Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials

Aims

To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of anti-epileptic drugs (AEDs) for refractory epilepsy.

Methods

We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Group''s specialized register, MEDLINE (1950 to March 2009), EMBASE (1980 to March 2009), and Current Contents Connect (1998 to March 2009) to conduct a systematic review of published studies, developed a treatment network and undertook a network meta-analysis.

Results

Forty-three eligible trials with 6346 patients and 12 interventions, including placebo, contributed to the analysis. Only three direct drug comparator trials were identified, the remaining 40 trials being placebo-controlled. Conventional random-effects meta-analysis indicated all drugs were superior in efficacy to placebo (overall odds ratio (OR] 3.78, 95% CI 3.14, 4.55) but did not permit firm distinction between drugs on the basis of the efficacy or tolerability. A Bayesian network meta-analysis prioritized oxcarbazepine, topiramate and pregabalin on the basis of short term efficacy. However, sodium valproate, levetiracetam, gabapentin and vigabatrin were prioritized on the basis of short-term efficacy and tolerability, with the caveat that vigabatrin is recognized as being associated with serious visual disturbance with chronic use.

Conclusion

Of the wide range of AEDs licensed for the treatment of refractory epilepsy, sodium valproate, levetiracetam and gabapentin demonstrated the best balance of efficacy and tolerability. Until regulators mandate greater use of active comparator trials with longer term follow-up, network meta-analysis provides the only available means to quantify these clinically important parameters.     

The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs

A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research.     

Evaluation of health status in epilepsy using the EQ-5D questionnaire: a prospective,observational, 6-month study of adjunctive therapy with anti-epileptic drugs

ABSTRACT

Aims: The aims of this project were to evaluate the impact of adjunctive treatment with an anti-epileptic drug (AED) on the health status of people with epilepsy and to investigate how seizure frequency affects their health status.

Methods: Adult epilepsy patients, refractory to current treatment, were included in this prospective observational study. Patients commencing adjunctive therapy with one of five AEDs (topiramate, lamotrigine, gabapentin, clobazam, vigabatrin) were eligible for inclusion. The study took place at the outpatient clinics of the National Hospital for Neurology and Neurosurgery, Queen Square, London. Patients completed the EQ-5D, a generic health status measure, at baseline and again after 3 and 6 months. Information was also collected on medications and seizure frequency.

Results: In total, 125 patients entered the study and were followed up for 6 months. Patients treated with topiramate had a significant increase (?p < 0.05) in EQ-5D score from baseline, indicating an improvement in their health status whereas scores for lamotrigine, clobazam and gabapentin all showed a non-significant decline. When the data were analysed according to seizure frequency, only patients who became seizure-free on adjunctive treatment had a significant increase in their health status. The group who had a 50% reduction in seizure frequency did not have increased health status.

Conclusions: In summary, adjunctive treatment with topiramate significantly increased health status as measured by the EQ-5D. These data also suggest that achievement of seizure-freedom is the key to improving health status in this patient group.     

Recent advances in the pharmacotherapy of epilepsy: brivaracetam and perampanel as broad-spectrum antiseizure drugs for the treatment of epilepsies and status epilepticus

ABSTRACT

Introduction: Antiseizure drugs (ASDs) play a central and crucial role in the treatment of epilepsy patients, as the majority require anticonvulsant treatment for an extended period of time. Since up to 30% of patients are refractory to medical treatment, new therapeutic options are necessary. Perampanel (PER) and brivaracetam (BRV) are the latest approved ASDs that may be considered in a variety of epilepsy syndromes. PER has a distinct and selective mode of action on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and is licensed for use in focal and generalized epilepsies. BRV is a derivative of levetiracetam but exhibits a 20-fold higher affinity and a faster brain entry time as a synaptic vesicle glycoprotein 2A (SV2A) ligand.

Areas covered: This article reviews the advances in the epileptic treatment and provides a comparison of PER and BRV. Both drugs have shown comparable results in randomized controlled trials, and both are well tolerated.

Expert opinion: PER and BRV have the potential to perform as important, broad-spectrum ASDs with significant market shares. BRV’s intravenous formulation and fast penetration into the brain and PER’s unique mode of action will result in the more frequent use of both drugs in status epilepticus.     

