A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia

Short-term clinical trials of omega-3 polyunsaturated fatty acids (n-3 PUFA) as add-on therapy in patients with schizophrenia revealed mixed results. The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid. A randomized placebo-controlled trial was designed to compare the efficacy of 26-week intervention, composed of either 2.2 g/day of n-3 PUFA, or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. Seventy-one patients (aged 16–35) were enrolled in the study and randomly assigned to the study arms. The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale (PANSS). Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA (p = 0.016; effect size (ES) = 0.29). A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group (69.4 vs 40.0%; p = 0.017). N-3 PUFA intervention was also associated with an improvement in general psychopathology, measured by means of PANSS (p = 0.009; ES = 0.32), depressive symptoms (p = 0.006; ES = 0.34), the level of functioning (p = 0.01; ES = 0.31) and clinical global impression (p = 0.046; ES = 0.29). The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients.     

强迫症团体认知行为治疗与药物治疗的随机对照研究

目的分析团体认知行为治疗(group cognitive-behavioral therapy,GCBT)对强迫症患者的疗效。方法本研究采用随机对照试验设计,与常规抗强迫药物治疗做对照。将符合入组标准的94例未用药强迫症患者,采用Excel软件中的RAND函数产生随机数字表形成随机分组序列的简单随机分组法,随机分为GCBT组(47例)和药物治疗组(47例)。经12周的结构化GCBT治疗和常规抗强迫药物治疗,采用t检验、卡方检验和方差分析比较2组间Y-BOCS、HAMA14和HAMD24平均减分率和减分值的差异。结果(1)2组基线Y-BOCS及HAMA14评分差异无统计学意义(t=0.281,P=0.779;t=0.795,P=0.429),但GCBT组HAMD24评分显著低于药物治疗组(t=2.316,P<0.05)。2组各有16例患者退出治疗,总脱落率为34%(32/94)。(2)12周治疗结束时,2组患者的Y-BOCS评分较基线显著降低,GCBT组和药物治疗组治疗前后Y-BOCS平均减分率[(37.0±27.4)%比(45.5±22.9)%]和平均减分值[(9.0±6.3)分比(11.0±5.8)分]比较差异无统计学意义[F(1,62)=0.069,P=0.794;F(1,62)=0.001,P=0.975]。GCBT组和药物治疗组的有效率和治愈率差异无统计学意义(χ^2=1.653,P=0.199;χ^2=0.088,P=0.767)。(3)GCBT组HAMA14减分率和减分值与药物治疗组治疗前后比较差异无统计学意义(t=-0.922,P=0.362;t=1.082,P=0.286)。(4)GCBT组HAMD24减分率与药物治疗组治疗前后比较差异无统计学意义,但药物治疗组HAMD24减分值显著高于GCBT组(t=2.239,P=0.029)。结论GCBT与常规抗强迫药物治疗强迫症患者的强迫和焦虑症状的疗效相当,常规药物治疗对抑郁症状的疗效优于GCBT。     

唑尼沙胺添加治疗部分性癫的临床疗效及安全性:多中心随机双盲安慰剂对照研究

目的观察唑尼沙胺分散片添加治疗部分性发作或继发全面性发作、全面性强直-阵挛发作及失神发作的疗效及安全性。方法 240例诊断明确的部分性发作患者,被随机分为唑尼沙胺组(120例)或对照组(120例)。回顾性基线期(12周)后,予初始剂量唑尼沙胺或安慰剂100mg/次,1次/d,3周内递增至100 mg/次,3次/d;分别在治疗第0、2、4、8和16周时进行随访,评价治疗第5～16周时临床综合疗效的完全控制率和总有效率,以及药物安全性和不良反应。结果治疗第5～16周时,唑尼沙胺组患者癫癎完全控制率为34.04%(32/94)、总有效率74.47%(70/94),对照组分别为13.08%(14/107)和42.99%(46/107);两组临床综合疗效的完全控制率和总有效率比较,差异具有统计学意义(均P=0.000)。唑尼沙胺组患者常见药物不良反应包括食欲不振、嗜睡、疲劳、头晕、肝功能异常等,与对照组不良反应发生率比较差异有统计学意义(P=0.003)。结论唑尼沙胺作为添加药物治疗部分性发作或继发全面性发作、全面性强直-阵挛发作的疗效优于安慰剂,而且有较好的安全性和耐受性,是临床可以选择的新型抗癫癎药物之一。     

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.     

