Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder of which patients display persistent pattern of inattention and hyperactivity/impulsivity or a combination of the two at an abnormal level that their social, academic, or occupational functioning is impaired [
When making a diagnosis of ADHD, clinicians should determine that the diagnostic criteria have been met by assessing information obtained from primarily parents, guardians, and teachers [
Behavioral therapy and pharmacotherapy are two kinds of treatments commonly used in ADHD. Recommendation of treatment for ADHD varies depending on the patient’s age. While evidence-based behavioral therapy is recommended as the first line of treatment for preschool-aged children (4-5 years of age), school-aged children (6–11 years of age) and adolescents (12–18 years of age) are recommended a combination of medication and behavioral therapy [
Stimulants are reported to be highly effective for most children in reducing the core symptoms of ADHD and thus are used as first line medication for ADHD patients [
Methylphenidate (Ritalin) is the most commonly used stimulant for the treatment of ADHD [
While stimulants are effective for many children with ADHD, they may cause side effects, with the most common ones being decreased appetite, insomnia, and headache (Cohen’s d 0.67, 0.40, and 0.33 resp.) [
Herbal medicine is a treatment measure used in traditional Oriental medicine. Although herb usually refers to materials from plant sources, in respect of traditional Oriental medicine, herbal materials can be originated from plants, animals, or minerals. In this review, traditional Oriental herbal medicine (TOHM) is defined as medicine made by materials used under traditional Oriental medical theory. Herbal materials that are not documented in the Korean Pharmacopoeia, the Japanese Pharmacopoeia, Pharmacopoeia of the People’s Republic of China, Zhong Hua Ben Cao, and Zhong Yao Da Ci Dian (Chinese Medical Great Dictionary) are considered outside the context of TOHM. TOHM should be taken orally and studies employing other route of administration, such as intravenous or transdermal, are excluded from this review.
Even though ADHD was not described in literature of traditional Oriental medicine, in traditional Oriental medical theory, ADHD is related to congenital deficiency or insufficient postnatal nourishment that leads to imbalances in the body. It is suggested that the disorder is related to the heart, the liver, the spleen, and the kidneys [
A study on ADHD using an animal model of spontaneous hypertensive rat treated with an Oriental herbal decoction comprised of Caulis Polygoni Multiflori (stem of
This review aims to evaluate the efficacy of TOHM as a treatment for ADHD in patients under the age of 18. TOHM is natural and often perceived to have fewer side effects than conventional ADHD pharmacotherapy. Various research and clinical studies have been conducted on TOHM’s efficacy on ADHD, but very few articles review the evidence of efficacy of the treatment. A systematic review on complementary medicines for ADHD suggested that a Chinese herbal medicine may be effective for ADHD [
English, Chinese, Korean and Japanese articles on randomized clinical trials (RCTs) of Oriental herbal treatment on ADHD published between January 1, 1990, and December 31, 2010, were searched from various databases. The details of search terms used in different databases are presented in the appendix. The following databases were searched: Cochrane Library, EMBASE, MEDLINE, AMED, CINAHL Plus, PsyINFO, SinoMed–CBM—Chinese Database, China Journal Net—Chinese Database, WanFang Data—Chinese Database, Oriental Medicine Advanced Searching Integrated System (OASIS)—Korean Database, Scholarly and Academic Information Navigator (CiNii)—Japanese Database, Database of Grants-in-Aid for Scientific Research (KAKEN)—Japanese Database, Japanese Institutional Repositories Online (JAIRO)—Japanese Database, Academic Research Database Repository (NII-DBR)—Japanese Database.
Other than searching from databases, the reference lists of the included studies were referred to in order to identify more potential articles.
Randomized clinical trials of TOHM. The efficacy of TOHM treatment should be compared to either a placebo or a conventional medication used for treating ADHD. If there was a baseline treatment, it had to be the same in both the treatment and control groups. Studies only comparing different TOHM formulae, or comparing TOHM with other traditional Oriental treatment such as acupuncture were excluded. Studies without indicating “randomized" were considered not randomized and excluded.
Subjects under the age of 18 who were diagnosed with ADHD based on DSM-IV.
Traditional Oriental herbal medicine must be used. Herbs that are not documented in the Korean Pharmacopoeia, the Japanese Pharmacopoeia, Pharmacopoeia of the People’s Republic of China, Zhonghua Bencao, and Zhongyao Dacidian were not considered. Other treatment measures of Oriental medicines such as acupuncture and moxibustion were excluded.
