We present a systematic review of existing research that aims to assess the efficacy and safety of herbal medications (HM), as either monotherapy or adjunct to orthodox medications (OM), mainly comprised of cholinesterase inhibitors, for vascular dementia (VaD). We included 47 studies conducted in mainland China, each testing different HM. Of 43 HM monotherapy studies, 37 reported HM to be significantly better than OM or placebo; six reported similar efficacy between HM and OM. All four HM adjuvant studies reported significant efficacy. No major adverse events for HM were reported. Heterogeneity in diagnostic criteria, interventions and outcome measures hindered comprehensive data analysis. Studies suggested that HM can be a safe and effective treatment for VaD, either alone or in conjunction with OM. However, methodological flaws in the design of the studies limited the extent to which the results could be interpreted. Thirty most commonly used herbal constituents, including Rhizoma Chuanxiong (Chuanxiong in Chinese), Radix Polygoni Multiflori (Heshouwu in Chinese) and Radix Astragali (Huangqi in Chinese). were ranked. Further multi-center trials with large sample sizes, high methodological quality and standardized HM ingredients are necessary for clinical recommendations to be made.
Vascular dementia (VaD) is one of the most common forms of dementia after Alzheimer’s disease (AD) [
VaD accounts for approximately 30% of dementia in the world today [
Drugs currently used in the treatment of VaD include cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) [
Owing to the limitations of OM and therapeutic prevention, some patients resort to herbal medications (HM). Traditionally, a number of herbs have been used for cognitive disorders. For example,
In China, a nation with its own system of medicine that has been continuously documented over two thousand years, the incorporation of Chinese herbal medicine (CHM) with Western medicine in the treatment of dementia has become a standard in recent decades.
In a previously conducted systematic review [
This systematic review was conducted to assess the safety and efficacy of HM, as either monotherapy or adjunct to OM in the treatment of VaD.
All published studies reporting randomized, controlled clinical trials comparing HM as monotherapy or adjuvant therapy, with placebo or OM as controls, were included. No restriction on the language of publication was imposed. As there is a lack of a single, specific criterion for the diagnosis of VaD [
We identified trials from the following electronic databases: (1) Ovid MEDLINE In-Process and Other Non-Indexed Citations and Ovid MEDLINE; (2) CINAHL; (3) EMBASE; (4) EBM Reviews; (5) AMED; (6) ACP Journal Club; (7) Cochrane Central Register of Controlled Trials; (8) Cochrane Database of Systematic Reviews; (9) Cochrane Methodology Register; (10) Database of Abstracts of Reviews of Effects; (11) Health Technology Assessment; (12) National Health Service Economic Evaluation; (13) China National Knowledge Infrastructure (CNKI); (14) Chinese Sci and Tech Journals (VIP); (15) CBM disc; (16) China Doctor Dissertations Full-Text Database; (17) China Master Theses Full-text Database. The search conducted in March 2011 followed a strategy (Table
Search strategy.
1 | exp Plant Extracts/or exp Drugs, Chinese Herbal/or exp Plants, Medicinal/or exp Medicine, Chinese Traditional/or exp China/or chinese medicine.mp. or exp Medicine, Oriental Traditional/or exp Phytotherapy/ |
2 | drugs non prescription.mp. or exp Drugs, Non-Prescription/ |
3 | medicinal herbs.mp |
4 | herbs medicinal.mp. |
5 | drugs non prescription.mp. or exp Drugs, Non-Prescription/ |
6 | alternative medicine.mp. or exp Complementary Therapies/ |
7 | complementary medicine.mp. |
8 | Phytotherapy/or Plants, Medicinal/or Plant Extracts/or Herb-Drug Interactions/or herbs.mp. or Drugs, Chinese Herbal/or Plant Preparations/ |
9 | exp Phytotherapy/or exp Plants, Medicinal/or exp Plant Extracts/or exp Herb-Drug Interactions/or exp Alkaloids/or herbs.mp. or exp Drugs, Chinese Herbal/or exp Plant Preparations/ |
10 | 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 |
11 | randomized controlled trials.mp. or exp Randomized Controlled Trials/ |
12 | exp Random Allocation/or exp Clinical Trials/or exp Double-Blind Method/or double blind.mp. or exp Placebos/ |
13 | single blind.mp. or exp Single-Blind Method/ |
14 | clinical trials.mp. |
15 | prospective studies.mp. or exp Prospective Studies/ |
16 | follow up studies.mp. or exp Follow-Up Studies/ |
17 | 11 or 12 or 13 or 14 or 15 or 16 |
18 | exp Mental Retardation/or exp Dementia/or exp vascular dementia/or progressive brain disorder.mp. or exp Memory Disorders/ |
19 | (vascular dementia).mp. |
20 | 18 or 19 |
21 | 10 and 17 and 20 |
Two independent reviewers (K. W. Chan and S. C. Man) assessed the trials for their eligibility. The inclusion of trials was confirmed upon consensus of reviewers. Risk of bias assessment of the trials was performed according to the revised Consolidated Standards of Reporting Trials (CONSORT) statement [
Using the search strategy as described, 116 studies were identified. Upon full-text examination we excluded 69, on the basis that (1) 13 were not randomized controlled trials, (2) four were repeat publications, (3) three did not state their inclusion criteria, (4) one included other forms of dementia, (5) 44 did not disclose adequate baseline information, and (6) four involved the use of non-HM intervention, such as acupuncture. These disqualifications left 47 studies for this systematic review.
There were a total of 3725 participants (2423 male, 1302 female) in the 47 included trials. Among them, three had cross-over design while the remaining were parallel design studies. The age of participants ranged from 45–89 years old, and their disease duration ranged from two months to 12 years. Thirty-two studies were performed in a single center; one was performed in multiple centers; 14 trials did not give this information. The duration of trials lasted from one to seven months. All of the trials were conducted in mainland China, and all the subjects were of Chinese ethnicity.
Methodological quality of studies (CONSORT checklist).
