An integrated analysis of the efficacy of desvenlafaxine compared with placebo in patients with major depressive disorder.
BACKGROUND
To assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) in outpatients with major depressive disorder.


METHODS
A meta-analysis of individual patient data was performed on the complete set of registration trials (nine randomized, double-blind, placebo-controlled 8-week studies) of desvenlafaxine. Patients received fixed (50, 100, 200, or 400 mg/day; n=1,342) or flexible doses (100-400 mg/day; n=463) of desvenlafaxine or placebo (n=1,108). The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression (HAM-D(17)); the primary intent to treat analyses used the last-observation-carried-forward method.


RESULTS
Significantly greater improvement with desvenlafaxine versus placebo on the HAM-D(17) total score was observed for the full data set (difference in adjusted means: -1.9; P<.001), each fixed-dose group (all P<.001), and the flexible-dose group (P=.024). Overall rates of HAM-D1(17) response (> or =150% decrease from baseline score: 53% vs 41%) and remission (HAM-D(17) < or =7: 32% vs 23%) were significantly greater for desvenlafaxine versus placebo (all P<.001). Discontinuation rates due to adverse events increased with dose (4% to 18%; placebo: 3%).


CONCLUSIONS
Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed.
Thase
Michael E
ME
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. thase@mail.med.upenn.edu
Kornstein
Susan G
SG
Germain
Jean-Michel
JM
Jiang
Qin
Q
Guico-Pabia
Christine
C
Ninan
Philip T
PT
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride