Amisulpride for schizophrenia

 

Abstract

Background

The treatment of schizophrenia with old, 'typical' antipsychotic drugs such as haloperidol can be problematic, because many people treated with these drugs will suffer from movement disorders. Amisulpride is said to be an "atypical" antipsychotic which induces less movement disorder and which is effective for the negative symptoms of schizophrenia.

Objectives

To evaluate the effects of amisulpride as compared with placebo, typical and atypical antipsychotic drugs for schizophrenia.

Search methods

The authors carried out electronic searches of Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4, 1999), Cochrane Schizophrenia Group's Register (November 2000), EMBASE (1980-1999), LILACS(1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). They checked all identified studies for further trial citations, and sought these studies in the Science Citation Index. They also contacted authors of trials and the manufacturer of amisulpride.

Selection criteria

All randomised controlled trials comparing amisulpride to placebo, typical or atypical antipsychotic drugs for schizophrenia or other non-affective serious mental illnesses.

Data collection and analysis

Data were independently extracted and analysed on an intention-to-treat basis. The relative risk (RR) and 95% confidence intervals (CI) of dichotomous data were calculated using a random effects model, and, where possible, the number needed to treat was calculated. Weighted mean differences (WMD) were calculated for continuous data.

Main results

This review currently includes 19 randomised studies with a total of 2443 participants. Most trials were of short duration. Data from 4 trials with 514 participants with predominantly negative symptoms suggest that low-dose (up to 300mg/day) amisulpride was a more acceptable treatment than placebo (n=514, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 3 to 7), the improvement of the participants' global state (n=242, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 2 to 6) and the treatment of negative symptoms (n=177, WMD -10.1 CI -16.6 to -3.5). Amisulpride was shown to be more likely to cause extrapyramidal symptoms than placebo in two studies (n=269, RR 2.2 CI 1.2 to 4.2), but this result did not hold calculating the risk reduction so that an NNT-statistic could not be indicated.

Compared to typical antipsychotics, the pooled results of a total of fourteen trials suggest that amisulpride was more effective in improving global state (n=651, RR 0.7 CI 0.5 to 0.9, NNT 6 CI 4 to 11), the general mental state (n=695, WMD -4.2 CI -6.5 to -1.9) and the negative symptoms of schizophrenia (n=506, WMD -2.8 CI -4.3 to -1.3). Regarding positive symptoms, amisulpride was as effective as typical antipsychotics. Amisulpride was less prone to cause at least one general adverse event (n=751, RR 0.9 CI 0.8 to 0.97, NNH 9 CI 6 to 18), one extrapyramidal symptom (n=771, RR 0.7 CI 0.6 to 0.9, NNH 5 CI 4 to 9) or to require the use of antiparkinson medication (n=851, RR 0.6 CI 0.5 to 0.8, NNH 4 CI 3 to 6). No clear differences in other adverse events compared to typical drugs were found. Amisulpride also seemed to be more acceptable than conventional drugs as measured by the outcome 'leaving the studies early' (n=1512, RR 0.8 CI 0.7 to 0.9, NNT 16 CI 9 to 69) than conventional drugs, but this result might have been overestimated due to a publication bias which could not be excluded with certainty.

A single trial compared amisulpride to another 'atypical' antipsychotic, risperidone. With the exception of agitation, which was more frequent in the amisulpride group (n=228, RR 3.4 CI 1.2 to 10.1, NNH 11 CI 6 to 50) no significant differences were recorded on efficacy or acceptability.

Authors' conclusions

This systematic review confirms that amisulpride is an effective 'atypical' antipsychotic drug for those with schizophrenia. Amisulpride may offer a good general profile, at least compared to high-potency 'typical' antipsychotics. It may also yield better results in some specific outcomes related to efficacy, such as improvement of global state and general negative symptoms. It might be more acceptable and more tolerable than high-potency conventional antipsychotics, especially regarding extrapyramidal side-effects.

Longer term randomised trials are needed to evaluate the comparative value of amisulpride, particularly compared to other expensive atypical antipsychotics. These should focus on important outcomes which have not been sufficiently monitored such as service use, family burden and quality of life.

 

Plain language summary

Amisulpride for schizophrenia

Amisulpride is a new antipsychotic compound. This review suggests that it is more effective than a placebo for the treatment of schizophrenia. Amisulpride also has some advantages for the treatment of the general and negative symptoms of schizophrenia, and it is associated with less movement disorder than high-potency conventional drugs. In terms of other side-effects, no relevant differences were found.