Buprenorphine augmentation improved symptoms of OCD,compared to placebo - Results from a randomized,double-blind and placebo-controlled clinical trial

BackgroundIn the search for new psychopharmacologic options in the treatment of obsessive-compulsive disorders (OCD), some findings suggested that augmentation with buprenorphine, a partial-opioid agonist used to treat opioid addiction, moderate acute pain and moderate chronic pain, is worthy of consideration. Accordingly, to explore this possibility further, a double-blinded, placebo-controlled clinical trial was performed.MethodA total of 43 patients (mean age: 34.41 years; SD = 6.58; 53.5% males) with refractory OCD and treated with SSRIs or clomipramine at therapeutic dosages were randomly assigned either to an adjuvant buprenorphine or to an adjuvant placebo condition. Patients completed the Yale-Brown-Obsessive-Compulsive Scale (Y-BOCS) at baseline, weeks 3, 9 and 12 (study completion). Buprenorphine (2–4 mg; sublingual) and placebo (tablets with identical shape, color, consistency, and scent) were given daily.ResultsSymptoms of obsessive-compulsive disorders decreased over time, but more so in the buprenorphine than in the placebo condition. Substantial improvements were observed up to week 3 and then 9. Response and partial response were observed in the buprenorphine at week 9 more than in the placebo condition. The advantage had disappeared by week 12.ConclusionsThe pattern of results suggests that adjuvant buprenorphine augmentation can reduce symptoms of obsessive-compulsive disorders after only three weeks, compared to a placebo. Adjuvant buprenorphine seems to accelerate symptom improvement.     

Flexible vs. standard subthalamic stimulation in Parkinson disease: A double-blind proof-of-concept cross-over trial

BackgroundDeep brain stimulation (DBS) of the subthalamus (STN) is effective for the treatment of cardinal motor signs of Parkinson disease (PD). Structures around the STN can suppress dyskinesia and tremor (zona incerta) and improve gait and balance (substantia nigra pars reticulata).ObjectiveIs the newer 8-contact linear lead connected to a ‘flexible’ DBS system superior to standard 4-contact stimulation in PD patients receiving STN DBS?MethodsAfter 3 months of open label programming, 10 patients were randomized to standard or flexible stimulation before crossing over to the other arm (3 months each period). Patients and assessors were blinded.ResultsA trend to improvement in Patient Global Impression of Change scores was seen with standard to flexible stimulation and worsening from flexible to standard stimulation (mean ± SD: 0.7 ± 1.2 and −0.4 ± 1.5 respectively, p = 0.152). There was a significant reduction in the number of troublesome symptoms reported prior to DBS (2.6 ± 3.3 per patient), more so with flexible stimulation (0.4 ± 0.6 vs. 1.5 ± 1.6 with standard stimulation, p = 0.001 and p = 0.034). There was no significant difference between the flexible and standard stimulation groups.ConclusionFurther studies confirming that flexible stimulation is superior to standard DBS are warranted.     

Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: A randomized placebo-controlled trial

Purpose:   To evaluate efficacy and safety of adjunctive treatment with rufinamide 1600 mg twice daily in subjects aged ≥16 years with refractory partial seizures.
Methods:   This double-blind, placebo-controlled, randomized, parallel-group, multicenter trial included an 8-week baseline phase and a 13-week double-blind phase. Treatment was initiated with rufinamide 400 mg twice daily or placebo; rufinamide was titrated to 1600 mg twice daily. Percentage change in partial seizure frequency was the primary outcome measure. Secondary outcome measures included total partial seizure frequency and the percentage of subjects experiencing a ≥50% reduction in partial seizure frequency.
Results:   Three hundred thirteen subjects were randomized; 156 subjects received rufinamide and 157 received placebo. Rufinamide-treated subjects experienced a 20.4% median reduction in partial seizure frequency relative to baseline, while placebo-treated subjects had an increase of 1.6% (p = 0.02). Exclusion of subjects taking carbamazepine in a post hoc analysis resulted in a reduction of 29.2% versus 0.7% in the placebo group (p = 0.05), whereas the treatment difference in subjects taking carbamazepine was not significant. Of rufinamide-treated subjects, 28.2% experienced a ≥50% decrease in partial seizure frequency versus 18.6% of placebo-treated subjects (p = 0.04). The most common adverse events associated with rufinamide treatment were dizziness, nausea, diplopia, and ataxia; they occurred primarily during the titration phase.
Discussion:   Adjunctive therapy with rufinamide 3200 mg/day compared with matching placebo demonstrated efficacy and was generally well tolerated in adults with partial seizures. Further study of this agent in adults with partial seizures taking a range of baseline AEDs is warranted.     

Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults

Background

Recent preclinical findings, case reports and non-blinded studies have suggested that glutamatergic interventions may be efficacious for Obsessive-Compulsive Disorder (OCD).

Methods

We enrolled 24 adult outpatients with OCD on stabilized treatment regimens in a double-blind trial of adjunctive glycine, an NMDA glutamate receptor agonist. Participants were randomly assigned 1:1 to either placebo or glycine titrated to 60 g/day, with follow-up visits scheduled at 4, 8 and 12 weeks. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the principal outcome measure.

Results

Regimen non-adherence, principally related to complaints about the taste and/or nausea, resulted in only 14 individuals who were evaluable by predetermined criteria. Those receiving glycine (n = 5) experienced a mean decrease of 6.04 points in Y-BOCS score, compared with a 1.00 point decrease for those receiving placebo (n = 9). Using a hierarchical linear model, compared with placebo, individuals who received glycine had an average 0.82 decrease in Y-BOCS score for each week they remained in the study, not quite reaching statistical significance (p = 0.053). Two of those receiving glycine were responders, versus none receiving placebo (p = 0.11, ns, Fisher exact). Despite the dropouts, two participants were known to have subsequently continued taking glycine through their regular treating psychiatrist for over a year.

Conclusions

The glycine condition approached efficacy for treatment of OCD in this study, with the high dropout rate related to problems with palatability and small sample size the principal caveats. This may indicate a new strategy for treatment of OCD, although confirmatory studies are clearly needed. (ClinicalTrials.gov NCT00405535.)     

Lacosamide as adjunctive therapy for partial‐onset seizures: A randomized controlled trial

Purpose: To evaluate the efficacy and safety of lacosamide (400 and 600 mg/day) as adjunctive treatment in patients with uncontrolled partial‐onset seizures taking one to three concomitant antiepileptic drugs (AEDs). Methods: This multicenter, double‐blind, placebo‐controlled trial randomized patients 1:2:1 to placebo, lacosamide 400 mg, or lacosamide 600 mg/day. After an 8‐week baseline period, patients began treatment with placebo or lacosamide 100 mg/day, were force‐titrated weekly (100 mg/day increments) to the target dose, and entered a 12‐week maintenance period. Results: A total of 405 patients were randomized and received trial medication. Most (82.1%) were taking two to three concomitant AEDs. Median percent reductions in seizure frequency per 28 days from baseline to maintenance (intention‐to‐treat, ITT) were 37.3% for lacosamide 400 mg/day (p = 0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for placebo, with responder rates of 38.3% and 41.2%, respectively, compared to placebo (18.3%, p < 0.001; ITT). Patients randomized to lacosamide showed large reductions in secondarily generalized tonic–clonic seizures, with median percent reductions in seizure frequency of 59.4% for lacosamide 400 mg/day and 93.0% for lacosamide 600 mg/day compared to 14.3% for placebo, and responder rates of 56.0% and 70.2% compared to placebo (33.3%). Dose‐related adverse events included dizziness, nausea, and vomiting. Discussion: Adjunctive treatment with lacosamide 400 and 600 mg/day reduced seizure frequency for patients with uncontrolled partial‐onset seizures. Lacosamide 400 mg/day provided a good balance of efficacy and tolerability; lacosamide 600 mg/day may provide additional benefit for some patients as suggested by secondary efficacy analyses, including response in patients with secondarily generalized tonic–clonic seizures.     

Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures

PURPOSE: This study was designed to evaluate efficacy and safety of zonisamide (ZNS) as adjunctive treatment for patients with refractory partial seizures. METHODS: This randomized, double-blind, placebo-controlled study was conducted at four epilepsy treatment centers. It included a baseline phase (8 to 12 weeks) and a double-blind treatment phase (12 weeks). Initially, patients randomized to ZNS treatment were given a 7-mg/kg/d dosage. When investigators found that adverse effects could be reduced by gradually introducing ZNS, patients were allowed to begin treatment at lower doses (100 mg or approximately 1.5 mg/kg/d) titrated over several weeks to a maximum of 400 to 600 mg/d. Primary and secondary efficacy measures were the median percentage reduction from baseline in seizure frequency and the proportion of patients achieving a > or =50% reduction from baseline (responder rate). Patient and physician global assessments also served as indicators of efficacy. Safety was assessed primarily by treatment-emergent adverse events. RESULTS: ZNS-treated patients had a 28.9% reduction in seizure frequency, which differed significantly from the 4.7% increase in placebo-treated patients. The responder rate for ZNS-treated patients was 26.9%, compared with 16.2% for placebo-treated patients. At study's end, 66.2% of ZNS-treated patients and 12.3% of placebo-treated patients considered their condition improved; similarly, physicians assessed 63.6% of ZNS-treated patients and 10.8% of placebo-treated patients as improved. The most frequently reported adverse events with ZNS treatment included somnolence, irritability, dizziness, nausea, and fatigue. CONCLUSIONS: As adjunctive treatment, ZNS was generally well tolerated and significantly improved seizure control among patients with refractory partial seizures.     

苯妥英治疗强迫症的双盲对照研究

符合DSMⅢ—R和CCMD—2诊断标准的62例强迫症患者,随机分为三组:氯丙咪嗪组(22例)、苯妥英组(20例)、安慰剂组(20例),采用双盲对照研究法,每组经4周治疗,在治疗前后,经Y-BOCS、MSCPOR、HAMD量表测定及临床疗效评定。资料提示氯丙咪嗪组、苯妥英组、安慰剂组的痊愈,显进者分别为68％、55％、0％,而Y-BOCS、MSCPOR减分率分别为54.6％、46.05％、3.2％。提示氯两咪嗪组、苯妥英组对治疗强迫症明显优于安慰剂组。     

舒肝解郁胶囊剂量加倍治疗中度抑郁症的随机、双盲、平行对照、多中心临床研究

目的评价舒肝解郁胶囊剂量加倍治疗中度抑郁症的疗效和安全性。方法采用随机、双盲、平行对照、多中心临床试验方法,募集中度抑郁症患者随机分为高剂量组和常规剂量组。高剂量组采用舒肝解郁胶囊(每粒0.36 g)强化治疗,每日2次、每次4粒,常规剂量组为舒肝解郁胶囊与外观和舒肝解郁胶囊一致的模拟剂各2粒,每日2次,两组均连续治疗56 d。以汉密尔顿抑郁量表17项(Hamilton depression scale,HAMD-17)和汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)评价疗效,安全性评价采用患者不良事件和实验室检查。结果共纳入高剂量组和常规剂量组各120例患者。经过56 d治疗,以HAMD-17考察,高剂量组痊愈率为84.2%,常规剂量组为63.3%,两组差异有统计学意义(P0.05)。治疗14 d后,高剂量组HAMD-17减分率高于常规剂量组[(35.4%±17.0%)vs.(27.1%±16.0%)],治疗56 d,高剂量组减分率仍高于常规剂量组[(79.0%±18.9%)vs.(65.9%±23.1%)],差异具有统计学意义(P0.01)。两组中位起效时间均为14 d,组间差异无统计学意义(P0.05)。以HAMA考察,治疗56 d高剂量组焦虑症状痊愈率达93.3%,总分下降72.5%,常规剂量组焦虑症状痊愈率77.5%,总分下降64.4%,两组间差异均有统计学意义(P0.05)。两组不良反应发生率(17.5%vs.11.7%)差异无统计学意义(P0.05)。结论舒肝解郁胶囊对中度抑郁症的抑郁症状和伴随的焦虑症状有较好疗效,剂量加倍能加快抑郁症状缓解速度,提高近期症状改善幅度,安全性尚可。     

A multicenter, randomized, placebo-controlled trial of levetiracetam in children and adolescents with newly diagnosed absence epilepsy

