The potential role of atypical antipsychotics for the treatment of posttraumatic stress disorder

Despite the fact that the majority of currently available treatment guidelines propose antidepressants as the first-line pharmacological therapy for posttraumatic stress disorder (PTSD), a substantial portion of patients fail to show an adequate response following this type of treatment. In this context, a number of small, open-label studies and randomized controlled clinical trials (RCTs) have found atypical antipsychotics (AAs) to be a beneficial treatment for patients with PTSD. Thus, the present meta-analysis was conducted to enhance the sample size power and further the current understanding of the role of AAs for the treatment of PTSD. An extensive search of several databases identified 12 appropriate RCTs and available data from 9 of these (n = 497) were included in the final meta-analysis. AAs may have potential benefits for the treatment of PTSD as indicated by changes from baseline of the total score on the Clinician Administered PTSD Scale (CAPS; standardized mean difference [SMD] = −0.289, 95% confidence intervals [CIs] = −0.471, −0.106), P = 0.002). Additionally, AAs were found to be significantly more effective (P < 0.0001) than a placebo in terms of change from baseline for the intrusion sub-score on the CAPS (SMD = −0.373, 95% CIs = −0.568, −0.178) but there were no significant reductions for the avoidance and hyperarousal sub-symptoms. The responder rate and rate of improvement of depressive symptoms were also significantly higher in the AA group than the placebo group (P = 0.004 and P < 0.0001, respectively). However, the present results should be interpreted carefully and be translated into clinical practice only with due consideration of the limited quality and quantity of existing RCTs included in this analysis.     

Chemokines in post-traumatic stress disorder: A network meta-analysis

BackgroundPrevious studies on the association between chemokines concentrations and post-traumatic stress disorder (PTSD) yielded inconsistent results. Therefore, the purpose of this network meta-analysis was to summarize these results.MethodsThe databases of PubMed, Web of Science, Psyc-ARTICLES, Embase and Cochrane Library were searched for relevant articles published not later than January 15, 2020. Then, eligible studies were selected based on predefined study selection criteria. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated as group differences in chemokines concentrations. Moreover, network meta-analysis was used to rank chemokines effect values according to their respective surface under cumulative ranking curve (SUCRA) probabilities.FindingsA total of 18 eligible studies that investigated the association between 9 different chemokines and PTSD were identified. They involved 1,510 patients and 2,012 controls. Results of the meta-analysis showed that the concentrations of CCL3, CCL4 and CCL5 in the PTSD patients were significantly higher than that in the controls (SMDs of 4.12, 6.11 and 1.53 respectively). However, although not statistically significant, concentrations of CCL2 tended to be lower in PTSD patients than in the controls (SMD = -0.76); whereas concentrations of CXCL12 tended to be higher in PTSD patients than in the controls (SMD = 0.37). SUCRA probabilities showed that, among all the chemokines studied, the effect of CCL5 was the highest in PTSD patients.InterpretationConcentrations of CCL3, CCL4 and CCL5 may be associated with a trauma and/or PTSD. Also, CXCL12 and CCL2 may be the underlying biomarkers for trauma and/or PTSD. Thus, future studies with large population based samples are needed to further assess these associations. In addition, future research should explore possible mechanisms underlying these associations, with the aim to develop new diagnostics for PTSD. PROSPERO CRD42019147703.     

The effects of prazosin on sleep disturbances in post-traumatic stress disorder: a systematic review and meta-analysis

