Department of Neurology, IU Alzheimer׳s Disease and Related Disorders, 355 W. 16th Street, Suite 4700, Indianapolis, IN 46202, USA.
Evidence-Based Medicine Quality Assurance, Elsevier, 1600 JFK Blvd 20th floor, Philadelphia, PA 19103, USA.
Eur Neuropsychopharmacol. 2017 Mar;27(3):217-231. doi: 10.1016/j.euroneuro.2017.01.002. Epub 2017 Jan 19.
We evaluated the most current evidence regarding the benefits and harms of atypical antipsychotics in adults with dementia. In June 2016, following a protocol developed a priori, we systematically searched several databases for published and unpublished data from randomized controlled trials (RCT), observational studies, and meta-analyses; conducted direct meta-analyses using a random effects model; and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. One high-quality meta-analysis and published and unpublished data from 8 RCTs and 12 large observational studies met inclusion criteria. When compared with placebo, aripiprazole, risperidone, and olanzapine but not quetiapine result in modest (standardized mean difference <0.5 standard deviations) improvement in neuropsychiatric symptoms. Aripiprazole, risperidone, quetiapine, and olanzapine are associated with increased odds of acute myocardial infraction, and risperidone and olanzapine are associated with increased odds of hip fracture. Observational studies suggest no differences in all-cause mortality between atypical antipsychotics. Observational studies suggest that atypical antipsychotics are associated with lower risk of all-cause mortality and extrapyramidal symptoms but higher risk of stroke when compared with conventional antipsychotics. To manage agitation in adults with progressive dementia, clinicians may recommend atypical antipsychotics with continuous monitoring of behavioral symptoms, informing patients and their families or caregivers of the significant risk of adverse effects and baseline risk of acute myocardial infraction and bone fractures.
我们评估了目前关于非典型抗精神病药在痴呆成人中获益和危害的最有效证据。2016 年 6 月，根据预先制定的方案，我们系统地检索了几个数据库，以寻找已发表和未发表的随机对照试验（RCT）、观察性研究和荟萃分析数据；使用随机效应模型进行直接荟萃分析；并根据推荐评估、制定与评估（GRADE）工作组的分级标准评估证据质量。一项高质量的荟萃分析以及 8 项 RCT 和 12 项大型观察性研究的已发表和未发表数据符合纳入标准。与安慰剂相比，阿立哌唑、利培酮和奥氮平而非喹硫平可使神经精神症状适度改善（标准化均数差＜0.5 个标准差）。阿立哌唑、利培酮、喹硫平和奥氮平与急性心肌梗死的发生几率增加相关，而利培酮和奥氮平与髋部骨折的发生几率增加相关。观察性研究表明，在全因死亡率方面，非典型抗精神病药之间没有差异。观察性研究表明，与传统抗精神病药相比，非典型抗精神病药与全因死亡率和锥体外系症状的风险降低相关，但与卒中的风险增加相关。为了治疗进行性痴呆成人的激越，临床医生可能会建议使用非典型抗精神病药，同时持续监测行为症状，向患者及其家属或照护者告知不良反应的显著风险以及急性心肌梗死和骨折的基线风险。
