Ruo-Yang Li, De-Liang Zhu, Ke-Yu Chen
Abstract
Objective
To evaluate the efficacy and safety of multi-drug therapy based on eszopiclone in the treatment of insomnia after stroke using a network meta-analysis method and to provide evidence for clinical practice.
Method
Computer searches of PubMed, Excerpt Medica Database (Embase), Cochrane Library Central Register of Controlled Trials, APA PsycInfo, CNKI, WanFang, Sinomed and other databases were performed to search for clinical randomized controlled studies (RCTs) on multi-drug therapy based on eszopiclone in the treatment of insomnia patients after stroke. The search time was from the establishment of each database until July 2023. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. Stata 14.0 was applied to perform network meta-analysis using Review Manager 5.3 software for traditional meta-analysis.
Introduction
Stroke, one of the most common diseases in the world, is characterized by a high incidence rate, recurrence rate, disability rate and mortality. The motor dysfunction, cognitive dysfunction, swallowing dysfunction, central nervous system pain, sleep disorders and other sequelae caused by its onset seriously burden the lives of patients and their families. Insomnia after stroke is one of the common sequelae of stroke, and relevant research data show that more than half of acute stroke patients have sleep disorders such as insomnia [1]. Insomnia after stroke is usually related to environmental factors, psychological factors, stroke site, etc. It has been reported that patients with pontine stroke experience almost complete sleep loss, while stroke in the thalamus leads to a lack of brain waves, leading to insomnia. Stroke in the supratentorial, left hemisphere, or paramedian thalamus can lead to reduced nonrapid eye movements, while stroke in the right hemisphere can lead to reduced rapid eye movements [1, 2]. At the same time, studies have shown that long-term low-quality sleep will increase the risk of relapse and the incidence of poststroke depression [3].
Method
Registration
This meta-analysis is registered on international prospective register of systematic reviews (registration number CRD42023451889).
Literature search
The search strategy uses a combination of theme words and keywords, and the search terms were adjusted based on the search results. The search time was from the establishment of the database to Oct 2023. The retrieval databases included the following: PubMed, Excerpt Medica Database (Embase), Cochrane Library Central Register of Controlled Trials, American Psychological Association (APA) PsycInfo, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese biomedical literature service system. Collect relevant literature on the treatment of insomnia after stroke using multi-drug therapy based on ESZ, search using keywords and their synonyms, and adjust accordingly according to different databases. The search terms mainly include: stroke, insomnia, nonbenzodiazepine, dexzopiclone, eszopiclone, randomized controlled trials, RCTs, et al. The detailed search strategy can be found in the S1 appendix.
Results
Literature search results
According to the literature search results, a total of 211 articles were obtained. After initial screening, 111 articles were excluded, leaving the remaining 100 articles. After reading the title and abstract, 50 articles were excluded, and after reading the entire text, 32 articles were excluded. The total number of articles included in this study was 18 [12–29]. A total of 11 drug therapies were involved, including the following: eszopiclone combined with sweet dream oral liquid (A traditional Chinese patent medicines and simple preparations composed of acanthopanax senticosus, polygonatum, etc. It mainly treats insomnia and dreaminess) (ESZ+SDOL), eszopiclone combined with a shugan jieyu capsule (A traditional Chinese patent medicines and simple preparations composed of Hypericum perforatum L, Acanthopanax senticosus and other traditional Chinese medicines, which mainly treats insomnia and depression.) (ESZ+SGJYC), eszopiclone combined with agomelatine (ESZ+AGO), eszopiclone combined with flupentixol and melitracen tablets (ESZ+FMT), eszopiclone combined with yangxue qingnao granules (A traditional Chinese patent medicines and simple preparations composed of angelica sinensis, rhizoma chuanxiong and other traditional Chinese medicines, mainly used to promote blood circulation and dredge collaterals.) (ESZ+YXQNG), eszopiclone combined with mirtazapine(ESZ+MIR), ESZ, FMT, eszopiclone combined with a xuefu zhuyu capsule (A traditional Chinese patent medicines and simple preparations composed of peach kernel, safflower and other traditional Chinese medicines, mainly used for promoting blood circulation and removing blood stasis.) (ESZ+XFZYC), and escitalopram (ESC), eszopiclone combined with escitalopram (ESZ+ESC). The process and results of literature retrieval are shown in Fig 1.
Discussion
Insomnia after stroke is the most common sequela after stroke. It is well known that good sleep quality is one of the benign factors for the prognosis of stroke. In recent years, there have been an increasing number of clinical trials of drug interventions for insomnia after stroke, and eszopiclone has gradually become one of the main drugs in the research of insomnia after stroke. Its advantages are small dependence, fast onset and good clinical efficacy. The literature included in this study involves 11 kinds of drugs combined with ESZ, of which ESZ+SDOL, ESZ+SGJYC, ESZ+YXQNG and ESZ+XFZYC are all Chinese patent medicines combined with ESZ. The difference lies in the different components and action targets in the patent medicine; ESZ+MIR, ESZ+AGO and ESZ+ESC are combination therapies of ESZ and antidepressants; FMT in ESZ+FMT are a compound preparation, which is composed of flupentixol and melitracen, and it has good clinical efficacy in the treatment of anxiety and depression. Many meta-analyses have suggested the significant clinical efficacy of ESZ in the treatment of insomnia [30–32], but the number of meta-analyses related to ESZ and its combination therapy in the treatment of insomnia after stroke is still small. This study combined the results of previous RCTs with the network meta-analysis method to evaluate the clinical efficacy and safety of ESZ combined with drug therapy in the treatment of insomnia after stroke and finally ranked the results according to efficacy.
Conclusion
In summary, multi-drug therapy based on ESZ can improve the sleep quality of insomnia patients after stroke to varying degrees. Current evidence suggests that ESZ+SDOL and ESZ+SGJYC may have the best effect in reducing PSQI; In terms of reducing MESSS, ESZ+SDOL may have the best effect; In terms of clinical efficacy in improving sleep, ESZ+XFZYC has the best clinical efficacy. Further quantitative analysis is needed for adverse reactions. Due to the limitations of the quantity and quality of included literature, the above conclusions still need to be verified by more high-quality RCTs.
Citation: Li R-Y, Zhu D-L, Chen K-Y (2024) Efficacy and safety of eszopiclone combined with drug therapy in the treatment of insomnia after stroke: A network meta-analysis and systematic review. PLoS ONE 19(2): e0297064. https://doi.org/10.1371/journal.pone.0297064
Editor: Huijuan Cao, Beijing University of Chinese Medicine, CHINA
Received: September 1, 2023; Accepted: December 26, 2023; Published: February 5, 2024
Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0297064#abstract0
