A recent 12-week controlled trial comprising 538 patients with chronic PTSD (symptoms for more than 6 months) and a CAPS score greater than 60, evaluated venlafaxine extended release (ER) versus sertraline(Drug information on sertraline) and placebo.5 Patients were randomized to venlafaxine ER in a flexible dosage range of 37.5 mg to 300 mg daily, 25 to 200 mg of sertraline daily, or placebo. A total of 350 patients (66%) completed the study. The mean decrease in CAPS scores (the primary outcome measure) was 41.8 for patients treated with venlafaxine ER, 39.4 for sertraline, and 33.9 for placebo (P < .05). The mean decrease in sertraline scores was comparable statistically to that seen with venlafaxine ER and significantly greater than the decrease in patients receiving placebo.
In a 6-month, double-blind, placebo-controlled multicenter, international study at 56 sites, patients (N = 329) meeting DSM-IV criteria for PTSD were randomized to receive either venlafaxine ER or placebo.6 Dosing was flexible based on side-effect profile and clinical response with a dosage range of 37.5 to 300 mg of venlafaxine ER daily or matching placebo for a treatment period of 24 weeks. The primary efficacy variable was the CAPS.
Mean change from baseline in the CAPS was a decrease of 51.7 for venlafaxine ER and 43.9 for the placebo group (Table 1). Remission rates, defined as a CAPS score of 20 or less, were significantly higher for the venlafaxine ER group versus placebo. Venlafaxine ER also demonstrated significantly greater improvement in re-experiencing (P = .008) and avoidance symptoms (P = .006) but not in hyperarousal symptoms. Improvement in other outcome measures was also greater in the venlafaxine group versus the placebo group. These data provide further evidence for the long-term efficacy of an SNRI for the treatment of PTSD.
Treatment of PTSD with venlafaxine versus placebo: endpoint change scores6
|Clinician-Administered Posttraumatic Stress Disorder Scale (LOCF)|
|Week 12*||Week 24†|
|Mean ± SD||Mean ± SD|
|Venlafaxine ER||−47.5 ± 25.86||−51.7 ± 27.16|
|Placebo||−37.6 ± 27.55||−43.9 ± 28.93g|
LOCF, last observation carried forward; SD, standard deviation; ER, extended release.
*P < .001; †P = .006.
A trial with paroxetine(Drug information on paroxetine) investigated long-term treatment in patients with PTSD.7 The primary objective of the open-label study was to investigate changes in hippocampal volume and declarative memory during a 9- to 12-month treatment period. Patients who completed a double-blind treatment phase were given up to 50 mg daily of paroxetine in a flexible dose schedule based on response. Twenty-three patients completed the full course of treatment and had neuropsychological testing. Twenty patients underwent MRI to assess hippocampal volume. There was a 4.6% increase in mean hippocampal volume and a significant improvement in declarative memory. Paroxetine treatment resulted in a mean reduction of 54% in PTSD symptoms as measured by the CAPS. There was no correlation between changes in CAPS scores and hippocampal volume or memory scores.
In another trial with an antidepressant, Martenyi and colleagues8 assessed the efficacy and tolerability of fluoxetine(Drug information on fluoxetine) versus placebo in preventing relapse in patients with PTSD. Following a 12-week double-blind, placebo-controlled acute treatment phase, responders were randomized to receive 24 weeks of treatment with fluoxetine (n = 69) or placebo (n = 62). The primary outcome variable was time to relapse. Patients who received fluoxetine in the acute phase were less likely to relapse than patients who received placebo (P = .027). Fluoxetine was well tolerated. This study supports the longer term efficacy of this SSRI in the prevention of relapse and also suggests that responders to active medication are more likely to be responsive in continuation treatment than responders to placebo.
Perhaps the longest follow-up study has been conducted by Hertzberg and colleagues.9 These investigators assessed patients with chronic PTSD (n = 10) 3 to 4 years after they had participated in a 12-week open trial of nefazodone(Drug information on nefazodone). The dosage of nefazodone was increased to a range of 400 to 600 mg daily from a starting dosage of 100 mg daily. Nine of the 10 patients reported that the nefazodone was effective for them and wanted to continue with the treatment. The majority of patients continued to have decreased PTSD symptoms at the 3- to 4-year follow-up, with 7 of 10 much improved, 2 minimally improved, and 1 with worse symptoms compared with baseline assessments. Caution is warranted in light of recent findings of hepatoxicity with nefaz-odone. With this in mind, this study suggests that much longer maintenance treatment may continue to be beneficial in PTSD.
Kim and colleagues10 assessed the effectiveness of 24 weeks of continuation treatment with mirtazapine(Drug information on mirtazapine) after participation in an 8-week open-label trial. Of the 15 patients who had completed the 8-week study, 12 patients completed the continuation trial . On measures of PTSD symptom severity, there was improvement from baseline to week 24. Mirtazapine was well tolerated with no serious adverse effects reported.