Insomnia is a widespread health complaint in general population which deserves appropriate recognition and attention. It is not only a risk factor for cardiovascular diseases (such as arterial hypertension, chronic heart failure, and myocardial infarction), obesity and type 2 diabetes, but also a common disease which frequently coexists with nervous system diseases (dementia, depression) [
Cognitive behavior therapy and drug therapy are the main methods of treating insomnia. Since cognitive behavior therapy does not work for everyone in all situations, drug therapy is still the most common method for treating insomnia so far [
Chinese medicine has a long history in the treatment of insomnia. Based on the conception of holism and the theory of syndrome differentiation and treatment, traditional Chinese medicine treats insomnia and regulates the patient’s body as a whole. It has unique advantages in improving sleep and life quality of the patients, and has little side effect.
Banxia (Pinellia Tuber) is the dried tuber of
Previous meta-analysis [
This systematic review and meta-analysis are based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: PRISMA statement search strategy [
Six databases including PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched from inception to April 2020 for the relevant RCTs of Banxia formulae for insomnia, with “insomnia” and “traditional Chinese medicine” as search terms, a subject word plus free words as search form. In order to ensure that eligible herbal formulae were included as many as possible, the specific herb name “Banxia” was not explicitly searched, and no restriction on language and publication period was set in this review. In addition, we also searched for references that have been included in relevant literature or systematic review.
Duplicate publications
Studies not meeting the inclusion criteria
Combined treatment of Banxia formulae and other therapy were used in the experimental group
Traditional Chinese medicine by oral administration was used in the experimental group and the control group at the same time
Studies with missing data
Studied assessed as high risk of bias by RoB2
The titles and abstracts of the retrieved articles were read by 2 independent review authors to exclude the obvious disqualified RCTs. Then, the full texts of the studies that potentially met the predefined inclusion criteria were obtained and read in order to select the eligible RCTs. When there were different opinions, the 2 review authors can reach consensus by discussing with the corresponding author of this article.
The methodological quality of the included RCTs was assessed by 2 independent review authors according to the Cochrane RoB2 criteria [
The disagreements on the methodological quality between the 2 review authors were solved by discussion and consulting a third author.
The data extraction was performed independently by 2 review authors according to the predesigned standard data extraction forms including the following items: lead author, publication year, country of origin, characteristics of participant, course of treatment, adverse events, and outcome measures. Disagreements were resolved in line with the principle of consensus through consultation. If the study reported the outcome data at different time points, the data of the last time point was extracted. For the trials with more than 2 groups or factorial designs allowing multiple comparisons, only the information and data reported in the original articles were extracted.
In each included study, the Banxia formula and its composition were recorded, with a frequency analysis of common drugs combined with Banxia.
The mean difference (
The statistical heterogeneity of the trials was assessed by
The publication bias was identified by Egger’s test, if an outcome was reported in at least 10 trials.
The sensitivity analysis was performed by excluding one study from the meta-analysis. If the estimated value of the point exceeded the 95%
A total of 2523 studies were retrieved from the 6 electronic databases. After the duplicates were removed, 1956 studies remained. In the remaining 1956 studies, 122 were eligible. By reading the full text of the 122 studies, 108 were excluded, among which 24 studies were with inappropriate interventions, 43 studies were without control group, 1 study was without full text, 7 studies were not real RCTs, 25 studies did not use Banxia formula, 7 studies had high risk of bias according to Cochrane RoB2, and 1 study was repeated publication. Finally, 14 studies including 910 participants were included and a meta-analysis was conducted on them [
Flow diagram of literature search and selection.
Basic characteristics of the 14 included studies are summarized in Table
Basic characteristics of the included studies.