Purpose: To evaluate the potential efficacy of levetiracetam as an antiabsence agent in children and adolescents with newly diagnosed childhood or juvenile absence epilepsy. Methods: Patients were randomized in a 2:1 ratio to receive de novo monotherapy with levetiracetam (up to 30 mg/kg/day) or placebo for 2 weeks under double‐blind conditions. Responder status (primary end point) was defined as freedom from clinical seizures on days 13 and 14 and from electroencephalographic (EEG) seizures during a standard EEG recording with hyperventilation and intermittent photic stimulation on day 14. The double‐blind phase was followed by an open‐label follow‐up. Key Findings: Nine of 38 patients (23.7%) were responders in the levetiracetam group, compared with one of 21 (4.8%) in the placebo group (p = 0.08). Seven of 38 patients (18.4%) were free from clinical and EEG seizures during the last 4 days of the trial (including 24‐h EEG monitoring on day 14) compared with none of the patients treated with placebo (p = 0.04). Seventeen patients remained seizure‐free on levetiracetam after 1 year follow‐up. Of the 41 patients who discontinued levetiracetam due to lack of efficacy (n = 39) or adverse events (n = 2), 34 became seizure‐free on other treatments. Significance: Although superiority to placebo just failed to reach statistical significance for the primary end point, the overall findings are consistent with levetiracetam having modest efficacy against absence seizures. Further controlled trials exploring larger doses and an active comparator are required to determine the role of levetiracetam in the treatment of absence epilepsy.     

多中心、随机、双盲、安慰剂对照评价唑尼沙胺添加治疗癫(癎)部分性发作的疗效和安全性

目的 评价唑尼沙胺作为添加治疗癫(癎)部分性发作的疗效和安全性.方法 确诊为有癫(癎)部分性发作的217例癫(癎)患者,随机分配入唑尼沙胺治疗组(n=111)与安慰剂组(n=106)进行随机、双盲、安慰剂对照、多中心平行设计添加治疗.在3个月回顾性基线期后,给予患者初始剂量唑尼沙胺(100 mg/片)或安慰剂每次1片,每日1次口服,4周内递增至每次2片,每日2次.分别在治疗0、2、4、8、12和16周时进行随访.主要疗效指标为治疗结束后与基线期比较发作次数减少的中位百分比;次要疗效指标为发作次数减少大于50%的比例.同时观察研究药物的安全性与不良反应情况.结果 总发作次数减少率中位数在唑尼沙胺组为33.33%,安慰剂组为0;唑尼沙胺组总发作次数减少>50%者38例(34.23%),安慰剂组21例(19.81%),差异有统计学意义(χ3=5.7159,P=0.0168).唑尼沙胺组治疗后无发作13例(11.71%),有效25例(22.52%),临床有效率为34.23%;安慰剂组无发作5例(4.72%),有效16例(15.09%),临床有效率为19.81%,2组间比较差异有统计学意义(U=2.4701,P=0.0135).唑尼沙胺组与安慰剂组比较,其不良反应发生率差异无统计学意义,唑尼沙胺组较常见的不良反应有思睡、乏力、食欲下降、胃肠道不适、失眠和便秘.结论 唑尼沙胺作为部分性癫(癎)发作的添加药物有确定的疗效,安全耐受性较好,具有一定临床应用价值.     

Once-daily extended-release levetiracetam as adjunctive treatment of partial-onset seizures in patients with epilepsy: A double-blind, randomized, placebo-controlled trial

Purpose:   Double-blind randomized trial to assess efficacy and tolerability of once-daily extended-release levetiracetam (LEV XR) tablets (2 × 500 mg) as add-on therapy in patients (12–70 years old) with partial-onset seizures (POS) refractory to one to three antiepileptic drugs.
Methods:   After an 8-week prospective baseline-period, eligible patients were randomized (1:1) to once-daily LEV XR 1,000 mg/day or placebo for 12 weeks. Evaluations included changes from baseline in POS-frequency/week, responders (≥50% reduction in POS-frequency/week), seizure-freedom, adverse events, laboratory tests, physical and neurologic examinations, vital signs, body-weight, and 12-lead electrocardiogram.
Results:   Of 188 patients screened, 158 were randomized (intention-to-treat population): LEV XR (n = 79) or placebo (n = 79). Seventy-one (89.9%) LEV XR and 72 (91.1%) placebo patients completed the trial. Median POS-frequency/week reduction was 46.1% on LEV XR and 33.4% on placebo. Estimated reduction with LEV XR over placebo was 14.4% (p   =   0.038). Thirty-four (43%) LEV XR and 23 (29.1%) placebo patients experienced ≥50% reduction in POS-frequency/week. Eight (10.1%) patients receiving LEV XR and one (1.3%) receiving placebo were free of POS during the 12-week treatment period. Forty-one (53.2%) LEV XR and 43 (54.4%) placebo patients reported ≥1 adverse event. Adverse events reported with an incidence >5% and seen more often with LEV XR than with placebo were somnolence, influenza, irritability, nasopharyngitis, dizziness, and nausea .
Discussion:   Once-daily LEV XR 1,000 mg was effective and well-tolerated as adjunct therapy in patients with POS. Ten percent of patients randomized to LEV XR experienced freedom from POS. These results support the clinical value of this new LEV XR formulation.     

