Ziprasidone versus other atypical antipsychotics for schizophrenia

 

Abstract

Background

In many countries of the industrialised world second generation ('atypical') antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various new generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of ziprasidone differs from that of other second generation antipsychotics.

Objectives

To evaluate the effects of ziprasidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.

Search methods

We searched the Cochrane Schizophrenia Group Specialised Register (April 2007) and references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information.

Selection criteria

We included all randomised, at least single-blind, controlled trials comparing oral ziprasidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone or zotepine in people with schizophrenia or schizophrenia-like psychoses.

Data collection and analysis

We extracted data independently. For continuous data, we calculated weighted mean differences (MD) for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate.

Main results

The review currently includes nine randomised controlled trials (RCTs) with 3361 participants. The overall rate of premature study discontinuation was very high (59.1%). Data for the comparisons of ziprasidone with amisulpride, clozapine, olanzapine, quetiapine and risperidone were available. Ziprasidone was a less acceptable treatment than olanzapine (leaving the studies early for any reason: 5 RCTs, n=1937, RR 1.26 CI 1.18 to 1.35, NNH 7 CI 5 to 10) and risperidone (3 RCTs, n=1029, RR 1.11 CI 1.02 to 1.20, NNH 14 CI 8 to 50), but not than the other second generation antipsychotic drugs. Ziprasidone was less efficacious than amisulpride (leaving the study early due to inefficacy: 1 RCT, n=123, RR 4.72 CI 1.06 to 20.98, NNH 8 CI 5 to 50) olanzapine (PANSS total score: 4 RCTs, n=1291, MD 8.32 CI 5.64 to 10.99) and risperidone (PANSS total score: 3 RCTs, n=1016, MD 3.91 CI 0.27 to 7.55). Based on limited data there were no significant differences in tolerability between ziprasidone and amisulpride or clozapine. Ziprasidone produced less weight gain than olanzapine (5 RCTs, n=1659, MD -3.82 CI -4.69 to -2.96), quetiapine (2 RCTs, n=754, RR 0.45 CI 0.28 to 0.74) or risperidone (3 RCTs, n=1063, RR 0.49 CI 0.33 to 0.74). It was associated with less cholesterol increase than olanzapine, quetiapine and risperidone. Conversely ziprasidone produced slightly more extrapyramidal side-effects than olanzapine (4 RCTs, n=1732, RR 1.43 CI 1.03 to 1.99, NNH not estimable) and more prolactin increase than quetiapine (2 RCTs, n=754, MD 4.77 CI 1.37 to 8.16), but less movement disorders (2 RCTs, n=822, RR 0.70 CI 0.51 to 0.97, NNT not estimable) and less prolactin increase (2 RCTs, n=767, MD -21.97 CI -27.34 to -16.60) than risperidone.

Authors' conclusions

Ziprasidone may be a slightly less efficacious antipsychotic drug than amisulpride, olanzapine and risperidone. Its main advantage is the low propensity to induce weight gain and associated adverse effects. However, the high overall rate of participants leaving the studies early limits the validity of any findings.

 

Plain language summary

Ziprasidone versus other atypical antipsychotics for schizophrenia

Ziprasidone is one of a group of new 'atypical' antipsychotics used for treating schizophrenia. This review wanted to find out if there was evidence to support that there is any difference between ziprasidone and the other atypical medications. Because of the large number of people that dropped out of the studies it is difficult to draw any firm conclusions, however, people taking ziprasidone did not do as well regarding their symptoms, as those taking olanzapine and risperidone and perhaps amisulpride, but they were less likely to gain weight.

