Comprehensive Analysis of Remission (COMPARE) with Venlafaxine versus SSRIs

To compare venlafaxine and selective serotonin reuptake inhibitors (SSRIs; fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram) in the treatment of depression. Meta-analysis of 34 randomized, double-blind studies identified by a worldwide search of all research sponsored by Wyeth Pharmaceuticals through January 2007. Patients were treated with venlafaxine ( n = 4191; mean dose 151 mg/day) or SSRIs ( n = 3621); nine studies also included a placebo control group ( n = 932). The primary outcome measure was intent-to-treat (ITT) remission rates (Hamilton Rating Scale for Depression ≤7) at week 8. The overall difference in ITT remission rates was 5.9% favoring venlafaxine (95% confidence interval [CI]: .038–.081; p < .001). Based on this difference, the number needed to treat (NNT) to benefit is 17 (95% CI: 12–26). In the nine placebo controlled studies, the drug-placebo differences were 6% (.02–.09) for the SSRIs and 13% (.09–.16) for venlafaxine. For the specific SSRIs, the difference versus fluoxetine (mean dose = 37 mg/day; 20 studies) was significant (6.6% [95% CI: .030–.095]); smaller differences versus paroxetine (mean dose = 25 mg/day; eight studies; 5%), sertraline (mean dose = 127 mg/day; three studies; 3%), and citalopram (mean dose = 38 mg/day; two studies; 4%) were not significant. Attrition rates due to adverse events were higher with venlafaxine than with SSRI therapy, 11% and 9% respectively ( p = .0011). These results indicate that venlafaxine therapy is statistically superior to SSRIs as a class, but only to fluoxetine individually. The clinical significance of this modest advantage seems limited for the broad grouping of major depressive disorder. Nonetheless, an NNT of 17 may be of public health relevance given the large number of patients treated for depression and the significant burden of illness associated with this disorder

Treatment of post-traumatic stress disorder with venlafaxine extended release: a 6-month, randomized, controlled trial

Context No large-scale posttraumatic stress disorder drug trials have been conducted to evaluate treatment effects beyond 12 weeks outside of those with selective serotonin reuptake inhibitors. Objective To evaluate the efficacy of venlafaxine extended release (ER), a serotonin norepinephrine reuptake inhibitor, in posttraumatic stress disorder. Design 6-month, double-blind, placebo-controlled trial. Setting International study at 56 sites. Patients Adult outpatients (N = 329) with a primary diagnosis of posttraumatic stress disorder as defined in the DSM-IV, symptoms for 6 months or longer, and a 17-item Clinician-Administered Posttraumatic Stress Disorder Scale score of 60 or higher. Intervention Patients randomly assigned to receive flexible doses of venlafaxine ER (37.5-300 mg/d) or placebo for 24 weeks. Main Outcome Measures Primary measure was the change from baseline in the Clinician-Administered Posttraumatic Stress Disorder Scale score. Secondary measures included remission, defined as a Clinician-Administered Posttraumatic Stress Disorder Scale score of 20 or lower, and changes in symptom cluster scores, frequency of remission, and time to remission. Measures of stress vulnerability, resilience, depression, quality of life, functioning, and global illness severity were also taken. Results Mean changes from baseline in Clinician-Administered Posttraumatic Stress Disorder Scale total scores at end point were –51.7 for venlafaxine ER and –43.9 for placebo (P = .006). Improvement was significantly greater for the venlafaxine ER group than for the placebo group in cluster scores for reexperiencing (P = .008) and avoidance/numbing (P = .006), but not for hyperarousal. Remission rates were 50.9% for venlafaxine ER and 37.5% for placebo (P = .01). The venlafaxine ER group also showed significantly greater improvement at end point than the placebo group (P&lt;.05) on all other reported outcome measures. The mean maximum daily dose of venlafaxine ER was 221.5 mg/d. Withdrawal rates were similar between groups with no significant difference in dropouts attributable to adverse events. Conclusion In this study, venlafaxine ER was effective and well tolerated in short-term and continuation treatment of patients with posttraumatic stress disorder

Effects of venlafaxine extended release on resilience in posttraumatic stress disorder: an item analysis of the Connor-Davidson Resilience Scale

The aim was to evaluate the efficacy of venlafaxine extended release (ER) on characteristics of resilience, measured by the Connor-Davidson Resilience Scale, in patients with posttraumatic stress disorder (PTSD). Data were evaluated from a randomized, 6-month, international, multicenter study of adult outpatients with a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PTSD for ?6 months, and 17-item Clinician-Administered PTSD Scale score ?60. Patients were assigned randomly to treatment with flexible-dose venlafaxine ER (37.5-300 mg/day) or placebo. Changes from baseline scores and effect sizes of response to treatment with venlafaxine ER compared with placebo were computed for each item, as well as for the newly developed 2-item and 10-item subscales. Effect sizes across items ranged from 0.41 (moderate) to 0.08 (very weak). The effect size for the Resilience Scale-2 (2-item subscale) was 0.32, which was comparable to the effect sizes of 0.35 for the 25-item full scale and 0.34 for the 10-item subscale. Venlafaxine ER improved resilience on individual Connor-Davidson Resilience Scale items that reflect four factors (hardiness, persistence/tenacity, social support, and faith in a benevolent or meaningful world), to varying degrees in patients with PTSD. The findings suggest that assessment of treatment response might be enhanced by routine evaluation of resilience