抗癫痫药物及其他危险因素对妊娠癫痫妇女及胎儿的影响

目的 对抗癫痫药物及其他危险因素对妊娠癫痫妇女及胎儿的影响进行前瞻性研究。方法 （1）癫痫妇女孕早期或妊娠前咨询入组。（2）孕期主要观察指标：对高危患者进行检查,包括血浆中AFP的水平、染色体检查、羊水穿刺细胞学及分子生物学检查、分子遗传分析、B超等。（3）畸形的确认：根据国际疾病控制中心编写的严重先天性缺陷一览表（1998年修订）。（4）危险因素分析：妊娠年龄、畸形的家族史、吸烟、饮酒、单用或联用抗癫痫药物、抗癫痫药物剂量、癫痫的分型、妊娠前3月内癫痫发作频率等。结果 共入组57例妊娠癫痫妇女,共有41例 妊娠癫痫妇女顺利生产,其中29例患者生产并随访1年或以上,其他 12例患者生产后随访不足1年,仅有一例新生儿死亡且无明显先天性畸形 （占2.44%）,其他的新生儿均无先天性畸形。这些已生产的妊娠癫痫妇女在怀孕期间服用较低剂量的抗癫痫药物,卡马西平用量200～700mg/d,丙戊酸钠250～750 mg/d,托吡酯37.5～150 mg/d,奥卡西平450 mg/d,拉莫三嗪62.5～150 mg/d,氯硝安定2～4 mg/d。新生儿死亡的孕妇服用卡马西平300 mg/d。结论 本组妊娠癫痫妇女按照癫痫发作类型和癫痫综合征类型服用较低剂量的抗癫痫药物,并在专科医师的指导下和长期随访情况下用药,没有出现先天性畸型新生儿。这一方面可能是在专科医师指导下使用致畸性小的抗癫痫药物的结果,亦有可能是观察病例数不够多的原因,提示该项目研究应该持续进行。     

Sedative drugs used for mechanically ventilated patients in intensive care units: a systematic review and network meta-analysis

Background: The effects of different sedative drugs on all-cause mortality rate, duration of ICU stay, and risk of delirium in mechanically ventilated ICU patients are unclear. This meta-analysis aimed to compare the effectiveness and safety of individual sedative drugs and drug combinations in mechanically ventilated ICU patients.

Materials and methods: Medline, Embase, Cochrane, EBSCOhost, and ISI Web of Science databases were searched for studies that assessed sedation in ICU mechanically ventilated patients. A Bayesian random-effects model was used to combine the direct comparisons and indirect evidence.

Results: Thirty-one randomized, controlled trials were included, which consisted of 4491 patients who received one of seven sedative drugs or a combination of drugs. There were no significant differences regarding the all-cause mortality rate. Compared to propofol, inhalation anesthetics (hazard ratio [HR] 0.121; 95% credible interval [CrI] -7.58 to 7.62), alpha agonists (HR 2.2; 95% CrI 0.776 to 5.22), propofol with benzodiazepines (HR 0.306; 95% CrI -6.97 to 7.65), ketamine with benzodiazepines (HR 6.57; 95% CrI -6.05 to 19.1) and placebo (HR 2.4; 95% CrI -5.37 to 10.3), benzodiazepines (HR 3.62; 95% CrI 0.834 to 6.2) may increase the duration of ICU stay. Compared to alpha agonists, propofol (HR 2.4; 95% CrI 0.304 to 21.1) and placebo (HR 6.12; 95% CrI 0.745 to 54.6), benzodiazepines (HR 2.59; 95% CrI 1.08 to 7.4) were associated with incremental risks of delirium.

Conclusion: Compared to propofol, benzodiazepines may increase the duration of ICU stay. Compared to alpha agonists, benzodiazepines were associated with an increased risk of delirium.     

The PlA1/A2 polymorphism of glycoprotein IIIa in relation to efficacy of antiplatelet drugs: a systematic review and meta-analysis

Aim

The PlA1/A2 polymorphism of glycoprotein IIIa (GPIIIa) has been associated with both antiplatelet drug resistance and increased cardiovascular events. The aim of this study was to conduct the first meta-analysis investigating the association between carriage of the PlA2 allele and resistance to currently licensed antiplatelet drugs.

