Meta-Analysis of the Effectiveness and Safety of Shugan Jieyu Capsules for the Treatment of Insomnia
Summary
The presented protocol describes an investigation strategy and systematic review to evaluate the clinical effectiveness and safety of Shugan Jieyu capsules for treating insomnia.
Abstract
A systematic review and meta-analysis were conducted to evaluate the clinical effectiveness and safety of Shugan Jieyu capsules for treating insomnia by searching seven databases up to February 21, 2022. The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the studies was assessed using the risk of bias assessment tool. This article describes in detail how to retrieve and screen the literature. The detailed steps for conducting the meta-analysis are also included in the protocol. Fourteen studies were found to be eligible, including 1,283 insomnia patients (644 with and 639 without Shugan Jieyu capsules at baseline). The meta-analysis showed a better total clinical effectiveness (odds ratio [OR]: 5.71, 95% confidence interval [CI]: 3.56 to 9.15) and a lower Pittsburgh Sleep Quality Index (PSQI) score (mean difference [MD]: −2.95, 95% CI: −4.97 to −0.93) with combined Shugan Jieyu capsules and Western medicine compared to Western medicine alone. The secondary outcomes showed that the Shugan Jieyu capsule group had significantly reduced adverse reactions and improvements in sleep duration, night awakening, nightmares with excessive dreaming, daytime sleepiness, and low energy. Further multicenter randomized trials must be encouraged to provide more concrete evidence on whether Shugan Jieyu capsules are beneficial in routine clinical practice.
Introduction
Insomnia is a sleep disorder characterized by difficulty in falling asleep, difficulty in maintaining sleep, and premature or intermittent waking1, which can cause discomfort and disrupt daily functioning. According to the China Sleep Study Report (2022), over 300 million Chinese people suffered from sleep disorders in 2021, with a prevalence of insomnia among adults as high as 38.2%2.
Western medicine for insomnia treatment typically involves psychological therapies or medication3. Psychotherapies, such as simple insomnia behavior therapy and cognitive insomnia behavior therapy, aim to modify the behaviors that contribute to sleep difficulties. Sedative-hypnotic drugs, which act quickly to induce sleep, are also commonly used to treat insomnia4. However, these drugs can have toxic side effects, including respiratory depression, hypotension, and excessive sedation. The prolonged usage of these drugs can lead to dependence, resulting in significant harm and burden to the patients and their families5,6,7. In traditional Chinese medicine (TCM), insomnia is referred to as "no sleep" or "sleeplessness" and is believed to result from deficiencies in organs such as the liver, kidneys, spleen, and heart, as well as dysfunction of the heart and mind8. In the history of traditional Chinese medicine, several experts have described the mechanisms underlying insomnia; specifically, insomnia is thought to occur due to disorder of the function of the internal organs, the loss of harmony between the qi and blood, and the disorder of yin and yang, which lead to a loss of nourishment or the disturbance of the heart and mind. The basic pathological alternation of insomnia is the loss of yang and yin9. Utilizing the active ingredients of TCM and following the principles of TCM compounding for complex conditions, research10,11,12,13 has shown that TCM plays a critical role in preventing and treating insomnia. One example of a TCM treatment for insomnia is the Shugan Jieyu capsule14, which comprises Hypericumperforatum L15,16 and Acanthopanax senticosus17.
Acanthopanax senticosus18,19, a traditional Chinese herb, has been used for tonifying the middle qi and kidney and calming the mind. It has been found to effectively improve symptoms such as insomnia, excessive dreaming, and neurasthenia. Hypericum perforatum20, another traditional Chinese herb, has demonstrated antidepressant properties, with its active components potentially possessing similar antidepressant effects to tricyclic antidepressants (TCAS) and selective serotonin reuptake inhibitors (SSRIs), but with better tolerability. The combination of Hypericum perforatum and Acanthopanax senticosus has been found to regulate neurotransmitters, improve neuronal synaptic plasticity, and clinically relieve insomnia caused by mental illness; indeed, it improves the sleep quality and cognitive function of patients with liver-depression type insomnia21,22. Syndrome differentiation is a unique characteristic of TCM. The Shugan Jieyu capsule containing Hypericum perforatum and Acanthopanax senticosus is formulated to treat insomnia caused by stagnation of liver qi. It has been reported to be effective in improving the condition and safety of patients21,22. Combining these two herbs has been proven to relieve depression, calm the mind, soothe the liver, and strengthen the spleen23,24,25. However, there currently needs to be more conclusive evidence regarding the clinical effectiveness and safety of Shugan Jieyu capsules in treating insomnia.