Included trials treatment | Publication language | No. of participants (male/female; age years) | Treatment | Outcome index | Duration | Intergroup difference | ||
---|---|---|---|---|---|---|---|---|
Experimental | Control | Experimental | Control | |||||
Chen 2019 [ | Chinese | 25/15; 38.8 | 23/17; 38.6 | Huanglian wendan decoction | Tranquillizer | (1) Total effective rate | 20 d | (1) |
(4) Adverse event(s) | (4) | |||||||
Ding 2014 [ | Chinese | 12/18; 62.5 | 13/17; 63.5 | Wendan decoction | Tranquillizer | (1) Total effective rate | 28 d | (1) |
Fei 2018 [ | Chinese | 8/18; 40.62 | 6/14; 41.05 | Chaihu wendan decoction | Estazolam | (1) Total effective rate | 4 w | (1) |
(2) PSQI total score | (2) | |||||||
(3) TCM syndrome score | (3) | |||||||
(4) Adverse event(s) | (4) | |||||||
Fu 2018 [ | Chinese | 10/17; 57.33 | 8/18; 55.08 | Banxia Shumi decoction | Estazolam | (1) Total effective rate | 3 w | (1) |
(2) PSQI total score | (2) | |||||||
(3) TCM syndrome score | (3) | |||||||
(4) Adverse event(s) | (4) | |||||||
Guo 2016 [ | Chinese | 17/13; 42.33 | 14/16; 40.43 | Banxia Shumi decoction | Zopiclone | (1) Total effective rate | 21 d | (1) |
(2) PSQI total score | (2) | |||||||
(3) TCM syndrome score | (3) | |||||||
(4) Adverse event(s) | (4) | |||||||
Huang 2013 [ | Chinese | 15/5; 36.82 | 10/10; 41.16 | Wendan decoction | Tranquillizer | (1) Total effective rate | 20 d | (1) |
(4) Adverse event(s) | (4) | |||||||
Liu 2018 [ | Chinese | 14/16; 52.43 | 13/17; 51.57 | Banxia Xiexin decoction | Alprazolam | (1) Total effective rate | 4 w | (1) |
(2) PSQI total score | (2) | |||||||
(4) Adverse event(s) | (4) | |||||||
Wang 2012 [ | Chinese | 34/28; 68.4 | 24/26; 69.6 | Huoxue Huayu Tongluo decoction | Estazolam | (1) Total effective rate | 30 d | (1) |
Yin 2018 [ | Chinese | 14/16; 24.74 | 14/16; 24.33 | Banxia Xiexin decoction | Estazolam | (1) Total effective rate | 21 d | (1) |
(2) PSQI total score | (2) | |||||||
(3) TCM syndrome score | (3) | |||||||
Zhang 2012 [ | Chinese | 21/39; 19–65 | 10/20; 18–63 | Banxia formula | Tranquillizer | (1) Total effective rate | 4 w | (1) |
Zhang 2013 [ | Chinese | 16/23; 23–65 | 17/24; 22–64 | Anshen Huatan decoction | Estazolam | (1) Total effective rate | 4 w | (1) |
Zhang 2017 [ | Chinese | 15/13; 59 | 12/12; 48 | Banxia Shumi decoction and Huanglian wendan decoction | Alprazolam | (1) Total effective rate | 2 w | (1) |
(4) Adverse event(s) | (4) | |||||||
Zhang 2019 [ | Chinese | 8/21; 49.38 | 6/22; 44.21 | Banxia Xinxie decoction and Huanglian wendan decoction | Lorazepam | (1) Total effective rate | 4 w | (1) |
(2) PSQI total score | (2) | |||||||
(3) TCM syndrome score | (3) | |||||||
(4) Adverse event(s) | (4) | |||||||
Zheng 2016 [ | Chinese | 9/21; 40.13 | 12/18; 38.25 | Banxia Shumi decoction | Tranquillizer | (1) Total effective rate | 7 d | (1) |
PSQI, Pittsburgh Sleep Quality Index.
The composition of Banxia formulae in the included studies is listed in Table
The constituent of Banxia formulae in each included study.
