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. Treatment of acute stress disorder: a randomized controlled trial. Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study. Comparison of nefazodone and sertraline for the treatment of posttraumatic stress disorder. Treatment of acute stress disorder: a comparison of cognitive-behavioral therapy and supportive counseling. A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed adolescents receiving antidepressant medication. Cognitive behavior therapy, relaxation training, and tricyclic antidepressant medication in the treatment of depression. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. A randomized effectiveness trial of collaborative care for patients with panic disorder in primary care. Comparison of two treatments for traumatic stress: a community-based study of EMDR and prolonged exposure. Cognitive therapy and pharmacotherapy. Singly and together in the treatment of depression. A randomized controlled trial of cognitive therapy, a self-help booklet, and repeated assessments as early interventions for posttraumatic stress disorder. A pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms. Fluoxetine v. placebo in prevention of relapse in post-traumatic stress disorder. Management of depression in rheumatoid arthritis: a combined pharmacologic and cognitive-behavioral approach. Treatment of pharmacotherapy-refractory posttraumatic stress disorder among Cambodian refugees: a pilot study of combination treatment with cognitive-behavior therapy vs sertraline alone. The SSRIs drug Fluoxetine, but not the noradrenergic tricyclic drug Desipramine, improves memory performance during acute major depression. Psychotherapy alone and combined with pharmacotherapy in the treatment of depression. Comparative efficacy, speed, and adverse effects of three PTSD treatments: exposure therapy, EMDR, and relaxation training.
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. Recent trauma survivors with acute stress disorder (ASD) are likely to subsequently develop chronic posttraumatic stress disorder (PTSD). Cognitive behavioral therapy for ASD may prevent PTSD, but trauma survivors may not tolerate exposure-based therapy in the acute phase. There is a need to compare nonexposure therapy techniques with prolonged exposure for ASD.
                To determine the efficacy of exposure therapy or trauma-focused cognitive restructuring in preventing chronic PTSD relative to a wait-list control group.
                A randomized controlled trial of civilians who experienced trauma and who met the diagnostic criteria for ASD (N = 90) seen at an outpatient clinic between March 1, 2002, and June 30, 2006.
                Patients were randomly assigned to receive 5 weekly 90-minute sessions of either imaginal and in vivo exposure (n = 30) or cognitive restructuring (n = 30), or assessment at baseline and after 6 weeks (wait-list group; n = 30).
                Measures of PTSD at the 6-month follow-up visit by clinical interview and self-report assessments of PTSD, depression, anxiety, and trauma-related cognition.
                Intent-to-treat analyses indicated that at posttreatment, fewer patients in the exposure group had PTSD than those in the cognitive restructuring or wait-list groups (33% vs 63% vs 77%; P = .002). At follow-up, patients who underwent exposure therapy were more likely to not meet diagnostic criteria for PTSD than those who underwent cognitive restructuring (37% vs 63%; odds ratio, 2.10; 95% confidence interval, 1.12-3.94; P = .05) and to achieve full remission (47% vs 13%; odds ratio, 2.78; 95% confidence interval, 1.14-6.83; P = .005). On assessments of PTSD, depression, and anxiety, exposure resulted in markedly larger effect sizes at posttreatment and follow-up than cognitive restructuring.
                Exposure-based therapy leads to greater reduction in subsequent PTSD symptoms in patients with ASD when compared with cognitive restructuring. Exposure should be used in early intervention for people who are at high risk for developing PTSD. 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. 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. Acute stress disorder (ASD) is a precursor of chronic posttraumatic stress disorder (PTSD). Twenty-four participants with ASD following civilian trauma were given 5 sessions of either cognitive-behavioral therapy (CBT) or supportive counseling (SC) within 2 weeks of their trauma. Fewer participants in CBT (8%) than in SC (83%) met criteria for PTSD at posttreatment. There were also fewer cases of PTSD in the CBT condition (17%) than in the SC condition (67%) 6 months posttrauma. There were greater statistically and clinically significant reductions in intrusive, avoidance, and depressive symptomatology among the CBT participants than among the SC participants. This study represents the 1st demonstration of successful treatment of ASD with CBT and its efficacy in preventing chronic PTSD. To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care.