There are various forms of Chinese herbal medicine for treating insomnia, including decoction, patent medicine, plaster, and auricular point sticking26. Previous research has examined the effect of traditional Chinese herbs on insomnia using meta-analyses. It has been found that traditional Chinese herbs significantly improve the symptoms of patients with primary insomnia, are superior to placebo, and have promising potential for research and development27,28. This study aims to evaluate the clinical effectiveness and safety of the Shugan Jieyu capsule in treating insomnia through a systematic evaluation and meta-analysis in order to provide clinical evidence and guidance for using these capsules.
The inclusion criteria for this study were defined using the population, intervention or exposure, comparison, outcome(s) (PICO) framework29. The inclusion criteria for this study were as follows: (1) randomized controlled trials (RCTs) or semi-RCTs that enrolled patients diagnosed with insomnia30; (2) studies in which the experimental group received Western medicine in combination with Shugan Jieyu capsules, while the control group received Western medicine alone (Western medicines include alprazolam tablets31, risperidone32, estazolam tablets33, aripiprazole orally disintegrating tablets34, mirtazapine35, escitalopram oxalate tablets36, eszopiclone tablets37, zopiclone tablets38, and fluoxetine dispersible tablets39); (3) studies published in Chinese or English; (4) studies in which the primary outcomes were the overall clinical effectiveness and the Pittsburgh Sleep Quality Index (PSQI)40. According to the "Diagnostic Effectiveness Criteria for Chinese Medicine Evidence"41 and the "Guidelines for Clinical Research on New Chinese Medicines"42, effective clinical outcomes are defined as patients being clinically documented as cured or showing efficacious results. The secondary outcomes identified include sleep latency, sleep duration, nighttime awakening, nightmares with excessive dreaming, daytime sleepiness, lack of energy, and sleep quality, all evaluated by the PSQI scale and the frequency of adverse events. Among these outcome measures, sleep latency, sleep duration, nighttime awakening, nightmares, daytime sleepiness, lack of energy, and sleep quality are all evaluated using the PSQI scale43.
The exclusion criteria were defined according to the PICO framework. The exclusion criteria for this study were as follows: (1) studies unrelated to insomnia; (2) duplicate published research; (3) non-randomized controlled trials; (4) non-clinical patient studies, such as preclinical and animal model studies; and (5) case reports, comments, conferences, reviews, and dissertations.
Protocol
Representative Results
Discussion
In the present study, a comprehensive evaluation of the effectiveness and safety of Shugan Jieyu capsules for treating insomnia was conducted, and the following results were observed. In the experimental group, using Shugan Jieyu capsules in combination with conventional Western medicine improved the overall clinical effectiveness for patients with insomnia and resulted in higher PSQI scores. Additionally, the Shugan Jieyu capsules group showed improvements in clinical outcomes, such as sleep latency, night awakenin…
Disclosures
The authors have nothing to disclose.
Acknowledgements
This work was supported by the National Nature Foundation of China (grant number 82004504) and the Chinese Medicine Administration of Sichuan Province (grant number 2021MS199).
Materials
| Endnote | Clarivate | Free trial version | EndNote is a widely used reference management tool to help you collect, organize, and share your references. Official website: https://endnote.com/downloads |
| Microsoft Excel | Microsoft | Official Version | Microsoft Excel, a spreadsheet software with an intuitive interface, excellent computing capabilities and charting tools, is one of the most popular data processing software for personal computers. |
| Microsoft Word | Microsoft | Official Version | Microsoft Word offers a number of easy-to-use document creation tools, as well as a rich set of features for creating complex documents, as well as text formatting or image manipulation. |
| Revman | Cochrane collaboration | Official Version | Review Manager (RevMan) is the international Cochrane Collaboration's proprietary software for systematic reviewers to produce and maintain Cochrane systematic reviews. Official website: https://training.cochrane.org/online-learning/core-software-cochrane-reviews/revman/revman-5-download/download-and-installation |
| Database websites | |||
| CBM | http://www.sinomed.ac.cn/ | ||
| CNKI | https://www.cnki.net/ | ||
| Cochrane Library | https://www.cochranelibrary.com/ | ||
| Embase | https://www.embase.com/ | ||
| Pubmed | https://pubmed.ncbi.nlm.nih.gov/ | ||
| VIP | http://www.cqvip.com/ | ||
| Wan fang | https://www.wanfangdata.com.cn/ | ||
| Web of Science | http://www.webofscience.com/ |
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