Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India.
J Clin Psychiatry. 2022 Feb 1;83(1):22f14398. doi: 10.4088/JCP.22f14398.
Apathy is a common and important yet often ignored neuropsychiatric symptom of Alzheimer's disease (AD). Cholinesterase inhibitors and memantine, used to treat AD, appear ineffective against apathy. A meta-analysis of 4 randomized, placebo-controlled trials (RCTs) found that psychostimulants significantly attenuated apathy ratings in AD. However, the pooled sample size in this meta-analysis was just 156, and one of the trials was a 2-week crossover study with a large effect. A large RCT (n = 200) has now been published. This study found that methylphenidate (MPH; 20 mg/d) was superior to placebo in the attenuation of apathy scores in patients with possible or probable, mild to moderate AD; the advantage was evident by the end of the second month of treatment and remained evident to the end of 6 months. The effect size at 6 months was small (Cohen = 0.37). In this RCT, disappointingly, MPH was not superior to placebo on secondary outcomes, including informant-rated apathy, dependence, activities of daily living, quality of life, and neurocognitive performance; caregiver burden was not formally studied. Speculatively, the psychosocial intervention provided to all participants in this RCT may have boosted response in the placebo group, thereby attenuating differences in outcomes between the MPH and placebo groups. A reasonable conclusion is that whereas MPH may attenuate the severity of apathy in patients with AD across as long as 6 months, the absence of improvements in measures of dependence, activities of daily living, and quality of life suggest that this effect of MPH on apathy may not be clinically significant. An unanswered question is whether the benefits of MPH may be clinically significant in real world practice settings in which the delivery of behavioral interventions is not feasible.
淡漠是阿尔茨海默病（AD）常见且重要但常被忽视的神经精神症状。用于治疗 AD 的胆碱酯酶抑制剂和美金刚似乎对淡漠无效。对 4 项随机、安慰剂对照试验（RCT）的荟萃分析发现，精神兴奋剂显著减轻了 AD 患者的淡漠评分。然而，该荟萃分析的汇总样本量仅为 156，其中一项试验是为期 2 周的交叉研究，其效果较大。一项大型 RCT（n = 200）现已发表。该研究发现，哌醋甲酯（MPH；20 mg/d）在可能或可能患有轻度至中度 AD 的患者的淡漠评分减弱方面优于安慰剂；这种优势在治疗的第二个月末就显现出来，并持续到 6 个月末。6 个月时的效应大小较小（Cohen = 0.37）。在这项 RCT 中，令人失望的是，MPH 在包括照料者评定的淡漠、依赖、日常生活活动、生活质量和神经认知表现在内的次要结局上并不优于安慰剂；未正式研究照料者负担。推测一下，该 RCT 中所有参与者接受的心理社会干预可能提高了安慰剂组的反应，从而减轻了 MPH 组和安慰剂组之间结局差异。合理的结论是，尽管 MPH 可能在长达 6 个月的时间内减轻 AD 患者的淡漠严重程度，但在依赖、日常生活活动和生活质量方面的测量指标没有改善，表明 MPH 对淡漠的这种影响可能没有临床意义。一个未解决的问题是，在行为干预不可行的现实实践环境中，MPH 的益处是否具有临床意义。