The core symptoms of ADHD (hyperactivity, impulsivity, and inattention) were considered in this review. Core symptoms should be assessed by at least one of the following tools: Revised Conners’ Parent Rating Scale, Revised Conners’ Teacher Rating Scale, Conners’ Hyperactivity Index, Conners’ Abbreviated Symptoms Questionnaire, Conners’ Global Index for Parents, and/or Conners’ Global Index for Teachers.
The risk of bias of all the included studies was assessed according to Cochrane Handbook for Systematic Reviews of Invention version 5.1.0.
The search came up with 1240 results, and 12 studies [
Selection of studies flowchart.
All of the studies included in this review were conducted in China as single-centre trials. Five results in Japanese and eighteen results in Korean were identified. Only one Japanese article was about a clinical trial; however the trial was not a randomized trial and was therefore not selected.
Among the twelve included studies, none included the information on how sample size was derived and whether the study was statistically powered. The length of study ranged from 4 weeks to 24 weeks. Six studies had follow-up observation on subjects, ranging from 2 weeks to 12 months after finishing treatment, to evaluate whether the intervention sustained effectiveness after treatment is stopped while the other six studies did not report if follow-up observations were conducted. Ten of the included studies reported homogeneity of baseline characteristics, but only seven [
Selected studies characteristics.
Study | Method | Participants | Intervention | Outcomes |
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Cheng et al. 2006 |
Randomized Control Trial |
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The study defined treatment effect as follows: |
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Kong et al. 2007 [ |
Randomized Control Trial |
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There was no significant difference of treatment effectiveness between treatment group and control group. Followup 6 months and 12 months after treatment indicated that treatment had significantly more sustainable effect than control, and statistics showed that treatment group has significantly less side effects compared to control group. |
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Lai and Li 2006 [ |
Randomized Control Trial | Treatment/control: 21/19 |
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The study defined treatment effect as follows: |
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Li and Chen 1999 [ |
Randomized Control Trial |
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The study defined treatment effect as follows: |
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Li et al. 2004 |
Randomized Control Trial | Treatment/control: 58/48 |
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The study defined treatment effect as follows: |
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Lin et al.2007 [ |
Randomized Control Trial |
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The study defined treatment effect as follows: |
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Ma 2007 [ |
Randomized Control Trial |
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The study defined treatment effect as follows: |
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Ma et al. 2007 |
Randomized Control Trial | Treatment group/control group-Chinese medicine/control group-Ritalin: 55/53/51 |
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The study defined treatment effect as follows: |
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Wang and Shi 2003 [ |
Randomized Control Trial |
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The study defined treatment effect as follows: |
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Xu 2005 [ |
Randomized Control Trial |
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The study defined treatment effect as follows: |
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L. Yang and J. Yang 2005 [ |
Randomized Control Trial |
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The study defined treatment effect as follows: |
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Yu and Wang 2005 [ |
Randomized Control Trial |
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The study defined treatment effect as follows: |
In general, the risk of bias in the included articles is unclear. Very limited information was revealed in the studies to enable the reviewers to tell if the included studies were at risk of bias.
Only one of the included studies [
The blinding method was also not addressed in most of the studies, and only two of the included studies [
Most of the studies indicated no missing data. However, Ma et al. (2007) [
Study protocols were not available for any of the included studies, therefore it could not be discerned whether all pre-specified outcomes were reported. Lai and Li (2006) [
The risk of bias graph and summary are presented in Figures
Risk of bias graph of the included studies.
Risk of bias summary of the included studies. −: high risk of bias, +: low risk of bias, ?: unknown risk of bias.
Although all included studies specified the diagnostic criteria and method to assess treatment effect, only one study [
The herbal formulae used in the included twelve studies varied, and dosage forms of decoction, granules, oral liquids, pill, and so forth were used. Nine studies [
Details of the herbal treatments used in the included studies.
Cheng et al. 2006 [ |
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Kong et al. 2007 [ |
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Lai and Li 2006 [ |
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Li and Chen 1999 [ |
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Li et al. 2004 [ |
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Lin et al. 2007 [ |
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Ma 2007 [ |
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Ma et al. 2007 [ |
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Wang and Shi 2003 [ |
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Xu 2005 [ |
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L. Yang and J. Yang 2005 [ |
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Yu and Wang 2005 [ |
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Among the twelve studies, there were ten 2-arm studies [
The remaining one of the twelve included studies [
Among the included studies, six had follow-up observations to evaluate the sustainability of treatment effect of core symptom after stopping medication, while the other six studies did not specify if follow-up observation was done. The follow-up period varied from 2 weeks to 12 months after stopping the treatment. For the six studies with follow-up observation, five [
In general, TOHM was claimed to have fewer side effects than methylphenidate. Eight of the included studies [
Three studies [
This review included twelve studies, and though findings of this review suggested that the herbal preparations covered under the term TOHM may be effective in treating the core symptoms of ADHD; the overall evidence is not strong enough to draw solid conclusions, because in general the clinical trials were not of high quality and the herbal preparations far too different. Additionally, it cannot be ruled out that there is possibility of publication bias.