Methods

Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where antiplatelet resistance was measured using validated techniques, pooled odds ratios (ORs) were calculated using fixed effects and random effects models.

Results

Sixteen studies were eligible for statistical analysis and included 1650 PlA1 homozygous subjects and 668 carriers of the PlA2 allele. For carriers of the PlA2 allele, OR 0.924 (n = 2318; 95% CI 0.743, 1.151; P = 0.481) was observed for resistance to any antiplatelet drug, OR 0.862 (n = 2085; 95% CI 0.685, 1.086; P = 0.208) for resistance to aspirin and OR 1.429 (n = 233; 95% CI 0.791, 2.582; P = 0.237) for resistance to clopidogrel. In the aspirin cohort, sub-group analysis revealed no statistical association in either healthy subjects or those with cardiovascular disease. PlA2 carriage was marginally associated with aspirin sensitivity using the fixed effects model when identified by the PFA-100 assay (n = 1151; OR 0.743, 95% CI 0.558, 0.989; P = 0.041) but with significant heterogeneity (I² = 55%; P = 0.002). Significance was lost with analysis using a random effects model.

Conclusions

The totality of published data does not support an association between carriage of the PlA2 allele and antiplatelet drug resistance. Significant heterogeneity indicates the need for larger studies using validated and standardized assays.     

Pregabalin or placebo used adjunctively with levetiracetam in refractory partial-onset epilepsy: a post hoc efficacy and safety analysis in combined clinical trials

Abstract

Objective:

Some patients with epilepsy require treatment with >1 adjunctive antiepileptic drug (AED) to achieve adequate seizure remission. The purpose of this analysis was to evaluate the efficacy and safety of adding adjunctive pregabalin to an AED regimen that included levetiracetam in patients with refractory partial-onset epilepsy.     

Safety profile of two novel antiepileptic agents approved for the treatment of refractory partial seizures: ezogabine (retigabine) and perampanel

Introduction: Complex-partial seizures are frequently resistant to antiepileptic therapy. Two new medications with mechanisms of action novel within the antiepileptic class have recently received approval for the adjunctive treatment of partial (focal) seizures.

Areas covered: A Medline search was conducted to identify preclinical and clinical studies of ezogabine and perampanel. This was supplemented with additional articles obtained from online sources and information provided by the FDA and the manufacturers. The focus of this review is on the safety profiles of ezogabine (retigabine), a novel antiepileptic that targets voltage-gated potassium channels, and perampanel, a noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamate receptor antagonist.

Expert opinion: Central nervous system effects are predominant within the adverse event profiles of both ezogabine and perampanel. In addition, ezogabine exerts its inhibitory effects on potassium channels in the urogenital tract potentially resulting in urinary retention and related outcomes. Recent reports of blue discoloration of the skin and in the retinas of long-term ezogabine users have surfaced. Both drugs have demonstrated the ability to induce neuropsychiatric symptoms. Though both are welcome additions to the antiepileptic drug class, additional monitoring, appropriate counseling, and careful selection of patients are warranted to minimize adverse events.     

奥卡西平添加治疗成人难治性癫痫部分性发作的疗效分析

目的：探讨临床采用奥卡西平添加对于成人难治性癫痫部分性发作患者的治疗效果以及安全性。方法选择2009年2月到2012年6月期间收治的76例难治性癫痫部分发作患者作为研究对象,患者保持以往抗癫痫药物不变,在此基础上加用奥卡西平进行治疗,观察期为1年,采用自身对照开放性研究,观察该治疗方案的治疗效果、保留率、不良反应发生情况以及安全性。结果69例患者经过12月随访,保留率为90．79％,治疗总有效率为44．93％（31例）,与治疗前比较,总发生频率降低42．11％（χ2＝36．810, P＝0．000）,单纯部分发作癫痫（SPS）发生减少42．32％（χ2＝7．864,P＝0．046）,复杂性部分发作癫痫（CPS）发生减少39．67％（χ2＝7．872,P＝0．047）,部分性发作继全面性发作癫痫（SGS）发生减少41．96％（χ2＝7.869,P＝0．047）,其中34例（49．28％）患者出现嗜睡5例（14．71％）、眩晕3例（8．82％）、头痛13例（38.26％）、恶心6例（17．65％）、注意力不集中2例（5．88％）、疲乏5例（14．71％）等不良反应,均出现在加量期,均为轻中度,不进行特殊的临床处理,停药后自行缓解或者消退。结论奥卡西平对于成人难治性癫痫部分发作治疗效果显著,安全性、耐受性较好,值得在临床上广泛的推广和应用。     

Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis

Objective: Major depressive disorder (MDD) affects about 10–15% of the general population in a lifetime. A considerable number of patients fail to achieve full symptom remission despite adequate treatment and are considered treatment resistant (TRD). The current study compared the relative efficacy and tolerability of pharmacological and somatic TRD interventions by means of a Bayesian network meta-analysis.

Research design and methods: An electronic literature search of MEDLINE, MEDLINE In-Process, EMBASE, PsycInfo, EconLit and Cochrane Library databases for trials published between September 2003 and September 2014 was conducted. Key outcomes extracted were disease severity change from baseline, response and remission rates at various timepoints and discontinuation due to adverse events.

Results: Of the 3876 abstracts identified, 31 publications/randomised controlled trials (RCTs) were included in the analysis; 19 RCTs investigating 13 pharmacological interventions and 12 RCTs investigating electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS). The evidence synthesis investigating efficacy outcomes of TRD treatments demonstrated superior efficacy for ketamine compared to pharmacological and somatic interventions at 2 weeks after treatment initiation. At 4, 6 and 8 weeks, quetiapine augmentation (800?mg/day) and risperidone augmentation were found to be the first and second best treatments, respectively. Networks were small for response rate and remission rate outcomes at most timepoints. The most tolerable treatment was lamotrigine augmentation showing a comparable profile to placebo/sham.

Conclusions: This analysis revealed scarcity of long-term data on sustained remission that would allow a comparative long-term efficacy assessment. Key limitations of the analysis can be considered the search timeframe and the use of mapping formula for the depression scores.     

Efficacy and tolerability of milnacipran in the treatment of major depression in comparison with other antidepressants : a systematic review and meta-analysis

BACKGROUND: Milnacipran, a dual serotonin-noradrenaline reuptake inhibitor, is one of the newer antidepressants that clinicians use for the routine care of patients with major depression. We undertook a systematic review and meta-analysis of randomized controlled trials that compared the efficacy and tolerability of milnacipran with other antidepressants. OBJECTIVE: To assess the efficacy and tolerability of milnacipran in comparison with TCAs, SSRIs and other drugs in the acute phase of treatment for major depression. METHODS: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials registers, journals, conference proceedings, trial databases of the drug-approving agencies and ongoing clinical trial registers for all published and unpublished randomized controlled trials that compared the efficacy and adverse events of milnacipran versus any other antidepressant. The search was conducted in December 2006 and updated in May 2007. No language restrictions were applied. All relevant authors were contacted to supplement any incomplete reporting in the original papers. Randomized controlled trials comparing milnacipran with any other active antidepressants as monotherapy in the acute phase of treatment for major depression were selected. Participants were aged > or =18 years, of both sexes and with a primary diagnosis of unipolar major depression. Studies were excluded when the participants had specific psychiatric and medical co-morbidities.Two independent reviewers assessed the quality of trials for inclusion, and subsequently extracted data. Disagreements were resolved by consensus. Meta-analyses were conducted for efficacy and tolerability outcomes. Sixteen randomized controlled trials (n = 2277) were included in the meta-analyses. RESULTS: No differences were found in achieving clinical improvement, remission or overall tolerability when comparing milnacipran with other antidepressants. However, compared with the TCAs, fewer patients taking milnacipran were early treatment withdrawals due to adverse events (number needed to harm (NNH) = 15; 95% CI 10, 48). Significantly more patients taking TCAs experienced adverse events compared with milnacipran (NNH = 4; 95% CI 3, 7). CONCLUSIONS: The overall effectiveness and tolerability of milnacipran versus other antidepressants does not seem to differ in the acute phase of treatment for major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of premature withdrawal due to adverse events and the rates of patients experiencing adverse events. Milnacipran may benefit some patient populations who experience adverse effects from other antidepressants in the acute phase of treatment for major depression.     