Included trials | Formula | Ingredient | Dosage | ||
---|---|---|---|---|---|
Latin name | English name | Chinese name | |||
Chen 2019 [ | Huanglian wendan decoction | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Banxia | 15 g |
(2) Caulis bambusae in Taenia | (2) Bamboo shavings | (2) Zhuru | 15 g | ||
(3) Citri reticulatae pericarpium | (3) Tangerine peel | (3) Chenpi | 12 g | ||
(4) Fructus Aurantii immaturus | (4) Immature fruit of trifoliate-orange | (4) Zhishi | 10 g | ||
(5) Coptidis rhizoma | (5) Coptis root, Chinese goldthread | (5) Huanglian | 8 g | ||
(6) Zizyphus jujuba | (6) Chinese date | (6) Dazao | 5 g | ||
(7) Glycyrrhizae radix et rhizoma | (7) Liquorice root | (7) Zhigancao | 3 g | ||
(8) Zingiber officinale rosc. | (8) Ginger | (8) Shengjiang | 3 g | ||
Ding 2014 [ | Wendan decoction | (1) | (1) Nutgrass galingale rhizome | (1) Xiangfu | 20 g |
(2) Curcumae radix | (2) Aromatic turmeric root-tuber | (2) Yujin | 15 g | ||
(3) Albiziae cortex | (3) Silktree albizia bark | (3) Hehuanpi | 15 g | ||
(4) Caulis bambusae in Taenia | (4) Bamboo shavings | (4) Zhuru | 15 g | ||
(5) Fructus Aurantii Immaturus | (5) Immature fruit of trifoliate-orange | (5) Zhishi | 10 g | ||
(6) Citri reticulatae pericarpium | (6) Tangerine peel | (6) Chenpi | 10 g | ||
(7) Poria | (7) Indian buead tuckahoe | (7) Fuling | 15 g | ||
(8) Pinelliae rhizoma | (8) Pinellia ternata | (8) Fabanxia | 10 g | ||
(9) Ziziphi Spinosae Semen | (9) Spine date seed | (9) Suanzaoren | 15 g | ||
(10) Polygalae radix | (10) Thinleaf milkwort root | (10) Zhiyuanzhi | 10 g | ||
(11) Caulis polygoni multiflori | (11) Tuber fleeceflower stem | (11) Yejiaoteng | 15 g | ||
Fei 2018 [ | Chaihu wendan decoction | (1) Radix bupleuri | (1) Chinese thorowax root | (1) Chaihu | 10 g |
(2) Pinelliae rhizoma | (2) Pinellia ternata | (2) Fabanxia | 10 g | ||
(3) Scutellariae radix | (3) Baical skullcap root | (3) Huangqin | 10 g | ||
(4) Codonopsis radix | (4) Tangshen | (4) Dangshen | 10 g | ||
(5) Aurantii fructus | (5) Immature trifoliate-orange fruit | (5) Zhiqiao | 10 g | ||
(6) Citri reticulatae pericarpium | (6) Tangerine peel | (6) Chenpi | 10 g | ||
(7) Caulis bambusae in Taenia | (7) Bamboo shavings | (7) Zhuru | 10 g | ||
(8) Poria | (8) Indian buead tuckahoe | (8) Fuling | 10 g | ||
(9) Zingiber officinale rosc. | (9) Ginger | (9) Shengjiang | 5 g | ||
(10) Zizyphus jujuba | (10) Chinese date | (10) Hongzao | 10 g | ||
(11) Glycyrrhizae radix et rhizoma | (11) Liquorice root | (11) Zhigancao | 5 g | ||
Fu 2018 [ | Banxia Shumi decoction | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Fabanxia | 30 g |
(2) Setarie italica | (2) Husked sorghum | (2) Shumi | 15 g | ||
(3) Poria | (3) Indian buead tuckahoe | (3) Fuling | 20 g | ||
(4) Codonopsis radix | (4) Tangshen | (4) Dangshen | 15 g | ||
(5) Ganoderma | (5) Lucid ganoderma | (5) Lingzhi | 15 g | ||
(6) Albiziae cortex | (6) Silktree albizia bark | (6) Hehuanpi | 15 g | ||
(7) Polygalae radix | (7) Thinleaf milkwort root | (7) Yuanzhi | 15 g | ||
