Investigational drugs for treating agitation in persons with dementia

Introduction: Agitation is common and distressing in persons with dementia, but safe, effective treatments remain elusive. In this review, the authors describe investigational compounds in ongoing or recently completed clinical trials for this indication and provide an opinion on how they may meet current therapeutic needs.

Areas covered: Phase II and phase III clinical trials for agitation in persons with dementia were searched in US and EU clinical trial registries and in the medical literature for the period January 2013-February 2016

Expert opinion: The authors searches identified 24 recent clinical trials investigating new treatments for agitation in persons with dementia. Candidate drugs in phase III development included the antipsychotic brexpiprazole, the antidepressant citalopram, the novel compound AVP-786 (deuterated-dextromethorphan/quinidine combination) and the cannabinoid nabilone. Of the compounds in phase II clinical trials, ELND005 (scyllo-inositol) is intended to progress into phase III development, based on evidence from a subgroup analysis and biomarker data. After many years without an FDA/EMA (Food and Drug Administration/European Medicines Agency) approved medication to treat agitation in persons with dementia, we may see the arrival of the first approved drug in the near future.     

封闭和开放吸痰方法对ICU机械通气患者 疼痛和躁动影响的比较

目的 比较封闭和开放两种吸痰方法对ICU机械通气患者疼痛和躁动的影响。方法 研究对象为2017年5月~12月在首都医科大学大兴教学医院ICU接受机械通气治疗的60例患者。本研究采取单中心、随机对照试验设计的临床研究,采用随机数字表将纳入的患者分到封闭吸痰组和开放吸痰组,每组30例。封闭吸痰为试验组,开放吸痰为对照组。在吸痰操作之前、过程中、结束后即刻、结束后5 min、结束后20 min分别进行行为疼痛评分和Richmond镇静躁动评分。结果 两组的BPS和RASS评分在吸痰操作后均有增高,两种吸痰方法所引起的疼痛和躁动水平增加的幅度基本相同,差异无统计学意义（P＞0.05）。结论 上述两种吸痰方法对ICU机械通气患者疼痛和躁动的影响无显著差异,可能需要更大样本量的研究来证明。     

音乐疗法对老年痴呆患者激越行为影响的meta分析

目的 探讨音乐疗法对老年痴呆患者激越行为影响的效果。方法 通过检索国内外数据库中符合纳入、排除标准的随机对照试验,对纳入文献的质量进行评价并提取数据,再采用RevMan 5.3软件进行meta分析。结果 共纳入8篇文献。Meta分析结果显示,音乐干预能够改善老年痴呆患者的激越行为,合并效应具有统计学意义[WMD=-6.05,95%CI(-10.93,-1.17),P=0.020];干预时间在2个月以下合并效应无统计学意义[WMD=-5.24,95%CI(-11.79,-1.31),P=0.120];干预时间在3个月以上合并效应具有统计学意义[WMD=-8.34,95%CI(-11.42,-5.27),P＜0.001]。结论 音乐疗法能够降低老年痴呆患者激越行为,改善其生活质量,但干预时间应在3个月以上,此结论可在社区及家庭推广。     

Neuropsychiatric symptoms and Apolipoprotein E: Associations with eventual Alzheimer’s disease development