Reported page number of each item*1 | ||||||||||||||||||||||||
Abstracts | Method | Randomization | Results | Discussion | ||||||||||||||||||||
Number | Author | Year | Title and abstract | Introduction | Participant | Intervention | Objective | Outcome | Sample size | Sequence generation | Allocation concealment | Implementation | Blinding | Statistical methods | Participant flow | Recruitment | Baseline data | Numbers analyzed | Outcomes and estimation | Ancillary analyses | Adverse events | Interpretation | Generalisability | Overall evidence |
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | |||
1 | Wan et al. | 1998 | 25 | 25 | 25 | 25 | 24 | 25 | U | U | U | U | U | U | U | U | 25 | 26 | 26 | U | U | 27 | U | 27 |
2 | Zhao et al. | 1999 | 585 | 585 | 585 | 586 | 585 | 586 | U | U | U | U | U | 586 | U | 585 | 585 | 585 | 586 | U | 587 | 587 | 587 | 587 |
3 | Ji | 2000 | 10 | 10 | 10 | 11 | U | 11 | U | U | U | U | U | U | U | 10 | 10 | U | 11 | U | U | 11 | U | 11 |
4 | Lu et al. | 2000 | 290 | 290 | 290 | 290 | 290 | 290 | U | U | U | U | U | 290 | U | U | 290 | 290 | 290 | U | U | 290 | U | 290 |
5 | Luo | 2001 | 470 | U | 470 | 470 | 470 | 471 | U | U | U | U | 470 | 471 | U | 470 | 470 | 472 | 472 | 472 | U | 472 | 473 | 473 |
6 | Zhang et al. | 2001 | U | 51 | 51 | 51 | U | 51 | U | U | U | U | U | U | U | 51 | 51 | 52 | 52 | U | 52 | 52 | 52 | 52 |
7 | Zhou and Yi | 2001 | 14 | 14 | 14 | 14 | 14 | 14 | U | U | U | U | U | U | U | U | 14 | 15 | 15 | U | U | 15 | U | 15 |
8 | Cao et al. | 2002 | 80 | 80 | 80 | 80 | 80 | 80 | U | U | U | U | 80 | 81 | U | 80 | 80 | 81 | 81 | U | 81 | 81 | U | 81 |
9 | Hong et al. | 2002 | U | 3 | 3 | 3 | U | 3 | U | U | U | U | U | 3 | U | 3 | 3 | 4 | 4 | 4 | U | 5 | 5 | 5 |
10 | Huang et al. | 2002 | 301 | 301 | 301 | 302 | 301 | 302 | U | U | U | U | U | 302 | U | U | 302 | 301 | 302 | U | U | 303 | 303 | 303 |
11 | Liu et al. | 2002 | 526 | 526 | 526 | 526 | 526 | 526 | U | U | U | U | U | U | U | 526 | 526 | U | 527 | U | U | 527 | U | 527 |
12 | Wang et al. | 2002 | U | 295 | 296 | 296 | U | 296 | U | U | U | U | U | U | U | 295 | 295 | 296 | 296 | U | U | 296 | U | 296 |
13 | Yang et al. | 2002 | 48 | 48 | 49 | 49 | 48 | 49 | U | U | U | U | 48 | 49 | U | U | 48 | 49 | 49 | U | U | 50 | 51 | 51 |
14 | Cai et al. | 2003 | 482 | 482 | 482 | 482 | 482 | 482 | U | 482 | U | U | U | 483 | U | U | 482 | 483 | 483 | U | 483 | 483 | 483 | 483 |
15 | Guo et al. | 2003 | U | 931 | 931 | 931 | U | 931 | U | U | U | U | U | U | U | U | 931 | 931 | 931 | U | U | 931 | U | 931 |
16 | Jia et al. | 2003 | 20 | 20 | 20 | 20 | 20 | 21 | U | U | U | U | U | 21 | U | 20 | 20 | 21 | 21 | U | 21 | 22 | U | 22 |
17 | Cheng et al. | 2004 | 16 | 16 | 16 | 16 | 16 | 16 | U | U | U | U | U | 16 | U | U | 16 | 17 | 17 | U | U | 17 | 17 | 17 |
18 | Liao et al. | 2004 | 112 | 112 | 112 | 113 | 112 | 113 | U | U | U | U | U | 113 | U | 113 | 112 | 113 | 113 | U | 113 | 113 | 114 | 114 |
19 | Shen and Du | 2004 | 41 | 41 | 42 | 42 | 41 | 42 | U | U | U | U | U | 42 | U | 42 | 42 | 42 | 43 | U | U | 43 | 43 | 43 |
20 | Wang et al. | 2004 | 679 | 679 | 679 | 680 | 679 | 680 | U | 680 | 680 | 680 | 680 | 680 | 681 | U | 679 | 680 | 680 | U | 681 | 681 | 681 | 681 |
21 | Wang et al. | 2004 | 1691 | 1691 | 1691 | 1692 | 1691 | 1692 | U | U | U | U | U | 1692 | U | 1691 | 1691 | 1692 | 1692 | U | U | 1693 | U | 1693 |
22 | Wu et al. | 2004 | 3 | 3 | 3 | 3 | 3 | 3 | U | U | U | U | 3 | 3 | U | U | 3 | 4 | 4 | U | 4 | 4 | U | 4 |
23 | Yu et al. | 2004 | 424 | 424 | 424 | 424 | 424 | 424 | U | U | U | U | 424 | U | U | 424 | 424 | 425 | 425 | U | 425 | 425 | 425 | 425 |
24 | Zhao | 2004 | 8 | 9 | 9 | 9 | 8 | 9 | U | U | U | U | U | 9 | U | 9 | 9 | 9 | 9 | U | 9 | 9 | U | 10 |