(8) Acori Tatarinowii rhizoma | (8) Acorus tatarinowii | (8) Shichangpu | 10 g | ||
(9) Aurantii fructus | (9) Immature trifoliate-orange fruit | (9) Zhiqiao | 15 g | ||
(10) Glycyrrhizae radix et rhizoma | (10) Liquorice root | (10) Gancao | 5 g | ||
Guo 2016 [ | Banxia Shumi decoction | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Banxia | 15 g |
(2) Coicis Semen | (2) Ma-yuen jobstears seed | (2) Yiyiren | 30 g | ||
(3) Coptidis rhizoma | (3) Coptis root, Chinese goldthread | (3) Huanglian | 5 g | ||
(4) Prunellae Spica | (4) Common selfheal spike | (4) Xiakucao | 15 g | ||
(5) Plumula nelumbinis | (5) Lotus plumule | (5) Lianzixin | 5 g | ||
(6) Ziziphi Spinosae Semen | (6) Spine date seed | (6) Suanzaoren | 30 g | ||
(7) Albiziae cortex | (7) Silktree albizia bark | (7) Hehuanpi | 10 g | ||
(8) Caulis polygoni multiflori | (8) Tuber fleeceflower stem | (8) Shouwuteng | 30 g | ||
Huang 2013 [ | Wendan decoction | (1) Citri reticulatae pericarpium | (1) Tangerine peel | (1) Chenpi | 9 g |
(2) Pinelliae rhizoma | (2) Pinellia ternata | (2) Banxia | 6 g | ||
(3) Polygalae radix | (3) Thinleaf milkwort root | (3) Yuanzhi | 3 g | ||
(4) Caulis bambusae in Taenia | (4) Bamboo shavings | (4) Zhuru | 6 g | ||
(5) Flos albiziae | (5) Silktree albizzia flower | (5) Hehuanhua | 9 g | ||
(6) Poria | (6) Indian buead tuckahoe | (6) Fuling | 5 g | ||
(7) Curcumae radix | (7) Aromatic turmeric root-tuber | (7) Yujin | 6 g | ||
(8) Glycyrrhizae radix et rhizoma | (8) Liquorice root | (8) Zhigancao | 3 g | ||
(9) Schisandrae chinensis fructus | (9) Chinese magnolcavine fruit | (9) Wuweizi | 6 g | ||
(10) Acorus calamus | (10) | (10) Changpu | 6 g | ||
Liu 2018 [ | Banxia Xiexin decoction | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Banxia | 6 g |
(2) Scutellariae radix | (2) Baical skullcap root | (2) Huangqin | 9 g | ||
(3) Coptidis rhizoma | (3) Coptis root, Chinese goldthread | (3) Huanglian | 3 g | ||
(4) Codonopsis radix | (4) Tangshen | (4) Dangshen | 15 g | ||
(5) Zingiberis rhizoma | (5) Dried ginger | (5) Ganjiang | 6 g | ||
(6) Glycyrrhizae radix et rhizoma | (6) Liquorice root | (6) Gancao | 6 g | ||
(7) Magnoliae officinalis cortex | (7) Officinal magnolia bark | (7) Houpo | 9 g | ||
(8) Prunellae Spica | (8) Common Selfheal spike | (8) Xiakucao | 12 g | ||
(9) Coicis Semen | (9) Ma-yuen jobstears seed | (9) Yiyiren | 24 g | ||
(10) Zizyphus jujuba | (10) Chinese date | (10) Dazao | 3 | ||
Wang 2012 [ | Banxia formula | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Qingbanxia | 12 g |
(2) Citri reticulatae pericarpium | (2) Tangerine peel | (2) Chenpi | 10 g | ||
(3) Poria | (3) Indian buead tuckahoe | (3) Fuling | 20 g | ||
(4) Arisaema cum bile | (4) Bile arisaema | (4) Dannanxing | 8 g | ||
(5) Polygalae radix | (5) Thinleaf milkwort root | (5) Yuanzhi | 12 g | ||
(6) Acori Tatarinowii rhizoma | (6) Acorus tatarinowii | (6) Shichangpu | 12 g | ||
(7) Radix salviae miltiorrhizae | (7) Danshen root | (7) Danshen | 30 g | ||
(8) Rhizoma ligustici chuanxiong | (8) Sichuan lovage rhizome | (8) Chuanxiong | 9 g | ||
