 4%) were not significant. Attrition rates due to adverse events were higher with venlafaxine than with SSRI therapy, 11% and 9% respectively (p = .0011).


CONCLUSIONS
These results indicate that venlafaxine therapy is statistically superior to SSRIs as a class, but only to fluoxetine individually. The clinical significance of this modest advantage seems limited for the broad grouping of major depressive disorder. Nonetheless, an NNT 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.
Nemeroff
Charles B
CB
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30322, USA. cnemero@emory.edu
Entsuah
Richard
R
Benattia
Isma
I
Demitrack
Mark
M
Sloan
Diane M
DM
Thase
Michael E
ME
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015283:Citalopram / Q000627:therapeutic use; D003511:Cyclohexanols / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D016666:Fluvoxamine / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride
D015283:Citalopram; D003511:Cyclohexanols; D005473:Fluoxetine; D016666:Fluvoxamine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D000069470:Venlafaxine Hydrochloride