25 | Feng et al. | 2005 | 520 | 520 | 520 | 520 | 520 | 520 | U | U | U | U | U | 521 | U | 520 | 520 | 521 | 521 | U | U | 521 | 522 | 521 |
26 | Liu | 2005 | 50 | 50 | 50 | 50 | 50 | 50 | U | U | U | U | U | 50 | 51 | 50 | 51 | 51 | 51 | U | 51 | 51 | 51 | 51 |
27 | Liu et al. | 2005 | 1052 | 1052 | 1052 | 1052 | U | 1052 | U | U | U | U | U | 1053 | U | 1053 | 1052 | 1053 | 1053 | U | 1054 | 1054 | 1054 | 1054 |
28 | Liu and Chen | 2005 | 18 | 18 | 18 | 19 | 18 | 19 | U | U | U | U | U | 19 | U | U | 18 | 19 | 19 | U | U | 20 | U | 20 |
29 | Tang et al. | 2005 | 426 | 426 | 426 | 427 | 426 | 427 | U | U | U | U | U | 427 | U | 426 | 426 | 427 | 427 | U | 427 | 427 | 427 | 427 |
30 | Wang et al. | 2005 | 93 | U | 93 | 94 | 93 | 94 | U | 94 | 94 | U | 94 | 94 | U | 93 | 94 | 94 | 94 | U | 95 | 94 | U | 94 |
31 | Wang, Chen and Bai | 2005 | 3 | 3 | 3 | 3 | 3 | 4 | U | U | U | U | U | 4 | U | 3 | 3 | 3 | 4 | U | U | 4 | 5 | 5 |
32 | Wang et al. | 2005 | 260 | 260 | 261 | 261 | 260 | 261 | U | U | U | U | 261 | 261 | U | U | 260 | 261 | 261 | U | 261 | 262 | U | 262 |
33 | Wang | 2005 | 40 | 40 | 40 | 40 | 40 | 40 | U | U | U | U | U | 40 | U | 40 | 40 | 40 | 41 | U | U | 41 | 41 | 41 |
34 | Zhou et al. | 2005 | 11 | 11 | 11 | 11 | 11 | 12 | U | U | U | U | U | 12 | U | 11 | 11 | 12 | 12 | U | U | 13 | U | 13 |
35 | Gao | 2006 | 14 | 14 | 14 | 14 | 14 | 15 | U | U | U | U | U | U | U | 14 | 14 | 15 | 15 | U | U | 16 | U | 16 |
36 | Hao et al. | 2006 | 424 | 424 | 424 | 424 | 424 | 424 | U | U | U | U | U | 425 | U | U | 424 | 425 | 425 | U | 425 | 425 | U | 425 |
37 | Li et al. | 2006 | 48 | 48 | 48 | 48 | U | 48 | U | U | U | U | U | 48 | U | 48 | 48 | 48 | 48 | U | U | 49 | 49 | 49 |
38 | Mou | 2006 | 1607 | 1607 | 1607 | 1607 | 1607 | 1607 | U | U | U | U | U | U | U | U | 1607 | 1607 | 1607 | U | 1607 | U | U | 1607 |
39 | Shi and Wang | 2006 | 200 | 200 | 200 | 200 | 200 | 200 | U | 200 | U | U | 200 | 200 | U | U | 200 | 201 | 201 | U | U | 201 | 201 | 201 |
40 | Zhang and Lu | 2006 | 680 | 680 | 680 | 680 | 680 | 681 | U | U | U | U | U | U | U | U | 680 | 681 | 681 | U | U | 681 | 681 | 681 |
41 | Chen et al. | 2007 | 866 | 866 | 866 | 867 | 866 | 867 | U | 867 | U | U | 867 | 867 | U | 866 | 866 | 867 | 867 | U | U | 868 | 868 | 868 |
42 | Cui et al. | 2007 | 64 | 64 | 64 | 64 | 64 | 64 | U | 64 | U | U | U | 65 | U | 64 | 64 | U | 65 | U | U | 65 | U | 65 |
43 | He | 2007 | 60 | U | 60 | 60 | U | 60 | U | U | U | U | 60 | 60 | U | U | 60 | 60 | 60 | U | 61 | 61 | U | 61 |
44 | Jin et al. | 2007 | 1657 | 1657 | 1657 | 1658 | 1657 | 1658 | U | U | U | 1658 | 1658 | 1658 | U | U | 1657 | 1658 | 1658 | U | 1659 | 1659 | 1659 | 1659 |
45 | Yan | 2007 | 41 | U | 41 | 41 | 41 | 41 | U | U | U | U | U | U | U | U | 41 | 41 | 41 | U | U | 41 | 41 | 42 |
46 | Chang | 2008 | 241 | 240 | 240 | 241 | 240 | 241 | U | U | U | U | U | U | U | 240 | 241 | 241 | 241 | U | 241 | 241 | U | 241 |
47 | Li et al. | 2008 | 369 | 369 | 369 | 370 | 369 | 370 | U | U | U | U | U | 370 | U | 369 | 369 | 370 | 370 | U | 371 | 371 | 371 | 371 |
Key *1: U = the relevant item was not found in the paper.
We adopted the checklist of items suggested by CONSORT [
Except for 4 studies [
With regard to method, none of the 47 studies reported details for sample size calculations. Eight [
For the results section, only two studies [
In the discussion section, both the interpretation and overall evidence were adequately reported by the studies; generalizability, however, was not sufficiently illustrated by 13 studies.
All of the included studies claimed to have allocated participants randomly to study groups. Six [
Except for one study [
Study properties.