 

摘要

背景

比較Ziprasidone 與其他非典型抗精神用藥對精神分裂症的療效

在許多工業化國家，第二代抗精神用藥已成為治療精神分裂症患者的第一選擇。問題是不同第二代抗精神用藥的效果究竟有多少差異仍是個爭議。在此篇文獻回顧，我們檢驗了ziprasidone與其他第二代抗精神用藥的效用與耐受性有何差異。

目標

比較ziprasidone與其他第二代抗精神用藥對治療精神分裂症及類似精神分裂症的精神病的效果。

搜尋策略

我們搜尋了Cochrane Schizophrenia Group Trials Register (2007年4月),檢視所有研究的參考文獻。與藥廠、試驗作者接觸，以得到額外資訊。

選擇標準

我們納入所有“比較口服的ziprasidone與其他口服劑型的amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, 或 zotepine在治療精神分裂症患者或似精神分裂症的精神病患者的療效” 之隨機對照試驗 (至少是單盲研究)

資料收集與分析

我們獨立地擷取資料。對於連續變項，我們計算加權平均差(weighted mean differences)。對於二元變項，我們計算相對風險與其95%信賴區間，以意圖治療(intentiontotreat)為基礎，採取隨機效應模式 randomeffects model 。合適 之處我們就計算 NNT與NNH(numbers needed to treat/harm)。

主要結論

此篇文獻回顧納入9篇隨機對照試驗，共3361位參加者。提前離開治療的比例相當高(59.1%) 取得了分別比較ziprasidone 與 amisulpride、clozapine、olanzapine, quetiapine 及 risperidone的資料。與olanzapine相較(因任一理由提前離開研究: 5 RCTs, n = 1937, RR 1.26 CI 1.18 to 1.35, NNH 7 CI 5 to 10)，或是與risperidone相較 (3 RCTs, n = 1029, RR 1.11 CI 1.02 to 1.20, NNH 14 CI 8 to 50)，Ziprasidone是較不被接受的藥物治療，但與其他第二代抗精神用藥比較則非然。與amisulpride相較，Ziprasidone效用較低(因為沒效而提前離開研究: 1 RCT, n = 123, RR 4.72 CI 1.06 to 20.98, NNH 8 CI 5 to 50)、與olanzapine相較亦是 (PANSS total score: 4 RCTs, n = 1291, MD 8.32 CI 5.64 to 10.99) 、與risperidone比較，Ziprasidone也是效用較低(PANSS total score: 3 RCTs, n = 1016, MD 3.91 CI 0.27 to 7.55)。在有限的資料中顯示，耐受性方面ziprasidone與amisulpride 或clozapine比，沒有顯著差異。與olanzapine比，Ziprasidone導致的體重上升較少(5 RCTs, n = 1659, MD −3.82 CI −4.69 to −2.96)，與quetiapine (2 RCTs, n = 754, RR 0.45 CI 0.28 to 0.74) 或risperidone (3 RCTs, n = 1063, RR 0.49 CI 0.33 to 0.74)亦皆是如此。與olanzapine, quetiapine and risperidone比較，引起的膽固醇上升較少。但相反地，ziprasidone引起的椎體外症候群副作用是比olanzapine多 (4 RCTs, n = 1732, RR 1.43 CI 1.03 to 1.99, NNH not estimable)，泌乳激素上升比quetiapine 多(2 RCTs, n = 754, MD 4.77 CI 1.37 to 8.16)，但與risperidone比較的話，椎體外症候群副作用較少(2 RCTs, n = 822, RR 0.70 CI 0.51 to 0.97, NNT not estimable)，泌乳激素上升也較少(2 RCTs, n = 767, MD −21.97 CI −27.34 to −16.60)。

作者結論

Ziprasidone與amisulpride, olanzapine, risperidone相較，效用些微較低。優勢在於引起較少的體重上升與相關副作用。然而，高比例的提前退出率限制了結論的有效性。

翻譯人

本摘要由彰化基督教醫院李冠瑩翻譯。

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

總結

比較Ziprasidone 與其他非典型抗精神用藥對精神分裂症的療效:Ziprasidone屬於新一代非典型抗精神用藥，用以治療精神分裂症。這篇文獻回顧意圖找出是否有證據支持ziprasidone與其他非典型抗精神用藥間有差異。但因為許多病人退出研究，因此要得到一個確實的結論是有困難的，然而，服用ziprasidone的病人，就症狀改善而言，不如服用olanzapine 及 risperidone 甚或有可能包括amisulpride，但服用ziprasidone的病人，較少體重上升。