Traditional Chinese Medicine For Epilepsy

Traditional Chinese medicine for epilepsy (Review)
Li Q, Chen X, He L, Zhou D
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 3
http://www.thecochranelibrary.com

Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 One formula of TCMH versus single Western medication, Outcome 1 Xiaxingci granule versus
phenytoin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.2. Comparison 1 One formula of TCMH versus single Western medication, Outcome 2 Dianxianning pill
versus valproate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.3. Comparison 1 One formula of TCMH versus single Western medication, Outcome 3 Tianmadingxian
capsule. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.4. Comparison 1 One formula of TCMH versus single Western medication, Outcome 4 Zhixian I versus
phenytoin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.5. Comparison 1 One formula of TCMH versus single Western medication, Outcome 5 Antiepilepsy capsule
versus phenobarbital. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.6. Comparison 1 One formula of TCMH versus single Western medication, Outcome 6 Incidence of adverse or
harmful effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
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[Intervention Review]
Traditional Chinese medicine for epilepsy

Qifu Li1 , Xiaoyan Chen2 , Li He1 , Dong Zhou1
1 Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. 2 Department of Neurology, Shanghai
Changzheng Hospital, Second Military Medical University, Shanghai, China
Contact address: Dong Zhou, Department of Neurology, West China Hospital, Sichuan University, Guo xue xiang No.37, Chengdu,
Sichuan, 610041, China. zhoudong66@yahoo.de.
Editorial group: Cochrane Epilepsy Group.
Publication status and date: New, published in Issue 3, 2009.
Review content assessed as up-to-date: 23 November 2007.
Citation: Li Q, Chen X, He L, Zhou D. Traditional Chinese medicine for epilepsy. Cochrane Database of Systematic Reviews 2009,
Issue 3. Art. No.: CD006454. DOI: 10.1002/14651858.CD006454.pub2.
ABSTRACT
Background
Seizures are poorly controlled in many people with epilepsy, despite current antiepileptic treatments. Some turn to alternative or
complementary therapy to treat their condition and the use of traditional Chinese medicinal herbs (TCMH) is increasingly popular.
However, it remains unclear whether the existing evidence is rigorous enough to support its use.
Objectives
To determine the effectiveness and safety of traditional Chinese medicine in people with epilepsy.
Search methods
Our search included the Cochrane Epilepsy Groups Specialised Register and the Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1950 to 2007) and EMBASE (1974 to 2007).
Selection criteria
Randomised controlled trials evaluating traditional Chinese medicine in people of any age with any type of epilepsy, and comparing
one formula of TCM with no intervention, placebo or single Western medicine (monotherapy).
Data collection and analysis
Two review authors independently extracted trial data and assessed quality. We assessed the following outcomes: (a) seizure freedom
for at least one year; (b) 50% or greater reduction in seizure frequency; (c) percentage reduction in seizure frequency and duration; and
(d) adverse events.
Main results
Five short-term studies involving 1125 participants met the inclusion criteria. All the studies were of poor methodological quality and
had a high probability of selection, detection and performance bias.
Two studies assessed seizure freedom for one year. One found no difference between Xiaxingci granule and phenytoin for primary
generalized tonic-clonic seizures (RR 1.00; 95% CI 0.07 to 14.90).The other study found no difference between Dianxianning pill
and valproate (RR 13.00; 95% CI 0.74 to 227.72) for different types of epilepsy.
Three studies assessed a 50% or greater reduction in seizure frequency. One found an advantage for Tianmadingxian capsule when
compared to phenytoin (RR 1.37; 95% CI 1.23 to 1.53) in different types of epilepsy, the second an advantage for Zhixian I pill when
compared to phenytoin (RR 1.31; 95% CI 1.16 to 1.48) in primary generalized tonic-clonic seizure, and the third an advantage for
an Antiepilepsy capsule when compared to phenobarbital (RR 1.21; 95% CI 1.02 to 1.43) for primary and secondary generalized
tonic-clonic seizure. One study reported the incidence of adverse effects and the Peto odds ratio was 0.04 (99% CI 0.01 to 0.12, P <
0.00001) favouring TCMH compared to phenobarbital.
Authors conclusions
The current evidence is insufficient to support the use of traditional Chinese medicine as a treatment for epilepsy. Much larger, high
quality randomised clinical trials are needed to evaluate the effectiveness and safety of traditional Chinese medicinal herbs for treating
epilepsy.
PLAIN LANGUAGE SUMMARY

There is no strong evidence for the use of traditional Chinese medicine as a treatment for epilepsy.
Patients with epilepsy are currently treated with antiepileptic drugs, but a significant number of people continue to have seizures and
many experience adverse effects. As a result there is increasing interest in alternative or complementary therapies, including traditional
Chinese medicine.
The review authors found five, short-term randomised controlled trials involving 1125 participants. All the studies were of poor
methodological quality and had a high probability of bias. Although some studies included in this review seemed to show some benefit
of traditional Chinese medicine, the current evidence is insufficient to support its use as a treatment for epilepsy. Much larger, high
quality randomised clinical trials are needed to evaluate the effectiveness and safety of traditional Chinese medicinal herbs for treating
epilepsy.
BACKGROUND
Epilepsy is an important neurological condition, with an estimated
annual incidence of 50 per 100,000 and prevalence of 5 to 10 per
1000 in the developed world (Sander 1996). Approximately 3% of
the population will suffer from epilepsy at some point in their lives
(Hauser 1993). Although the majority of people with epilepsy will
go into remission, up to 30% will become drug-resistant despite
treatment with adequate doses of appropriate antiepileptic drugs
(AEDs) (Cockerell 1995). Their continuing attacks will result in
reduced quality of life, and may also lead to injuries, social isolation and depression (Villeneuve 2004). Hence, there is a constant
search for newer modes of treatment. Many people are turning
to alternative or complementary therapy to treat their condition
and the use of traditional Chinese medicinal herbs is becoming
increasingly popular.
Traditional Chinese medicine (TCM) is a 3000-year old theoretical and methodological holistic system for both the treatment
and prevention of disease (Fulder 1996). TCM has unique theories regarding aetiology, systems of diagnosis and treatment, which
are vital to its practice. TCM herb treatment consists typically of
complex prescriptions of a combination of several components.
The combination is based on Chinese diagnostic patterns (i.e.
inspection, listening, smelling, inquiry and palpation) and has a
completely different rationale compared to many Western drug
treatments (Liu 2000). Historically the Chinese have used traditional Chinese medicinal herbs (TCMH) to treat epilepsy. The first
known document on epilepsy in China appeared in The Huang
Di Nei Ching, written by a group of TCM physicians between
770 and 221 B.C. The description of epilepsy in this book, and
in many others published later, was confined to generalized convulsive seizures. No documentation of absence or simple partial
seizures was noted. The first classification of epilepsy, probably by
Cao Yuan Fang in A.D. 610, listed five types of epilepsy: Yang
Dian, Yin Dian, Feng (Wind) Dian, Shih (Wet) Dian and Ma
(Horse) Dian. The treatment of epilepsy, based on principles of