                A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the experimental protocol (n = 75) versus TAU SSRI plus brief CBT (n = 77). Participants were identified by a recent dispense of SSRI medication followed by telephone screening. Adolescents with a diagnosis of major depressive disorder (n = 152) were enrolled. The CBT program employed cognitive restructuring and/or behavioral activation training. Therapists consulted with prescribing pediatricians to improve medication adherence.
                Through 1-year follow-up, the authors found CBT advantages on the Short Form-12 Mental Component Scale (p = .04), reductions in TAU outpatient visits (p = .02), and days' supply of all medications (p = .01). No effects were detected for major depressive disorder episodes; a nonsignificant trend favoring CBT was detected on the Center for Epidemiology Depression Scale (p = .07).
                The authors detected a weak CBT effect, possibly rendered less significant by the small sample and likely attenuated by the unexpected reduction in SSRI pharmacotherapy in the CBT condition. Small, incremental improvements over monotherapy, such as observed in this study, most likely represent the new norm in adolescent depression treatment research. Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another. This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy. To test the uniqueness hypothesis, relaxation training, a nonpharmacologic, noncognitive treatment, was chosen as a comparison for cognitive behavioral therapy as well as drug therapy. Treatment duration was 16 weeks. The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied. For both cognitive behavioral therapy and relaxation training, outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis. The posttreatment scores on the Beck Depression Inventory of 82% of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score < or = 9 which was not significantly greater than that for the group receiving relaxation training (73%), so a unique effect was not demonstrated for cognitive behavioral therapy. The outcome for tricyclic antidepressant medication (29% improved to criteria) was significantly worse than that for cognitive behavioral therapy. The patient's pretreatment initial expectancy was not predictive. 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. Effectiveness studies have tested interventions to improve quality of care for depression in primary care, but none, to our knowledge, have been completed for panic disorder (PD) in this setting. This study sought to test the clinical effectiveness of PD pharmacotherapy embedded in a disease management framework of "collaborative care" (CC).
                One hundred fifteen patients with PD from 3 primary care clinics were randomized to CC or "usual care" (UC). Patients in CC (n = 57) received educational videotapes and pamphlets; pharmacotherapy with the selective serotonin reuptake inhibitor paroxetine; 2 psychiatrist visits and 2 telephone calls in the first 8 weeks; and up to 5 telephone calls between 3 and 12 months' follow-up. Usual care patients (n = 58) were treated by their primary care physician. Telephone assessments of panic, anxiety sensitivity, depression, and disability variables were performed at 3, 6, 9, and 12 months' follow-up. Adequacy of pharmacotherapy was assessed with an algorithm based on a review of efficacy studies.
                Patients in CC were more likely to receive adequate (type, dose, duration) medication and more likely to adhere to this medication at 3 and 6 months. Random regression analyses showed that CC patients improved significantly more over time compared with UC patients on anxiety, depression, and disability measures, with the greatest effects at 3 and 6 months.
                Compared with UC, CC interventions significantly improved both quality of care and clinical and functional outcomes in primary care PD patients. Clinical differences were greatest in the first 6 months, corresponding to the greater quality of care and the greater intensity of intervention. This pilot study compared the efficacy of two treatments for postraumatic stress disorder (PTSD): Eye Movement Desensitization and Reprocessing (EMDR) and Prolonged Exposure (PE). Data were analyzed for 22 patients from a university-based clinic serving the outside community (predominantly rape and crime victims) who completed at least one active session of treatment after three preparatory sessions. Results showed both approaches produced a significant reduction in PTSD and depression symptoms, which were maintained at three-month follow-up. Successful treatment was faster with EMDR as a larger number of people (7 of 10) had a 70% reduction in PTSD symptoms after three active sessions compared to 2 of 12 with PE. EMDR appeared to be better tolerated as the dropout rate was significantly lower in those randomized to EMDR versus PE (0 of 10 vs. 3 of 10). However all patients who remained in treatment with PE had a reduction in PTSD scores. Finally, Subjective Units of Distress (SUDS) ratings decreased significantly during the initial session of EMDR, but changed little during PE. Postsession SUDS were significantly lower for EMDR than for PE. Suggestions for future research are discussed.
