Remission with venlafaxine extended release or selective serotonin reuptake inhibitors in depressed patients: a randomized, open-label study.

BACKGROUND: This randomized, open-label, rater-blinded, multicenter study compared treatment outcomes with the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine extended release (ER) with selective serotonin reuptake inhibitors (SSRIs) in primary care patients with major depressive disorder. METHOD: Study data were collected from November 29, 2000, to March 4, 2003. Outpatients who met diagnostic criteria for major depressive disorder according to the Mental Health Screener, a computer-administered telephone interview program that screens for the most common mental disorders, and had a total score on the 17-item Hamilton Depression Rating Scale (HDRS(17)) ≥ 20 were randomly assigned to receive up to 6 months of open-label venlafaxine ER 75-225 mg/d (n = 688) or an SSRI (n = 697): fluoxetine 20-80 mg/d, paroxetine 20-50 mg/d, citalopram 20-40 mg/d, and sertraline 50-200 mg/d. The primary outcome was remission (HDRS(17) score ≤ 7) at study end point using the last-observation-carried-forward method to account for early termination. A mixed-effects model for repeated measures (MMRM) analysis evaluated secondary outcome measures. RESULTS: Fifty-one percent of patients completed the study. Month 6 remission rates did not differ significantly for venlafaxine ER and the SSRIs (35.5% vs 32.0%, respectively; P = .195). The MMRM analysis of HDRS(17) scores also did not differ significantly (P = .0538). Significant treatment effects favoring the venlafaxine ER group were observed for remission rates at days 30, 60, 90, and 135 and a survival analysis of time to remission (P = .006), as well as Clinical Global Impressions-severity of illness scale (P = .0002); Hospital Anxiety and Depression Scale-Anxiety subscale (P = .03); 6-item Hamilton Depression Rating Scale, Bech version (P = .009); and Quick Inventory of Depressive Symptomatology-Self-Report (P = .0003). CONCLUSIONS: Remission rates for patients treated with venlafaxine ER or an SSRI did not differ significantly after 6 months of treatment. Results of most secondary analyses suggested that SNRI treatment had a greater antidepressant effect versus the SSRIs studied.

Short-term efficacy and safety of desvenlafaxine in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder.

BACKGROUND: The risk for major depressive disorder (MDD) increases during the menopausal transition. Nonetheless, no large, placebo-controlled studies have prospectively assessed the efficacy of antidepressants in perimenopausal or postmenopausal women. This randomized, double-blind, placebo-controlled trial evaluated the short-term efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) in perimenopausal and postmenopausal women with DSM-IV-defined MDD. METHOD: 387 depressed perimenopausal and postmenopausal women aged 40 to 70 years were randomly assigned to placebo or desvenlafaxine (100 or 200 mg/d at the discretion of the investigator) in an 8-week, flexible-dose trial conducted from September 2006 to June 2008. The primary efficacy variable was change from baseline in 17-item Hamilton Depression Rating Scale (HDRS(17)) total score, analyzed using a mixed-effects model for repeated-measures analysis. Safety data were collected throughout the trial. RESULTS: The reduction in adjusted HDRS17 total scores from baseline to week 8 (mean daily dose after titration, 162 to 176 mg/d) was significantly greater for desvenlafaxine (-12.64) compared with placebo (-8.33; P < .001). Statistical separation from placebo was observed at week 1 and was sustained through week 8. Both the perimenopausal and postmenopausal subgroups achieved significant reductions in HDRS(17) total scores with desvenlafaxine treatment (perimenopausal, P = .003; postmenopausal, P < .001). Response (58.6%) and remission (38.2%) rates were significantly higher for desvenlafaxine compared with placebo (31.6% [P < .001] and 22.4% [P = .008], respectively). In all, 19/256 (7.4%) desvenlafaxine-treated patients and 4/125 (3.2%) placebo-treated patients discontinued due to adverse events. Treatment-emergent adverse events were reported by 94/125 (75.2%) placebo-treated patients and 218/256 (85.2%) desvenlafaxine-treated patients. CONCLUSIONS: Short-term treatment with desvenlafaxine was effective and generally well tolerated in perimenopausal and postmenopausal women with MDD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00369343.

Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study.

This 12-week, double-blind, multicenter trial evaluated the efficacy of venlafaxine extended release (ER), sertraline, and placebo in adult outpatients (N = 538) with a primary diagnosis of posttraumatic stress disorder (PTSD), as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, symptoms for 6 months or more and 17-item Clinician-administered PTSD Scale (CAPS-SX17) score of 60 or more. Patients were randomly assigned to receive placebo or flexible doses of venlafaxine ER (37.5-300 mg/d) or sertraline (25-200 mg/d) for 12 weeks or less. The primary outcome was the baseline-to-end point change in total CAPS-SX17 score (last observation carried forward). Secondary measures included CAPS-SX17 symptom cluster scores for reexperiencing/intrusion, avoidance/numbing, and hyperarousal; frequency of remission (CAPS-SX17 < or =20); and changes in Davidson Trauma Scale total score and symptom cluster scores for avoidance/numbing, hyperarousal, and reexperiencing/intrusion. Mean changes in CAPS-SX17 scores were -41.8, -39.4, and -33.9 for venlafaxine ER (P < 0.05 vs. placebo), sertraline, and placebo, respectively. Mean changes for venlafaxine ER, sertraline, and placebo in CAPS-SX17 cluster scores were -13.0, -11.7, and -11.0 for reexperiencing; -17.1, -16.8, and -13.7 (P < 0.05 both active treatments vs. placebo) for avoidance/numbing; and -11.8, -10.9, and -9.2 (P < 0.05 venlafaxine vs. placebo) for hyperarousal. Week 12 remission rates were venlafaxine ER 30.2% (P < 0.05 vs. placebo), sertraline 24.3%, and placebo 19.6%. The venlafaxine ER group had significantly better Davidson Trauma Scale total and cluster scores than placebo. Mean maximum daily doses were 225-mg venlafaxine ER and 151-mg sertraline. Both treatments were generally well tolerated. Study results suggest that venlafaxine ER is effective and well tolerated in the short-term treatment of PTSD.