BackgroundNightmares are a highly prevalent and distressing feature of post-traumatic stress disorder (PTSD). Previous studies have reached mixed conclusions regarding the effects of prazosin on nightmares, sleep quality, and overall PTSD symptoms in patients with PTSD.MethodsMEDLINE, EMBASE, all EBM databases, PsycIFNO, and CINAHL were systematically searched from inception date to October 2018 for randomized clinical trials that included reporting of nightmares, sleep quality or overall PTSD symptoms. The analysis included data from eight trials involving 286 PTSD patients in the prazosin group and 289 PTSD patients in the placebo group.ResultsIn our meta-analysis, prazosin resulted in a statistically significant improvement in nightmares (standardized mean difference (SMD) = −1.13, 95% confidence interval (CI) = −1.91 to −0.36), but was not more beneficial than placebo for overall PTSD symptoms (SMD = −0.45, 95% CI = −0.95 to 0.05) and sleep quality (SMD = −0.44, 95% CI = −1.44 to 0.55). In terms of acceptability, there was no significant difference between the prazosin group and the placebo group with respect to discontinuation for all causes (odds ratio (OR) = 1.00, 95% CI = 0.62–1.62). In conclusion, the use of prazosin was associated with an improvement of nightmare symptoms.ConclusionOur findings indicate that additional studies are needed before considering downgrading the use of prazosin in the treatment of nightmares in patients with PTSD.     

Efficacy of group psychotherapy for social anxiety disorder: A meta-analysis of randomized-controlled trials

Group psychotherapy for social anxiety disorder (SAD) is an established treatment supported by findings from primary studies and earlier meta-analyses. However, a comprehensive summary of the recent evidence is still pending. This meta-analysis investigates the efficacy of group psychotherapy for adult patients with SAD. A literature search identified 36 randomized-controlled trials examining 2171 patients. Available studies used mainly cognitive-behavioral group therapies (CBGT); therefore, quantitative analyses were done for CBGT. Medium to large positive effects emerged for wait list-controlled trials for specific symptomatology: g = 0.84, 95% CI [0.72; 0.97] and general psychopathology: g = 0.62, 95% CI [0.36; 0.89]. Group psychotherapy was also superior to common factor control conditions in alleviating symptoms of SAD, but not in improving general psychopathology. No differences appeared for direct comparisons of group psychotherapy and individual psychotherapy or pharmacotherapy. Hence, group psychotherapy for SAD is an efficacious treatment, equivalent to other treatment formats.     

典型和非典型抗精神病药合并碳酸锂治疗双相情感障碍躁狂发作的对照研究

目的探讨典型和非典型抗精神病药物合并碳酸锂治疗双相情感障碍躁狂发作患者的疗效。方法将94例双相情感障碍躁狂发作患者分为典型抗精神病药物组（43例）和非典型抗精神病药物组（51例）,进行为期8周的疗效比较。采用Bech-Rafaelsen躁狂量表（BRMS）、临床大体印象量表（CGI）、副反应量表（TESS）以及药物依从性量表分别于入组前和入组第1、2、4、6和8周末时进行评定。结果治疗结束时,两组BRMS评分较入组时均显著减低（P〈0．01）;临床总有效率：典型抗精神病药物组83．7％,非典型抗精神病药物组82．3％;两组疗效差异无显著性。非典型药物组的不良反应较典型组少,药物依从性较典型组高。结论非典型抗精神病药物治疗双相情感障碍躁狂发作的疗效肯定,不良反应较少,安全性高,依从性好,适合临床应用。     

Efficacy and acceptability of interventions for co-occurring PTSD and SUD: A meta-analysis

Over the past 20 years, numerous treatments addressing comorbid Posttraumatic Stress Disorder (PTSD) and Substance Use Disorder (SUD) have been developed and tested. The current meta-analysis examined the efficacy and acceptability of the two central treatment types– trauma-focused and non-trauma-focused – compared with all comparators and with cognitive-behavioral manualized SUD treatments immediately post-treatment and at longest follow-up. Twenty-eight randomized clinical trials (N = 3247) were included. There were small to large within-group effects for all forms of active treatment (gs = 0.30–1.11). Trauma-focused but not non-trauma-focused treatments outperformed all comparators on PTSD outcomes at post-treatment. Neither trauma-focused nor non-trauma-focused treatment outperformed all comparators on SUD outcomes at post-treatment. Neither trauma- nor non-trauma-focused treatment outperformed manualized SUD treatments on PTSD outcomes at either time point. Manualized SUD treatments outperformed trauma-focused treatments on SUD outcomes at post-treatment and non-trauma-focused treatments on PTSD outcomes at follow-up. Regarding treatment retention, neither trauma-focused nor non-trauma-focused treatments significantly differed from all comparators or from manualized SUD treatments. Between-group results were largely unchanged in trim-and-fill analyses, but were not robust to fail-safe N. Few moderators were detected. Taken together, results suggest that trauma-focused, non-trauma-focused, and manualized SUD interventions are sound options for individuals with comorbid PTSD/SUD.     

