Factors impacting the efficacy of venlafaxine extended release 75–225 mg/day in patients with major depressive disorder: exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study in Japan

Abstract

Purpose

To explore the potential factors impacting the efficacy of venlafaxine extended release (ER) and treatment differences between 75 mg/day and 75–225 mg/day dose in patients with major depressive disorder (MDD).

Methods

We performed exploratory post hoc subgroup analyses of a randomized, double-blind, placebo-controlled study conducted in Japan. A total of 538 outpatients aged 20 years or older with a primary diagnosis of MDD who experienced single or recurrent episodes were randomized into three groups: fixed-dose, flexible-dose, or placebo. Venlafaxine ER was initiated at 37.5 mg/day and titrated to 75 mg/day for both fixed-dose and flexible-dose group, and to 225 mg/day for flexible-dose group (if well tolerated). Efficacy endpoints were changes from baseline at Week 8 using the Hamilton Rating Scale for Depression–17 items (HAM-D₁₇) total score, Hamilton Rating Scale for Depression–6 items score, and Montgomery–Asberg Depression Rating Scale total score. The following factors were considered in the subgroup analyses: sex, age, HAM-D₁₇ total score at baseline, duration of MDD, duration of current depressive episode, history of previous depressive episodes, history of previous medications for MDD, and CYP2D6 phenotype. For each subgroup, an analysis of covariance model was fitted and the adjusted mean of the treatment effect and corresponding 95% CI were computed. Due to the exploratory nature of the investigation, no statistical hypothesis testing was used.

Results

Venlafaxine ER improved symptoms of MDD compared with placebo in most subgroups. The subgroup with a long duration of MDD (>22 months) consistently showed greater treatment benefits in the flexible-dose group than in the fixed-dose group.

Conclusion

These results suggest that a greater treatment response to venlafaxine ER (up to 225 mg/day) can be seen in patients with a longer duration of MDD. Further investigations are needed to identify additional factors impacting the efficacy of venlafaxine ER.

Keywords:

• venlafaxine
• Hamilton Rating Scale for Depression
• HAM-D
• subgroup
• major depressive disorder
• MDD
• Montgomery–Asberg Depression Rating Scale
• MADRS

Supplementary material

Acknowledgments

This study was sponsored by Pfizer Inc. Editorial support was provided by Pearl Gomes of Cactus Communications and was funded by Pfizer Inc. We are grateful for the contributions of trial participants, principal investigators, and all other medical personnel to this study. Full control of the manuscript content was retained by all authors.

Disclosure

YA, YH, RI, and TI are employees of Pfizer Japan Inc. KK was an employee of Pfizer Japan Inc. at the time of the study. YW has received speaker’s honoraria from Pfizer Japan Inc., GlaxoSmithKline K.K., Otsuka Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Meiji Seika Pharma Co., Ltd, Eli Lilly Japan K.K., MSD K.K. a subsidiary of Merck & Co., Inc., Takeda Pharmaceutical Co., Ltd., and Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corp., and Sumitomo Dainippon Pharma Co., Ltd., within the past 5 years. The authors report no other conflicts of interest in this work.