(9) Paeoniae radix rubra | (9) Red paeony root | (9) Chishao | 15 g | ||
(10) Ziziphi Spinosae Semen | (10) Spine date seed | (10) Suanzaoren | 30–60 g | ||
(11) Spatholobi caulis | (11) Suberect Spatholobus stem | (11) Jixueteng | 30 g | ||
(12) Caulis polygoni multiflori | (12) Tuber fleeceflower stem | (12) Shouwuteng | 30 g | ||
(13) Glycyrrhizae radix et rhizoma | (13) Liquorice root | (13) Gancao | 10 g | ||
Yin 2018 [ | Banxia Xiexin decoction | (1) Mori cortex | (1) White mulberry root-bark | (1) Sangbaipi | 10 g |
(2) Pinelliae rhizoma | (2) Pinellia ternata | (2) Fabanxia | 10 g | ||
(3) Zingiberis rhizoma | (3) Dried ginger | (3) Ganjiang | 3–10 g | ||
(4) Coptidis rhizoma | (4) Coptis root, Chinese goldthread | (4) Huanglian | 3-5 g | ||
(5) Scutellariae radix | (5) Baikal skullcap root | (5) Huangqin | 10 g | ||
(6) Pogostemonis herba | (6) Cablin potchouli herb | (6) Huoxiang | 10 g | ||
(7) Atractylodis rhizoma | (7) Rhizoma atractylodis | (7) Cangzhu | 10 g | ||
(8) Magnoliae officinalis cortex | (8) Officinal magnolia bark | (8) Houpo | 10 g | ||
(9) Poria | (9) Indian buead tuckahoe | (9) Fuling | 10 g | ||
(10) Pulvis Talci | (10) Talc powder | (10) Huashi | 20 g | ||
(11) Medulla Tetrapanacis | (11) Ricepaperplant pith | (11) Tongcao | 10 g | ||
(12) Codonopsis radix | (12) Tangshen | (12) Dangshen | 10 g | ||
(13) Glycyrrhizae radix et rhizoma | (13) Liquorice root | (13) Gancao | 3 g | ||
Zhang 2012 [ | Huanglian wendan decoction | (1) Coptidis rhizoma | (1) Coptis root, Chinese goldthread | (1) Huanglian | 9 g |
(2) Caulis bambusae in Taenia | (2) Bamboo shavings | (2) Jiangzhuru | 9 g | ||
(3) Arisaema cum bile | (3) Bile arisaema | (3) Dannanxing | 9 g | ||
(4) Pinelliae rhizoma | (4) Pinellia ternata | (4) Jiangbanxia | 9 g | ||
(5) Citri reticulatae pericarpium | (5) Tangerine peel | (5) Chenpi | 9 g | ||
(6) Fructus Aurantii Immaturus | (6) Immature fruit of trifoliate-orange | (6) Zhishi | 12 g | ||
(7) Poria | (7) Indian buead tuckahoe | (7) Fushen | 15 g | ||
(8) Gardenia jasminoides ellis | (8) Cape jasmine | (8) Jiaozhizi | 12 g | ||
(9) Hyriopsis cumingii(Lea) or cristaria plicata(Leach) or pteria martensii(Dunker) | (9) Mother-of-pearl | (9) Zhenzhumu | 30 g | ||
(10) Glycyrrhizae radix et rhizoma | (10) Liquorice root | (10) Zhigancao | 6 g | ||
(11) Zingiber officinale rosc. | (11) Ginger | (11) Shengjiang | 6 g | ||
(12) Zizyphus jujuba | (12) Chinese date | (12) Dazao | 10 g | ||
Zhang 2013 [ | Anshen Huatan decoction (free-frying Chinese medicine granule) | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Jiangbanxia | 10 g |
(2) Caulis polygoni multiflori | (2) Tuber fleeceflower stem | (2) Shouwuteng | 30 g | ||
(3) Citri reticulatae pericarpium | (3) Tangerine peel | (3) Chenpi | 12 g | ||
(4) Poria | (4) Indian buead tuckahoe | (4) Fushen | 20 g | ||
(5) Aurantii fructus | (5) Immature trifoliate-orange fruit | (5) Zhiqiao | 12 g | ||
(6) Caulis bambusae in Taenia | (6) Bamboo shavings | (6) Zhuru | 10 g | ||