Efficacy of cognitive behavioral therapy and fluoxetine for the treatment of binge eating disorder: a randomized double-blind placebo-controlled comparison.

BACKGROUND: Cognitive behavioral therapy (CBT) and certain medications have been shown to be effective for binge eating disorder (BED), but no controlled studies have compared psychological and pharmacological therapies. We conducted a randomized, placebo-controlled study to test the efficacy of CBT and fluoxetine alone and in combination for BED. METHODS: 108 patients were randomized to one of four 16-week individual treatments: fluoxetine (60 mg/day), placebo, CBT plus fluoxetine (60 mg/day) or CBT plus placebo. Medications were provided in double-blind fashion. RESULTS: Of the 108 patients, 86 (80%) completed treatments. Remission rates (zero binges for 28 days) for completers were: 29% (fluoxetine), 30% (placebo), 55% (CBT+fluoxetine), and 73% (CBT+placebo). Intent-to-treat (ITT) remission rates were: 22% (fluoxetine), 26% (placebo), 50% (CBT+fluoxetine), and 61% (CBT+placebo). Completer and ITT analyses on remission and dimensional measures of binge eating, cognitive features, and psychological distress produced consistent findings. Fluoxetine was not superior to placebo, CBT+fluoxetine and CBT+placebo did not differ, and both CBT conditions were superior to fluoxetine and to placebo. Weight loss was modest, did not differ across treatments, but was associated with binge eating remission. CONCLUSIONS: CBT, but not fluoxetine, demonstrated efficacy for the behavioral and psychological features of BED, but not obesity.     

Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials.

OBJECTIVE: Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease (AD) and other dementia. Several clinical trials have not shown efficacy, and there have been concerns about adverse events. The objective of this study was to assess the evidence for efficacy and adverse events of atypicals for people with dementia. METHODS: MEDLINE, the Cochrane Register of Controlled Trials, meetings, presentations, and information obtained from sponsors were used in this study. Published and unpublished randomized, placebo-controlled, double-blind, parallel-group trials in patients with AD or dementia of atypical antipsychotics marketed in the United States were studied. Clinical and trials characteristics, outcomes, and adverse events were extracted. Data were checked by a second reviewer. Fifteen trials including 16 contrasts of atypical antipsychotics with placebo met selection criteria: aripiprazole (k = 3), olanzapine (k = 5), quetiapine (k = 3), and risperidone (k = 5). A total of 3,353 patients were randomized to drug and 1,757 to placebo. Standard meta-analysis methods were used to summarize outcomes. RESULTS: Quality of the reporting of trials varied. Efficacy on rating scales was observed by meta-analysis for aripiprazole and risperidone, but not for olanzapine. Response rates were frequently not reported. There were smaller effects for less severe dementia, outpatients, and patients selected for psychosis. Approximately one-third dropped out without overall differences between drug and placebo. Adverse events were mainly somnolence and urinary tract infection or incontinence across drugs, and extrapyramidal symptoms or abnormal gait with risperidone or olanzapine. Cognitive test scores worsened with drugs. There was no evidence for increased injury, falls, or syncope. There was a significant risk for cerebrovascular events, especially with risperidone; increased risk for death overall was reported elsewhere. CONCLUSIONS: Small statistical effect sizes on symptom rating scales support the evidence for the efficacy of aripiprazole and risperidone. Incomplete reporting restricts estimates of response rates and clinical significance. Dropouts and adverse events further limit effectiveness. Atypicals should be considered within the context of medical need and the efficacy and safety of alternatives. Individual patient meta-analyses are needed to better assess clinical significance and effectiveness.     

