A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan

Abstract

The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75–225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (−10.76; P=0.031), but not in the flexible-dose (−10.37; P=0.106) group compared with placebo (−9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan.

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

“…The original study was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III study to evaluate the efficacy and safety of venlafaxine ER 75 mg/day (fixed-dose) and venlafaxine ER 75–225 mg/day (flexible-dose), compared with placebo ( ClinicalTrials.gov : NCT01441440). 5 After a 2-week screening period, eligible patients were randomized in a 1:1:1 ratio to each treatment group for 8 weeks, followed by a 2-week tapering period.…”

“…The details of drug administration and dose titration have been reported elsewhere. 5 Initial dose of venlafaxine was 37.5 mg/day. In Week 1, the dose could be increased to 75 mg/day, and in Week 2, based on tolerability, it could be increased to 150 mg/day in the flexible-dose group.…”

“…Higuchi et al 5 reported the primary results of an 8-week, double-blind, placebo-controlled, randomized, Phase III study of 538 patients conducted in Japan using fixed-dose (75 mg/day) and flexible doses (75–225 mg/day) of venlafaxine ER. The study findings showed a statistically significant difference in the change from baseline in Hamilton Rating Scale for Depression–17 items (HAM-D 17 ) total score 6 in the fixed-dose group (−10.76; P =0.031), but not in the flexible-dose group (−10.37; P =0.106), compared with the placebo group (−9.25).…”

Qualitative treatment-subgroup interactions in the antidepressant treatment of major depression: Application of QUINT to individual participant data from seven placebo-controlled randomized controlled trials

“…Of these, five companies have agreed to provide the requested data representing six trials examining six antidepressants. Three companies have provided anonymized individual-level data for four trials examining duloxetine, escitalopram, mirtazapine and paroxetine [16,17,18,22], whereas one provided access to such data for two trials examining bupropion and paroxetine [14,23] and another company for a trial examining venlafaxine [15] at their dedicated internet portal only. We used all data that were included in the regulatory submission and the clinical study report of these trials.…”

Association of 5-HT1A Receptors with Affective Disorders

“…One double-blind, controlled, randomized study compared two treatment schedules with venlafaxine: one fixed (75 mg/day) the other flexible (75-225 mg/day). It found that the fixed program gave a better response to this antidepressant treatment than the flexible approach [91]. Similarly, the use of SNRIs in young depressed patients (7-18) did not produce better therapeutic effects than a placebo treatment, though duloxetine has shown therapeutic potential in such patients [92].…”