Olanzapine in the treatment of post-traumatic stress disorder: a pilot study. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder. Comparison of nefazodone and sertraline for the treatment of posttraumatic stress disorder. A controlled trial of desipramine in 18 men with posttraumatic stress disorder. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial. A preliminary study of risperidone in the treatment of posttraumatic stress disorder related to childhood abuse in women. Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder. A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults. Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study. Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms. A placebo-controlled study of nefazodone for the treatment of chronic posttraumatic stress disorder: a preliminary study. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. Treatment of posttraumatic stress disorder with amitriptyline and placebo. Fluoxetine in post-traumatic stress disorder. Randomised, double-blind study. Fluoxetine in posttraumatic stress disorder. Inositol treatment of post-traumatic stress disorder. Pharmacotherapy of post-traumatic stress disorder with a novel psychotropic. Efficacy and tolerability of mirtazapine and sertraline in Korean veterans with posttraumatic stress disorder: a randomized open label trial. A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Lack of efficacy for fluoxetine in PTSD: a placebo controlled trial in combat veterans. Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo. Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial. Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine. Fluoxetine v. placebo in prevention of relapse in post-traumatic stress disorder. A controlled trial of phenelzine in posttraumatic stress disorder.
Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind, placebo-controlled evaluation in which 15 patients were randomized 2:1 to either olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day. Eleven patients completed the study. Patients in both groups showed improvement in PTSD symptoms, but no between-group differences in treatment response were observed and a high placebo response rate was found. Both treatments were tolerated well, although the olanzapine treatment group had more weight gain. Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD. The lack of difference between olanzapine and placebo may in part be due to olanzapine's not being effective in PTSD or, alternatively, a small sample size, a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients. The authors report a random-assignment, double-blind crossover trial comparing alprazolam and placebo in posttraumatic stress disorder (PTSD). Ten patients fulfilling DSM-III criteria for PTSD completed 5 weeks of treatment on each agent. Improvement in anxiety symptoms was significantly greater during alprazolam treatment but modest in extent. Symptoms specific to PTSD were not significantly altered. The impact of nonspecific symptomatic effects on the outcome of drug trials in PTSD is considered. A large multi-center, double-blind, parallel trial to assess the efficacy of brofaromine in the treatment of post traumatic stress disorder (PTSD) failed to show a significant difference between the brofaromine and placebo treatment groups. The placebo response rate in this study was higher than that in previously published double-blind, placebo-controlled studies of PTSD. Posttraumatic stress disorder (PTSD) is a prevalent condition that has been shown to be responsive to pharmacotherapy. Few head-to-head comparisons of medications used in the treatment of PTSD have been published. This 12-week, randomized, double-blind study compares the effectiveness, safety, and tolerability of nefazodone and sertraline for the treatment of PTSD. Thirty-seven male and female outpatients meeting DSM-IV criteria for PTSD were randomly assigned to receive nefazodone (maximum dose 600 mg/day; average dose 463 mg/day) or sertraline (maximum dose 200/day; average dose 153 mg/day). The primary outcome measures were the 17-item total severity score of the Clinician Administered PTSD Scale, Part 2 (CAPS-2) and the Clinical Global Impression Improvement Scale (CGI-I). Other assessments included the Davidson Trauma Scale (DTS), the Top-8 PTSD Rating Scale, Sheehan Disability Scale (SDS), Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Scale (HAM-A), and Pittsburgh Sleep Quality Index (PSQI). Twenty-six subjects had at least one post-randomization CAPS-2 assessment and were therefore included in the data analysis. There were no statistically significant differences between treatment groups on any of the outcome measures. There was a significant effect for time in both groups, indicating an improvement in PTSD symptoms, depression, sleep, and quality of life over time. CAPS-2 scores for all of the PTSD symptom clusters decreased significantly over time. This study did not find significant differences in the effectiveness of nefazodone and sertraline for the treatment of PTSD. Larger trials are warranted.