Implementing a randomized clinical trial on a pediatric psychiatric inpatient unit at a children's hospital: the case of clonidine for post-traumatic stress

Randomized clinical trials (RCTs) of psychotropic medications are uncommon among child and adolescent populations, and even rarer on pediatric, psychiatric inpatient units. We mention some of these studies, and then discuss the advantages and challenges of conducting a RCT among youngsters on an inpatient psychiatric unit in a pediatric hospital, using as an example our ongoing study of clonidine for intrusive symptoms of post-traumatic stress. Our purpose is to alert potential investigators to the obstacles they may encounter while implementing a RCT, while also pointing the way to potential resources. Advantages of inpatient units for RCTs include easy access to patients, with the potential for careful monitoring of both patients’ clinical status and of medication administration. Challenges include the need for the psychiatric researcher to form liaison with other important areas within the hospital, such as the Institutional Review Board, the Pharmacy, and sometimes a General Clinical Research Center and a Clinical Research Program. The functions of these departments are discussed, and additional support for clinicians in hospital settings without these departments is described. Other issues include training clinical nurses to conduct research while making adequate provisions for their time to do so. Attitudes on a clinical psychiatric inpatient unit toward research also merit consideration. Furthermore, as with any study in a hospital setting, recruitment presents its own set of challenges. Finally, one must be cognizant of how clinical information flows between clinicians and researchers.     

The efficacy and safety of teriflunomide based therapy in patients with relapsing multiple sclerosis: A meta-analysis of randomized controlled trials

The aim of this study was to evaluate the efficacy and safety of teriflunomide in reducing the frequency of relapses and progression of physical disability in patients with relapsing multiple sclerosis (RMS). Literatures were searched in Pubmed, Medline and Embase to screen citations from January 1990 to April 2015. Studies of parallel group design comparing teriflunomide and placebo for RMS were screened. After independent review of 234 citations by two authors, seven studies were identified as meeting the inclusion criteria. The results showed teriflunomide (7 and 14 mg) could significantly reduce annualized relapse rate and teriflunomide at the higher dose could also decrease the disability progression (risk ratio (RR) = 0.69, 95% confidence interval (CI): 0.55–0.87). And teriflunomide significantly reduce annualized rates of relapses with sequelae-EDSS/FS, relapses leading to hospitalization, and relapses requiring IV corticosteroids. Patients treated with teriflunomide 14 mg have a lower annualized rate of relapses with sequelae-investigator (RR = 0.37, 95% CI: 0.26–0.52). Teriflunomide 7 mg has a higher incidence of diarrhea (RR = 1.73, 95% CI: 1.32–2.26) and hair thinning (RR = 1.99, 95% CI: 1.4–2.81), while teriflunomide 14 mg has a higher incidence of diarrhea (RR = 1.71, 95% CI: 1.34–2.18), hair thinning (RR = 2.81, 95% CI: 2.02–3.91) and nausea (RR = 1.65, 95% CI: 1.03–2.31) compared with placebo. The incidence of elevated alanine aminotransferase levels was also higher with teriflunomide than with placebo. However, the incidence of serious adverse events was similar across groups. In conclusion, teriflunomide significantly reduces annualized relapse rates and disability progression with a similar safety and tolerability profile to placebo.     

Efficacy of group psychotherapy for posttraumatic stress disorder: Systematic review and meta-analysis of randomized controlled trials

Objective: The present meta-analysis evaluates the efficacy of group psychotherapy for post-traumatic stress disorder (PTSD) in adults directly compared to no treatment or active treatments examined in randomized controlled trials (RCTs). Method: Electronic databases were searched for eligible studies. Effects on PTSD symptoms, depression, and anxiety were extracted. Between- and within-group effect sizes (Hedges’ g) were calculated using a random-effects model. Data were adjusted to account for dependencies among observations in groups. Results: Twenty RCTs were included comprising 2244 individuals. Results showed significant effects of group psychotherapy in reducing symptoms of PTSD compared to no-treatment control groups (k?=?13; g?=?0.70; 95% CI: 0.41; 0.99). No significant differences in efficacy were found between group psychotherapy and other active treatments (k?=?8; g?=?0.13; 95% CI: ?0.16; 0.42). Moderator analyses confirmed gender and trauma type as important moderators of within-treatment effects for PTSD. Conclusions: Group treatments are associated with improvements in symptoms of PTSD. Particularly, the efficacy of exposure-based cognitive-behavioral group therapy (group CBT) is empirically well demonstrated. Still little is known about the effects of group treatment approaches other than CBT and the comparative efficacy to alternative treatments such as individual therapy or pharmacotherapy.