ObjectiveAlzheimer’s disease (AD) is the result of neurodegeneration, which manifests clinically as deficits in memory, thinking, and behavior. It was hypothesized that neuropsychiatric symptoms and the apolipoprotein E genotype increase the likelihood of Alzheimer’s disease development.MethodsUtilizing data from the National Alzheimer’s Coordinating Center, information from evaluations of 11,453 cognitively intact participants was analyzed. Survival analysis was used to explore relationships between individual neuropsychiatric symptoms as determined by the Neuropsychiatric Inventory Questionnaire, apolipoprotein E, and eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic (additive and multiplicative) interactions.ResultsThis study provided evidence for an increased hazard of developing AD among participants with any of the symptoms assessed by the NPI-Q. The hazard of developing AD was almost thirteen times higher for _ε4 carriers with delusions and eleven times greater for those with apathy and disinhibition. Statistically significant hazards (p > 0.001) were also realized by _ε4 carriers with hallucinations; agitation; depression; anxiety; elation; apathy; irritability; and motor, sleep, and appetite disturbances.ConclusionsFindings suggest that neuropsychiatric symptoms are associated with eventual AD diagnosis among a group of cognitively asymptomatic participants at baseline. Many studies begin with a group of participants already impacted by AD diagnosis. The longitudinal analysis of a group of participants who, at baseline, demonstrated no observable signs of AD was a strength of this study. This investigation contributes to the literature exploring an increased hazard of AD due to potential modifiable risk factors and genetic biomarkers such as apolipoprotein E.     

地佐辛复合芬太尼超前镇痛预防全麻苏醒期躁动的临床观察

目的：观察地佐辛复合芬太尼超前镇痛对全麻患者苏醒期躁动的预防作用。方法：选取行全身麻醉上腹部手术患者100例,A S AⅠ～Ⅱ级,随机分为地佐辛组（A组）、芬太尼组（B组）、地佐辛复合芬太尼组（C组）和对照组（D组）,每组25例。A、B、C三组切皮前10min分别给予静脉注射地佐辛0．2mg／kg、芬太尼1μg／kg、地佐辛0．15mg／kg＋芬太尼0．6μg／kg。围术期以首次剂量1／2,间隔30～40min静脉注射持续镇痛;D组静注等量生理盐水。麻醉维持采用持续输注丙泊酚、瑞芬太尼,间断静脉注射罗库溴胺。记录四组患者手术缝皮后（T0）、拔管时（T1）、拔管后5min （T2）,血压（BP）、心率（HR）的变化;记录睁眼时间、拔管时间;拔管前Riker镇静躁动评分、RSS躁动评分。结果：A组、D组T1、T2时的BP、HR明显高于T0时（P＜0．05）,B组、C组同时间点BP、HR明显低于D组（P＜0．05）;B组睁眼时间、拔管时间明显长于A组、D组;C组Riker镇静躁动评分患者躁动发生率明显低于D组（ P＜0．05）。结论：地佐辛＋芬太尼联合超前镇痛能预防全麻患者苏醒期躁动,不会延长患者的睁眼时间和拔管时间。     

右美托咪定对患儿七氟醚复合麻醉恢复期躁动的影响

目的：评价右美托咪定对患儿七氟醚复合麻醉恢复期躁动的影响。方法择期行扁桃体及腺样体切除术的阻塞性呼吸睡眠综合征患儿60例,采用随机数字表法,根据七氟醚复合麻醉药物的不同,将患儿分为两组（ n＝30）：右美托咪定组（ D组）和瑞芬太尼组（ R组）。记录拔管时间、麻醉后恢复室（ PACU）停留时间;PACU 期间记录躁动发生情况、持续时间,采用患儿麻醉苏醒期躁动量化评分表（PAED）评分评价躁动程度。患儿入PACU即刻（T0）及15 min（T1）、30 min（T3）、60 min（T3）时行疼痛视觉模拟评分（VAS）和镇静评分（Ramsay）分别评价疼痛程度和镇静程度。记录PACU期间患者不良反应的发生情况。结果与R组比较, D组躁动发生率和PEAD评分降低,躁动持续时间缩短,术后各时点VAS评分降低,Ramsay评分升高（P＜0．05）;两组患儿拔管时间、PACU停留时间、PACU期间不良反应比较差异无统计学意义（ P＞0．05）。结论右美托咪定可安全有效地预防患儿七氟醚复合麻醉恢复期躁动的发生。     