Study | Design | Sample and characteristics | Diagnostic criteria | Herbal intervention | Control | Outcome measures | ITT*1 | Drop out*2 | ADR*3 | |
---|---|---|---|---|---|---|---|---|---|---|
1 | Wan et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 2 months duration | 68 VaD patients, age: 58–82; duration: 4.37–15.85 yr | DSM-3-R, HDS, HIS, “TCM dementia differential criteria”*a | Fucong 150 mL, | Piracetam | MMSE, HDS, BEAM, hemodynamic changes | N | N | U |
2 | Zhao et al. [ | Randomized: method not mentioned; single blind; parallel design; 2 months duration | 46 VaD patients; age: 57–76; duration: 6 m –1 yr | DSM-4, HIS, HDS, MMSE, “Protocol for new herbal drugs study on dementia”* b | Xianlong | Hydergine | TCD, hemodynamic changes | N | N | U |
3 | Ji [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 2 months duration | 68 VaD patients; age: 58–82; duration: 1.45-3.24 yr | DSM-3-R, HDS, HIS, “TCM dementia differential criteria”* a | Dangguishaoy | Piracetam | MMSE, HDS | N | N | U |
4 | Lu et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 60 days duration | 50 VaD patients; age: 56–82; duration: 2–6 yr | DSM-3-R, MMSE, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”* c | Shentong 10 g, | Hydergine | MMSE, BBS | N | N | U |
5 | Luo et al. [ | Randomized: method not mentioned; double blind: method not mentioned; parallel design; 75 days duration | 68 VaD patients; age: 49–79; duration: 0.99–2.07 yr | DSM-4, ICD 10, HIS, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”* c | Shenmayizhi | Hydergine | MMSE, ADL, BEAM, Neurological deficits | N | N | U |
6 | Zhang et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 3 months duration | 61 VaD patients; age: 60–77; duration: 6 m–2.5 yr; | NINDS-AIREN, HIS, HDS, “protocol for new herbal drugs study on dementia”* b | Jiannaotongluo | Aniracetam | HDS, hemodynamic changes | N | N | U |
7 | Zhou and Yi [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 3 months duration | 46 VaD patients; age: 60–80; duration: 8 m–3 yr | DSM-3, “protocol for new herbal drugs study on dementia,”*b “protocol for new herbal drugs study on stroke”* b | Yinaoling | Piracetam | HDS, FAQ, CCSE | N | N | U |
8 | Cao et al. [ | Randomized: method not mentioned; double blind: method not mentioned; parallel design; 60 days duration | 53 VaD patients; age: 58–75; duration: 3 m–12 m | DSM-4 | Congsheng | Hydergine | MMSE, BBS, TCD, EKG, SELF | N | N | N |
9 | Hong et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 60 days duration | 86 VaD patients; age: 45–76; duration: 5 m–3 yr | DSM-4, MMSE, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia,”* c CORELATION, HIS | Shouxing | Piracetam | MMSE, ADL | N | N | U |
10 | Huang et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 3 months duration | 58 VaD patients; age: 57–79; duration: 6 m–3 yr | DSM-4, MMSE, ADL, HIS, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”* c | Naohuandan | Piracetam | MMSE, ADL, E2, T, hemodynamic changes | N | N | U |
11 | Liu et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 2 months duration | 64 VaD patients; age: 54–81; duration: 0.8–3 yr | DSM-4, HIS, CT, MRI | Tongqiaohuoxue- | Duxil 1 tablet | MMSE, HDS, hemodynamic changes | N | N | U |
12 | Wang et al. [ | Randomized: method not mentioned; single blind: method not mentioned; parallel design; 30 days duration | 300 VaD patients; age: 52–83; duration: 7 m–7 yr | DSM-3-R, DSM-4, MMSE, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia,”* c HIS, CT, MRI | Yizhitongluo | Piracetam | MMSE, HDS, GDS, ADL, hemodynamic changes, SELF | N | N | U |
13 | Yang et al. [ | Randomized: method not mentioned; single blind: method not mentioned; parallel design; 2 months duration | 90 VaD patients; age: 50–81; duration: 3 M–6.5 yr | DSM-4-R, ICD10, CDR, MMSE, HDS-R, CORNELL, “protocol for new herbal drugs study on dementia”* b | Zhinao 1.5 g | Hydergine | MMSE, HDS, ADL, neurological deficits, hemodynamic changes, TCD, EEG, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”*c | N | N | U |
14 | Cai et al. [ | Randomized: computer generated sequence; single blind: method not mentioned; parallel design; 3 months duration | 63 VaD patients; age: 65–78; duration: 3 m–94 m | DSM-4-R, MMSE, HIS, CT, MRI | Kangxing | Hydergine | MMSE, ADL, hemodynamic changes, “protocol for new herbal drugs study on stroke” | N | Y | N |
15 | Guo et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 2 months duration | 53 VaD patients; age: 55–73; duration: 1 yr–5 yr | DSM-4, “protocol for new herbal drugs study on dementia,”* b “protocol for new herbal drugs study on stroke”* b | Bunaotongqiao | Duxil 1 tablet | MMSE, HDS, hemodynamic changes, | N | N | U |
16 | Jia et al. [ | Randomized: method not mentioned; single blind: method not mentioned; parallel design; 60 days duration | 162 VaD patients; age: 54–71; duration: 0.8–3 yr | DSM-4, CDR, imaging, HDS | Luoshukang | Duxil 1 tablet | MMSE, BBS, “protocol for new herbal drugs study on dementia”* b | N | N | N |
17 | Cheng et al. [ | Randomized: method not mentioned; single blind: method not mentioned; parallel design; 2 months duration | 36 VaD patients; age: 62–83; duration: 0.5–9 yr | DSM-4-R, HIS, CT, MMSE, FAQ, HDS-R, ADL | Naozhitong 4 | Nimodipine | MMSE, FAQ, HDS-R, ADL, NO | N | N | U |
18 | Liao et al. [ | Randomized: computer-generated sequence; single blind: method not mentioned; parallel design; 2 months duration | 60 VaD patients; age: 71–74; duration: 3.2–5.6 hr | DSM-4, CT, MRI, HIS, MMSE, HDS, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”*c | Shoulingjiannao | Hydergine | MMSE, HDS, “protocol for the selection of anti-aging herbal medicine and the corresponding outcome measures”* d | N | N | N |