Yin Yang Wu Xing, consisted of herbs, acupuncture, massage,

food therapy and therapeutic exercise (Lai 1991).
Traditional Chinese medicinal herbs are taken, or made, from natural plants. Typical TCM treatment uses one herb as the basic drug
to treat the major disease problem. This is then mixed with other
herbs to treat additional symptoms, creating a multifunction formulation for the disease. In recent decades, many pharmacological functions have been suggested by experimental research. For
example, gouteng (Uncaria rhynchophylla, UR) has anticonvulsive
and free radical scavenging activities (Hsieh 1999a; Hsieh 1999b);
shitei-To was found to have anticonvulsant effects (Minami 1999);
qingyangshen (QYS) was found to have antiepileptic properties
and have a therapeutic effect on kainic acid (KA) induced experimental seizures (Guo 1993). Other herbs, such as tianma (Gastrodia rhizome), changpu (Acorus calamus) and dannanxing (Arisaema
cum bile), were also shown to have anticonvulsant effects (Wang
1996). All these herbs are usually used in Chinese medicine for the
treatment of epilepsy. Although the active ingredient for each herb
is not known, there are both clinical reports and animal studies
that suggest the prescription may inhibit seizures (Wang 1996).
TW970, a modified formula of the Chinese medicine chaihulongu-muli-tang can reduce the seizure frequency in patients with
refractory epilepsy and this may be due to antioxidant effects
(Hung 2002). Zheng tai instant powder is a complex prescription
of traditional Chinese medicine, indicated for generalized tonic
clonic seizure due to its effect on the central nervous system, energy
metabolism, neurotransmitters and haemorheology (Hu 2000).
TCM has been widely used for many years to treat epilepsy and
there is a great deal of clinical literature. However, the benefits and
adverse reactions of these treatments have not been systematically
reviewed, partly because there is no standard dose of active ingredients and prescriptions vary between patients. This review aims
to summarize the existing evidence on the comparative effectiveness and safety of traditional Chinese medicinal herbs for treating
epilepsy.
OBJECTIVES
METHODS
Criteria for considering studies for this review
Types of studies
Randomised studies using adequate or quasi (i.e. day of the week)
methods of randomisation. Studies may be single blinded, double
blind or unblinded.
Types of participants
People of any age, either gender and of any ethnic origin with
epilepsy of any type and syndrome(ILAE 1981; ILEA 1989), at
any stage of diagnosis.
Types of interventions
Traditional Chinese medicinal herbs (TCMHs) are defined as
preparations derived from plants, or parts of plants, including single herbs or mixtures of different herbs. We included any types
of preparation, such as decoction, oral liquid, tablet, capsule or
powder. We also included single chemicals extracted from a plant,
or synthetic chemicals based on plant constituents.
We considered the following comparisons:
1. one formula of TCMH versus no interventions;
2. one formula of TCMH versus placebo;
3. one formula of TCMH versus single Western medication
(monotherapy).
We excluded studies of TCMH in combination with antiepileptic
drugs (AEDs) versus AEDs alone. We will include these studies in
the update of this review.
Types of outcome measures
Primary outcomes
To assess whether traditional Chinese medicinal herbs (TCMHs)

(one formulation) for the treatment of people with epilepsy of any
type and syndrome:
1. Seizure freedom for at least 48 weeks (Glauser 2006).

2. Satisfactory seizure control: 50% or greater reduction in
seizure frequency.
3. Absolute or percentage reduction in seizure frequency and
duration.
1. are associated with a greater probability of patients

becoming seizure free, or having a significant reduction in the
frequency or duration of seizures (or both); or
Secondary outcomes
2. are associated with adverse events

when compared with other antiepileptic drugs (AEDs), placebo
or no treatment.
1. Improved quality of life, if assessed by standardized,

validated, reliable scales.
2. Incidence of adverse or harmful effects:
i) organ damage: irreversible end organ damage;
ii) cognitive side effects;

iii) allergic reactions (e.g. skin rashes, Steven Johnson

syndrome).
3. Withdrawals due to side effects or due to lack of efficacy.
Search methods for identification of studies

