Division of Geriatric Psychiatry (DPD, LSP, EDH, DAD, GHP), New York State Psychiatric Institute, NY; Department of Psychiatry (DPD, SL, HA, EDH, BAD, GHP), Columbia University Medical Center, NY; Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, (DPD, EDH), Columbia University Medical Center, NY; Center for Cognitive Neuroscience and Aging, Department of Psychiatry and Behavioral Sciences (EC, LL), University of Miami Miller School of Medicine Miami, FL; Division of Geriatric Psychiatry (BPF, IVV), McLean Hospital, Harvard Medical School, MA; Departments of Psychiatry and Neurology (MMH, NI), University of Texas Southwestern Medical Center, TX; Mental Health Data Science, Department of Psychiatry (SL, HA), Columbia University Medical Center and New York State Psychiatric Institute, NY.
Division of Geriatric Psychiatry (DPD, LSP, EDH, DAD, GHP), New York State Psychiatric Institute, NY; Department of Psychiatry (DPD, SL, HA, EDH, BAD, GHP), Columbia University Medical Center, NY; Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, (DPD, EDH), Columbia University Medical Center, NY; Center for Cognitive Neuroscience and Aging, Department of Psychiatry and Behavioral Sciences (EC, LL), University of Miami Miller School of Medicine Miami, FL; Division of Geriatric Psychiatry (BPF, IVV), McLean Hospital, Harvard Medical School, MA; Departments of Psychiatry and Neurology (MMH, NI), University of Texas Southwestern Medical Center, TX; Mental Health Data Science, Department of Psychiatry (SL, HA), Columbia University Medical Center and New York State Psychiatric Institute, NY.
Am J Geriatr Psychiatry. 2022 Jan;30(1):32-42. doi: 10.1016/j.jagp.2021.04.014. Epub 2021 May 12.
A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted.
To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD).
In a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150-600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed.
Fifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ=1.26, p = 0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher's exact test p <0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p's<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (β=5.06; 95%CI,1.18 to 8.94, p = 0.01). Oral dose and serum levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on safety outcomes.
Low-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted of likely lithium-responsive behavioral symptoms that overlap with mania.
病例系列研究表明锂对痴呆相关激越有效，但尚未开展安慰剂对照试验。
评估低剂量锂治疗阿尔茨海默病（AD）激越。
在一项四中心试验中，伴有激越/激惹评分≥4（NPI）的 AD 患者被随机、双盲分组，接受碳酸锂 150-600mg/天或安慰剂治疗 12 周。主要疗效终点为 NPI 激越/激惹评分变化；次要疗效终点为治疗反应（NPI 激越/激惹和精神病评分降低≥30%，临床总体印象量表（CGI）评分为明显改善或非常明显改善）。评估锂的安全性。
77 例患者中 58 例（75.3%）完成试验。线性混合效应模型分析显示，锂治疗对激越/激惹的疗效不比安慰剂更优。锂组的反应率为 31.6%，安慰剂组为 17.9%（χ=1.26，p=0.26）。锂组（10/38=36.8%）的中重度或显著改善（CGI）比例明显高于安慰剂组（0/39=0%，Fisher 确切概率法 p<0.001）。探索性分析显示，锂治疗在 NPI 妄想和易激惹/不稳定方面的疗效优于安慰剂（p<0.05）。锂组较安慰剂组 Young 躁狂评定量表（YMRS）评分较高的患者疗效改善更明显（β=5.06；95%CI，1.18 至 8.94，p=0.01）。口服剂量和血清水平与疗效结果具有相似的关联。锂在安全性结局上与安慰剂无显著差异。
低剂量锂治疗 AD 激越无效，但与整体临床改善和良好的安全性相关。对于重叠有躁狂特征的可能对锂有反应的行为症状，可能需要更大规模的试验。