                Copyright 2004 Wiley-Liss, Inc. Eighteen male U.S. veterans meeting DSM-III criteria for posttraumatic stress disorder (PTSD) completed a 4-week double-blind, crossover study comparing administration of 200 mg/day of desipramine with placebo. Response was measured by using the Beck Depression Inventory, the Hamilton Rating Scale for Depression, the Hamilton Rating Scale for Anxiety, and the Impact of Event Scale. Overall, the only apparent response to desipramine was in some symptoms of depression; there were no changes in anxiety and other PTSD symptoms. Posttraumatic stress disorder (PTSD) is a common illness associated with significant disability. Few large, placebo-controlled trials have been reported.
                Outpatients with a DSM-III-R diagnosis of moderate-to-severe PTSD were randomized to 12 weeks of double-blind treatment with either sertraline (N = 100) in flexible daily doses in the range of 50 to 200 mg or placebo (N = 108). Primary outcome measures consisted of the Clinician-Administered PTSD Scale (CAPS-2) total severity score, the patient-rated Impact of Event Scale (IES), and the Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) ratings.
                Mixed-effects analyses found significantly steeper improvement slopes for sertraline compared with placebo on the CAPS-2 (t = 2.96, P =.003), the IES (t = 2.26, P =.02), the CGI-I score (t = 3.62, P<.001), and the CGI-S score (t = 4.40, P<.001). An intent-to-treat end-point analysis found a 60% responder rate for sertraline and a 38% responder rate for placebo (chi(2)(1) = 8.48, P =.004). Sertraline treatment was well tolerated, with a 9% discontinuation rate because of adverse events, compared with 5% for placebo. Adverse events that were significantly more common in subjects given sertraline compared with placebo consisted of insomnia (35% vs 22%), diarrhea (28% vs 11%), nausea (23% vs 11%), fatigue (13% vs 5%), and decreased appetite (12% vs 1%).
                The results of the current study suggest that sertraline is a safe, well-tolerated, and significantly effective treatment for PTSD. Based on an earlier pilot study, as well as a theoretical consideration of its mechanism of action, we undertook a placebo-controlled, double-blind trial of mirtazapine in posttraumatic stress disorder.
                Twenty-nine patients were randomized to receive drug up to 45 mg/day or placebo double-blind on a 2:1 ratio for 8 weeks, with data being available for analysis in 26. Primary outcome measures comprised the Short Posttraumatic Stress Disorder Rating Interview (SPRINT) Global Improvement item and total score. Secondary measures comprised the Davidson Trauma Scale, Structured Interview for Posttraumatic Stress Disorder and Hospital Anxiety Depression Scale. Adverse events were also measured.
                On the Short Posttraumatic Stress Disorder Rating Interview Global Improvement measure, rates of response were 64.7% and 20.0% for mirtazapine and placebo. Treatment effects in favor of mirtazapine were noted on the Short Posttraumatic Stress Disorder Rating Interview global, Structured Interview for Posttraumatic Stress Disorder, and Hospital Anxiety Depression Scale anxiety subscale scores. The drug was well tolerated.
                Mirtazapine was more effective than placebo on some measures in posttraumatic stress disorder and general anxiety symptoms. This study evaluated the effectiveness of risperidone in women for the treatment of posttraumatic stress disorder (PTSD) related to childhood physical, sexual, verbal, and emotional abuse.
                Subjects were outpatient adult women, aged 18 to 64 years, with chronic PTSD related to childhood physical, sexual, verbal, or emotional abuse. Data were collected from November 18, 2001, to June 7, 2003. Subjects met DSM-III-R criteria for PTSD and criteria for PTSD on the Clinician-Administered PTSD Scale, 1-month version (CAPS-1). Subjects were randomly assigned to receive risperidone (N = 12) in flexible daily dosages in the range of 0.5 to 8 mg or placebo (N = 9) for 8 weeks. The primary outcome measures were changes in score from baseline on the CAPS-1 and the Clinician-Administered PTSD Scale, 1-week version (CAPS-2).
                Risperidone-treated patients had a significantly greater reduction in total score on the CAPS-2 (z = -2.44, p = .015). Risperidone-treated patients also had significantly greater reductions in the intrusive (z = -5.71, p < .001) and hyperarousal (z = -2.74, p = .006) subscale scores of the CAPS-2.