The included studies that discussed side effect issues all suggested that TOHM had fewer side effects compared to methylphenidate. However, such result should be interpreted with caution, because first of all it was not clear whether the side effect cases, both in the TOHM group and the methylphenidate group, were investigated to find out if they were related to the intervention. Secondly, it was not addressed in most studies whether blinding was done. As mentioned, since TOHM is indigenous to the study population, and is often perceived as natural with fewer side effects, if measures are not properly done to blind subjects from knowing what treatment they are getting, it may cause bias in reporting side effects.
In the future, should more clinical trials on ADHD using TOHM as treatment be conducted, clinical investigators should consider to address the issues discussed below in order to improve the robustness of data.
In the diagnosis of ADHD and assessment of treatment efficacy, tools such as rating scales are often used. In order to make precise assessment, information should be obtained from different parties including parents, guardians, and teachers under different settings, such as home and school [
Among the included studies, the herbal medicines themselves varied. Some of the studies did not tell what herbs were used, some did not specify the amount of herbs used, and the treatment dosage was not clear in some studies. Also, the treatment period varied for each study. Due to such heterogeneity, it is not possible to deduce from the data which herbal formulae or ingredients may be effective for ADHD, nor to conclude that TOHM is effective for ADHD in children and adolescents. Although it is inevitable that different studies may use different herbs and have different treatment periods, the materials used and the amount should be stated clearly in the publication of clinical trial results. As various herbal treatments are used in different clinical studies the results even of the positive studies cannot be compared. Clinical investigators may have to consider repeating a study with the same herbal treatment, or to conduct a clinical trial in multiple sites.
Due to the complex nature of herbs, how the consistency of herbal treatment is maintained throughout a clinical study is often an issue to consider. Most of the studies included in this review used the herbal treatment substances in form of decoctions or other preparations such as granules or oral liquid prepared by the clinical sites. It was not addressed how the consistency of treatment substances was kept throughout the studies, or how the treatment substances were standardized to ensure quality. In addition, in three of the studies [
In this review, the reviewers performed a thorough search in various databases. Other than major databases that have information of articles published mostly in English, additional Chinese, Korean, and Japanese databases were searched to identify potential studies. Articles written in English, Chinese, Korean, and Japanese languages were screened in order to include as many suitable studies in the review as possible.
Due to limited resources, the reviewers could only seek published studies. For a robust review, nonpublished data should also be sought. Also, the reviewers were not able to contact the authors of included studies for clarification and further information on their studies.
Even though the reviewers did a thorough search of published studies, the included studies were all conducted on Chinese population. Little could be told about the effect of TOHM on ADHD on populations of other countries.
This review included twelve studies on different herbal preparations from TOHM as a treatment for children and adolescents with ADHD. Findings suggest that some of them may have similar efficacy to methylphenidate, but solid conclusions could not be drawn due to quality problems of the clinical trials. In conclusion, currently there is no strong evidence to suggest that TOHM is effective in treating the core symptoms of ADHD. More studies with low risk of bias and using the same herbal preparation are required before further conclusions can be drawn.
ADHD (or attention-deficit/hyperactivity disorder or hyperkinetic disorder or minimal brain dysfunction) and alternative medicine (or complementary medicine or Chinese medicine or kampo or Korean medicine or Oriental medicine or phytotherapy or herbal).
ADHD and Chinese medicine (in Chinese). Attention-deficit/hyperactivity disorder (in Chinese) and Chinese medicine (in Chinese). Hyperactivity (in Chinese) and Chinese medicine (in Chinese). Minimal brain dysfunction (in Chinese) and Chinese medicine (in Chinese). Hyperkinetic disorder (in Chinese) and Chinese medicine (in Chinese).
ADHD. Attention-deficit/hyperactivity disorder (in Korean).
ADHD and Kampo (in Japanese). Attention-deficit/hyperactivity disorder (in Japanese) and Kampo (in Japanese).