Onset of activity and time to response on individual CAPS-SX17 items in patients treated for posttraumatic stress disorder with venlafaxine XR: A pooled analysis

This pooled analysis of data from two randomized, placebo-controlled trials of venlafaxine extended release (ER) assessed onset of activity and time to response on the 17 symptoms of post-traumatic stress disorder (PTSD) listed in DSM-IV and measured by the 17-item Clinician-Administered PTSD Scale (CAPS-SX17). The intent-to-treat (ITT) population comprised 687 patients (placebo, n=347; venlafaxine ER, n=340). Significant (p&lt;0.05) separation between venlafaxine ER and placebo was observed on most CAPS-SX17 items, with earliest onset of activity and response (week 2) on items 5 (physiological reactivity on exposure to cues) and 14 (irritability or anger outbursts), and (week 4) items 1 (intrusive recollections) and 4 (psychological distress at exposure to cues). Onset of activity and response occurred later (generally, weeks 6-8) on items 9 (diminished interest/participation in activities), 10 (detachment or estrangement), 11 (restricted range of affect), 12 (sense of foreshortened future), all associated with numbing, 15 (difficulty concentrating), 16 (hypervigilance), 17 (exaggerated startle response), associated with hyperarousal, and 6 (avoidance of thoughts/feelings or conversations). Significant differences between venlafaxine ER and placebo were largely absent throughout the treatment period and at the primary week-12 end-point for items 2 (distressing dreams), 7 (avoidance of activities, places or people), 8 (inability to recall important aspect of trauma) and 13 (difficulty falling/staying asleep). These results indicate that symptoms of physiological reactivity and psychological distress in response to cues, and irritability/anger outbursts show early and robust improvement with venlafaxine ER treatment, while symptoms of numbing and hyperarousal take longer. The early and persistent effect of venlafaxine ER over placebo on anger/irritability is noteworthy in view of the clinical significance of these symptoms in PTSD.<br/

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

Treatment of Post-traumatic Stress Disorder Using Venlafacine XR: A 6-month, Placebo-controlled Study

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A pooled analysis of gender and trauma type effects on responsiveness to treatment of PTSD with venlafaxine extended release or placebo

Objective: to examine effects of gender and trauma type on response to treatment with venlafaxine extended release (ER) or placebo in patients with posttraumatic stress disorder (PTSD).Method: data were pooled from 2 flexible-dose, parallel-group, randomized, double-blind, placebo-controlled trials: a 12-week trial conducted in the United States (March 2001 to December 2002) and a 24-week trial conducted in 12 countries outside the United States (October 2001 to December 2003). Six hundred eighty-seven outpatients with DSM-IV-diagnosed PTSD and a 17-item Clinician-Administered PTSD Scale abbreviated 1-week Symptom Status version (CAPS-SX-17) score &gt;= 60 were randomly assigned to treatment with venlafaxine ER (37.5 mg/day-300 mg/day, N = 340) or placebo (N = 347). The primary efficacy end point was the CAPS-SX-17 total score at week 12. Secondary end points included CAPS-SX-17 cluster scores for reexperiencing, avoidance/numbing, and hyperarousal and scores on the Connor-Davidson Resilience Scale (CD-RISC), Clinical Global Impressions-Severity of Illness scale, Sheehan Disability Scale (SDS), and 17-item Hamilton Rating Scale for Depression (HAM-D-17). Analysis-of-covariance models were used to test for differences by gender and trauma type (accidental injury, combat, nonsexual abuse, adult sexual abuse, childhood sexual abuse, unexpected death, and other), treatment (venlafaxine ER vs. placebo), and the treatment-by-trauma-type interaction.Results: using last-observation-carried-forward analysis, significant effects of treatment with venlafaxine ER were found on the CAPS-SX-17 total score and on all CAPS-SX-17 cluster scores and most other secondary measures. No significant treatment-by-gender interactions were observed. Trauma type significantly affected treatment responsiveness on symptom-related disability (SDS, p = .0057) and resilience (CD-RISC, p = .0012), with a nearly significant effect on depression (HAM-D-17, p = .0625).Conclusion: overall, there does not appear to be a significant effect of gender on the efficacy of venlafaxine ER in the treatment of PTSD. Trauma type may affect treatment outcome but seems to affect domains such as disability and resilience more than core PTSD symptom