                The results of the current study indicate that low-dosage risperidone is a safe and effective treatment for intrusive and hyperarousal symptoms in adult women with chronic PTSD from childhood physical, sexual, verbal, and emotional abuse. The efficacy of sertraline in the treatment of civilian posttraumatic stress disorder (PTSD) has been established by two large placebo-controlled trials. The purpose of the current pilot study was to obtain preliminary evidence of the efficacy of sertraline in military veterans suffering from PTSD. Outpatient Israeli military veterans with a DSM-III-R diagnosis of PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200 mg/day; N = 23, 83% male, mean age = 41 years) or placebo (N = 19, 95% male, mean age = 38 years). Efficacy was evaluated by the Clinician-Administered PTSD Scale (CAPS-2) and by Clinical Global Impression Scale-Severity (CGI-S) and -Improvement (CGI-I) ratings. Consensus responder criteria consisted of a 30% or greater reduction in the CAPS-2 total severity score and a CGI-I rating of "much" or "very much" improved. The baseline CAPS-2 total severity score was 94.3 +/- 12.9 for sertraline patients, which is notably higher than that reported for most studies of civilian PTSD. On an intent-to-treat endpoint analysis, sertraline showed a numeric but not statistically significant advantage compared with placebo on the CAPS-2 total severity and symptom cluster scores. In the study completer analysis, the mean CGI-I score was 2.4 +/- 0.3 for sertraline and 3.4 +/- 0.3 for placebo (t = 2.55, df = 30, p = 0.016), CGI-I responder rates were 53% for sertraline and 20% for placebo (chi2 = 3.62, df = 1, p = 0.057), and combined CGI-I and CAPS-2 responder rates (>or=30% reduction in baseline CAPS-2 score) were 41% for sertraline and 20% for placebo (chi2 = 1.39, df = 1, p = 0.238). Sertraline treatment was well tolerated, with a 13% discontinuation rate as a result of adverse events. This pilot study suggests that sertraline may be an effective treatment in patients with predominantly combat-induced PTSD, although the effect size seems to be somewhat smaller than what has been reported in civilian PTSD studies. Adequately powered studies are needed to confirm these results and to assess whether continued treatment maintains or further improves response. This study evaluated the efficacy of paroxetine for symptoms and associated features of chronic posttraumatic stress disorder (PTSD), interpersonal problems, and dissociative symptoms in an urban population of mostly minority adults. Adult outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of single-blind placebo (N = 70). Those not rated as significantly improved were then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks, with a flexible dosage design (maximum 60 mg by week 7). Significantly more patients treated with paroxetine were rated as responders (14/21, 66.7%) on the Clinical Global Impression-Improvement Scale (CGI-I) compared to patients treated with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also superior to placebo on reduction of dissociative symptoms [Dissociative Experiences Scale (DES) score] and reduction in self-reported interpersonal problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week maintenance phase, paroxetine response continued to improve, but placebo response did not. Paroxetine was well tolerated and superior to placebo in ameliorating the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms, and interpersonal problems in the first trial conducted primarily in minority adults. This study evaluated the efficacy and safety of paroxetine for the treatment of patients with chronic posttraumatic stress disorder (PTSD).
                Outpatients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale, part 2, were randomly assigned to take placebo (N=186), 20 mg/day of paroxetine (N=183), or 40 mg/day of paroxetine (N=182) for 12 weeks. Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale, part 2, and rates of response ("very much improved" or "much improved") for global improvement on the Clinical Global Impression scale.
                Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis. Moreover, paroxetine treatment resulted in statistically significant improvement compared to placebo on all three PTSD symptom clusters (reexperiencing, avoidance/numbing, and hyperarousal), social and occupational impairment, and comorbid depression. Paroxetine was effective for both men and women. Treatment response did not vary by trauma type, time since trauma, or severity of baseline PTSD or depressive symptoms. Both doses were well tolerated.