右美托咪定和丙泊酚用于神经外科躁动患者镇静的比较研 究简

目的 评价神经外科躁动患者应用右美托咪定和丙泊酚镇静治疗的效果及不良反应.方法 选择2010年3月～2011年3月入住武汉大学人民医院ICU中的神经外科急重症及术后躁动患者60例,随机分为两组,右美托咪定组（D组）和丙泊白酚组（P组）,监测给药前（T1）及给药后10 min（T2）、1 h（T3）、2 h（T4）、6 h（T5）和次日清晨7：00（T6）的平均动脉压、心率、呼吸频率、脉搏血氧饱和度,记录药物起效时间、达到Ramsay镇静评分2～4级时药物平均输注速度.结果 两组药物起效时间比较差异有高度统计学意义（P＜0.01）,D组患者用药后血压及心率均有所下降（P＜0.05）,用药后呼吸频率与T1相比虽有所下降,但差异无统计学意义（P＞0.05）;P组镇静治疗后血压较给药前下降,差异有统计学意义（P＜0.05）,与T1比较,T2～4的心率明显下降（P＜0.05）,用药后10 min内即观察到呼吸频率下降,T2与T1相比差异有统计学意义（P＜0.05）.结论 右美托咪定和丙泊酚微量泵持续输入用于神经外科躁动患者镇静安全有效,丙泊酚可应用于躁动患者的快速镇静,右美托咪定镇静过程中无明显呼吸抑制发生,但要注意防范血压下降和心率减慢的不良反应.     

右美托咪定对开胸手术患者苏醒期躁动的影响

目的探讨静脉输注右美托咪定对开胸手术患者麻醉苏醒期躁动的影响。方法选择ASAⅠ或Ⅱ级择期行开胸手术的患者40例,分为右美托咪定组（A组）和生理盐水对照组（B组）。A组患者在麻醉诱导前给予右美托咪定负荷剂量0．8μg／kg（给药时间〉10min）及0．4μg／（kg·h）的维持量。B组以同等方法泵人生理盐水。术中采用多功能脑电监测仪（BIS）,了解麻醉深度。观察患者苏醒期躁动情况。结果苏醒期各个时点A组心率、血压增高的程度均低于B组（P〈0．05）。躁动例数A组较B组少（P〈0．05）。结论右美托咪定可使全麻开胸手术患者苏醒期的血流动力学更稳定,躁动减少。     

右美托咪定联合曲马多预防青壮年男性全麻病人苏醒期躁动评价

目的 观察右美托咪定用于预防青壮年男性全麻患者苏醒期躁动的效果和安全性.方法 选择60例18 ～ 45岁择期全麻手术的男性患者,随机分为3组:A组:全麻插管后静脉泵注右美托咪定1μg/kg,10 min后改为0.4 μg/(kg.h)至手术结束前30 min停药,缝皮前静注曲马多1 mg/kg;B组:术中泵注等量生理盐水,缝皮前静注曲马多2 mg/kg;C组:术中及缝皮前均给予等量生理盐水.记录3组患者T0-T4各时点的SBP、DBP、HR,记录3组患者的唤醒时间、拔管时间、拔管后5 min的躁动评分及不良反应.结果 3组患者在T0、T1时点SBP、DBP、HR差别无统计学意义;T2时点SBP、DBP、HR,A组明显低于B、C组(P＜0.01),T3时点SBP、DBP、HR,A、B组明显低于C组(P＜0.01),T4时点A组SBP、DBP、HR明显低于C组(P＜0.01),亦低于B组.B组SBP、DBP、HR低于C组(P＜0.05).3组患者唤醒时间、拔管时间差别无统计学意义,躁动评分A、B组明显低于C组(P＜0.01),且A组低于B组;术后24 h恶心呕吐的发生率A、C组低于B组(P＜0.05).结论 右美托咪定联合曲马多可有效提高青壮年男性全麻病人的复苏质量,且不增加复苏时间.两者合用可减少曲马多用量,减少术后恶心呕吐的发生.