A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial)
A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial)
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DOI：
10.1371/journal.pmed.0050076
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发表时间：
2008-04-01
期刊：
影响因子：
15.8
通讯作者：
Juszczak, Edmund
中科院分区：
文献类型：
--
作者：
Ballard, Clive;Lana, Marisa Margallo;Juszczak, Edmund
背景抗精神病药物在痴呆患者中的安全性和有效性越来越受到关注，但很少有长期试验为临床实践提供信息。本研究的目的是确定长期使用精神抑制剂治疗对阿尔茨海默病患者整体认知能力下降和神经精神症状的影响。方法和结果设计：随机、盲法、安慰剂对照平行两组治疗中止试验。设置：牛津郡、纽卡斯尔和盖茨黑德、伦敦和英国爱丁堡。参与者：患者目前处方的抗精神病药硫利达嗪，氯丙嗪，氟哌啶醇三氟拉嗪或利培酮的行为或精神障碍的痴呆症至少3个月。干预措施：继续抗精神病药治疗12个月或切换到相同的安慰剂。主要结局为严重损害成套测验（SIB）总评分。结果：165例患者被随机分配（83例继续治疗，82例安慰剂，即，停止治疗），其中128例（78%）开始治疗（64例继续/64例安慰剂）。其中，26例失访（每组13例），导致每组51例患者分析主要结局。在基线和6个月之间SIB评分的估计平均变化方面，继续治疗组和安慰剂组之间没有显著差异;恶化的估计平均差异（有利于安慰剂）为-0.4（95%置信区间[CI] -6.4至5.5），根据基线值进行校正（p = 0.9）。对于神经精神症状，在基线和6个月之间NPI评分的估计平均变化方面，继续治疗组和安慰剂组（分别为n = 56和53）之间没有显著差异;恶化的估计平均差异（有利于继续治疗）为-2.4（95% CI -8.2至3.5），根据基线值进行校正（p = 0.4）。这两个结果在12个月时变得更加明显。有一些证据表明，这些患者与初始NPI-15受益于持续treatment.ConclusionsFor大多数AD患者的神经精神症状，神经阻滞剂的撤出没有整体的不利影响功能和认知状态。抗精神病药可能在更严重的神经精神症状的维持治疗中有一定的价值，但这种益处必须与治疗的副作用相权衡。试验注册：科克伦对照试验中心注册处/国家研究注册处（#ISRCTN33368770）。
BackgroundThere have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease.Methods and FindingsDesign: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial.Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom.Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo.Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo.Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI).Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) -0.4 (95% confidence interval [CI] -6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) -2.4 (95% CI -8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI -15 benefited on neuropsychiatric symptoms from continuing treatment.ConclusionsFor most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).