                Doses of 20 and 40 mg/day of paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD. Three new antidepressants were used in treating posttraumatic stress disorder (PTSD) and symptoms of depression in Bosnian refugees. Thirty-two Bosnian refugees seeking treatment at a mental health clinic participated in a case series study. All received open trials of Sertraline (n = 15), Paroxetine (n = 12), or Venlafaxine (n = 5), with standard clinical doses. Overall, Sertraline and Paroxetine produced statistically significant improvement at 6 weeks in PTSD symptom severity in depression, and in Global Assessment of Functioning. Venlafaxine produced improvement in PTSD symptom severity and in Global Assessment of Functioning, did not yield improvement in symptoms of major depressive disorder; and had a high rate of side effects. Notwithstanding improvement of symptoms, all 32 refugees remained PTSD positive at the diagnostic level at the 6-week follow-up. 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. Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder.
                To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity.
                Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997.
                Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers.
                A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault).
                Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93).
                Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression-Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups. Results Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, -33.0 vs -23.2 [P =.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01).
                Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD. Amitriptyline hydrochloride was compared with placebo in 46 veterans with chronic posttraumatic stress disorder. Treatment continued up to 8 weeks, and efficacy was measured by five observer and two self-rated scales. Percent recovery rates were higher for amitriptyline than placebo on two measures. In patients who completed 4 weeks (n = 40), better outcome with amitriptyline was noted on the Hamilton depression scale only. In the group completing 8 weeks of treatment (n = 33), the drug was superior to placebo on Hamilton depression, Hamilton anxiety, Clinical Global Impression severity, and Impact of Event scales. There was no evidence for drug effects on the structured interview for posttraumatic stress disorder. Drug-placebo differences were greater in the presence of comorbidity in general, although recovery rates were uniformly low in the presence of major depression, panic disorder, and alcoholism. At the end of treatment, 64% of the amitriptyline and 72% of the placebo samples still met diagnostic criteria for posttraumatic stress disorder. Most pharmacotherapy trials in post-traumatic stress disorder (PTSD) have been conducted upon male combat veterans. Outcome studies relating to civilians are therefore needed.
                To demonstrate that fluoxetine is more effective than placebo in treating PTSD.
                Civilians with PTSD (n = 53) were treated for 12 weeks with fluoxetine (up to 60 mg/day) or placebo. Assessments of PTSD severity, disability, stress vulnerability, and high end-state function were obtained.
                Fluoxetine was more effective than placebo on most measures at week 12, including global improvement (much or very much improved: fluoxetine 85%, placebo 62%, difference 0.24, 95% CI 0.01-0.47; very much improved: fluoxetine 59%, placebo 19%, difference 0.40, 95% CI 0.16-0.64), and high end-state function (fluoxetine 41%, placebo 4%, difference 0.37, 95% CI 0.17-0.57).
                Fluoxetine was superior for measures of PTSD severity, disability, stress vulnerability, and high end-state function. The placebo-group response was low when viewed as a broad outcome based on a portfolio of ratings, but was higher with a traditional global rating criterion. This study was designed to establish the efficacy of the serotonin reuptake blocker fluoxetine in the treatment of posttraumatic stress disorder (PTSD).
                64 subjects (22 women and 42 men; 31 veterans and 33 nonveterans) with PTSD entered a 5-week randomized double-blind trial comparing fluoxetine (N = 33) and placebo (N = 31).
                By Week 5 fluoxetine, but not placebo, significantly reduced overall PTSD symptomatology, as assessed by the Clinician-Administered PTSD Scale (CAPS) score. Changes were most marked in the arousal and numbing symptom subcategories. Non-VA patients responded much better than VA patients. Fluoxetine was an effective antidepressant independent of its effects on PTSD.
                Fluoxetine is an effective pharmacotherapeutic agent for treating PTSD and its associated features, particularly in patients without chronic treatment histories. nan This was a multicenter, randomized, double-blind, parallel trial conducted in outpatients in three countries. Following screening and placebo washout, patients received brofaromine (a combined MAO-A inhibitor/5-HT transport inhibitor) or placebo in a flexible dosing design. Based upon the CAPS, a standardized post-traumatic stress disorder (PTSD) interview, findings from a cohort involving both subchronic and chronic traumatic stress marginally favored brofaromine over placebo; however, not to a statistically significant degree. With a more conservation definition of the syndrome, employing a primary cohort of patients with PTSD of one year or greater duration, brofaromine significantly reduced PTSD symptoms in comparison with placebo. In all analyses a substantial proportion of patients in both drug and placebo groups remained symptomatic throughout. Findings were supported by an analysis of secondary measures. Brofaromine may be of benefit in the therapy of PTSD. The aim of this study was to investigate the potential use of mirtazapine in Korean veterans diagnosed with PTSD, by comparing it with sertraline, a drug approved for use in PTSD in the USA.