                Copyright 2002 John Wiley & Sons, Inc. Eight-seven moderately to severely depressed psychiatric outpatients were randomly assigned to 12 weeks of cognitive therapy (CT) (n = 24), pharmacotherapy (n = 24), CT plus pharmacotherapy (n = 22), or CT plus active placebo (n = 17). Seventy patients completed the treatment protocol. Seventeen dropped out before the end of the treatment period. Patients who completed treatment showed significant improvement in mean scores on two common measures of severity of depression (the Beck Depression Inventory and the Hamilton Rating Scale for Depression) between evaluation and termination. Improvement did not differ as a function of the different treatment modalities. Inclusion of dropout patients' end-point scores did not alter these results. Treatment gains in all groups were maintained at one-month follow-up assessment. A portion of this study replicated an earlier study. While the results were not identical, they indicated that either CT or antidepressant drug treatment can be effective in treating outpatients with primary, nonbipolar depression of moderate or greater severity. Combining treatments did not lead either to additive effects or negative interactions. It is unclear what psychological help should be offered in the aftermath of traumatic events. Similarly, there is a lack of clarity about the best way of identifying people who are unlikely to recover from early posttraumatic symptoms without intervention.
                To determine whether cognitive therapy or a self-help booklet given in the initial months after a traumatic event is more effective in preventing chronic posttraumatic stress disorder (PTSD) than repeated assessments.
                Randomized controlled trial. Patients Motor vehicle accident survivors (n = 97) who had PTSD in the initial months after the accident and met symptom criteria that had predicted persistent PTSD in a large naturalistic prospective study of a comparable population.
                Patients were recruited from attendees at local accident and emergency departments.
                Patients completed a 3-week self-monitoring phase. Those who did not recover with self-monitoring (n = 85) were randomly assigned to receive cognitive therapy (n = 28), a self-help booklet based on principles of cognitive behavioral therapy (n = 28), or repeated assessments (n = 29).
                Symptoms of PTSD as assessed by self-report and independent assessors unaware of the patient's allocation. Main assessments were at 3 months (posttreatment, n = 80) and 9 months (follow-up, n = 79).
                Twelve percent (n = 12) of patients recovered with self-monitoring. Cognitive therapy was more effective in reducing symptoms of PTSD, depression, anxiety, and disability than the self-help booklet or repeated assessments. At follow-up, fewer cognitive therapy patients (3 [11%]) had PTSD compared with those receiving the self-help booklet (17 [61%]; odds ratio, 12.9; 95% confidence interval, 3.1-53.1) or repeated assessments (16 [55%]; odds ratio, 10.3; 95% confidence interval, 2.5-41.7). There was no indication that the self-help booklet was superior to repeated assessments. On 2 measures, high end-state functioning at follow-up and request for treatment, the outcome for the self-help group was worse than for the repeated assessments group.
                Cognitive therapy is an effective intervention for recent-onset PTSD. A self-help booklet was not effective. The combination of an elevated initial symptom score and failure to improve with self-monitoring was effective in identifying a group of patients with early PTSD symptoms who were unlikely to recover without intervention. To examine the potential benefits of adding a selective serotonin reuptake inhibitor, sertraline, versus placebo, to trauma-focused cognitive-behavioral therapy (TF-CBT) for improving posttraumatic stress disorder and related psychological symptoms in children who have experienced sexual abuse.
                Twenty-four 10- to 17-year-old female children and adolescents and their primary caretakers were randomly assigned to receive TF-CBT + sertraline or TF-CBT + placebo for 12 weeks.
                Both groups experienced significant improvement in posttraumatic stress disorder and other clinical outcomes from pre- to posttreatment with no significant group x time differences between groups except in Child Global Assessment Scale ratings, which favored the TF-CBT + sertraline group.
                Only minimal evidence suggests a benefit to adding sertraline to TF-CBT. A drawback of adding sertraline was determining whether TF-CBT or sertraline caused clinical improvement for children with comorbid depression. Current evidence therefore supports an initial trial of TF-CBT or other evidence-supported psychotherapy for most children with PTSD symptoms before adding medication. 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. To examine the effectiveness of cognitive-behavioral and pharmacologic treatment of depression in rheumatoid arthritis (RA).
                Subjects (n = 54) with confirmed diagnoses of both major depression and RA were randomly assigned to 1 of 3 groups: 1) cognitive-behavioral/pharmacologic group (CB-PHARM), 2) attention-control/pharmacologic group, or 3) pharmacologic control group. Measures of depression, psychosocial status, health status, pain, and disease activity were collected at baseline, posttreatment (10 weeks), 6-month followup, and 15-month followup. Data were analyzed to compare the treatment effectiveness of the groups; data also were aggregated to examine the effects of antidepressive medication over time. Lastly, a no-treatment control group was defined from a cohort of persons who declined participation.