Clinical or Methodological Significance of this Article: This review provides an empirical base for group therapy as a viable treatment alternative for future PTSD practice guidelines. Although less is known about its comparative efficacy to alternative PTSD treatments such as individual therapy or pharmacotherapy, sufficient evidence exists to recommend group therapy (particularly exposure-based group CBT) for those who might not be able to access alternative treatments. Trauma type and gender proved to be important moderators of group treatment outcome. The results further indicate that the evidence base of recommendations for group therapy in current international treatment guidelines needs to be updated.     

Efficacy and safety of atypical antipsychotics for psychosis in Parkinson's disease: A systematic review and Bayesian network meta-analysis

IntroductionWe performed a systematic review and Bayesian network meta-analysis to clarify the relative efficacy and safety of pimavanserin compared to atypical antipsychotics for psychosis in Parkinson's disease (PD).MethodsPubMed, Embase, Cochrane Central Register of Controlled Trials, and Japana Centra Revuo Medicina Web were searched for relevant articles until October 31, 2019. Eligible randomized controlled trials were synthesized for efficacy (Brief Psychiatry Rating Scale [BPRS] and Clinical Global Impression Scale [CGI-S]) and safety (Unified Parkinson's Disease Rating Scale part III [UPDRS-III] and dropouts due to adverse events). The mean differences (BPRS, CGI-S, and UPDRS-III) or odds ratios (dropouts due to adverse events) between each active drug and placebo were estimated and summarized as means and 95% credible intervals, respectively.ResultsWe identified 17 relevant trials. Clozapine showed significant efficacy (BPRS, −5.6 [−8.4 to −2.7] and CGI-S, −1.2 [−1.7 to −0.7]), with low impact on motor functions (UPDRS-III, −1.1 [−3.8 to 1.5]), but an increase in dropouts due to adverse events (2.9 [0.9 to 9.6]) as compared to placebo. Pimavanserin also showed significant efficacy (CGI-S, −0.5 [−0.9 to −0.2]) and similar impact on motor functions (UPDRS-III, 0.2 [−1.4 to 1.9]), but a tendency of increase in dropouts due to adverse events (2.2 [0.5 to 12.4]) as compared to placebo.ConclusionsClozapine showed an efficacy with low impact on motor functions that was consistent with previous reports. Although the efficacy of pimavanserin may be inferior to that of clozapine, it had a favorable profile for the treatment of psychosis in PD.     

Efficacy and safety of noradrenalin reuptake inhibitor augmentation therapy for schizophrenia: A meta-analysis of double-blind randomized placebo-controlled trials

Background

We performed an updated meta-analysis of noradrenalin reuptake inhibitor (NRI) augmentation therapy in patients with schizophrenia treated with antipsychotics based on a previous meta-analysis (Singh et al.).

Methods

PubMed, Cochrane Library databases, and PsycINFO citations were searched from their inception to June 10, 2013 without language restrictions. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing NRI augmentation therapy with placebo. The outcome measure for efficacy was the psychopathology of schizophrenia and the measures for safety were discontinuation rate and several side effects. We used standardized mean differences (SMD) to estimate treatment effects for continuous variables, and risk ratios (RR) for dichotomous variables, with their 95% confidence intervals (CIs). A random-effects model was used.

Results

Nine studies (4 atomoxetine studies, 3 reboxetine studies, 1 reboxetine–betahistine combination study and 1 mazindol study, total n = 298) were identified. No statistically significant effects of NRI augmentation therapy on overall (p = 0.90), positive (p = 0.81), and negative (p = 0.89) symptoms were found. NRI augmentation therapy was marginally superior to placebo for efficacy of depressive symptoms (SMD = −1.08, p = 0.05). Dropout due to all-cause (p = 0.70), inefficacy (p = 0.64), or adverse events (p = 0.18) was similar in both groups. NRI augmentation therapy showed a significantly lower increase or larger reduction in body weight than placebo (SMD = −0.47, p = 0.03). Reboxetine augmentation was associated with less weight gain that placebo in antipsychotic treated schizophrenia patients (SMD = −0.78, p = 0.0001).