19 | Shen and Du [ | Randomized: method not mentioned; single blind: method not mentioned; parallel design; 3 months duration | 70 VaD patients; age: 65–77; duration: 6 m –3 yr | DSM-4, NINDS-AIREN, CT, MRI, “protocol for new herbal drugs study on dementia”* b | Bushenjianpiy-angxuehuoxue | Hydergine | MMSE, ADL, ET, NO, HCY, E2, T | N | N | U |
20 | Wang et al. [ | Randomized: method not mentioned; double blind: details given; crossover design; 7 months duration (3 m + 1 m wash out + 3 m) | 18 VaD patients; age: 54–83; duration: 1–7 yr | DSM-4, CT, MRI, HDS, MMSE, ADL-R, “protocol for new herbal drugs study on dementia”* b | Shenlong | Placebo | HDS, MMSE-R, ADL-R, “protocol for new herbal drugs study on dementia” *b | N | N | Y (2, mouth dryness, sore throat) |
21 | Wang et al. [ | Randomized: method not mentioned; single blind: method not mentioned; parallel design; 3 months duration | 100 VaD patients; age: 50–78; duration: 0.7–1.8 hr | DSM-4, HIS, ADL, MMSE, SDS, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”* c, “protocol for new herbal drugs study on dementia”* b | Huitian 0.8 g | Piracetam | MMSE, ADL, hemodynamic changes, “protocol for new herbal drugs study on dementia” *b | N | N | U |
22 | Wu et al. [ | Randomized: method not mentioned; double blind: method not mentioned; parallel design; 30 days duration | 46 VaD patients; age: 62–77; duration: 0.8–4.7 yr | DSM-4, CCDVD, CDSVD-R, MMSE, HIS | Extract from | Hydergine 2 | MMSE, BBS, ADL, hemodynamic changes | N | 2 | N |
23 | Yu et al. [ | Randomized: method not mentioned; single blind: method not mentioned; parallel design; 14 days duration | 123 VaD patients; age: 57–74; duration: 0.4–1.4 yr | DSM-4, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia,”* c CT | Fucong 30 mL | Piracetam 0.8 g tid + vitamin E 0.1 g tid (51) | SOD, LPO, TG, TCH, HDL, EEG | N | N | Y (2, mouth dryness, sore throat) |
24 | Zhao [ | Randomized: method not mentioned; double blinding not mentioned; Parallel design; 2 months duration | 90 VaD patients; age: 49–81; duration: 0.5–3.5 yr | DSM, CT, MRI, clinical presentation | Jiannaoqingxin | Duxil 1 tablet bid (40) | MMSE, MMSE-R, hemodynamic changes, HDS | N | N | N |
25 | Feng et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 6 months duration | 50 VaD patients; age: 59–82; duration: 2–5 yr | Portera-sanchey | Yizhi bid (30) | Piracetam | MMSE, BBS, ADL | N | N | U |
26 | Liu [ | Randomized: method not mentioned; no blinding is applied; parallel design; 2 months duration | 142 VaD patients; age: 64–68; duration: 1.9–4.2 yr | DSM-R, CT, MRI, HIS | Bushenyinao | Cerebroprot-ein Hydrolysate iv. 30 mL/day (44) | HDS, hemodynamic changes | N | 46 | Y |
27 | Liu et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 2 months duration | 92 VaD patients; age: 45–80; duration: 1–12 yr | DSM, MMSE, ADL, CDR, HIS, “protocol for new herbal drugs study on dementia”* b | Huatuozaizao | Duxil 1 tablet | MMSE, ADL, TC, TG, HDL-C, ET, NO, SELF, “protocol for new herbal drugs study on dementia” *b | N | N | N |
28 | Liu and Chen [ | Randomized: computer generated sequence; double blinding not mentioned; parallel design, 8 weeks duration | 86 hospitalized VaD patients; age: 60–79; duration: 4 m–6.5 yr | DSM-4, HDS, HIS | Buyanghuanwu | Hydergine | HDS, FAQ, hemodynamic changes, MQ, “protocol for new herbal drugs study on dementia”*b | N | N | U |
29 | Tang et al. [ | Randomized: computer generated sequence; double blinding not mentioned; parallel design; 3 months duration | 80 VaD patients; age: 53–80; duration: 6 m–12 yr | DSM-3-R, MMSE, CT, MRI, HIS, “TCM manual for neurological diseases”* e | Bushenhuoxie bid (40) | Duxil 1 tablet bid, Nimodipine 30 mg tid (40) | MMSE, ADL, WBHSV, WBLSV, PV, HCT, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”* c | N | N | N |
30 | Wang et al. [ | Randomized: method not mentioned; double blind: details given; crossover design; 7 months duration (3 m + 1 m wash out + 3 m) | 36 VaD patients; age: 52–83; duration: 1–7 yr. | DSM-4, ADL-R | Shenlong | Placebo bid (36) | MMSE-R, BBS, HDS, ADL-R | N | N | Y (4, sore throat, mouth dryness) |
31 | Wang et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 3 months duration | 140 VaD patients; age: 50–78; duration: 0.9–1.8 yr | DSM-4, HIS, ADL, MMSE, SDS, “protocol for new herbal drugs study on dementia,”* b “TCM diagnostic criteria, differentiation and outcome measures on senile dementia” *c | Jiannaocongming | Piracetam | MMSE, ADL, hemodynamic changes | N | N | U |
32 | Wang et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 6 months duration | 80 hospitalized VaD patients; age: 46–78; duration: 6–122 m | DSM-4, NINDS-AIREN, MMSE, HDS, FAQ, HIS, “protocol for new herbal drugs study on dementia”*b | Tongxinluo | Huperzine A | MSME, HDS, FAQ, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”* c | N | N | Y (nausea, decrease in appetite, etc.) |
33 | Wang [ | Randomized: method not mentioned; double blinding not mentioned, parallel design; 45 days duration | 66 VaD patients; age: 51–76; duration: 0.5–6 yr | DSM-4-R, MMSE, HDS, CT, MRI | Buyanghuanwu od + Piracetam 1.2 g bid, | Piracetam | HDS-R | N | N | U |
34 | Zhou et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 3 months duration | 62 VaD patients; age: 59–76; duration: 0.5–6 yr | CCMD-2-R, DSM-4, MMSE, HDS, HIS | Yiqifuzhi | Piracetam | Hemodynamic changes, SOD, MDA, “protocol for new herbal drugs study on dementia”* b | N | N | U |
35 | Gao [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 3 months duration | 98 VaD patients; age: 54–75; duration: 0.2–1.8 yr | DSM-4, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia”* c, ADL, MMSE | Shumaiyinao | Piracetam | MMSE, hemodynamic changes, Vmin, Qmin, RI | N | N | U |
36 | Hao et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 6 months duration | 100 VaD patients; age: 48–81; duration: 7–118 m | ICD10, CT, MMSE, IADL, HIS | Tongxinluo | Piracetam | MMSE, NPI, IADL, HIS | N | N | Y (16, GI discom-fort) |