We searched the Cochrane Epilepsy Groups Specialised Register,
the Cochrane Central Register of Controlled Trials (CENTRAL)
(The Cochrane Library 2007, Issue 1), MEDLINE on OVID (1950
to April week 1, 2007), EMBASE (1974 to June 2007), CINAHL
(1982 to April week 1, 2007), AMED (the Allied and Complementary Medicine Database, 1985 to April 2007), the China Biological Medicine Database (CBM-disc, 1979 to June 2007) and
the VIP Chinese Science and Technique Journals Database (1989
to June 2007). The search terms used to search MEDLINE are set
out in Appendix 1.
We handsearched the Journal of Chinese Integrative Medicine, Chinese Medical Journal, Chinese Journal of Internal Medicine, Chinese Journal of Integrated Traditional and Western Medicine, Chinese Journal of Integrative Medicine and other Traditional Chinese
Medicine journals.
We searched the reference lists of all relevant papers for further
studies. In addition, we contacted colleagues and experts in the
field to identify any unpublished or ongoing studies. There was
no language restriction either in the search or in the inclusion of
studies.
Data collection and analysis
Selection of studies
To determine the studies to be assessed further, two authors (QL
and DZ) independently scanned the titles, abstract sections and
keywords of every record. The two authors retrieved full articles
for further assessment if the information given suggested that the
study:
1. included participants with epilepsy;
2. compared Chinese herbal medicine with any other active or
placebo intervention;
3. used random or quasi-random allocation to the comparison
groups.
If there was any doubt regarding these criteria from the information given in the title and abstract, we retrieved the full article for
clarification. Two authors (QL and DZ) independently assessed
each of these studies for inclusion and there were no recorded disagreements. We excluded studies that did not meet the inclusion
criteria and have stated the reasons in Characteristics of excluded
studies.
Data extraction and management

Two review authors (QL and DZ) independently assessed included
studies for quality and any differences of opinion were resolved by
the mutual consent. The following data were extracted, if available.
1. General information
i) Published/unpublished; title; authors; reference/
source; contact address; country; urban/rural etc.; language of
publication; year of publication; duplicate publications; sponsor;
setting.
2. Study methods
i) Method of generation of random list.
ii) Method of concealment of randomisation.
iii) Stratification factors.
iv) Blinding methods.
3. Participants
i) Number (total and per group).
ii) Sex and age distribution.
iii) Seizure types and epilepsy syndrome.
iv) Time between first seizure and randomisation.
v) Aetiology of epilepsy.
vi) Presence of neurological signs.
vii) Number and types of antiepileptic drugs (AEDs)
taken.
4. Intervention and control
i) Type of herbal medicines.
ii) Details of treatment regime (dose, route, timing).
iii) Type of control.
iv) Details of control treatment (dose, route, timing).
5. Follow-up data
i) Duration of follow up.
ii) Dates of treatment withdrawal and reasons for
treatment withdrawal.
iii) Withdrawal rates.
6. Outcome data
i) As described in the types of outcome measures
7. Analysis data
i) Methods of analysis (intention-to-treat and per
protocol analysis).
ii) Comparability of groups at baseline (yes or no).
Assessment of risk of bias in included studies

Two review authors independently assessed included studies for
quality using two methods.
The Cochrane approach was used to assess allocation concealment.
The method of allocation concealment in each trial was scored
using the following grading system:
Grade A: adequate concealment;
Grade B: uncertain concealment;
Grade C: inadequate concealment;
Grade D: allocation concealment not used.

We also divided studies into the following three categories according to the simple approach set out in The Cochrane Handbook for
Systematic Reviews of Interventions (Handbook 2008). The quality
criteria include blinding and losses to follow up as well as allocation concealment.
A - all quality criteria met: low risk of bias.
B - one or more of the quality criteria only partly met: moderate
risk of bias.
C - one or more criteria not met: high risk of bias.
The description of the quality of each study was given based on
these components. Two review authors (QL and DZ) independently assessed each trial selected for inclusion in the review. There
were no recorded disagreements.
Data synthesis
We analysed data using Review Manager 5.0 (RevMan 2008). We
used relative risks with 95% confidence intervals (CI) for binary
outcomes. We used standardised mean differences with 95% CI
for continuous outcomes. Where possible all analyses included all
participants in the treatment groups to which they had been allocated. For the efficacy outcome (50% or greater reduction in
seizure frequency), we planned to undertake three analyses: (1)
primary (intention-to-treat) analysis; (2) worst case; (3) best case,
to address the potential problem of missing outcome data. However, not all included studies reported loss to follow up data, so we
were unable to perform these analyses.
We assessed clinical heterogeneity by comparing the distribution of
important participant factors between studies (age, gender, seizure
type, duration of epilepsy, number of AEDs taken at time of randomisation) and study factors (randomisation concealment, blinding, losses to follow up). We assessed statistical heterogeneity with
the I2 statistic; a value greater than 50% was considered to indicate
significant heterogeneity. However, the preparation and composition of herbal medicines in each study varied and there was clear
heterogeneity of intervention, so meta-analysis was not attempted.
We planned to assess the impact of important patient characteristics including seizure type, duration and aetiology of epilepsy, and
presence of neurological signs upon outcome, assuming sufficient
data were available. We also planned to undertake sensitivity analyses including: (i) all studies; (ii) only those using adequate methods of allocation concealment, such as sealed opaque envelopes
or telephone randomisation. For the analysis of adverse events, as
stated above, we calculated Peto odds ratios (ORs) with 99% CIs
for the comparison between randomised groups.
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded

studies; Characteristics of studies awaiting classification.
Studies identified
We initially found 16 controlled studies of traditional Chinese
medicine (TCM) assessing the treatment of epilepsy. We excluded
nine studies for the following reasons (see also the Characteristics
of excluded studies). In four studies (Chen 1998; Li 1997; Wang
2001; Xu 2005) the diagnostic criteria for epilepsy were unclear
or did not meet the ILAE (International League Against Epilepsy)
classifications. Three studies (Lin 1999; Liu 1994b; Yin 2001)
were excluded according to our preset that AEDs have been used
in combination with traditional Chinese herbs. Two studies (Chen
2000; Wu 2002) used healthy volunteers as the control group.
Another two studies (Ma 2003a; Ma 2003b) are currently awaiting
assessment for inclusion in this review. For one study (Ma 2003a)
the study design was unclear and we were not able to contact the
author for further information. The other trial report (Ma 2003b)
mentioned randomisation but patients were allocated in a 6:1 ratio
to treatment or control. We therefore decided to contact the author
for further information about the randomisation process, but we
have been unable to contact them. Ultimately, five studies (Liu
1994a; Song 2001; Tian 2006; Xiang 1998; Xin 1999) fulfilled
our inclusion criteria. Details are given in the table Characteristics
of included studies and are summarised below. All the studies were
conducted in China and were published in Chinese. We did not
find any ongoing studies.
Design
All the included studies were of single centre, parallel design and
had a control group. All of them mentioned randomisation but
the randomisation procedures were unclear. None of the studies
were blinded and their duration ranged from two months to three
years.
Participants
The number of participants in the studies ranged from 40 to
401, with a total of 1125 in the five studies in this review. The
age of participants ranged from two to 70 years with mean ages,
where given, ranging from 6.25 to 30.84 years. All studies had
adults and children as participants, except Xin 1999, which included only children aged from three to 13 years old. Two studies
(Liu 1994a; Xiang 1998) only included primary generalized tonicclonic seizure and one study (Xin 1999) included both primary
and secondary generalized tonic-clonic seizure. The remaining two
(Song 2001; Tian 2006) included all partial or generalized. All
the included participants had a verified diagnosis of Xian Zheng
according to the TCM system and four studies (Liu 1994a; Tian
2006; Xin 1999; Song 2001) also required the detailed types in
Xian Zheng, according to the criteria of the China Ministry of

Health. All studies except one (Xin 1999) reported the time between first seizure and randomisation, and this ranged from three
months to more than 30 years. None of the studies mentioned
whether the included participants were newly diagnosed. Only
one study (Tian 2006) mentioned that most of the participants
had antiepileptic drug monotherapy or biotherapy history before
entering the studies, but did not give details. The baseline seizure
frequency was reported in three studies (Tian 2006; Xiang 1998;
Xin 1999), and all the three studies included the patients who
had a seizure at least once a month. Although none of the studies
reported the aetiologies of epilepsy, three (Liu 1994a; Tian 2006;
Xiang 1998) excluded secondary or symptomatic epilepsy caused
by stroke, trauma or tumour. Neurological signs were not mentioned in any of the studies.
Risk of bias in included studies

All of the included studies were of low quality (C). An overview of
study quality can be found in the table Characteristics of included
studies.
Randomisation
Although all the studies mentioned that the patients were randomly allocated to the intervention and control groups, none of
them described the allocation sequence in detail. None of the
included studies mentioned allocation concealment. We tried to
contact the authors of studies by telephone in order to obtain more
detailed information, however we were unable to reach them. We
also wrote to the authors but did not receive any replies.
Interventions
The preparation and composition of herbal medicines in each
study varied and each trial compared one formulation of TCMH
with a single antiepileptic drug (see Table 1). Several herbs, such as
changpu (Acorus calamus), dannanxing (Arisaema cum bile), banxia
(Rhizoma pinelliae), fu ling (Poria), yuanzhi (Polygala) and tianma
(Gastrodia rhizome) were tested. TCMH was given in the form
of patient prescription in four studies (Liu 1994a; Song 2001;
Tian 2006; Xin 1999 ). Two studies (Tian 2006; Xin 1999) used
capsules, one granule (Liu 1994a) and one pill (Song 2001). All the
tested herbs were prepared by the trial authors hospital, except the
antiepilepsy capsule, which was produced by a pharmaceutical
company.
The different intervention and comparators are listed below.
Liu 1994a compared Xiaxingci granule with phenytoin.
Song 2001 compared Dianxianning pill with valproate.
Tian 2006 compared Tianmadingxian capsule with phenytoin.
Xiang 1998 compared Zhixian I with phenytoin.
Xin 1999 compared Antiepilepsy capsule with phenobarbital.
The duration of treatment was two months (Xiang 1998), 12
weeks (Liu 1994a) and three months (Song 2001; Tian 2006; Xin
1999).
Outcomes measures
Two studies (Liu 1994a; Song 2001) used seizure freedom as an
outcome measure. All studies reported the number of participants
with percentage reduction in seizure frequency (such as 50% or
greater, 75% or greater) as one of the major outcomes. All studies
except one (Tian 2006) also reported the electroencephalogram
(EEG) results before and after treatment. One study (Xin 1999)
reported the number of participants with good (75% or greater)
or moderate (50% to 74%) reduction in seizure duration. None of
the studies mentioned health-related quality of life as outcomes.
All studies except one (Tian 2006) assessed adverse events and
reported the incidence in detail. None of the studies reported
withdrawal due to side effects or due to lack of efficacy.
Blinding
None of the studies mentioned blinding.
Description of withdrawals, losses to follow up and

intention-to-treat analysis
A follow up of at least two months was used. One study (Liu 1994a)
had a follow up of 12 weeks, but in the outcomes mentioned a
seizure free interval of one year, which seems to be contradictory.
None of the studies described withdrawals and losses to follow up
or performed intention-to-treat analysis.
Similarity of comparison groups at baseline

All studies provided data on important baseline characteristics of
the intervention and control groups to judge the comparability.
Two studies (Tian 2006; Xin 1999) claimed that the two groups
were comparable at baseline. Age and gender appeared to be balanced in all studies and other baseline characteristics were partly
provided. The time between first seizure and randomisation was
reported in all except one (Xin 1999). The baseline seizure frequency was reported in two studies (Tian 2006; Xin 1999).
Effects of interventions
The five studies tested five different traditional Chinese medicines
compared with antiepileptic drugs (AEDs), and the reported outcomes included seizure freedom, 50% or greater reduction in
seizure frequency, percentage reduction in seizure frequency and
duration, improvement in EEG and adverse effects. We did not
perform a meta-analysis due to heterogeneity in interventions and
controls.