Conclusion

NRIs may exert an effect on depressive symptoms, and seem to be well-tolerated treatments.     

Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial

Ginkgo biloba special extract EGb 761, an anti-dementia drug, enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects. Moreover, EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline, therefore it was now tested for clinical efficacy in younger patients suffering from anxiety. One hundred and seven patients with generalized anxiety disorder (GAD, n=82) or adjustment disorder with anxious mood (ADWAM, n=25) according to the diagnostic and statistical manual of mental disorders, third edition - revised (DSM-III-R) were randomized to daily doses of 480 mg EGb 761, 240 mg EGb 761 or placebo for 4 weeks. Intention-to-treat (ITT) analyses were performed on the primary outcome measure, the Hamilton rating scale for anxiety (HAMA), and the secondary variables, the clinical global impression of change (CGI-C), the Erlangen anxiety tension and aggression scale (EAAS), the list of complaints (B-L'), and the patient's global rating of change. The HAMA total scores decreased by -14.3 (+/-8.1), -12.1 (+/-9.0) and -7.8 (+/-9.2) in the high-dose EGb 761, the low-dose EGb 761 and the placebo group, respectively. Changes were significantly different from placebo for both treatment groups with p=0.0003 (high-dose group) and p=0.01 (low-dose). Regression analyses revealed a dose-response trend (p=0.003). EGb 761 was significantly superior to placebo on all secondary outcome measures. It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline.     

随机、双盲、安慰剂对照、多中心研究唑尼沙胺添加用药治疗部分性癫(癎)发作的有效性和安全性

目的 评价唑尼沙胺(ZNS)作为添加用药治疗部分性癫(癎)发作的有效性和安全性.方法 采用多中心、随机、双盲、安慰剂对照、平行组、添加治疗设计.240例确诊为癫(癎)部分性发作的受试者按照1:1的比例随机分配到ZNS治疗组或安慰剂组.在前4周加鼋期内受试者自100 mg/d逐渐加量至300 mg/d,随后进入12周的稳定治疗期.在稳定期内可根据患者情况酌情减量,或加量至最大剂量400 mg/d.有效性评价的主要指标为稳定期部分性癫(癎)发作频率较基线值减少百分数的中位值,重要的次要评价指标为有效率,即部分性癫(癎)发作次数减少≥50%者的比例.同时对药物的安全性进行评价.结果 ZNS组受试者稳定期部分性癫(癎)发作频率较基线期减少百分数(48.4%)显著高于安慰剂组(26.6%),组间差异有统计学意义(F=4.904,P=0.028);ZNS组治疗部分性癫(癎)发作的有效率(48.6%)高于安慰剂组(34.9%),差异有统计学意义(X2=4.046,P=0.044),其中以复杂部分性癫(癎)的组间差异最为显著(分别为52.2%和33.3%,X2=5.607,P=0.018).ZNS组与安慰剂组不良事件发生率相当,与ZNS相关的不良事件多为头晕、头痛、嗜睡、食欲下降、恶心等.结论 ZNS能有效治疗部分性癫(癎),降低癫(癎)发作频率,对复杂部分性癫(癎)发作治疗效果尤为突出.ZNS耐受性良好,受试者用药安全性较高.     

Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children.