                Efficacy was evaluated by the clinician administered PTSD scale (CAPS-2), the Hamilton rating scale for depression (HAMD-17) and the clinical global impression scale (CGI), at baseline and at weeks 1, 2 and 6. A response was defined as a > or = 30 % decrease in CAPS-2 total severity, a > or = 50 % decrease in total HAMD-17 score, and a CGI-I score < 3.
                51 patients on mirtazapine (mean age/duration of illness: 59.1/33.5 years) and 49 on sertraline (mean age/duration of illness: 60.6/35.6 years) completed the study. The mean daily dosage was 34.1 mg for mirtazapine and 101.5 mg for sertraline. On the CAPS-2 total score more patients responded in the mirtazapine group at week 1 (13 vs 2 %) and week 2 (51 vs 31 %). At week 6 this difference was statistically significant (88 % vs 69 %, p = 0.039) on the CAPS-2 total score. The HAMD-17 total score and CGI-I score decreased in both groups, with no significant differences between th groups on all time points. The main side effects for the mirtazapine group were: dry mouth (19.6 %), constipation (19.6 %), somnolence (15.7 %) and weight gain (1.96 %); and for the sertraline group: indigestion (14.3 %), palpitation (6.1 %), agitation (2.0 %), epigastric soreness (2.0 %), insomnia (2.0 %) and sexual dysfunction (2.0 %).
                Mirtazapine appeared to be an effective and well-tolerated treatment for PTSD in Korean veterans.
                2004 John Wiley & Sons, Ltd. The anticonvulsant, lamotrigine, may be useful for symptom management in PTSD.
                Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo. Patients were randomized 2:1 to either lamotrigine or placebo. Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated.
                Fifteen subjects entered treatment, fourteen of whom returned for subsequent visits. Of 10 patients who received lamotrigine, 5 (50%) responded according to the DGRP, compared to 1 of 4 (25%) who received placebo. Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients. Treatments were generally well tolerated.
                Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD. These promising results warrant further large sample double-blind, placebo-controlled trials. Fluoxetine and placebo were studied in a population of combat veterans with severe, chronic PTSD.
                Twelve male veterans with PTSD were enrolled in a 12 week double-blind evaluation of fluoxetine and placebo. Mean fluoxetine dose at endpoint (week 12) was 48 mg/day with a range of 10 mg to 60 mg.
                One fluoxetine patient responded (17%) and two of the six placebo patients responded (33%).
                Fluoxetine patients did not show a greater response than placebo patients in this small sample of male combat veterans with severe, chronic PTSD. Fluoxetine has displayed an efficacious response in controlled studies of patients with PTSD who were predominantly female, suffered civilian (noncombat) traumas, and were overall experiencing less severe PTSD. The reasons for the low response rate to fluoxetine in our study is unknown and will await further study examining variables other than symptoms that might influence outcome, such as gender, comorbidity, prior treatment history, trauma type, severity and chronicity. Effects of double-blind treatment of chronic posttraumatic stress disorder (PTSD) with 2 SSRIs and placebo on emotional symptoms and autonomic reactivity were assessed prospectively. PTSD subjects received citalopram (n=25), sertraline (n=23), or placebo (n=10) for 10 weeks, with psychophysiologic assessments performed before and after treatment. Intent-to-treat analysis showed that all treatment groups improved significantly in total symptoms of PTSD (as measured by the Clinician Administered PTSD Scale), all 3 PTSD symptom clusters, and sleep time. However, subtle differences in improvements in PTSD symptom clusters, physiologic reactivity, and reported adverse events were identified. Citalopram treated subjects significantly lowered systolic and diastolic blood pressures, while sertraline and placebo treated patients significantly lowered only systolic blood pressure reactivity to individualized trauma scripts. The sertraline group showed significantly more improvement in avoidance/numbing symptoms than both other groups. Considering side effects, subjects on sertraline reported more gastrointestinal problems, with early terminators having more insomnia. Early terminators on citalopram reported more fatigue and appetite changes than other treatment groups, with completers reporting more sexual dysfunction. Results support a class effect of SSRIs in treating PTSD symptoms, but suggest a possible differential effect of drugs on symptom clusters, physiologic parameters, and side effects that may have clinical relevance. Implications of symptom reduction noted in the smaller placebo group are discussed relative to recent concerns about increasing placebo response in clinical trials. The objective of this double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with posttraumatic stress disorder (PTSD).
