Adjunctive olanzapine for SSRI-resistant combat-related PTSD: a double-blind, placebo-controlled study. Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo. Treatment of acute posttraumatic stress disorder with brief cognitive behavioral therapy: a randomized controlled trial. Fluoxetine in posttraumatic stress disorder. Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms. Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine. Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial. A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults. Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial.
Posttraumatic stress disorder (PTSD), particularly in combat veterans with chronic illness, is often refractory to standard pharmacological interventions. There is a need to test adjunctive treatments to boost response.
                Subjects were 19 patients with PTSD who were minimally responsive to 12 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) at maximum tolerated dose. Outcomes were compared among subjects whose treatment was augmented with 8 weeks of double-blind olanzapine or placebo administration.
                Olanzapine augmentation was associated with statistically significantly greater reduction than placebo in specific measures of posttraumatic stress, depressive, and sleep disorder symptoms. Clinician-rated global response rates did not, however, significantly differ between groups.
                This is most likely the first double-blind, placebo-controlled study of an adjunct to SSRIs for PTSD. Despite the small group size, the findings suggest a role for olanzapine or other atypical antipsychotics in treating SSRI-resistant PTSD. Sleep symptoms may especially benefit. 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 purpose of this study was to evaluate the efficacy of brief cognitive behavioral therapy for patients with acute posttraumatic stress disorder (PTSD) resulting from various types of psychological trauma.
                The authors randomly assigned 143 patients with acute PTSD (irrespective of the time criterion), within 3 months after experiencing a traumatic incident, to either brief cognitive behavioral therapy (N=79) or a waiting list comparison group (N=64). Cognitive behavioral therapy consisted of four weekly sessions containing education, relaxation exercises, imaginal exposure, in vivo exposure, and cognitive restructuring. Main outcome measure was PTSD score measured by structured interview; secondary outcomes were anxiety and depression measured by questionnaire. Assessments took place before the intervention and 1 week and 4 months after the intervention.
                Symptoms of PTSD, anxiety, and depression decreased in both groups over time. One week after the intervention, the cognitive behavioral therapy group had significantly fewer symptoms of PTSD than the comparison group, but this difference was smaller and no longer significant 4 months after the intervention. Similar results were found for anxiety and depression scores. Subgroup analyses showed that cognitive behavioral therapy led to significantly lower PTSD scores at 4 months in patients with baseline comorbid major depression and in patients who were included within the first month after the traumatic incident both at 1 week and at 4 months.
                Brief early cognitive behavioral therapy accelerated recovery from symptoms of acute PTSD but did not influence long-term results. Brief early cognitive behavioral therapy showed enhanced efficacy in patients with baseline comorbid depression and patients who were included within 1 month after their traumatic experience. 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. 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. 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. 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. 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. To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression.
                Pragmatic randomised controlled superiority trial.
                6 outpatient clinics in Manchester and Cambridge.
                208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included.
                103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase.
                Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised children's depression rating scale, the children's global assessment scale, and the clinical global impression improvement scale.
                At 12 weeks the treatment effect for the primary outcome was -0.64 (95% confidence interval -2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, -1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved.
                For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone.
                Current Controlled Trials ISRCNT 83809224.
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.