BACKGROUND: To evaluate short-term safety and efficacy of atypical antipsychotics in a single-site, prospective, open-label, 8-week study of risperidone and olanzapine monotherapy in preschoolers with bipolar disorder (BPD). METHODS: Risperidone was initiated at an open-label dose of .25 mg/day, increased weekly according to response and tolerability to a maximum does of 2.0 mg/day. Olanzapine was initiated at 1.25 mg/day and increased to no more than 10 mg/day. RESULTS: Thirty-one children aged 4-6 years were treated with olanzapine (n = 15, 6.3 +/- 2.3 mg/day) or risperidone (n = 16, 1.4 +/- .5 mg/day). At study end point (week 8 or last observation carried forward), there was a 18.3 +/- 11.9 point (t = -5.6, p < .001) reduction in risperidone-treated subjects and a 12.1 +/- 10.4 point (t = -4.4, p < .001) reduction in Young Mania Rating Scale (YMRS) scores in olanzapine-treated subjects that did not differ between groups (t = 1.4, p = .2). Response criteria (Clinical Global Impression improvement of "Much" or "Very Much" improved or a YMRS change of >or= 30% or more) indicated no difference in rate of response with risperidone and olanzapine (69% vs. 53%, chi(2)((1)) = .8, p = .4). CONCLUSIONS: This prospective open study suggests that treatment with risperidone or olanzapine may result in a rapid reduction of symptoms of mania in preschool children with BPD. Because of substantial residual symptomatology and adverse effects, however, a pressing need exists to identify additional safe and effective treatments for the management of BPD in this high-risk population.     

Cognitive behavioral therapy guided self-help and orlistat for the treatment of binge eating disorder: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Cognitive behavioral therapy (CBT) has efficacy for binge eating disorder (BED) but not obesity. No controlled studies have tested whether adding obesity medication to CBT facilitates weight loss. We performed a randomized, placebo-controlled study of orlistat administered with guided self-help CBT (CBTgsh). METHODS: Fifty obese BED patients were randomly assigned to 12-week treatments of either orlistat plus CBTgsh (120 mg three times a day [t.i.d.]) or placebo plus CBTgsh and were followed in double-blind fashion for 3 months after treatment. RESULTS: Seventy-eight percent of patients completed treatments without differential dropout between orlistat+CBTgsh and placebo+CBTgsh. Intent-to-treat remission rates (zero binges for past 28 days on Eating Disorder Examination Interview) were significantly higher for orlistat+CBTgsh than placebo+CBTgsh (64% versus 36%) at posttreatment but not at 3-month follow-up (52% in both). Intent-to-treat rates for achieving 5% weight loss were significantly higher for orlistat+CBTgsh than placebo+CBTgsh at posttreatment (36% versus 8%) and 3-month follow-up (32% versus 8%). Significant and comparable improvements in eating disorder psychopathology and psychological distress occurred in both treatments. CONCLUSIONS: The addition of orlistat to CBTgsh was associated with greater weight loss than the addition of placebo to CBTgsh. Clinical improvements were generally maintained at 3-month follow-up after treatment discontinuation.     

Riluzole combination therapy for moderate-to-severe major depressive disorder: A randomized,double-blind,placebo-controlled trial

Recent evidences suggest that glutamatergic dysregulation implicated in neural plasticity and cellular resilience may contribute to the pathophysiology of Major Depressive Disorder (MDD). Riluzole, which exerts its effect by targeting glutamate neurotransmission, has shown antidepressant effect in recent preclinical, observational and open label studies. This study aimed to assess the efficacy and tolerability of riluzole in patients with MDD. Sixty-four inpatients with diagnosis of moderate to severe major depressive disorder participated in a parallel, randomized, controlled trial, and sixty patients underwent 6 weeks treatment with either riluzole (50 mg/bid) plus citalopram (40 mg/day) or placebo plus citalopram (40 mg/day). All participants were inpatients for the whole duration of the study. Patients were assessed using Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4 and 6. The primary outcome measure was to assess the efficacy of riluzole compared to placebo in improving the depressive symptoms. General linear model repeated measures demonstrated significant effect for time × treatment interaction on HDRS [F (1.86, 107.82) = 8.63, p < 0.001]. Significantly greater improvement was observed in HDRS scores in the riluzole group compared to the placebo group from baseline HDRS score at weeks 2, 4 and 6 (p < 0.001, p = 0.001, p = 0.002, respectively). Significantly greater response with greater speed to treatment was observed in the riluzole group than the placebo group. No serious adverse event occurred. This study showed a favorable safety and efficacy profile in patients with major depressive disorder. Larger controlled studies with longer treatment periods are needed to investigate long term safety, efficacy and optimal dosing.