 

摘要

背景

Amisulpride使用於精神分裂症患者

使用老的"典型"的抗精神病藥物治療精神分裂症，如haloperidol可能會發生問題，因為許多使用這些藥物治療的人會產生運動障礙症(movement disorders)。Amisulpride被認為是一種"非典型的抗精神病藥物，較少引起運動障礙症，而且對於精神分裂症的負向症狀是有療效的

目標

比較Amisulpride與安慰劑、典型及非典型抗精神病藥物治療精神分裂的療效

搜尋策略

作者們進行電子搜索Biological Abstracts(1982年 – 1999年)、CINAHL(1982年 – 1999年)、Cochrane Library(第4期，1999年)、Cochrane Schizophrenia Group's Register(2000年11月)、EMBASE(1980年 – 1999年)、LILACS(1982年 – 1999年)、MEDLINE (1966年 – 1999年)和PsycLIT(1974年 – 1999年)。他們檢查所有相關研究的引文是否有其他的試驗資料，並聯繫作者和amisulpride的製造商

選擇標準

所有的隨機對照試驗，比較amisulpride與安慰劑或典型/非典型抗精神病藥物,治療精神分裂症或其他非情感性的嚴重精神疾病

資料收集與分析

獨立提取資料,並以意圖治療病人為分析基礎。使用隨機效應模型計算二元資料的相對危險度(RR)和95％CI，並在可能的情況計算益一需治數。連續資料則計算其加權平均差(WMD)

主要結論

本回顧目前包括19個隨機試驗,總共有2443名受試者。大多數試驗都是短期的，4個試驗中共514參與者都是以負向症狀為主,結果顯示:與安慰劑相比,低劑量(每日300毫克以下)amisulpride是可接受的治療選擇(n = 514, RR0.6, CI0.5 – 0.8,益一需治數為3 – 7),受試者的"整體狀態"改善(n = 242, RR0.6, CI0.5至0.8,益一需治數為3, CI2 – 6)和負向症狀的治療(n = 177,加權平均差 −10. CI −16.6到 −3.5).兩個研究呈現Amisulpride 比安慰劑容易引起錐體外徑症狀(n = 269, RR2.2, CI 1.2 −4.2),但是這一結果沒有計算減少的風險,無法得到其益一需治數.與典型抗精神病藥物相比,匯整14個試驗資料後顯示, amisulpride能更有效地改善整體狀態(n = 651, RR0.7, CI0.5 – 0.9,益一需治數6, CI4 – 11),一般精神狀態(n = 695,加權平均差 −4.2, CI −6.5 – 1.9)和精神分裂症的負向症狀(n = 506,加權平均差 −2.8, CI −4.3 – 1.3)。關於正向的症狀, Amisulpride與典型抗精神病藥物的療效相當。Amisulpride較不容易造成一項以上的全身性副作用(n = 751, RR0.9, CI0.8 0.97,害一需治數為9, CI6 – 18),1項錐體外徑症狀(n = 771, RR0.7, CI0.6 – 0.9,害一需治數為5, CI4 – 9)或需使用抗巴金森氏症(antiparkinson)藥物(n = 851, RR0.6, CI0.5 – 0.8,害一需治數為4, CI3 – 6)。與其他的典型藥物相比, 其他的不良反應沒有明顯的差別。由其‘提早離開研究’變項顯示, Amisulpride也似乎比傳統藥物更容易被接受(n = 1512, RR0.8, CI0.7 – 0.9,益一需治數為16, CI9 – 69),但這一結果可能由於出版偏差而被高估,不能確定排除出版偏差。一個單一試驗比較 Amisulpride與另一個‘非典型’藥物, risperidone。除激動情緒較常發生於 Amisulpride組(n = 228, RR3.4, CI1.2 – 10.1,害一需治數為11, CI6 – 50個)以外,其他的療效和接受度都無顯著差異

作者結論

本系統性回顧證實, Amisulpride是一種對精神分裂症有療效的‘非典型’抗精神病藥物。使用Amisulpride後一般狀況良好,至少與高強度的‘典型’抗精神病藥物相似。在某些療效指標方面, Amisulpride可能表現更好,如改善整體狀況和一般的負向症狀。比起高強度傳統抗精神病藥物, Amisulpride的接受度和耐受度更高,特別是關於錐體外徑副作用。需要較長期的隨機試驗來評估Amisulpride的相對價值,特別應與其他昂貴的非典型抗精神病藥物相比較。這些研究應著重於重要且尚未得到充分監測的結果變項,例如使用的醫療服務、家庭負擔和生活品質

翻譯人

本摘要由成功大學附設醫院尹子真翻譯

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌

總結

Amisulpride是一種新的抗精神病藥物。本回顧顯示,使用於治療精神分裂症時，比安慰劑有療效。 治療一般和負向精神分裂症症狀方面,使用Amisulpride也有一些好處,而且與運動障礙少於高強度傳統藥物。在其他副作用方面,則沒有發現相關差異