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丙戊酸盐用于治疗精神分裂症。

Valproate for schizophrenia.

作者信息

Schwarz Christian, Volz Anja, Li Chunbo, Leucht Stefan

机构信息

Psychiatry and Psychotherapy, Technische Universität München, Möhlstr. 28, Munich, Germany, 81675.

出版信息

Cochrane Database Syst Rev. 2008 Jul 16(3):CD004028. doi: 10.1002/14651858.CD004028.pub3.


DOI:10.1002/14651858.CD004028.pub3
PMID:18646098
Abstract

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used; valproate is one of these. OBJECTIVES: To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (last update February 2007). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted a pharmaceutical company and authors of relevant studies in order to identify further trials. SELECTION CRITERIA: We included all randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. Data were extracted independently by at least two reviewers. We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We analysed continuous data using weighted mean differences. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics. MAIN RESULTS: The update search identified two further relevant studies, thus the review currently includes seven studies with a total of 519 participants. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With one exception the studies were small, short-term and incompletely reported. Adding valproate was as acceptable as adding placebo to antipsychotic drugs (6 RCT, n=270, RR leaving the study early 1.7 CI 0.9 to 3.2). No significant effect of valproate as an adjunct to antipsychotic medication on the participants' global state or the general mental state at the endpoint was evident. However, one study showed a quicker onset of action in the combination group (Casey 2003). A single small study found the participants in the valproate group to be less aggressive than the control group (n=30, WMD -3.8, CI -5.1 to -2.5). Participants receiving valproate more frequently experienced sedation than those in the placebo group. In a single small study valproate significantly reduced tardive dyskinesia (n=30, WMD -3.3, CI -4.9 to -1.7). The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown. AUTHORS' CONCLUSIONS: Based on currently available randomised trial-derived evidence, there are no data to support or to refute valproate as a sole agent for schizophrenia. There is some evidence for positive effects on aggression and tardive dyskinesia, but given that these results were based on only a single small study they cannot be considered robust. Given the paucity of the available database further large, simple well-designed and reported trials are necessary. Ideally these would focus on people with schizophrenia and aggression, on those with treatment resistant forms of the disorder and on those with schizoaffective disorders.

摘要

背景:许多精神分裂症患者采用普通抗精神病药物治疗未能取得满意的治疗效果。在这些情况下,会使用各种附加药物;丙戊酸盐就是其中之一。 目的:综述丙戊酸盐治疗精神分裂症及类精神分裂症性精神病的疗效。 检索策略:我们检索了Cochrane精神分裂症研究组的注册库(最后更新时间为2007年2月)。该注册库通过对BIOSIS、CINAHL、学位论文摘要、EMBASE、LILACS、MEDLINE、PSYNDEX、PsycINFO、RUSSMED、Sociofile进行系统检索,并辅以对相关期刊和众多会议论文集的手工检索编制而成。我们还联系了一家制药公司和相关研究的作者,以确定更多试验。 入选标准:我们纳入了所有比较丙戊酸盐与抗精神病药物或安慰剂(或无干预)的随机对照试验,无论丙戊酸盐是作为单一药物还是作为抗精神病药物的辅助药物用于治疗精神分裂症和/或类精神分裂症性精神病。 数据收集与分析:我们独立检查文献引用,如有可能还检查摘要,订购论文并再次检查和进行质量评估。数据由至少两名审阅者独立提取。我们使用相对危险度(RR)和95%置信区间(CI)分析二分数据。我们使用加权均数差分析连续数据。在可能的情况下,我们计算了治疗所需人数(NNT)或伤害所需人数统计量。 主要结果:更新检索又发现了两项相关研究,因此本综述目前纳入了七项研究,共519名参与者。所有试验均考察了丙戊酸盐作为抗精神病药物辅助药物的有效性。除一项研究外,其他研究规模小、为期短且报告不完整。在抗精神病药物中添加丙戊酸盐与添加安慰剂一样可以接受(6项随机对照试验,n = 270,提前退出研究的RR为1.7,CI为0.9至3.2)。丙戊酸盐作为抗精神病药物的辅助药物,在终点时对参与者的整体状态或一般精神状态没有明显影响。然而,一项研究显示联合用药组起效更快(凯西,2003年)。一项小型研究发现丙戊酸盐组的参与者比对照组攻击性更低(n = 30,加权均数差为 -3.8,CI为 -5.1至 -2.5)。与安慰剂组相比,接受丙戊酸盐治疗的参与者更常出现镇静作用。在一项小型研究中,丙戊酸盐显著降低了迟发性运动障碍(n = 30,加权均数差为 -3.3,CI为 -4.9至 -1.7)。丙戊酸盐对重要亚组的影响,如患有精神分裂症且有攻击行为的患者或患有分裂情感性障碍的患者,尚不清楚。 作者结论:基于目前可得的随机试验证据,没有数据支持或反驳丙戊酸盐作为精神分裂症单一药物的使用。有一些证据表明其对攻击行为和迟发性运动障碍有积极作用,但鉴于这些结果仅基于一项小型研究,不能认为其可靠。鉴于现有数据库资料匮乏,有必要开展更多大规模、设计简单且报告完善的试验。理想情况下,这些试验应聚焦于患有精神分裂症且有攻击行为的患者、治疗抵抗型精神分裂症患者以及患有分裂情感性障碍的患者。

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