37 | Li et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 3 months duration | 60 VaD patients; age: 45–80; duration: 1–12 yr | DSM-4, ADL, MMSE, HIS, “protocol for new herbal drugs study on dementia”* b | Tongmaiyizhi | Duxil 1 tablet | MMSE, ADL, “protocol for new herbal drugs study on dementia”* b | N | N | U |
38 | Mou [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 60 days duration | 60 VaD patients; age: 57–89; duration: 2.5–4 yr | DSM-4, HDS | Self-derived | Nimodipine | MMSE | N | N | U |
39 | Shi and Wang [ | Randomized: computer generated sequence; double blind: method not mentioned; parallel design; 3 months duration | 78 VaD patients; age: 50–80+; duration: 5 m–1.5 yr | DSM-4, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia,”* c “Diagnostic manual for geriatrics”* f | Self-derived CHM 2 bid + nimodipine 40 mg tid, hydergine 2 mg tid (46) | nimodipine | ADL, MMSE | N | N | U |
40 | Zhang and Lu [ | Randomized: method not mentioned; double blinding not mentoned; parallel design; 3 months duration | 72 VaD patients; age: 57–71; duration: 0.3–5.6 yr | DSM-4, ICD10, HIS, HDL, TC | Bushenjiannao | Piracetam | MMSE, HDS, hemodynamic changes, “protocol for new herbal drugs study on dementia”*b | N | N | U |
41 | Chen et al. [ | Randomized: method not mentioned; double blind: method not mentioned; parallel design; 3 months duration | 68 VaD patients; age: 60–86; duration: 1–7 yr | DSM-4, HDS, MMSE, CT, MRI | Shenlong | Piracetam | MMSE, BBS, HDS, “protocol for new herbal drugs study on dementia”*b | N | N | U |
42 | Cui et al. [ | Randomized: computer generated sequence; double blinding not mentioned; parallel design; 3 months duration | 67 VaD patients; age: 56–83; duration: 2 m–31 m | DSM-4, NINDS-AIREN, HIS, CDR | Shuangshencuzhi | Duxil 1 tablet | MMSE, BBS, HCY, CT, MRI | N | 5 | U |
43 | He [ | Randomized: method not mentioned; single blind: method not mentioned; parallel design; 8 weeks duration | 90 VaD patients; age: 48–80; duration: 2 m–6.5 yr | NINDS-AIREN, SDSVD, CDR, HIS, “criteria for the diagnosis, the differentiation of syndrome and the evaluation of efficacy of vascular dementia for research studies”* g | Kangnao | Hydergine | MMSE, hemodynamic changes, SELF | N | N | N |
44 | Jin et al. [ | Randomized: method not mentioned; double blind: details given; crossover design (12 w + 4 w wash out + 12 w); | 72 VaD patients; age: 55–83; duration: 1–7 yr | DSM-4-R, MMSE, ADL, HDS, CT, MRI, “protocol for new herbal drugs study on dementia”* b | Jiannaoyizhi | Placebo tid (72) | MMSE-R, HDS, ADL-R, “protocol for new herbal drugs study on dementia”*b, “protocol for new herbal drugs study on stroke”* b | N | N | Y (2, sore throat, mouth dryness) |
45 | Yan [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 1 month duration | 79 VaD patients; age: 51–78; duration: 0.5–9 yr. | DSM-4-R, HDS-R, MMSE, CT, MRI | Buyanghuanwu + Cerebroprotein Hydrolysate 10 mL 20 d, Aniracetam 0.12 g tid; Nimodipine 20 mg tid (36) | Cerebroprot-ein Hydrolysate 10 mL 20 d, Aniracetam 0.12 g tid; Nimodipine 20 mg tid (43) | HDS-R | N | N | U |
46 | Chang et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 12 weeks duration | 66 VaD patients; age: 60–78; duration: 1.3–3.6 yr | DSM-4, HIS, “TCM diagnostic criteria, differentiation and outcome measures on senile dementia,”*c MMSE, CT, MRI, HDS | Qihong 300 mL | Piracetam 0.4 g bid (33) | HDS, MMSE | N | N | U |
47 | Li et al. [ | Randomized: method not mentioned; double blinding not mentioned; parallel design; 2 months duration | 120 VaD patients; age: 59–75; duration: 0.6–6.2 yr | DSM-4, MMSE-R, CDR, NINDS-AIREN, SDSVD, HIS, CSDD, “protocol for new herbal drugs study on dementia”* b | Shouwuyizhi | Piracetam 0.8 g tid (40) | MMSE, HDS, WMS, SDSVD, TCD, hemodynamic changes, SELF | N | N | N |
Key: *1: N: intention-to-treat analysis is not used; Y: intention-to-treat analysis is applied.
*2: N: no report of drop-out; Y: drop-out reported (with no. of dropouts in bracket).
*3: N: report as no adverse events; Y: adverse events reported (with no. and details in bracket); U= adverse events unknown.
BEAM: brain electrical activity mapping
Only two studies [
A number of batteries were employed to evaluate the baseline characteristics and outcome measures. The most commonly employed set of evaluative questionnaires included MMSE [
The different batteries used in the studies resulted in variation in outcome measures. As the data were not suitable for meta-analysis, only qualitative appraisal could be carried out.
There were altogether 43 trials testing herbal medicine as a monotherapy for VaD. Among them 15 studies compared different HM preparations with Piracetam alone (a nootropic agent). One study compared HM with another stronger nootropic compound Aniracetam. One study compared HM with Piracetam + hydergine and one study compare HM with Piracetam + Vitamin E + respiratory stimulant Duxil (Almitrine). Hydergine, (also known as ergoloid mesylates, another nootropic agent), was tested alone against HM in 11 studies. Five studies reported HM having similar efficacy to these nootropics; the remaining 23 claimed HM to be significantly better.
Seven studies compared HM with Duxil (Almitrine) alone, a respiratory stimulant originally used to treat patients with chronic obstructive pulmonary disease. In one study, HM is compared with Duxil + Nimodipine (a dihydropyridine calcium channel blocker for the treatment of high blood pressure). One study reported HM to have similar efficacy with Duxil; the other seven claimed that HM is better than Duxil.
Furthermore, HM was compared with Nimodipine in two studies, Huperzine A in one study, cerebroprotein hydrolysate in one study, and placebo in three studies. All of these studies concluded that HM is better than the control intervention.
