Quetiapine for schizophrenia

 

Abstract

Background

Quetiapine is an atypical antipsychotic with, theoretically, a low propensity for movement disorder adverse effects. It is used for the treatment of schizophrenia and other psychoses.

Objectives

To determine the effects of quetiapine for schizophrenia in comparison to placebo, and other antipsychotics.

Search methods

Electronic searches of the Cochrane Schizophrenia Group's Register of Trials (Febuary 2003), Biological Abstracts (1982-2000), CINAHL (1982-2000), the Cochrane Library (2000, Issue 1),EMBASE (1980-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), SIGLE on CD (1980-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. We contacted AstraZeneca Pharmaceuticals for information regarding unpublished trials. The review was updated in February 2003.

Selection criteria

All randomised controlled trials where adults with schizophrenia or similar illnesses were assigned to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported.

Data collection and analysis

Citations and, where possible, abstracts were inspected independently by reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. We analysed data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI). Only homogeneous data were interpreted as favouring treatment or control. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics (NNH). We calculated relative risk (RR) for dichotomous data, and weighted mean differences (WMD) for continuous data.

Main results

Despite the fact that 3443 people were randomised in 12 quetiapine studies, there are almost no data on service utilisation, economic outcomes, social functioning and quality of life. Over half of those within the quetiapine versus placebo comparison were lost to follow up (53% quetiapine vs 61% placebo, n=716, 4RCTs, RR 0.84 CI 0.7 to 0.9, NNT 11 CI 7 to 55) so it is impossible to interpret any ratings of global or mental state within this comparison with confidence. People allocated quetiapine, however, did not have more movement disorders than those given placebo (n=395, 2 RCTs, RR needing medication for EPSE 0.62 CI 0.3 to 1.2). The same applies to the comparison of >/= 250 mg/day quetiapine with < 250 mg/day quetiapine (49% dropout >/= 250 mg/day vs 58% < 250 mg/day, n=1066, 3 RCTs, RR 0.84 CI 0.8 to 0.9, NNT 11 CI 7 to 29). It should be noted that two deaths occurred in the higher dose group (n=618, 1 RCT, RR 0.1 CI 0.0 to 2.1). When quetiapine was compared with typical antipsychotics, about 36% of both groups failed to complete the short-term studies (n=1624, 6 RCTs, RR 0.87 CI 0.8 to 1.0). Average change in global state was heterogeneous and equivocal (n=762, 3 RCTs, WMD in short term 0.19 CI 0.00 to 0.38, I squared 76%). Mental state measures were also equivocal (n=1247, RR not improved 0.97 CI 0.9 to 1.1) including specific measures of negative symptoms (n=305, 1 RCT, MD change in SANS short term 0.94 CI -0.2 to 2.0). Movement disorders were less prevalent for those allocated quetiapine (n=1117, 4 RCTs, RR needing medication for extrapyramidal adverse effects 0.47 CI 0.4 to 0.6, NNT 4 CI 4 to 5, I squared 88%). Dry mouth (n=649, 2 RCTs, RR short term 2.85 CI 1.5 to 5.6, NNH 17 CI 7 to 65) and sleepiness (n=959, 3 RCTs, RR 1.51 CI 1.1 to 2.2, NNH 18 CI 8 to 181) may also be more prevalent for people given quetiapine compared with the older drugs. In the quetiapine versus risperidone comparison, over 30% of people left the study before completion (n=728, 1 RCT, RR 0.94 CI 0.7 to 1.2). Four people, all treated with quetiapine, died during the study (n=728, 1 RCT, RR 2.86 CI 0.2 to 52.8). Continuous mental state measures did not show clear differences between the two drugs (n=637, 1 RCT, MD PANSS 1.2 CI -2.0 to 4.4). However, considerably fewer people given quetiapine needed medication for extrapyramidal side effects compared with those allocated to risperidone (n=712, 1 RCT, RR 0.27 CI 0.2 to 0.5, NNT 11 CI 10 to 16). Quetiapine caused more dizziness (n=728, 1 RCT, RR 1.85 CI 1.0 to 3.3, NNH 18 CI 7 to 487), more dry mouth (n=728, 1 RCT, RR 2.11 CI 1.2 to 3.8, NNH 14 CI 6 to 82) and more sleepiness than risperidone (n=728, 1 RCT, RR 2.03 CI 1.4 to 2.9, NNH 7 CI 4 to 17).