Primary outcome measures
I. Xiaxingci granule versus phenytoin
We found one study (Liu 1994a) comparing Xiaxingci granule

with placebo, which recruited 40 participants. All participants
were diagnosed with primary generalised tonic-clonic seizure.
(1) Seizure freedom

The study described the number of participants who were seizure
free for one year. No statistically significant difference was found
between Xiaxingci granule and phenytoin in this study (RR 1.00;
95% CI 0.07 to 14.90, P = 1.00).
(2) 75% or greater reduction in seizure frequency
III. Tianmadingxian capsule versus phenytoin
We found one study (Tian 2006) comparing Tianmadingxian capsule with phenytoin, which recruited 334 participants. All participants were diagnosed with epilepsy according to the classifications
of ILEA 1989.

There was a statistically significant difference between the treatment and control groups favouring Tianmadingxian capsule (RR
1.37; 95% CI 1.23 to 1.53, P < 0.00001).

The study showed a statistically significant difference between
Tianmadingxian capsule and phenytoin, favouring Tianmadingxian capsule (RR 2.38; 95% CI 1.83 to 3.09, P < 0.00001).
Xiaxingci granule was no better or worse than phenytoin (RR 1.50;

95% CI 0.28 to 8.04, P = 0.64).
Xiaxingci granule was no better or worse than phenytoin (RR 1.00;
95% CI 0.81 to 1.23, P = 1.00).

Tianmadingxian capsule and phenytoin, favouring Tianmadingxian capsule (RR 1.19; 95% CI 1.10 to 1.28, P < 0.00001).
IV. Zhixian I versus phenytoin

II. Dianxianning pill versus valproate
We found one study (Song 2001) comparing Dianxianning pill

with valproate, which recruited 150 participants. All participants
were diagnosed with epilepsy according to the classifications of
ILEA 1989.
We found one study (Xiang 1998) comparing Zhixian I with

phenytoin, which recruited 200 participants. All participants were
diagnosed with primary generalized tonic-clonic seizure.

(1) Seizure freedom
The study described the number of participants who were seizure
free for one year. There was no statistically significant difference
(RR 13.00; 95% CI 0.74 to 227.72, P = 0.08).
The study used Zhixian I versus phenytoin and a statistically significant difference was found favouring Zhixian I (RR 1.31; 95%
CI 1.16 to 1.48, P < 0.0001).

A statistically significant difference was found favouring Dianxianning pill (RR 2.73; 95% CI 2.00 to 3.74, P < 0.00001).

Zhixian I and phenytoin, favouring Zhixian I (RR 1.42, 95% CI
1.20 to 1.68, P < 0.0001).

Dianxianning pill was no better or worse than valproate (RR 0.98;
95% CI 0.92 to 1.04, P = 0.52).

Zhixian I and phenytoin, favouring Zhixian I (RR 1.10; 95% CI
1.03 to 1.18, P = 0.006).

V. Antiepilepsy capsule versus phenobarbital
(3) Withdrawals due to side effects or due to lack of efficacy
We found one study (Xin 1999) comparing Antiepilepsy capsule

with phenobarbital, which recruited 401 participants. All participants were diagnosed with primary generalized tonic-clonic seizure
and partial secondary tonic-clonic seizure.
Since none of the studies reported loss to follow up, we could not
analyse the withdrawals due to side effects or due to lack of efficacy.

We found that there was a slight difference between antiepilepsy
capsule and phenobarbital, favouring Antiepilepsy capsule (RR
1.21; 95% CI 1.02 to 1.43, P = 0.03).
Subgroup and sensitivity analysis

None of the studies contained stratified data and individual raw
data on aetiology, duration and frequency were not available. We
were therefore unable to analyse studies according to different aetiology, duration or frequency. Five studies were included and no
study had the highest possible quality, with adequate concealment
of randomisation, therefore we did not perform the planned sensitivity analysis.

The study reported a statistically significant difference between
antiepilepsy capsule versus phenobarbital, favouring antiepilepsy
capsule (RR 1.46; 95% CI 1.13 to 1.88, P = 0.003).
(3) 75% or greater reduction in seizure duration

Only this study reported the number of participants with 75% or
50% or greater reduction in seizure duration. We found that there
was no difference between Antiepilepsy capsule and phenobarbital for the outcome 75% or greater reduction in seizure duration
(RR 1.29; 95% CI 0.98 to 1.69, P = 0.07).
(4) 50% or greater reduction in seizure duration

The participants treated with Antiepilepsy capsule seemed to have
more likelihood of achieving a 50% or greater reduction in seizure
duration (RR 1.25; 95% CI 1.05 to 1.48, P = 0.01).
Secondary outcome measures
(1) Quality of life measures
Quality of life measures were not recorded in any studies, therefore

they could not be examined.
DISCUSSION
Summary
In this review we have included data from 1125 patients from five
studies in which participants were randomised to either traditional
Chinese medicine (TCM) or antiepileptic drugs (AEDs). All the
studies were of low methodological quality. No studies were conducted using adequate methods of randomisation, allocation concealment or blinding of both investigators and patients. They provide only limited descriptions of baseline and follow up data. All
studies stated that random assignment was used, but there was insufficient information to judge whether or not this was conducted
properly. All the included studies therefore had a high probability
of selection, detection and performance bias. Although the studies
did report some benefit (in terms of patients becoming seizure free
or having a 50% or greater reduction in seizure frequency), we
are unable to draw a reliable conclusion on the effect of TCM for
epilepsy. No adverse effects were found in two studies and only
slight gastrointestinal discomfort was reported in the two other
studies reporting this.
Limitation of the included studies

