Ruiz-Franco Maria Luisa, Amaya-Pascasio Laura, Gil-Rodríguez Mercedes, Arjona-Padillo Antonio, García-Pinteño José, Rodriguez-Sanchez Antonio Jose, Sánchez-Kuhn Ana, Flores Pilar, Martinez-Sanchez Patricia
Stroke Unit, Department of Neurology, Torrecárdenas University Hospital, Almería, Spain.
Fundation for Biosanitary Research of Eastern Adnalusia (FIBAO), Torrecárdenas University Hospital, Almería, Spain.
Front Neurol. 2025 Nov 26;16:1702325. doi: 10.3389/fneur.2025.1702325. eCollection 2025.
Post-stroke apathy is a prevalent yet frequently underdiagnosed neuropsychiatric syndrome, reported in up to one-third of stroke survivors, and is consistently associated with poorer functional recovery and cognitive decline. We aimed to review the current evidence on available pharmacological and non-pharmacological treatments for post-stroke apathy, and to evaluate their efficacy and safety.
A systematic review was conducted following PRISMA guidelines and registered in the PROSPERO database (CRD42022332559). We searched PubMed, Web of Science, and Scopus for randomized and non-randomized clinical trials published until November 2024. Eligible studies included adults with ischemic or hemorrhagic stroke and a defined diagnosis of apathy. Interventions included pharmacological treatments and non-pharmacological strategies, such as neuromodulation techniques. Data extraction and risk of bias assessment were independently performed by two reviewers using the RoB-2 tool.
Ten clinical trials involving 2,359 patients were included. Pharmacological interventions with escitalopram and donepezil (alone or combined with intensive language action therapy) showed potential benefits. Nefiracetam yielded mixed results depending on dose and coexisting depression. Non-pharmacological approaches such as problem-solving therapy, motor relearning programs, strategy training, and complex rehabilitation programs demonstrated significant improvement in apathy scores. High-frequency repetitive transcranial magnetic stimulation also showed efficacy. However, heterogeneity in study design and apathy assessment scales limited direct comparisons.
Several interventions, including escitalopram, donepezil, motor relearning programs, strategy training, and rTMS, have demonstrated potential effectiveness in treating post-stroke apathy. Nevertheless, evidence remains scarce and heterogeneous, underscoring the need for larger, high-quality randomized controlled trials to establish definitive treatment guidelines.
中风后冷漠是一种常见但常被漏诊的神经精神综合征，在多达三分之一的中风幸存者中都有报告，并且一直与较差的功能恢复和认知衰退相关。我们旨在回顾目前关于中风后冷漠的可用药物和非药物治疗的证据，并评估其疗效和安全性。
按照PRISMA指南进行系统综述，并在PROSPERO数据库（CRD42022332559）中注册。我们在PubMed、科学网和Scopus上搜索截至2024年11月发表的随机和非随机临床试验。符合条件的研究包括患有缺血性或出血性中风且被明确诊断为冷漠的成年人。干预措施包括药物治疗和非药物策略，如神经调节技术。由两名评审员使用RoB-2工具独立进行数据提取和偏倚风险评估。
纳入了10项涉及2359名患者的临床试验。艾司西酞普兰和多奈哌齐的药物干预（单独使用或与强化语言行动疗法联合使用）显示出潜在益处。奈非西坦的结果因剂量和并存的抑郁症而异。解决问题疗法、运动再学习计划、策略训练和综合康复计划等非药物方法在冷漠评分方面显示出显著改善。高频重复经颅磁刺激也显示出疗效。然而，研究设计和冷漠评估量表的异质性限制了直接比较。
包括艾司西酞普兰、多奈哌齐、运动再学习计划、策略训练和重复经颅磁刺激在内的几种干预措施已显示出治疗中风后冷漠的潜在有效性。然而，证据仍然稀少且存在异质性，这突出表明需要进行更大规模、高质量的随机对照试验来制定明确的治疗指南。