Four trials evaluated HM as an adjunct therapy for VaD. Two of them evaluated the adjunct effect of the CHM decoction BuYangHuanWuTang. Wang compared it with the coadministration of Piracetam and Nimodipine; Yan compared it with the co-administration of Aniracetam, Nimodipine, together with the injection of cerebroprotein hydrolysate. Shi and Wang studied the CHM decoction which, according to TCM theory, could “tonify the kidney, activating blood,” and tested its adjunct effect with nimodipine + hydergine (In TCM theory, the brain is considered an outgrowth of “kidney” energy. Neurodegenerative disorders such as dementia are caused by stagnation of “blood,” accumulation of “phlegm,” and deficiency of the “kidney.” In order to resist or halt the condition, TCM treatment targets the nourishment of the kidney by means of “kidney invigorating,” “blood activating” and “phlegm dissipating” herbal decoctions [
Among those 43 studies which tested HM as monotherapy, 25 studies did not report any cases of withdrawal. Ten studies claimed they did not observe any adverse events in groups treated with HM. Eight studies reported a number of mild adverse events, such as mouth dryness, sore throat, constipation, nausea, loss of appetite, and dyspepsia. These adverse events could be resolved without treatment. Serious adverse events were not observed. Occurrence of adverse events remained unclear in the four studies which tested HM as adjunct therapy.
The dropouts or withdrawals were unclear in 44 out of 47 studies. Wu et al. [
Thirty-one out of 47 studies tested herbal mixtures prepared in the form of granules or capsules. Fifteen studies tested their herbal mixtures in the form of decoctions. One study tested the extract from a single herb. As some of the studies tested the same herbal mixture, altogether 42 different herbal mixtures were tested among these 47 studies (Table
Statistics on herbal intervention.
Number | Chinese name | English name | Form of preparation | Frequency | Study |
---|---|---|---|---|---|
1 | Buyanghuanwu | Decoction/capsule | 3 | Liu and Chen [ | |
2 | Shenlong | Decoction | 3 | Wang et al. [ | |
3 | Tongxinluo | Capsule | 2 | Wang et al. [ | |
4 | Xianlong | Capsule | 1 | Zhao et al. [ | |
5 | Fucong | Decoction | 1 | Wan et al. [ | |
6 | Dangguishaoyao | Decoction | 1 | Ji [ | |
7 | Shentong | Capsule | 1 | Lu et al. [ | |
8 | Shenmayizhi | Capsule | 1 | Luo [ | |
9 | Jiannaotongluo | Capsule | 1 | Zhang et al. [ | |
10 | Yinaoling | Oral liquid | 1 | Zhou and Yi [ | |
11 | Congsheng | Capsule | 1 | Cao et al. [ | |
12 | Shouxing | Capsule | 1 | Hong et al. [ | |
13 | Naohuandan | Capsule | 1 | Huang et al. [ | |
14 | Tongqiaohuoxue-buyanghuanwu | Decoction | 1 | Liu et al. [ | |
15 | Yizhitongluo | Capsule | 1 | Wang et al. [ | |
16 | Zhinao | Capsule | 1 | Yang et al. [ | |
17 | Kangxing | Capsule | 1 | Cai et al. [ | |
18 | Bunaotongqiao | Decoction | 1 | Guo et al. [ | |
19 | Luoshukang | Capsule | 1 | Jia et al. [ | |
20 | Naozhitong | Capsule | 1 | Cheng et al. [ | |
21 | Shoulingjiannao | Capsule | 1 | Liao et al. [ | |
22 | Bushenjianpiyangxuehuoxue | Decoction | 1 | Shen and Du [ | |
23 | Huitian | Tablet | 1 | Wang et al. [ | |
24 | Extract from Herba Cistanchis | Herbal extract | 1 | Wu et al. [ | |
25 | Fucongxiang | Oral liquid | 1 | Yu et al. [ | |
26 | Jiannaoqingxin | Decoction | 1 | Zhao 2004 | |
27 | Yizhi | Decoction | 1 | Feng et al. [ | |
28 | Bushenyinao | Capsule | 1 | Liu [ | |
29 | Huatuozaizao | Tablet | 1 | Liu et al. [ | |
30 | Bushenhuoxie | Decoction | 1 | Tang et al. [ | |
31 | Jiannaocongming | Oral liquid | 1 | Wang et al. [ | |
32 | Yiqifuzhi | Granule | 1 | Zhou et al. [ | |
33 | Shumaiyinao | Capsule | 1 | Gao [ | |
34 | Tongmaiyizhi | Tablet | 1 | Li et al. [ | |
35 | Self-derived CHM 1 | Decoction | 1 | Mou [ | |
36 | Self-derived CHM 2 | Decoction | 1 | Shi and Wang [ | |
37 | Bushenjiannao | Decoction | 1 | Zhang and Lu [ | |
38 | Shuangshencuzhi | Granule | 1 | Cui et al.[ | |
39 | Kangnao | Tablet | 1 | He [ | |
40 | Jiannaoyizhi | Capsule | 1 | Jin et al. [ | |
41 | Qihong | Oral liquid | 1 | Chang et al. [ | |
42 | Shouwuyizhi | Capsule | 1 | Li et al. [ |
The 30 most commonly used herbal constituents.