(2) Incidence of adverse or harmful effects
All studies except one (Tian 2006) mentioned adverse events (see
Characteristics of included studies) and two studies (Liu 1994a;
Song 2001) showed no obvious adverse effect in the TCM group.
The other two studies (Xiang 1998; Xin 1999) reported only slight
gastrointestinal discomfort after TCM. Xin 1999 reported the
incidence of adverse effects both in the Antiepilepsy capsule and
phenobarbital group and the Peto odds ratio was 0.04 (99% CI
0.01 to 0.12, P < 0.00001), favouring the Antiepilepsy capsule.
None of the studies reported any cognitive side effects, allergic
reaction skin rashes or Steven Johnson syndrome.
The included studies were of poor methodological quality in terms

of randomisation, allocation concealment and blinding. We will
make further attempts to contact the relevant authors for more
detailed information on allocation concealment and randomisation as this review is updated in the future.
The included studies were quite heterogeneous in their populations. The age of participants varied greatly, ranging from 2 to 70,
but only one study (Xin 1999) focused on children. The effects of
TCM on different age groups needs further investigation.
None of studies used a placebo control. There is marked clinical
heterogeneity due to differences in TCM formulations. Four tested

herbs were prepared by the authors hospital and there may be

potential conflict of interest in promoting the therapeutic effect of
TCM. There is still a lack of information about quality standards
for the development of herbal preparations and the manufacture
of the herbal products. Future studies should provide information
about standardisation including compositions, quality control and
detailed regimens.
The primary goal of treatment for epilepsy is the control of seizures,
or even for patients to become seizure free, however the follow-up
period used in the studies was quite unclear or short. Most of the
included studies reported end-of-treatment responses and there is
a lack of long-term follow-up data. Some important outcomes,
such as percentage reduction of seizure duration, quality of life
and cognitive side effects, were assessed by only a single study or
none.
Although the study results seem to show TCM is a relatively safe
treatment modality, we cannot be assured of the safety of TCM for
epilepsy patients since the small sample sizes might have limited
power to detect rare adverse effects. The safety of using TCM is
still to be proved.
No studies reported a sample size calculation, which is essential
for ensuring adequate sample size and statistical power. None reported the loss to follow up, and there may be selective reporting
of outcome data. None of included studies mentioned ethical issues or whether the participants gave informed consent.
Limitations of this systematic review

Although we conducted comprehensive searches, only Chinese
language publications were found and included and no multicentre, large-scale randomised controlled trial (RCT) was identified. We undertook extensive searches for unpublished material
and few of the studies identified qualified for inclusion, but at the
same time we cannot disregard the fact that studies with negative
findings may remain unpublished.
TCM is widely used for treating epilepsy in China. In this review we only included studies of TCM versus AEDs, according
to our protocol. We excluded some RCTs where TCM in combination with AEDs was compared with AEDs. In addition, studies
of traditional Chinese medicinal herbs (TCMHs) compared with
acupuncture for epilepsy are not included. These studies may be
included in a future review.
Although TCM is widely accepted in China, there are still some
complicated problems that need to be noted. Chinese herbal
medicines are quite often composed of mixtures of up to 20 different herbs. They are also sometimes customised by practitioners
for each individual patient, based on the differentiation of the patients symptoms. Study designs could be adapted to this individ-
ualised treatment by stratification of practitioners or by the pattern of the syndromes. However, most of the constituents of the
pharmacological preparations cannot be specified precisely. There
may be variation between different formulations and batches of
treatment, although the variation is an inevitable consequence of
the nature of TCM and the Chinese government does specify the
limits of variation that are acceptable. This variation is a factor
that may contribute to any heterogeneity between different study
results, making meta-analysis difficult.
AUTHORS CONCLUSIONS
Implications for practice
The current evidence is insufficient to support traditional Chinese medicine (TCM) as a treatment for epilepsy. Much larger,
high quality randomised clinical trials are needed to evaluate the
effectiveness and safety of traditional Chinese medicinal herbs for
treating epilepsy.
Implications for research

More high quality randomised controlled studies following the
CONSORT criteria (Moher 2001) are required to assess the effects of traditional Chinese medicine for epilepsy. Future clinical
studies should include a broad age range of patients, and have a
very large sample size to delineate the effect of TCM on patients
with different seizure types. Relevant clinical events, such as being
seizure free for at least 48 weeks, a 50% or greater reduction in
seizure frequency and duration, or quality of life, should be included as outcomes assessed in these studies. A longer-term follow up should be used to determine the genuine effectiveness of
TCM and its long-term effects. Adverse reactions should be rigorously investigated to assess safety. Future studies should improve
the description of herbal medicines being tested, e.g. plant species,
geographical origin, harvest season, preparation procedures and
quality of the products.
ACKNOWLEDGEMENTS
We would like to acknowledge the Cochrane Epilepsy Group for
their technical support. We thank Professor Tony Marson and
Rachael Kelly (Cochrane Epilepsy Group), Dr Sridharan Ramaratnam (Department of Neurology, Apollo Hospitals, India), Professor Paula Williamson (University of Liverpool) and Professor
Taixiang Wu (Chinese Cochrane Center, China) for their kind
advice and encouragement in the preparation of this review.