                Male and female outpatients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale (CAPS-2) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 12 weeks. The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale (CGI-1). Additional key outcome measures were the change from baseline in the reexperiencing, avoidance/ numbing, and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale (SDS). Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale. The proportion of patients achieving response and remission was also determined.
                307 patients constituted the intent-to-treat population. At week 12, compared with the placebo group (N = 156), the paroxetine group (N = 151) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures. Significantly greater improvement on the CAPS-2 total score was observed for paroxetine compared with placebo from week 4 (p < .05), and significantly greater proportions of paroxetine-treated patients achieved response (p < .001) and remission (p = .008) by week 12. The improvement in PTSD symptoms was similar in male and female patients. Functional improvement at the study endpoint was significantly greater (p < .05) in the paroxetine group in all 3 domains of the SDS (work, social life, family life). Treatment with paroxetine was well tolerated, with the frequency and type of adverse events recorded for the paroxetine group corresponding to the known safety profile of this medication. Conclusion: Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD. Improvement is obtained for all 3 symptom clusters (reexperiencing, avoidance/numbing, hyperarousal) and is associated with significant reduction in disability after 12 weeks of treatment. Sixty male veterans with posttraumatic stress disorder (PTSD) participated in an 8-week, randomized trial comparing phenelzine (N = 19), imipramine (N = 23), and placebo (N = 18). Mean treatment retention was better on phenelzine (7.4 weeks) than on imipramine (5.6 weeks) or placebo (5.5 weeks). By week 5, both medications significantly reduced PTSD symptoms, as assessed by the Impact of Events Scale (IES), but the 44% improvement on phenelzine was greater than the 25% improvement on imipramine. The intrusion, but not the avoidance, subscale of the IES showed significant improvement, and the initial mild to moderate depressive symptoms did not significantly improve. Little is known about the effect of pharmacotherapy in the prevention of post-traumatic stress disorder (PTSD) relapse.
                To assess the efficacy and tolerability of fluoxetine in preventing PTSD relapse.
                This was a double-blind, randomised, placebo-controlled study. Following 12 weeks of acute treatment, patients who responded were rerandomised and continued in a 24-week relapse prevention phase with fluoxetine (n=69) or placebo (n=62). The primary efficacy assessment was the prevention of PTSD relapse, based on the time to relapse.
                Patients in the fluoxetine/fluoxetine group were less likely to relapse than patients in the fluoxetine/placebo group (P=0.027). There were no clinically significant differences in treatment-emergent adverse events between treatment groups.
                Fluoxetine is effective and well tolerated in the prevention of PTSD relapse for up to 6 months. Thirteen patients meeting DSM-III criteria for posttraumatic stress disorder participated in a random-assignment, double-blind crossover trial comparing phenelzine (45-75 mg/day) and placebo. Ten patients completed at least 4 weeks of each treatment phase. Clinical response to phenelzine did not differ from placebo, and overall improvement by the end of the study could not be attributed to the active drug. The findings are discussed in the light of preliminary reports suggesting that phenelzine may be an effective treatment for posttraumatic stress disorder.
Medication treatments can be effective in treating PTSD, acting to reduce its core symptoms, as well as associated depression and disability. The findings of this review support the status of SSRIs as first line agents in the pharmacotherapy of PTSD, as well as their value in long-term treatment. However, there remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.