(7) Albiziae cortex | (7) Silktree albizia bark | (7) Hehuanpi | 30 g | ||
(8) Os draconis | (8) Dragon’s bones | (8) Longgu | 20 g | ||
(9) Ostreae concha | (9) Common oyster shell | (9) Muli | 20 g | ||
(10) Glycyrrhizae radix et rhizoma | (10) Liquorice root | (10) Gancao | 6 g | ||
(11) Ziziphi Spinosae Semen | (11) Spine date seed | (11) Suanzaoren | 30 g | ||
(12) Cortex magnoliae officinalis | (12) Officinal magnolia bark | (12) Hupo | 9 g | ||
Zhang 2017 [ | Banxia Shumi decoction and Huanglian wendan decoction | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Banxia | 15 g |
(2) Setarie italica | (2) Husked sorghum | (2) Shumi | 15 g | ||
(3) Citri reticulatae pericarpium | (3) Tangerine peel | (3) Chenpi | 9 g | ||
(4) Poria | (4) Indian buead tuckahoe | (4) Fuling | 12 g | ||
(5) Fructus AIIurantii Immaturus | (5) Immature fruit of trifoliate-orange | (5) Zhishi | 10 g | ||
(6) Coptidis rhizoma | (6) Coptis root, Chinese goldthread | (6) Huanglian | 5 g | ||
(7) Caulis Bambusae in Taenia | (7) Bamboo shavings | (7) Zhuru | 12 g | ||
(8) Massa medicata fermentata | (8) Medicated leaven | (8) Shenqu | 15 g | ||
Zhang 2019 [ | Banxia Xiexin decoction and Huanglian wendan decoction | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Fabanxia | 9 g |
(2) Os draconis | (2) Dragon’s bones | (2) Longgu | 30 g | ||
(3) Ostreae concha | (3) Common oyster shell | (3) Muli | 30 g | ||
(4) Coptidis rhizoma | (4) Coptis root, Chinese goldthread | (4) Huanglian | 6 g | ||
(5) Scutellariae radix | (5) Baical skullcap root | (5) Huangqin | 12 g | ||
(6) Acori Tatarinowii rhizoma | (6) Acorus tatarinowii | (6) Shichangpu | 10 g | ||
(7) Polygalae radix | (7) Thinleaf milkwort root | (7) Yuanzhi | 10 g | ||
(8) Citri reticulatae pericarpium | (8) Tangerine peel | (8) Chenpi | 10 g | ||
(9) Fructus AIIurantii Immaturus | (9) Immature fruit of trifoliate-orange | (9) Zhishi | 10 g | ||
(10) Caulis bambusae in Taenia | (10) Bamboo shavings | (10) Zhuru | 10 g | ||
(11) Poria | (11) Indian buead tuckahoe | (11) Fuling | 10 g | ||
(12) Paeoniae radix alba | (12) White paeony root | (12) Baishao | 15 g | ||
(13) Codonopsis radix | (13) Tangshen | (13) Dangshen | 10 g | ||
(14) Glycyrrhizae radix et rhizoma | (14) Liquorice root | (14) Gancao | 6 g | ||
(15) Zizyphus jujuba | (15) Chinese date | (15) Dazao | 3 | ||
Zheng 2016 [ | Banxia Shumi decoction | (1) Pinelliae rhizoma | (1) Pinellia ternata | (1) Fabanxia | 40 g |
(2) Poria | (2) Indian buead tuckahoe | (2) Fuling | 30 g | ||
(3) | (3) Common yam rhizome | (3) Shanyao | 30 g | ||
(4) Albiziae cortex | (4) Silktree albizia bark | (4) Hehuanpi | 30 g | ||
(5) Os draconis | (5) Dragon’s bones | (5) Longgu | 18 g | ||
(6) Ostreae concha | (6) Common oyster shell | (6) Muli | 18 g | ||
(7) Caulis polygoni multiflori | (7) Tuber fleeceflower stem | (7) Shouwuteng | 30 g | ||
(8) Codonopsis radix | (8) Tangshen | (8) Dangshen | 12 g | ||
(9) Atractylodis macrocephalae rhizoma | (9) Largehead atractylodes Rh | (9) Baizhu | 10 g |
The top 7 frequency Chinese herbal medicines of formulae.
