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.

Our results support the concept of using database research as a cost-effective pharmacovigilance tool that is free of selection bias . Further investigation using database research is required to confirm our preliminary observations.

PurposeTo 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).MethodsWe 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.ResultsVenlafaxine 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.ConclusionThese 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.

BackgroundMany of the posttraumatic stress disorder (PTSD) treatment guidelines recognize the use of selective serotonin reuptake inhibitors as first-line pharmacological treatment. In Japan, there were no published studies investigating the effectiveness and safety of sertraline for PTSD in a clinical setting.MethodsWe conducted a retrospective medical chart review of the dosage, effectiveness, and safety of sertraline for the PTSD treatment in Japan. Data were collected from medical charts of patients of PTSD, caused by various types of trauma, who were treated with sertraline between July 2006 and October 2012 during their regular clinical practice. To evaluate the effectiveness, the investigators retrospectively assessed the severity and improvement of the symptoms using the Clinical Global Impressions − Severity and the Clinical Global Impressions − Improvement.ResultsThe study population was 122 Japanese patients aged ≥18 years with a diagnosis of PTSD who were treated with sertraline (median duration, 10.6 months). Doses ranged from 12.5 to 150 mg/day, mostly 25 and 50 mg/day. The median duration of observation was 10.8 months. Out of those, 50% of patients were regarded as responders by using the Clinical Global Impressions - Improvement at the end of sertraline treatment or the last observation. Two-thirds (65.6%) of patients improved in the severity of PTSD, as assessed by Clinical Global Impressions - Severity, whereas 32.8% showed no change, and 1.6% worsened. Subgroups analyses and logistic regression analyses suggested that the type of traumatic events was the factor with the highest influence on the response rate. The adverse events in this chart review were consistent with the known safety profile of sertraline. There were no reports of serious or severe adverse events considered to be related to sertraline.ConclusionsOur study suggested the effectiveness of sertraline for the treatment of PTSD in a Japanese clinical setting, and the obtained safety profile was consistent with the generally known safety profile of sertraline.Trial registrationClinicalTrials.gov (Identification No. NCT01607593). Registered May 21, 2012.

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