Onset of activity and time to response on individual CAPS-SX17 items in patients treated for post-traumatic stress disorder with venlafaxine ER: a pooled analysis

This pooled analysis of data from two randomized, placebo-controlled trials of venlafaxine extended release (ER) assessed onset of activity and time to response on the 17 symptoms of post-traumatic stress disorder (PTSD) listed in DSM-IV and measured by the 17-item Clinician-Administered PTSD Scale (CAPS-SX17). The intent-to-treat (ITT) population comprised 687 patients (placebo, n=347; venlafaxine ER, n=340). Significant (p&lt;0.05) separation between venlafaxine ER and placebo was observed on most CAPS-SX17 items, with earliest onset of activity and response (week 2) on items 5 (physiological reactivity on exposure to cues) and 14 (irritability or anger outbursts), and (week 4) items 1 (intrusive recollections) and 4 (psychological distress at exposure to cues). Onset of activity and response occurred later (generally, weeks 6-8) on items 9 (diminished interest/participation in activities), 10 (detachment or estrangement), 11 (restricted range of affect), 12 (sense of foreshortened future), all associated with numbing, 15 (difficulty concentrating), 16 (hypervigilance), 17 (exaggerated startle response), associated with hyperarousal, and 6 (avoidance of thoughts/feelings or conversations). Significant differences between venlafaxine ER and placebo were largely absent throughout the treatment period and at the primary week-12 end-point for items 2 (distressing dreams), 7 (avoidance of activities, places or people), 8 (inability to recall important aspect of trauma) and 13 (difficulty falling/staying asleep). These results indicate that symptoms of physiological reactivity and psychological distress in response to cues, and irritability/anger outbursts show early and robust improvement with venlafaxine ER treatment, while symptoms of numbing and hyperarousal take longer. The early and persistent effect of venlafaxine ER over placebo on anger/irritability is noteworthy in view of the clinical significance of these symptoms in PTSD

Prevention of recurrent episodes of depression with venlafaxine ER in a 1-year maintenance phase from the PREVENT Study

OBJECTIVES: To test the long-term efficacy and safety of venlafaxine extended-release (ER) in preventing recurrence in patients with major depression. METHOD: This multiple-phase study, entitled Prevention of Recurrent Episodes of Depression With Venlafaxine for Two Years (PREVENT), was conducted from December 2000 through July 2005 in patients with recurrent unipolar depression (DSM-IV) who were initially randomly assigned to double-blind treatment with venlafaxine ER (75 mg/day to 300 mg/day) or fluoxetine (20 mg/day to 60 mg/day) for 10 weeks of acute treatment. Responders then received 6 months of continuation treatment. Those who remained responders were then enrolled into a 12-month maintenance period. Venlafaxine ER responders were randomly assigned to receive double-blind treatment with venlafaxine ER or placebo. Fluoxetine responders were not randomly assigned but continued taking fluoxetine in order to maintain the blind during the maintenance study. Time to recurrence of depression (17-item Hamilton Rating Scale for Depression total score \u3e 12 and \u3c 50% reduction from acute phase baseline) with venlafaxine ER versus that of placebo were compared. RESULTS: The efficacy evaluable sample consisted of 129 patients in each group. The mean daily dose of venlafaxine ER was 224.7 mg (SD = 66.7). The cumulative probability of recurrence through 12 months, based on the primary definition, was 23.1% (95% CI = 15.3 to 30.9) for venlafaxine ER and 42.0% (95% CI = 31.8 to 52.2) for placebo (p = .005, log-rank test). CONCLUSION: Patients who had been successfully treated with venlafaxine ER during acute and continuation therapy were significantly less likely to experience recurrence with venlafaxine ER than with placebo over a 12-month maintenance treatment period. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00046020