Authors' conclusions

Quetiapine is effective for the treatment of schizophrenia, but it is not much different from first-generation antipsychotics and risperidone with respect to treatment withdrawal and efficacy. In comparison to first-generation antipsychotics and risperidone, quetiapine has a lower risk of movement disorders but higher risks of dizziness, dry mouth and sleepiness. More clearly reported pragmatic randomised controlled trials should be carried out to determine its position in everyday clinical practice. Studies of medium and long-term effects, including cost-effectiveness, quality of life, social functioning and service utilisation, in comparison with the effects of typical and atypical antipsychotics should be priority areas.

 

Plain language summary

Quetiapine for schizophrenia

We looked for randomised controlled trials to determine the effects of quetiapine for schizophrenia in comparison to placebo and other antipsychotics. We included results of ten short-term trials and two medium-term studies. Quetiapine is effective for the treatment of schizophrenia but not much different from first-generation antipsychotics and risperidone in the respects of treatment withdrawal and efficacy. In comparison to typical antipsychotics and risperidone, it has a lower risk of movement disorders but higher risks of dizziness, dry mouth and sleepiness.

 

摘要

背景

Quetiapine治療精神分裂症

Quetiapine為非典型抗精神病藥物,理論上應有較低的移動障礙副作用傾向. 用於治療精神分裂症和其他精神疾病

目標

確定Quetiapine,安慰劑和其他抗精神病藥物在治療精神分裂症的效果

搜尋策略

電子搜索the Cochrane Schizophrenia Group's Register of Trials (Febuary 2003), Biological Abstracts (1982 – 2000), CINAHL (1982 – 2000), the Cochrane Library (2000, Issue 1), EMBASE (1980 – 2000), MEDLINE (1966 – 2000), PsycLIT (1974 – 2000), SIGLE on CD (1980 – 1997), SocioFile (1974 – 1997)和很多之前學會,手動搜尋特定期刊. 連絡阿斯特捷利康製藥公司(AstraZeneca Pharmaceuticals)已取得未發表試驗的資料. 於2003年2月更新此回顧.

選擇標準

納入所有隨機對照試驗比較Quetiapine,安慰劑和其他抗精神病藥物,用於精神分裂症成人或相似疾病病人的療效. 且有寫出臨床相關結果

資料收集與分析

文獻和摘要(如果有的話)由檢閱者獨立檢查. 排序論文和重新評估研究品質. 獨立擷取資料. 計算固定效果RR和估計95%CI. 使用固定效果模式,計算連續資料的加權平均差和CI.只有同質資料才可解釋為某治療組或對照組較好. 可行則計算需要治療人數(NNT)或致成危害需要人?(NNH). 二元資料則計算RR,連續資料則計算加權平均差.