Efficacy and acceptability of atypical antipsychotics for the treatment of post-traumatic stress disorder: A meta-analysis of randomized,double-blind,placebo-controlled clinical trials

As some evidences demonstrated that atypical antipsychotics (AA) may be efficacious in treating post-traumatic stress disorder (PTSD), we preformed a meta-analysis of randomized, double-blind, placebo-controlled clinical trials (RCTs) of AAs for the treatment of PTSD. Two hundred and fifty one papers were searched and screened. Eight RCTs met the inclusion criteria. AAs may be superior to placebo in the treatment of PTSD, as indicated by the changes in Clinician Administered PTSD Scale (CAPS) total scores (weighted mean differences (WMD)=−5.89, 95% confidence interval (CI) [−9.21, −2.56], P=0.0005) and also in CAPS subscale intrusion (WMD=−2.58, 95% CI[−3.83, −1.33], P<0.0001 ) and subscale hyperarousal (WMD=−2.94, 95% CI[−5.45, −0.43], P=0.02). The acceptability measured by dropout rates between AAs and placebo showed no statistical difference (OR=1.24, 95%CI [0.78, 1.97], P=0.36). PTSD symptom cluster, especially in intrusion and hyperarousal. However, we should be careful to generalize the conclusion because of the small number of included trails. We expect more RCTs will be done in the future so as to clarify the specific value of AAs for PTSD.     

A double-blind, placebo-controlled trial of adjunctive donepezil in treatment-resistant mania

INTRODUCTION: Because there is a high rate of partial response to standard thymoleptic medication, novel augmentation strategies for treatment-resistant bipolar disorder are needed. In an open trial, donepezil augmentation was associated with improvement in manic symptoms in 9 of 11 subjects. METHOD: We conducted a 6-week, double-blind, placebo-controlled trial of donepezil for treatment-resistant bipolar mania. Eligible subjects had a Young Mania Rating Scale (YMRS) score of at least 15 despite two or more weeks of proven therapeutic levels of lithium or valproate. Subjects who completed the trial were eligible for an 8-week open trial of donepezil. Subjects were started on donepezil 5 mg/day and were eligible for dose increase to 10 mg/day after 4 weeks. RESULTS: Twelve subjects were enrolled. Eleven subjects received at least 1 week of study medication and were included in the analysis. No subjects in the donepezil group (0/6) and 60% (3/5) in the placebo group met response criteria of >30% reduction in YMRS score (Fisher's Exact p = 0.061). YMRS scores were higher at trial endpoint in the donepezil group 20.17 (3.66) compared with the placebo group [11.20 (4.60), Z = -2.476, p = 0.01]. There were no differences at trial endpoint in Hamilton Rating Scale for Depression (HAM-D) or Brief Psychiatric Rating Scale (BPRS) scores in either the intent-to-treat or the completer analyses. CONCLUSIONS: Donepezil does not appear to be an effective adjunctive treatment for refractory manic symptoms. The strength of the conclusion of this trial is limited by the possibility of a false-negative result due to the small sample.     

