Treatment of chronic posttraumatic stress disorder in combat veterans with citalopram: an open trial.

Posttraumatic stress disorder (PTSD) is a serious mental illness which exhibits significant impairment of psychosocial and occupational function. At present, serotonin reuptake inhibitors (SRIs) show therapeutic promise for the treatment of PTSD. However, results in the veteran population have been less robust or often negative. In this study, a relatively new and the most selective SRI, citalopram, was evaluated for the treatment of PTSD. Veterans with chronic PTSD (N = 18) were enrolled in an 8-week open trial of citalopram after providing written informed consent. The primary outcome measures were the Clinician-Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Anxiety (HAM-A), and the Clinical Global Impression Scale (CGI). Seventeen patients completed at least 4 weeks of the 8-week trial. During treatment, there was a moderate response with 42% of patients demonstrating a > or =30% reduction in total CAPS score at week 8. Comparable results were demonstrated in the Hamilton Depression Rating Scale (HAM-D), HAM-A, Global Assessment of Function (GAF), and CGI rating scales. In a follow-up analysis, a treatment effect was shown for CAPS B at week 4, but was not sustained at week 8. Overall, citalopram was generally well tolerated with reported adverse events being benign in nature. These pilot results demonstrate a moderate effect of citalopram in the treatment of combat-induced PTSD. However, the sample size was small and patient population is limited to veterans with combat-induced PTSD. Further study in a larger and more diverse patient sample is warranted prior to final conclusions on efficacy of citalopram for the treatment of PTSD.

Substance use disorder comorbidity in major depressive disorder: an exploratory analysis of the Sequenced Treatment Alternatives to Relieve Depression cohort.

Patients with major depressive disorder (MDD) often present with concurrent substance use disorders (SUD) involving alcohol and/or illicit drugs. This analysis compares the depressive symptomatic presentation and a range of clinical and demographic features of patients with MDD and concurrent SUD symptoms vs those without SUD symptoms, to clarify how these two differ and to determine whether concurrent SUD symptoms may alter the clinical presentation of MDD. The first 1500 outpatients with nonpsychotic MDD enrolled in the Sequenced Treatment Alternatives to Relieve Depression study were divided into those with and without concurrent SUD symptoms as ascertained by a self-report instrument, the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Of the 1484 cases with completed baseline PDSQ, 28% (n = 419) of patients with MDD were found to endorse symptoms consistent with current SUD. Patients with symptoms consistent with SUD were more likely to be men (P < .0001), to be either divorced or never married (P = .018), to have a younger age of onset of depression (P = .014), and to have a higher rate of previous suicide attempts (P = .014) than those without SUD symptoms. Patients with major depressive disorder who have symptoms consistent with SUD endorsed greater functional impairment attributable to their illness than those without concurrent SUD symptoms (P = .0111). The presence of SUD symptoms did not alter the overall depressive symptom pattern of presentation, except that the dual-diagnosed patients had higher levels of hypersomnia (P = .006), anxious mood (P = .047), and suicidal ideation (P = .036) compared to those without SUD symptoms. In conclusion, gender, marital status, age of onset of major depression, functional impairment, and suicide risk factors differ in depressed patients with concurrent SUD symptoms compared to those without SUD comorbidity.

A placebo-controlled study of nefazodone for the treatment of chronic posttraumatic stress disorder: a preliminary study.

Nefazodone is a unique serotonergic antidepressant that acts as both a presynaptic serotonin reuptake inhibitor and a postsynaptic 5-hydroxytryptamine 2A receptor antagonist. Based on the positive results of open-label trials of nefazodone, including one from our group, we tested nefazodone's efficacy in the treatment of posttraumatic stress disorder (PTSD) under placebo-controlled conditions. Forty-one patients with chronic PTSD, predominantly male combat veterans, were enrolled in a randomized, double-blind, placebo-controlled 12-week trial of nefazodone. The primary outcome measure was the Clinician-Administered PTSD Scale. Fifteen patients were randomized to placebo and 26 were randomized to nefazodone. In a repeated-measures analysis of variance with last observation carried forward, patients on nefazodone showed a significant improvement in the percentage change of Clinician-Administered PTSD Scale Total score from baseline compared with those on placebo (P = 0.04; effect size = 0.6). Sample size was not powered to test group differences in the Clinician-Administered PTSD Scale criterion B, C, or D subscale. However, the criterion D subscale showed significant improvement in patients treated with nefazodone compared with those treated with placebo (P = 0.007). In addition, the Hamilton Rating Scale for Depression showed significant improvement compared with placebo (P = 0.008). The nefazodone group also reported an improvement on the PTSD Checklist (self-report scale; P = 0.08) and the Clinician-Administered Dissociative States Scale (P = 0.06). This pilot study supports the efficacy of nefazodone for the treatment of PTSD. However, larger placebo-controlled studies in more diverse patient population are warranted.

Baclofen treatment for chronic posttraumatic stress disorder.

OBJECTIVE: Previous studies have shown the efficacy of gamma-aminobutyric acid B (GABA(B)) receptor agonists in treating anxiety in patients with panic disorder and in treating depression and anxiety in alcoholic patients. We hypothesized that baclofen, a GABA(B) agonist, would be an effective treatment in the symptomatic management of veterans with chronic posttraumatic stress disorder (PTSD). METHODS: Fourteen male veterans with chronic, combat-related PTSD were enrolled in an open-label, 8-week, monotherapy trial of baclofen titrated to a maximum of 80 mg/d in 3 divided doses. The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS), and secondary outcome measures included the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression, the Global Assessment of Functioning Scale, and the Clinical Global Impressions. RESULTS: In the 11 patients who completed the 8-week trial, the mean total CAPS score decreased significantly from baseline (from 82.9 +/- 16.1 to 63.5 +/- 21.2). The avoidance and hyperarousal subscales showed significant decreases (from 36.2 +/- 6.2 to 26.5 +/- 9.6 and from 31.9 +/- 6.5 to 22.1 +/- 7.1, respectively), whereas the re-experiencing subscale remained unchanged. Significant improvements were also noted on all secondary outcome measures. Treatment response was noted within the first 4 weeks of treatment and was maintained throughout the trial. Baclofen therapy was well tolerated, as only 1 patient dropped out due to adverse effects. CONCLUSIONS: Baclofen therapy was effective in treating both the PTSD symptoms and accompanying depression and anxiety in patients with chronic PTSD due to combat. Larger, double-blind, placebo-controlled studies are needed to confirm the efficacy of baclofen in the treatment of PTSD.