The efficacy and safety of brivaracetam at different doses for partial-onset epilepsy: a meta-analysis of placebo-controlled studies

Objective: This meta-analysis systematically assessed the efficacy and safety of different doses of brivaracetam (BRV) compared with placebo as adjunctive therapy for adults with partial-onset epilepsy.

Methods: Electronic and clinical trials databases were searched for randomized controlled trials of BRV published up to May 2015. We assessed the risk of bias of the included studies using the Cochrane Risk of Bias tool. The outcomes of interest included 50% responder rates, seizure freedom, the incidence of withdrawal and treatment-emergent adverse events (TEAEs).

Results: Five trials met the inclusion criteria. Compared with placebo, 20, 50, 100 and 150 mg/day BRV was associated with significantly higher 50% responder rates. In addition, the effect of 50 mg BRV on seizure freedom was significantly different than that of placebo. Both fatigue and nasopharyngitis were significantly associated with 20 mg BRV, whereas fatigue and irritability were associated with 50 mg BRV. Somnolence was associated with 150 mg BRV. No significant differences were observed for the other common TEAEs.

Conclusion: The use of BRV at doses > 5 mg/day resulted in statistically significant reduction in seizure frequency in respect to the 50% responder rate. BRV was reasonably tolerated by patients. These findings warrant confirmation in future studies.     

在老年患者中精简神经系统用药疗效与安全性的系统评价与Meta分析

目的：评价神经系统用药处方精简在老年患者中的疗效与安全性。方法：采用Cochrane系统评价方法,以"神经类药物"、"处方精简"和"老年患者"为检索词,检索Cochrane Library、PubMed、EbscoHost、MEDLINE、Scopus、Web of Science、EMBASE and ProQuest数据库,对符合纳入标准的随机对照试验（RCT）进行质量评价并按设计要求提取有效信息并进行Meta分析。结果：研究共纳入20项RCT,共纳入患者3 509例,质量为高、中、低者分别为6、5、9篇。Meta分析结果显示：针对神经类药物的处方精简可以降低跌倒发生率（OR 0.45,95% CI 0.28~0.74,P=0.002）,对死亡率（OR 0.82,95% CI 0.44~1.53,P=0.53）、住院率（OR 0.42,95% CI 0.14~1.28,P=0.13）及不良反应（OR 1.18,95% CI 0.89~1.57,P=0.24）影响差异无统计学意义。亚组分析显示,神经类药物的处方精简明显降低了65岁至79岁患者跌倒风险（OR 0.44,95% CI 0.27~0.74,P=0.002）,有效降低了认知功能正常患者的跌倒风险（OR 0.07,95% CI 0.02~0.21,P<0.000 01）,采用直接精简神经类药物的干预方式能够有效降低患者的跌倒风险（OR 0.16,95% CI 0.07~0.37,P<0.000 1）。结论：神经类药物的处方精简在老年患者中应用可以减少跌倒发生率。     

Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis

OBJECTIVES: To compare the clinical effectiveness of zaleplon, zolpidem or zopiclone (Z-drugs) with either benzodiazepines licensed and approved for use in the UK for the short-term management of insomnia (diazepam, loprazolam, lorazepam, lormetazepam, nitrazepam, temazepam) or with each other. METHODS: MEDLINE, EMBASE, PsycINFO, Science Citation Index/Web of Science were searched from 1966 to March 2003 and The Cochrane Library, reference lists of included studies and a number of psychopharmacology journals. Randomized controlled trials comparing either benzodiazepines with the Z-drugs or any two of the Z-drugs in patients with insomnia were included. Outcome measures included: sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia and daytime alertness. RESULTS AND CONCLUSIONS: Twenty four eligible studies were identified with a total study population of 3,909 (17 studies comparing a Z-drug with a benzodiazepine and 7 comparing a Z-drug). Insufficient or inappropriately reported data meant that meta-analysis was possible only for a small number of outcomes. There are few clear, consistent differences between the drugs. Some evidence suggests that zaleplon gives shorter sleep latency but shorter duration of sleep than zolpidem, reflecting the pharmacological profiles of the drugs.     