REFERENCES
References to studies included in this review

Liu 1994a {published data only}
Liu QS, Long JX, He ZY. The clinical observation of
Xiaxingci granule of treatment for primary generalized
tonic-clonic seizure. Hu Nan Zhong Yi Xue Yuan Xue Bao
(Journal of Hunan College of Traditional Chinese Medicine)
1994;14(4):334.
Song 2001 {published data only}
Song PX. Clinical study of Dianxianning for 100 epilepsy
cases. Shang Dong Zhong Yi Za Zhi (Shandong Journal of
Traditional Chinese Medicine) 2001;20(5):3389.
Tian 2006 {published data only}
Tian ZH. Clinical observation of Tianmadingxian capsule
on epilepsy. He Bei Zhong Yi (Hebei Journal of Traditional
Chinese Medicine) 2006;28(7):48991.
Xiang 1998 {published data only}
Xiang JT, Jiang HY. Zhixian I for tonic-clonic seizure. Hu
Nan Zhong Yi Yao Dao Bao (Hunan Guiding Journal of
TCMP) 1998;4(11):1920.
Xin 1999 {published data only}
Xin L, Wei YL, Ye QF, Qu ZQ. Anti-epilepsy capsule for
301 cases of children epilepsy. Liao Ning Zhong Yi Za Zhi
(Liaoning Journal of Traditional Chinese Medicine) 1999;26
(11):4967.
References to studies excluded from this review

Chen 1998 {published data only}
Chen YT. Dingxian prescription treatment for 145 epileptic
cases. Nan Jing Zhong Yi Yao Da Xue Xue Bao (Journal of
Nanjing University of TCM) 1998;14(4):246.
Chen 2000 {published data only}
Chen LC, Chou MH, Lin MF, Yang LL. Lack of
pharmacokinetic interaction between valproic acid and a
traditional Chinese medicine, Paeoniae Radix, in healthy
volunteers. Journal of Clinical Pharmacy & Therapeutics
2000;25(6):4539.
Li 1997 {published data only}
Li Y. 153 cases of epilepsy treated by modified capsule of
five tigers powder fexpelling wing-evill. Guo Yi Lun Tan
(Forum on Traditional Chinese Medicine) 1997;12(4):267.
Lin 1999 {published data only}
Lin YL, Zhuang HC, Lin ZX, Xie TL, Zhan JW. The
therapeutic effect of Ningxian capsule treatment for 180
epileptic cases. Fu Jian Yi Yao Za Zhi (Fu Jian Medical
Journal) 1999;21(6):678.
Liu 1994b {published data only}
Liu YX, Wang MZ, Sun MZ, Niu SX, Sun XF, Li JK.
Clinical analysis of 72 epileptic patients treated with alkaline
extract of Euphorbia Fisheriana. Zhong Guo Zhong Xi Yi Jie
He Za Zhi (Chinese Journal of Integrated Medicine) 1994;4
(5):2824.
Wang 2001 {published data only}

Wang FL, Zhang MM, Wang FC, Wang ZH. The study of
Dingxian powder treatment for epilepsy. Liao Ning Zhong
Yi Za Zhi (Liaoning Journal of TCM) 2001;28(12):743.
Wu 2002 {published data only}
Wu HM, Liu CS, Tsai JJ, Ko LY, Wei YH. Antioxidant
and anticonvulsant effect of a modified formula of ChaihuLongu-Muli-Tang. American Journal of Chinese Medicine
2002;30:33946.
Xu 2005 {published data only}
Xu Zi. The observation of Ditantongguan potion treatment
for 23 pediatric epilepsy. Xin Jiang Zhong Yi Yao (Xinjiang
TCM) 2005;23(3):201.
Yin 2001 {published data only}
Yin HJ, Guo ZY. Clinical study of Ginkgo biloba extract
in the treatment of epilepsy. Yi Yao Dao Bao (Herald of
Medicine) 2001;20(2):98.
References to studies awaiting assessment

Ma 2003a {published data only}
Ma R, Zhang XL. The clinical observation of Xifeng capsule
treatment for 200 pediatric tonic-clonic epilepsy. Journal of
Traditional Chinese Medicine 2004;45(5):3635.
Ma 2003b {published data only}
Ma R, Li S, Li X, Hu S, Sun X, Liu Y, et al.Clinical
observation on 930 child epilepsy cases treated with antiepilepsy capsules. Journal of Traditional Chinese Medicine
2003;23(2):10912.
Additional references
Cockerell 1995
Cockerell OC, Johnson L, Sander JWAS, Hart YM,
Shorvon SD. Remission of epilepsy: results from the
National General Practice Study of Epilepsy. Lancet 1995;
346:1404.
Fulder 1996
Fulder S. The Handbook of Alternative and Complementary
Medicine. Oxford: Oxford University Press, 1996.
Glauser 2006
Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A,
Chadwick D, Guerreiro C, et al.ILAE treatment guidelines:
evidence-based analysis of antiepileptic drug efficacy and
effectiveness as initial monotherapy for epileptic seizures
and syndromes. Epilepsia 2006;47(7):1094120.
Guo 1993
Guo Q, Kuang P. Effect of qingyangshen on hippocampal
alpha- and beta-tubulin gene expression during kainic acid
induced epileptogenesis. Journal of Traditional Chinese
Medicine 1993;13(4):2816.
Handbook 2008
Higgins JPT, Green S, editors. Cochrane Handbook
for Systematic Reviews of Interventions 5.0.0 [updated