                Baseline comparisons on demographic and dependent measures revealed a need to assess covariates on age and education; baseline scores on dependent measures also were entered as covariates. Analyses of covariance revealed no statistically significant group differences at postintervention, 6-month followup, or 15-month followup, except higher state and trait anxiety scores for the CB-PHARM group at the 15-month followup. In the longitudinal analyses of the effects of antidepressive medication, significant improvement in psychological status and health status were found at posttreatment, 6-month followup, and 15-month followup, but no significant improvements were shown for pain or disease activity. In addition, the comparison of the aggregated pharmacologic group with a no-treatment group revealed a statistically significant benefit for the 3 groups that received the antidepressive medication.
                In persons with RA, cognitive-behavioral approaches to the management of depression were not found to be additive to antidepressant medication alone, but antidepressant intervention was superior to no treatment. Cambodian refugees with posttraumatic stress disorder (PTSD) represent a cohort in severe need of treatment, but little information is available to guide treatment choices. We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy (CBT) for treating PTSD. Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22-26 years during the Pol Pot period (1975-1979). These patients were randomly assigned to either sertraline alone or combined treatment. We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms. Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD, and that a program of CBT emphasizing information, exposure, and cognitive-restructuring can be successfully modified for Khmer-speaking refugees. Accumulating evidence suggests that noradrenergic and serotonergic drugs are equally effective in ameliorating the depressive symptoms of major depression. Major depression is associated also with memory impairments, but the comparative effects of the antidepressant drugs on memory are not clear. We previously found that serotonergic neurotransmission is of particular importance for some aspects of episodic memory. We set out to test whether treatment with the selective serotonergic drug Fluoxetine (Prozac) would be advantageous in this respect over treatment with the selective noradrenergic tricyclic antidepressant drug Desipramine (Deprexan). Seventeen patients with major depressive episode, randomly assigned for treatment with either Fluoxetine (n = 8) or Desipramine (n = 9), were assessed for their clinical situation and for memory performance at the beginning of treatment, after 3 weeks, and after 6 weeks of pharmacological treatment. We found that although clinically both drugs were equally effective, the improvement of memory performance in the Fluoxetine-treated patients was significantly greater compared with that of the Desipramine-treated patients. The results support the role of serotonin in memory. More studies in larger samples of patients are required, but it may be that in cases where memory impairment is a major symptom, it would be beneficial to consider serotonergic antidepressant drugs for treatment. Furthermore, in cases where, for various reasons, the treatment of choice is noradrenergic, it may be worthwhile to consider a supplementary serotonergic drug to improve memory deficits. The relative efficacy of psychotherapy and combined therapy in the treatment of depression is still a matter of debate.
                To investigate whether combined therapy has advantages over psychotherapy alone.
                A 6-month randomised clinical trial compared Short Psychodynamic Supportive Psychotherapy (n=106) with combined therapy (n=85) in ambulatory patients with mild or moderate major depressive disorder diagnosed using DSM-IV criteria. Antidepressants were prescribed according to a protocol providing four successive steps in case of intolerance or inefficacy: venlafaxine, selective serotonin reuptake inhibitor, nortriptyline and nortriptyline plus lithium. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression, the Clinical Global Impression of Severity and of Improvement, and the depression sub-scale of the Symptom Checklist.
                The advantages of combining antidepressants with psychotherapy were equivocal. Neither the treating clinicians nor the independent observers were able to ascertain them, but the patients experienced them clearly.
                The advantages of combining antidepressants with psychotherapy are equivocal. The authors examined the efficacy, speed, and incidence of symptom worsening for 3 treatments of posttraumatic stress disorder (PTSD): prolonged exposure, relaxation training, or eye movement desensitization and reprocessing (EMDR; N = 60). Treaments did not differ in attrition, in the incidence of symptom worsening, or in their effects on numbing and hyperarousal symptoms. Compared with EMDR and relaxation training, exposure therapy (a) produced significantly larger reductions in avoidance and reexperiencing symptoms, (b) tended to be faster at reducing avoidance, and (c) tended to yield a greater proportion of participants who no longer met criteria for PTSD after treatment. EMDR and relaxation did not differ from one another in speed or efficacy.
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.