分子靶向药物治疗难治性甲状腺癌的疗效及安全性的meta分析

目的　对分子靶向药物治疗难治性甲状腺癌的疗效及安全性进行meta分析,为临床应用提供有价值的循证医学证据。方法　检索PubMed、Embase、the Cochrane Library、Web of Science、中国知网、万方数据知识服务平台以及中国生物医学文献服务系统从建库到2022年4月13日关于甲状腺癌分子靶向治疗的文献,筛选文献提取数据,评价纳入研究的偏倚风险,采用RevMan5.4软件进行meta分析。结果　共纳入8项研究,试验组（分子靶向药物）样本量为1 201例,对照组（安慰剂）样本量为748例。meta分析结果显示,相比于安慰剂,分子靶向药物有更佳的客观缓解率（objective response rate,ORR）（RR=14.19,95%CI 4.12～48.93,P<0.000 1）以及疾病控制率（disease control rate,DCR）（RR=1.40,95%CI 1.20～1.63,P<0.000 1）,并且明显提高了难治性甲状腺癌患者的无进展生存期（progression-free survival,PFS）（HR=0.35,95%CI 0.25～0.51,P<0.000 01）。试验组≥3级不良事件（adverse events,AEs）发生率高于对照组（RR=3.85,95%CI 2.90～7.10,P<0.000 1）,主要为腹泻、高血压、疲劳、手足综合征、食欲下降以及体质量下降。结论　分子靶向药物具有良好的疗效,并且通过调整剂量和给予支持治疗可使大部分AEs得以控制。因此,分子靶向药物可成为治疗难治性甲状腺癌新的选择。                         

Chlorpromazine versus every other antipsychotic for schizophrenia: A systematic review and meta-analysis challenging the dogma of equal efficacy of antipsychotic drugs

It is one of the major psychiatric dogmas that the efficacy of all antipsychotic drugs is same. This statement originated from old, narrative reviews on first-generation antipsychotics, but this old literature has never been meta-analysed. We therefore conducted a meta-analysis of randomised controlled trials on the efficacy of chlorpromazine versus any other antipsychotic in the treatment of schizophrenia. If the benchmark drug chlorpromazine were significantly more or less effective than other antipsychotics, the notion of equal efficacy would have to be rejected. We searched the Cochrane Schizophrenia Group׳s specialized register, MEDLINE, EMBASE, PsychInfo and reference lists of relevant articles. The primary outcome was response to treatment. We also analyzed mean values of schizophrenia rating scales at endpoint and drop-out rates. 128, mostly small, RCTs with 10667 participants were included. Chlorpromazine was compared with 43 other antipsychotics and was more efficacious than four (butaperazine, mepazine, oxypertine and reserpine) and less efficacious than other four antipsychotics (clomacran, clozapine, olanzapine and zotepine) in the primary outcome. There were no statistically significant efficacy differences between chlorpromazine and the remaining 28 antipsychotics. The most important finding was that, due to low numbers of participants (median 50, range 8–692), most comparisons were underpowered. Thus we infer that the old antipsychotic drug literature was inconclusive and the claim for equal efficacy of antipsychotics was never evidence-based. Recent meta-analyses on second-generation antipsychotics were in a better position to address this question and small, but consistent differences between drugs were found.     

托吡酯加用传统抗癫痫药治疗难治性癫痫部分性发作16例

目的：观察托吡酯加用传统抗癫痫药对难治性癫痫部分发作治疗的临床疗效和耐受性。方法：对16例难治性部分性发作患者加用托吡酯进行治疗,25mg/d为起始剂量,每周增加25mg,至200mg/d维持治疗,观察加用治疗前后癫痫发作频率的改变和耐受性。结果：观察24周后7例（43．8％）发作频率减少≥50％,其中3例（18．8％）停止发作,2例（12．5％）发作频率减少26％－49％,5例发作频率减少≤25％,1例发作频率明显增加,1例观察12周后失访。结论：托吡酯作为具有多重作用机制的抗癫痫新药,加用治疗难治性癫痫部分性发作的总有效率为56．3％（9／16）,无明显的必须停药的不良反应,耐受性良好。