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Antipsychotics for delirium

  • Review
  • Intervention

Authors


Abstract

Background

Delirium occurs in up to 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. Recently published reports have suggested that the standard drug for delirium, haloperidol, a typical antipsychotic that may cause adverse extrapyramidal symptoms among patients, may be replaced by atypical antipsychotics such as risperidone, olanzapine or quetiapine, that are as effective as haloperidol in controlling delirium, but that have a lower incidence of extrapyramidal adverse effects.

Objectives

To compare the efficacy and incidence of adverse effects of haloperidol with risperidone, olanzapine, and quetiapine in the treatment of delirium.

Search methods

The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 August 2006 using the search terms: haloperidol or haldol or risperidone or risperdal* or quetiapine or seroquel* or olanzapine or zyprexa* or aminotriazole or sertindole or leponex* or zeldox* or ziprasidone.

Selection criteria

Types of studies included unconfounded, randomised trials with concealed allocation of subjects. For inclusion trials had to have assessed patients pre- and post-treatment. Where cross-over studies are included, only data from the first part of the study were examined. Interrupted time series were excluded. Length of trial and number of measurements did not influence the selection of trials for study. Where indicated, individual patient data were requested for further examination.

Data collection and analysis

Two reviewers extracted data from included trials. Data were pooled where possible, and analysed using appropriate statistical methods. Odds ratios of average differences were calculated. Only 'intention to treat' data were included. Analysis included haloperidol treated patients, compared with placebo.

Main results

Three studies were found that satisfied selection criteria. These studies compared haloperidol with risperidone, olanzapine, and placebo in the management of delirium and in the incidence of adverse drug reactions. Decrease in delirium scores were not significantly different comparing the effect of low dose haloperidol (< 3.0 mg per day) with the atypical antipsychotics olanzapine and risperidone (Odds ratio 0.63 (95% CI 10.29 to 1.38; P = 0.25). Low dose haloperidol did not have a higher incidence of adverse effects than the atypical antipsychotics. High dose haloperidol (> 4.5 mg per day) in one study was associated with an increased incidence of extrapyramidal adverse effects, compared with olanzapine. Low dose haloperidol decreased the severity and duration of delirium in post-operative patients, although not the incidence of delirium, compared to placebo controls in one study. There were no controlled trials comparing quetiapine with haloperidol.

Authors' conclusions

There is no evidence that haloperidol in low dosage has different efficacy in comparison with the atypical antipsychotics olanzapine and risperidone in the management of delirium or has a greater frequency of adverse drug effects than these drugs. High dose haloperidol was associated with a greater incidence of side effects, mainly parkinsonism, than the atypical antipsychotics. Low dose haloperidol may be effective in decreasing the degree and duration of delirium in post-operative patients, compared with placebo.
These conclusions must be tempered by the observation that they are based on small studies of limited scope, and therefore will require further corroborating evidence before they can be translated into specific recommendation for the treatment of delirium.

摘要

背景

抗精神病藥物在瞻妄上的治療

約30%的住院病人會出現瞻妄的情況,這會延長住院天數以及增加罹病率及死亡率。最近有一些報導顯示治療瞻妄的標準藥物如haloperidol,容易有錐體外症狀的副作用,而這些可由一些非典型抗精神病藥物,像risperidone, olanzapine, quetiapine來取代,它們對於控制瞻妄的效果與haloperidol 一樣有效,但錐體外症狀的副作用發生率卻較低

目標

比較haloperidol與risperidone, olanzapine以及quetiapine在治療瞻忘的療效及副作用的發生率

搜尋策略

在2006年8月7日,從Specialized Register of the Cochrane Dementia and Cognitive Improvement Group資料庫中搜尋下列名詞:haloperidol或haldol或risperidone或risperdal或quetiapine或seroquel或olanzapine或zyprexa 或aminotriazolesertindole或leponex或zeldox或ziprasidone

選擇標準

研究方式包括非干擾、隨機、隱藏受試者的試驗。這些試驗需有治療前與治療後的評估。交叉試驗也被囊括進來,且只檢視這些試驗的第一部的資料,排除時序中斷的試驗。試驗的長短及量測的數目並不會影響我們對試驗的選擇。這意指在未來每個病人的資料仍需要檢測

資料收集與分析

2名評論者從選取的試驗中摘錄資料。若可能的話,則會匯總數據並使用適當統計工具分析,並計算平均差異的Odds ratios。只有包括意圖治療的數據。分析包括以haloperidol治療病人與安慰劑的比較

主要結論

3個研究是符合我們選取的要件。這些研究比較haloperidol rieperidone, olanzapine 以及安慰劑在治療瞻妄以及發生藥物副作用的情況。瞻妄指數的減少在使用低劑量的haloperidone(< 3.0 mg 每天)與非典型的抗精神病藥物(olanzapine 及 risperiodone)沒有明顯差異。(OR = 0.63)(95% CI 10.29 to 1.38; P = 0.25)。 低劑量的haloperidol 比起非典型的抗精神病藥物並不會有較高的副作用發生率。在其中一個研究中,高劑量的haloperidol (> 4.5 mg 每天)比起olanzapine會有較高錐體外徑路副作用發生的機會。在某一個研究中顯示,比起安慰劑,低劑量的haloperidol可以減輕術後病人瞻妄的嚴重度及時間,而非瞻妄的發生率。並沒有具控制組的試驗來比較quetiapine 及 haloperidol

作者結論

沒有足夠的證據顯示說低劑量的haloperidol 比非典型抗精神病藥物olanzapine及risperidone在治療瞻妄更有效或是更容易發生副作用。高劑量的haloperidol比起非典型抗精神病藥物,有較高副作用發生率,主要是帕金森氏症後群。低劑量的haloperidol比起安慰劑,確實可以減少術後病人瞻妄的時間及程度。這些上述結論尚需再精淬鍊,因其來自於有限範圍的小研究。因此在達成瞻妄治療的專業建議之前,仍須更進一步的確實證據

翻譯人

本摘要由高雄長庚醫院陳乃菁翻譯

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

總結

有一些來自隨機對照試驗(RCTs)的證據顯示抗精神病藥物在不同劑量治療不同瞻妄的表現確實是有效的。Haloperidol (<3.5 mg/d),risperidone及olanzapine有較少的副作用,但在治療瞻妄者一樣的有效。高劑量的haloperidol(>4.5 mg/d)與olanzapine相比,則常出現帕金森氏症的副作用。術前投與haloperidol可減輕術後瞻妄的期間與嚴重度。所有的研究規模都太小而需要重複進行

Plain language summary

There is some evidence from RCTs that antipsychotics are effective, in varying doses, for different presentations of delirium

Haloperidol (<3.5 mg/d), risperidone, and olanzapine were equally effective in treating delirium, with few adverse effects. Parkinsonian adverse effects were common with higher dose haloperidol (>4.5 mg/d) compared with olanzapine. Pre-operative haloperidol decreased severity and duration of post-surgery delirium. All studies were small and should be repeated.

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