English name | Chinese name | Frequency | The total frequency (%) |
---|---|---|---|
Pinellia ternata | Banxia | 14 | 100.0 |
Liquorice root | Gancao | 10 | 71.4 |
Tangerine peel | Chenpi | 9 | 64.3 |
Indian buead tuckahoe | Fuling | 9 | 64.3 |
Bamboo shavings | Zhuru | 8 | 57.1 |
Coptis root, Chinese goldthread | Huanglian | 7 | 50.0 |
Tangshen | Dangshen | 6 | 42.9 |
Figure
Assessment of risk of bias.
All the 14 included studies reported the total effective rate, which indicated the total effective rate of the experimental group was higher than that of the control group (
Meta-analysis of the total effective rate in experimental group and control group.
In order to evaluate whether the efficacy of Banxia formulae was affected by variable factors, subgroup analyses were conducted according to the course of treatment (≤21 d, >21 d), the dosage of Banxia (≤9 g, >9 g), and the processing method of Banxia (Banxia, Fabanxia, Jiangbanxia). The results of the subgroup analysis showed the total effective rate of the experimental group was significantly higher than that of the control group. The data was listed as follows: treatment duration ≤21 days (
The total effective rate analysis of different duration.
The total effective rate analysis of different dose of Banxia.
The total effective rate analysis of different proceeding method of Banxia.
The subgroup analysis did not show any significant differences among the subgroups divided according to treatment duration, the dosage of Banxia, and the processing method of Banxia (Table
Subgroup analysis of the total effective rate for each variable.
Variable | Effects model | RR | 95% CI | Figure | Heterogeneity (chi-squared test and | Total patients | |
---|---|---|---|---|---|---|---|
≤21 d | Fixed | 1.15 | 1.05–1.25 | 4 | 0.001 | 405 | |
>21 d | Fixed | 1.31 | 1.19–1.44 | 4 | <0.00001 | 505 | |
≤9 g | Fixed | 1.30 | 1.14–1.49 | 5 | 0.0001 | 247 | |
>9 g | Fixed | 1.21 | 1.12–1.30 | 5 | <0.00001 | 663 | |
Banxia | Fixed | 1.18 | 1.07–1.31 | 6 | 0.001 | 292 | |
Fabanxia | Fixed | 1.15 | 1.04–1.26 | 6 | 0.005 | 336 | |
Jiangbanxia | Fixed | 1.50 | 1.24–1.83 | 6 | <0.0001 | 170 |
Six studies reported the total score of PSQI. The results varied with the course of treatment. When the course of treatment ≤21 days, the efficacy on the total score of PSQI of the experimental group was equivalent to that of the control group (
The Pittsburgh Sleep Quality Index (PSQI) total score analysis of different duration.
Five studies analyzed the TCM syndrome score. Compared with the control group, the TCM syndrome score of the group treated by Banxia formula was significantly improved (SMD = −0.78, 95%
The TCM syndrome score analysis of Banxia formulae for insomnia.
Eight studies mentioned adverse events, in which 5 reported adverse events occurring during treatment and provided sufficient information about the adverse events [
Summary of adverse events.
Studies | Experimental | Control | Adverse events | |||
---|---|---|---|---|---|---|
Total | Total | Experimental | Control | |||
Chen 2019 [ | 0 | 40 | 4 | 40 | Fatigue, drowsiness, and loss of memory | |
Fu 2018 [ | 4 | 27 | 9 | 26 | Lip numbness, consciously thickened lips, tongue numbness and discomfort in throat, and bitter mouth | Drowsiness during the day, dizziness and fatigue, dry mouth, and bitter mouth |
Liu 2018 [ | 0 | 30 | 2 | 30 | Constipation | |
Zhang 2017 [ | 4 | 28 | 5 | 24 | Dry mouth, disgusting | Dizziness, fatigue, upset, and loss of appetite |
Zhang 2019 [ | 2 | 29 | 2 | 28 | Acid reflux, heartburn, and loose stools | Dizzy |
Adverse events in the experimental groups mainly included numbness in the lips or the tongue, throat discomfort, bitter taste in the mouth, dry mouth, nausea, acid reflux, heartburn, diarrhea, etc. Adverse events in the control group mainly included daytime drowsiness, dizziness, fatigue, dry mouth, bitter taste in the mouth, constipation, upset, drowsiness, deterioration of memory, and loss of appetite. There were no reports of any serious adverse events related to drugs used in the studies.
