Lonergan E, Britton A M, Luxenberg J, Wyller T
Cochrane Database Syst Rev. 2007 Apr 18(2):CD005594. doi: 10.1002/14651858.CD005594.pub2.
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.
To compare the efficacy and incidence of adverse effects of haloperidol with risperidone, olanzapine, and quetiapine in the treatment of delirium.
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.
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.
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.
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 - 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.
多达30%的住院患者会发生谵妄，且谵妄与住院时间延长以及发病率和死亡率增加相关。最近发表的报告表明，用于治疗谵妄的标准药物氟哌啶醇（一种典型的抗精神病药物，可能会使患者出现锥体外系不良反应）可能会被非典型抗精神病药物（如利培酮、奥氮平或喹硫平）所取代，这些药物在控制谵妄方面与氟哌啶醇一样有效，但锥体外系不良反应的发生率较低。
比较氟哌啶醇与利培酮、奥氮平和喹硫平治疗谵妄的疗效及不良反应发生率。
通过检索Cochrane痴呆与认知改善小组专业注册库（2006年8月7日）来确定试验，检索词为：氟哌啶醇或氟哌丁苯或利培酮或利司培酮或喹硫平或思瑞康或奥氮平或再普乐或氨基三唑或舍吲哚或氯氮平或齐拉西酮*或齐帕西酮。
纳入的研究类型为无混淆因素的随机试验，且受试者分配方案实施了隐藏。纳入的试验必须对患者进行治疗前和治疗后的评估。若纳入交叉研究，仅检查研究第一部分的数据。排除中断时间序列研究。试验时长和测量次数不影响试验的选择。如有需要，会索取个体患者数据以进行进一步审查。
两名评价员从纳入的试验中提取数据。尽可能合并数据，并使用适当的统计方法进行分析。计算平均差异的比值比。仅纳入“意向性分析”数据。分析包括将接受氟哌啶醇治疗的患者与安慰剂进行比较。
共发现三项符合选择标准且满足入选标准的研究。这些研究比较了氟哌啶醇与利培酮、奥氮平及安慰剂在谵妄管理和药物不良反应发生率方面的差异。低剂量氟哌啶醇（每日<3.0毫克）与非典型抗精神病药物奥氮平和利培酮相比，谵妄评分的降低无显著差异（比值比0.63，95%置信区间10.29 - 1.38；p = 0.25）。低剂量氟哌啶醇的不良反应发生率并不高于非典型抗精神病药物。在一项研究中，与奥氮平相比，高剂量氟哌啶醇（每日>4.5毫克）的锥体外系不良反应发生率增加。在一项研究中，与安慰剂对照相比，低剂量氟哌啶醇可降低术后患者谵妄的严重程度和持续时间，但未降低谵妄的发生率。尚无比较喹硫平与氟哌啶醇的对照试验。
没有证据表明低剂量氟哌啶醇在谵妄管理方面与非典型抗精神病药物奥氮平和利培酮相比疗效不同，或其药物不良反应发生率高于这些药物。与非典型抗精神病药物相比，高剂量氟哌啶醇的副作用发生率更高，主要是帕金森症。与安慰剂相比，低剂量氟哌啶醇可能对降低术后患者谵妄的程度和持续时间有效。这些结论必须谨慎对待，因为它们基于范围有限的小型研究，因此在转化为治疗谵妄的具体建议之前，还需要进一步的确证证据。