Chinese name | Scientific name | English name | Latin name | Freq. | Dose (g) | |
---|---|---|---|---|---|---|
1 | Rhizoma Chuanxiong | Szechwan Lovage Rhizome | 24 | 6–15 | ||
2 | Radix Polygoni Multiflori | Fleeceflower root | 24 | 10–20 | ||
3 | Radix Astragali | Milkvetch root | 22 | 15–120 | ||
4 | Radix Salviae Miltiorrrhizae | Danshen root | 14 | 10–20 | ||
5 | Radix Ginseng | Ginseng | 13 | 6–10 | ||
6 | Rhizoma Acori Talarinowii | Grassleaf Sweetflag Rhizome | 13 | 6–10 | ||
7 | Radix Angelica Sinensis | Chinese Angelica | 11 | 6–15 | ||
8 | Fructus Corni | Asiatic Cornelian Cherry fruit | 10 | 10–15 | ||
9 | Radix Polygalae | Thinleaf Milkwort root | 10 | 10–12 | ||
10 | Fructus Alpiniae Oxyphyllae | Sharpleaf Galangal fruit | 9 | 10–15 | ||
11 | Fructus Lycii | Barbary Wolfberry fruit | 8 | 10–20 | ||
12 | Flos Carthami | Safflower | 8 | 3–5 | ||
13 | Rhizoma Polygonati | Solomonseal Rhizome | 8 | 15–30 | ||
14 | Rhizoma Anemonis Altaicae | Irkutsk Anemone Rhizome | 8 | 8–12 | ||
15 | Radix Rehmanniae | Rehmannia root | 8 | 10–20 | ||
16 | Radix Peaoniae Rubra | Red Peony root | 7 | 6–15 | ||
17 | Rhizoma Gastrodiae | Tall Gastrodia Tuber | Gastrodia elata Bl. | 6 | 6–10 | |
18 | Semen Persicae | Peach seed | 6 | 3–12 | ||
19 | Herba Epimedii | Epimedium herb | 6 | 12 | ||
20 | Radix Curcumae Wenyujin | Turmeric Root Tuber | 6 | 10–15 | ||
21 | Radix Paeoniae Alba | White Peony root | 4 | 15 | ||
22 | Radix Codonopsis | Pilose Asiabell root | 4 | 10–20 | ||
23 | Fructus Ligustri Lucidi | Glossy Privet fruit | 3 | 10 | ||
24 | Rhizoma Dioscoreae | Common Yam Rhizome | 3 | 15–30 | ||
25 | Fructus Schisandrae Chinensis | Chinese Magnoliavine fruit | 3 | 10 | ||
26 | Radix Morindae Officinalis | Morinda root | 3 | 20 | ||
27 | Rhizoma Pinelliae | Pinellia Tuber | 3 | 10–12 | ||
28 | Rhizoma Atractylodis Macrocephalae | Largehead Atractylodes Rhizome | 3 | 10–15 | ||
29 | Cortex Cinnamomi | Cassia Bark | 3 | Unkno-wn | ||
30 | Herba Cistanches | Desertliving Cistanches | 3 | 10–20 |
The first five in descending order of frequency of use are Rhizoma Chuanxiong (Chuanxiong in Chinese), Radix Polygoni Multiflori (Heshouwu in Chinese), Radix Astragali (Huangqi in Chinese), Radix Ginseng (Renshen in Chinese), and Rhizoma Acori Tatarinowii (Shichangpu in Chinese).
Rhizoma Chuanxiong, originates from the plant
Though all the studies reported promising results of HM in the treatment of VaD, they demonstrated a number of weaknesses as well. The evidence drawn from the studies was insufficient for us to confirm the safety and efficacy of HM, because of the following issues The sample sizes of the studies ranged from 18 to 300, and none of them reported sample size calculations, as suggested by the CONSORT statement. Treatment effects can be exaggerated when sample size is inappropriate, and thus the results of these studies may not be conclusive. Different diagnostic criteria were used in the studies. Some of these criteria were even self-derived and their validities remained unknown. This produced much discrepancy. Differences in the baseline characteristics of the subjects limit the extent to which results can be compared with each other. Though all of the studies claimed to have participants allocated randomly, only a few reported the method of randomization. For those studies without detailed descriptions of randomization, we could not rule out the possibility of bias. Furthermore, unclear descriptions of allocation concealment, dropouts, and intention-to-treat analysis further hamper the ability to assess the validity of the evidence reported by these studies. Outcome measures varied and were incomplete in the studies. Some investigators employed self-developed scales, which could not be, or had not been, independently evaluated for their sensitivity and specificity. The validity is further questionable due to insufficient or inappropriate statistical treatment. Though meta-analysis techniques such as vote-counting may have been used for the analysis of the data, we avoid to do so because (1) the statistical significance or size of the results of the individual studies are ignored; and (2) vote-counting takes no account of the differential weights given to each study. [ Different HM were tested in the 47 studies included here, with great variation in terms of composition, dosage, and duration of interventions. This renders comparison of the studies impossible, and thus quantitative analysis could not be carried out. A number of studies (30 out of 47) did not mention safety issues. The investigators of these studies may have underestimated possible adverse events, and the safety of HM in these studies could not be guaranteed.
Regarding the published studies, methodology quality is the leading should concern. It is recommended that future clinical studies follow the guidelines as suggested by CONSORT to minimize bias as well as to ensure high validity, statistically reliable results and to permit comparison with other studies. Researchers should explicitly report methods for calculation of sample size. Widely recognized diagnostic criteria and outcome measures should be used. It is highly recommended to incorporate medical imaging techniques (such as perfusion computed tomography) to confirm the diagnosis of VaD. Appropriate statistical analyses should be carried out for baseline data and outcome results; long-term followup is also recommended and highly desirable.
Our review has identified the individual herbs that appear most frequently in formulas for VaD. The top five are Rhizoma Chuanxiong (Chuanxiong), Radix Polygoni Multiflori (Heshouwu), Radix Astragali (Huangqi), Radix Ginseng (Renshen), and Rhizoma Acori Talarinowii (Shichangpu). The clinical efficacy and safety of these herbs, over centuries of use and during recent controlled studies, are a powerful combination of attributes. We believe that further high-quality clinical studies on these individual constituents, as well as the herbal mixtures resulted, could lead to the discovery of new drugs for effective treatment and prevention of VaD.
Currently available RCTs suggested that HM might be more effective and safer than OM for treatment of VaD. However, these studies have a number of weaknesses, mainly due to their methodological insufficiencies. With regard to the reports that did meet our selection criteria, the results indicated that HM, in a predominance of instances, can be superior to OM and useful in the treatment of VaD. Further multicenter trials with large sample sizes, high methodological quality, and standardized HM ingredients are needed to confirm the value of HM in treating VaD, in order to establish specific clinical recommendations.
The paper was supported by research Grant FRG/08-09/I-01 from Hong Kong Baptist University, and also partly by research grant EYS/07-08/01 from Eu Yan Sang (Hong Kong) Limited. The authors especially thank Ms. Wai-Sheung Chan, Ms. Loretta Ho, and the Lions Club of South Kowloon, Hong Kong for their further financial support of this paper. They would also like to thank Dr. Martha Dahlen for her critical review and revision.