Meta-analysis showed that there was statistically significant difference in the incidence of adverse events between the two groups (
The adverse events analysis of Banxia formulae for insomnia.
In the Egger’s test for evaluating publication bias in total effective rate of the two groups,
Egger’s test of the total effective rate.
The sensitivity analysis did not indicate that the final outcome would change because of the exclusion of any individual study, which meant that no single study can significantly affect the pooled
Banxia is a classic Chinese medicine with a long history of treating insomnia. Many clinical trials and pharmacological studies [
Although 5 studies including 154 patients reported adverse events, only 10 patients had mild adverse events which was possibly related to Banxia formulae without powerful evidence. The meta-analysis showed that there was statistically significant difference in the incidence of adverse events between the two groups (
Some limitations existed in this study. Firstly, despite the efforts by us to search the commonly used databases at home and abroad as comprehensively as possible, all the finally included studies were conducted and published in China, because traditional Chinese medicine has not been widely promoted and used in other countries. Therefore, the results of this study have certain limitations. Secondly, although trials with high risk of bias were excluded based on RoB2, some included studies were still short on methodological details. Only two studies described an appropriate method of allocation concealment, and only two studies used single-blind method. Due to the condition limitations, the current designs for RCTs on Banxia formulae could not meet the demand of blind method compared with those for RCTs on conventional therapy. Thirdly, Egger’s test (
Modern pharmacological studies show that Banxia or Banxia preparations have sedative and hypnotic effects. There are also some studies about the mechanism of Banxia. Wu et al. found that ethanol fraction from Rhizoma Pinelliae Praeparatum possessed sedative, hypnotic, and anticonvulsant activities and these activities may be related to the GABAergic system [
In the included studies, there were 5 trials with Banxia and 9 trials with Banxia preparation (6 Fabanxia, 2 Jiangbanxia, 1 Qingbanxia). As for the dosage of Banxia, 4 trials were ≤9 g and 10 trials were >9 g, which showed the clinical application habit of Banxia. In this study, we found Banxia formulae can significantly improve the total effective rate of patients with insomnia, regardless of the dosage and processing method of Banxia, and the safety of Banxia formulae for insomnia is relatively stable. However, due to the lack of description of adverse events in the outcome, we did not analyze the safety of Banxia based on its dosage and processing methods, so further study on this aspect is needed.
At first, in order to facilitate more reliable comparison of study results, more clinical trials with large samples which is carefully designed according to international standards are needed. More attention should be paid to the principle of randomization and allocation concealment. Secondly, the standards of outcome measures and test drugs should be as uniform as possible, so as to strengthen the evidence and make the reevaluation more reliable. Finally, in this study, we found Gancao, Chenpi, Fuling, Zhuru, Huanglian, and Dangshen were the most frequently used herbs in Banxia formulae for treating insomnia, which should be considered firstly when formulating optimal Banxia formula for insomnia. At the same time, for the purpose of reducing toxicity, we recommend Banxia should be used with ginger or used in processed forms.
According to the current studies, the efficacy of Banxia formula in the treatment of insomnia is better than that of the conventional western medicines, and its safety is relatively stable. Current evidence-supported Banxia formulae could be used as a beneficial treatment for insomnia. However, due to the limitations of this study, further research and evaluation are needed.
Yan-Hua Lin and Cong Chen are the co-first authors.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Yan-Hua Lin and Cong Chen contributed equally to this work. S-YM developed the research ideas and then designed the search strategy. L-YH, ZX, and X-GX did data acquisition. L-YH, CC, and Y-MQ analyzed data. L-YH wrote the first draft of the manuscript. M-YF contributed to the revision. All authors interpreted the data analysis and critically revised the manuscript.
This work was supported by the Shandong Provincial Natural Science Foundation, China (grant no. ZR2017LH062).