主要結論

雖然12 個quetiapine試驗包含3443位受試者,但幾乎沒有關於使用服務,經濟結果,社會功能和生活品質的資料. quetiapine或安慰劑比較的組別裡,超過半數受試者失去追蹤. (53% quetiapine vs 61% 安慰劑, 樣本數為716, 4個隨機對照試驗, RR 0.84 CI 0.7 to 0.9, 需要治療人數為 11, CI 7 to 55) 故無法解讀整體或精神狀態的評分或計算其CI. 使用quetiapine的受試者與安慰劑組相比,沒有較多受試者發生移動障礙 (樣本數為395, 2 個隨機對照試驗, 需治療錐體外系副作用(EPSE)藥物的RR 為 0.62, CI 0.3 to 1.2). 高劑量組(大於或等於250mg/day quetiapine)的治療組和低劑量(小於250 mg/day quetiapine)組也有相同結果(高劑量組中途退出率為49%; 低劑量組中途退出率為58%, 樣本數為1066, 3個隨機對照試驗, RR 0.84 CI 0.8 to 0.9, 需要治療人數為 11, CI 7 to 29). 需注意高劑量組中有兩起死亡病例 (樣本數為618, 1 個隨機對照試驗, RR 0.1 CI 0.0 to 2.1). quetiapine 和傳統抗精神病藥物兩組皆有36%受試者無法完成短期試驗 (樣本數為1624,6個隨機對照試驗, RR 0.87, CI 0.8 to 1.0). 整體狀態平均改變量是異質的且相當(樣本數為762,3 個隨機對照試驗, 短期加權平均差為0.19, CI 0.00 to 0.38, I squared 76%). 精神狀態評量結果也相當 (樣本數為1247, 沒有進步的RR 為 0.97 CI 0.9 to 1.1), 其中負向症狀的量測也相當(樣本數為305,1 個隨機對照試驗, 短期SANS改變平均差為0.94 CI −0.2 to 2.0). quetiapine組較少發生移動障礙(樣本數為1117, 4 個隨機對照試驗, 需錐體外系副作用藥物的RR為 0.47, CI 0.4 to 0.6,需要治療人數為 4, CI 4 to 5, I squared 88%). Quetiapine組和舊藥組相比,口乾 (樣本數為649,2 個隨機對照試驗, 短期RR為2.85 CI 1.5 to 5.6, 傷害需要病例數為 17, CI 7 to 65) 和嗜睡(樣本數為959,3 個隨機對照試驗, RR 1.51, CI 1.1 to 2.2, 傷害需要病例數 18, CI 8 to 181)也較常見. Quetiapine與risperidone相比的試驗中,超過30%受試者提早離開試驗(樣本數為728,1 個隨機對照試驗, RR 0.94 CI 0.7 to 1.2). 4個患者於試驗期間死亡, 他們都使用使用quetiapine. (樣本數為728, 1 個隨機對照試驗, RR 2.86 CI 0.2 to 52.8). 持續精神狀態測量值於兩組間並沒有顯著差異 (樣本數為637, 1 個隨機對照試驗, PANSS平均差為1.2 CI −2.0 to 4.4). 但與risperidone組比起來,較少使用quetiapine的患者需要錐體外系副作用藥物 (樣本數為712,1 個隨機對照試驗, RR 0.27 CI 0.2 to 0.5, 需要治療人數為 11 CI 10 to 16). 與risperidone組比起來, Quetiapine 引起較多暈眩(樣本數為728,1 個隨機對照試驗, RR 1.85 CI 1.0 to 3.3, 傷害需要病例數 18 CI 7 to 487), 口乾 (樣本數為728,1 個隨機對照試驗, RR 2.11, CI 1.2 to 3.8, 傷害需要病例數為14 CI 6 to 82)和嗜睡(樣本數為728, 1 個隨機對照試驗, RR 2.03 CI 1.4 to 2.9, 傷害需要病例數 7 CI 4 to 17).

作者結論

Quetiapine可有效治療精神分裂症但在退出治療和療效方面與第一代藥物或risperidone差不多. 與第一代抗精神病藥物或risperidone相比, quetiapine組有較低的移動障礙風險但暈眩, 口乾和嗜睡風險高. 應有較清楚務實的隨機對照試驗,以確立Quetiapine每日臨床使用的療效. 需要優先研究傳統和非傳統抗精神病藥物的中長期療效試驗(包含成本效益,生活品質,社會功能和醫療服務使用).

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

納入所有隨機對照試驗比較Quetiapine,安慰劑和其他抗精神病藥物,用於精神分裂症成人的療效. 且有寫出臨床相關結果. 我們那洳10個短期試驗和2個中期試驗. Quetiapine可有效治療精神分裂症但在退出治療和療效方面與第一代藥物或risperidone差不多. 與第一代抗精神病藥物或risperidone相比, quetiapine組有較低的移動障礙風險但暈眩, 口乾和嗜睡風險高.