艾司西酞普兰治疗抑郁症的随机双盲对照试验

目的比较艾司西酞普兰和西酞普兰治疗抑郁症的疗效和安全性。方法本研究为6周的多中心、随机、双盲双模拟、平行阳性对照试验。共入组240例符合中国精神障碍分类与诊断标准第3版的抑郁症诊断标准的患者,其中试验组（艾司西酞普兰）120例和对照组（西酞普兰）120例。试验组剂量为10～20mg/d,对照组剂量为20～40mg/d,评估量表为17项汉密尔顿抑郁量表（HAMD-17）,汉密尔顿焦虑量表（HAMA）以及临床总体印象量表（CGI）。安全性评估包括评估不良事件、体检、实验室检查和心电图检查等。结果 212例患者完成了研究,试验组108例,对照组104例。全分析集（FAS）结果显示：治疗6周后,试验组的HAMD减分为（15.4±7.1）分,对照组为（14.5±7.1）分;试验组的有效率为78.3%,临床痊愈率为57.5%,对照组分别为73.3%、52.5%;两组差异无统计学意义。两组治疗后HAMA评分均下降,组间差异无统计学意义。两组在各访视点CGI严重程度评分差异皆无统计学意义。治疗第2周时,试验组的有效率高于对照组（分别为22.5%,10.8%,χ^2=5.88,P=0.02）,临床痊愈率也高于对照组（分别为11.7%,2.5%,χ^2=7.66,P〈0.01）。试验组中有39例（32.5%）发生不良反应,对照组中有37例（30.8%）发生不良反应,两组差异无统计学意义。试验组常见的不良反应为恶心（12.5%）、口干（10.0%）、头晕（9.2%）,对照组为恶心（14.2%）、口干（7.5%）。结论艾司西酞普兰治疗抑郁与西酞普兰的疗效相当,耐受性好,起效可能更快。     

A double-blind randomized controlled trial to study the efficacy of topiramate in a civilian sample of PTSD

Objective: To evaluate the efficacy and tolerability of topiramate in patients with posttraumatic stress disorder (PTSD). Method: We conducted a 12‐week double‐blind, randomized, placebo‐controlled study comparing topiramate to placebo. Men and women aged 18–62 years with diagnosis of PTSD according to DSM‐IV were recruited from the outpatient clinic of the violence program of Federal University of São Paulo Hospital (Prove‐UNIFESP), São Paulo City, between April 2006 and December 2009. Subjects were assessed for the Clinician‐Administered Posttraumatic Stress Scale (CAPS), Clinical Global Impression, and Beck Depression Inventory (BDI). After 1‐week period of washout, 35 patients were randomized to either group. The primary outcome measure was the CAPS total score changes from baseline to the endpoint. Results: 82.35% of patients in the topiramate group exhibited improvements in PTSD symptoms. The efficacy analysis demonstrated that patients in the topiramate group exhibited significant improvements in reexperiencing symptoms: flashbacks, intrusive memories, and nightmares of the trauma (CAPS‐B; P= 0.04) and in avoidance/numbing symptoms associated with the trauma, social isolation, and emotional numbing (CAPS‐C; P= 0.0001). Furthermore, the experimental group demonstrated a significant difference in decrease in CAPS total score (topiramate −57.78; placebo −32.41; P= 0.0076). Mean topiramate dose was 102.94 mg/d. Topiramate was generally well tolerated. Conclusion: Topiramate was effective in improving reexperiencing and avoidance/numbing symptom clusters in patients with PTSD. This study supports the use of anticonvulsants for the improvement of symptoms of PTSD.     

Bipolar disorder comorbidity in patients with a primary diagnosis of OCD

Objective: Bipolar disorder (BD) is considered to be a common comorbid condition in subjects with obsessive-compulsive disorder (OCD), but there is limited literature on the prevalence of BD and its clinical correlates in those with a primary diagnosis of OCD.

Methods: We studied the prevalence of BD in a sample of consecutively registered outpatients attending a specialty OCD clinic in India over a period of 13 months. One hundred and seventy-one patients with a primary diagnosis of OCD were assessed systematically using structured and semi-structured instruments.

Results: The prevalence of lifetime BD in OCD was 4%. The OCD?+?BD group had an episodic course of OCD and higher rate of lifetime suicide attempts.

Conclusions: BD may not be as highly prevalent in OCD as reported in literature. Those with OCD seem to have only a marginally higher risk for developing BD than the general population. A diagnosis of BD seems to have a pathoplastic effect on the course of OCD. Patients with OCD-BD comorbidity have to be specifically assessed for suicide risk.