10
February 2008]. The Cochrane Collaboration, 2008.

Available from www.cochrane-handbook.org.
Hauser 1993
Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy
and unprovoked seizure in Rochester, Minnesota:19351984. Epilepsia 1993;34(3):45368.
Hsieh 1999a
Hsieh CL, Chen MF, Li TC, Li SC, Tang NY, Hsieh CT.
Anticonvulsant effect of Uncaria rhynchophylla (Miq) Jack.
in rats with kainic acid-induced epileptic seizure. American
Journal of Chinese Medicine 1999;27:25764.
Hsieh 1999b
Hsieh CL, Tang NY, Chiang SY, Hsieh CT, Lin JG.
Anticonvulsive and free radical scavenging actions of two
herbs, Uncaria rhynchophylla (MIQ) Jack and Gastrodia
elata Bl., in kainic acid-treated rats. Life Sciences 1999;65
(20):207182.
Hu 2000
Hu H, Zhou Y, Sui Y, Qi M. An experimental study of
effect of zheng tai instant powder on grand mal epilepsy.
Journal of Traditional Chinese Medicine 2000;20:2105.
Hung 2002
Hung-Ming W, Liu CS, Tsai JJ, Ko LY, Wei Y. Antioxidant
and anticonvulsant effect of a modified formula of chaihulongu-muli-tang. American Journal of Chinese Medicine
2002;30:33946.
ILAE 1981
Commission on Classification and Terminology of the
International League Against Epilepsy. Proposal for revised
clinical and electroencephalographic classification of
epileptic seizures. Epilepsia 1981;22(4):489501.
ILEA 1989
Commission on Classification and Terminology of the
International League Against Epilepsy. Proposal for revised
classification of epilepsies and epileptic syndromes. Epilepsia
1989;30:38999.
Lai 1991
Lai C W, Lai Y H. History of epilepsy in Chinese traditional
medicine. Epilepsia 1991;32(3):299302.
Liu 2000
Liu JP, McIntosh H, Lin H. Chinese medicinal herbs for
chronic hepatitis B. Cochrane Database of Systematic Reviews
2000, Issue 4. [Art. No.: CD001940. DOI: 10.1002/
14651858.CD001940]
Minami 1999
Minami E, Shibata H, Nunoura Y, Nomoto M, Fukuda
T. Efficacy of shitei-to, a traditional Chinese medicine
formulation, against convulsions in mice. American Journal
of Chinese Medicine 1999;27(1):10715.
Moher 2001
Moher D, Schulz KF, Altman D. The CONSORT
statement: revised recommendations for improving the
quality of reports of parallel-group randomized trials. JAMA
2001;285(15):198791.
RevMan 2008
The Nordic Cochrane Centre. The Cochrane Collaboration.
Review Manager. 5.0. Copenhagen: The Nordic Cochrane
Centre. The Cochrane Collaboration, 2008.
Sander 1996
Sander JW, Shorvon SD. Epidemiology of the epilepsies.
Journal of Neurology, Neurosurgery, and Psychiatry 1996;61
(5):43343.
Villeneuve 2004
Villeneuve N. Quality-of-life scales for patients with drugresistant partial epilepsy. Reviews of Neurology (Paris) 2004;
160:37693.
Wang 1996
Wang Q. Advances in treatment of epilepsy with traditional
Chinese medicine. Journal of Traditional Chinese Medicine
1996;16(3):2307.
Indicates the major publication for the study

11
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Liu 1994a
Methods
DESIGN: randomised controlled trial

RANDOMISATION PROCEDURE: unclear
BLINDING: not used
DURATION OF FOLLOW UP: 12 weeks
Participants
COUNTRY AND SETTING: China; Changsha city, Hunan Province.

NUMBER AND SEX: treatment group (males): 20 (11); control: 20 (12).
AGE: treatment: 4 to 53 years old (mean 22.8 years); control: 5 to 53 years old (mean 25.7 years)
SEIZURE TYPES: primary generalized tonic-clonic seizure and verified diagnosis of wind phlegm types
of xian zheng in TCM
NEWLY DIAGNOSED: unclear
BASELINE SEIZURE FREQUENCY: no mention
TIME BETWEEN FIRST SEIZURE AND RANDOMISATION: treatment: 0.5 to 20 years (mean 6.
5 years); control: 0.5 to 18 years (mean 7.6 years)
Interventions
Both groups are monotherapy

Treatment group: Xiaxingci granule 4 g p.o, t.i.d
Control group: phenytoin total 10 mg/kg/d, 3 times a day
Both groups were 4 weeks as a course and 3 courses in total and there was a week for a rest between the
two courses
Outcomes
SEIZURE FREEDOM: seizure free for 1 year: treatment 1; control 1

REDUCTION IN SEIZURE FREQUENCY (number of patients): 75% or greater reduction (treatment
3, control 2); 25% to 75% reduction (treatment 14, control 15); less than 25% reduction (treatment 2,
control 2)
IMPROVEMENT RATE IN EEG: treatment group 15%; control group 10%
ADVERSE EVENTS: both groups had no obvious effect on blood routine examination, hepatic function
and renal function
Notes
(1) There was potential conflict of interest in the use of Xiaxingci granules made by the authors hospital
(2) The course and therapy was irregular
Risk of bias
Item
Authors judgement
Description
Allocation concealment?
Unclear
B - Unclear

12
Song 2001
Methods

BLINDING: not used
DURATION OF FOLLOW UP: 90 days to 1 year
Participants
COUNTRY AND SETTING: China; Taiyuan city, Shandong Province

NUMBER AND SEX: treatment group (males): 100 (46), control: 50 (28).
AGE: treatment group: 2 to 45 years old (2 to 15 years (60 patients), 20 to 30 years (30 patients), 35 to
45 years (10 patients)). Control: 3 to 45 years old (3 to 15 years (30 patients), 20 to 30 years (15 patients)
, 35 to 45 years (5 patients))
SEIZURE TYPES (number of patients): classifications in ILAE 1989 and verified diagnosis of xian zheng
in TCM. GTCS: treatment (35), control (15); absence: treatment (35), control (15); simple partial seizure:
treatment (10), control (5); complex partial seizure: treatment (10), control (5); myoclonic seizures:
treatment (5), control (5); and atonic seizures: treatment (5), control (5)
BASELINE SEIZURE FREQUENCY: no mention
TIME BETWEEN FIRST SEIZURE AND RANDOMISATION: 1 to 30 years (mean 9.87 years)
unclear in each group
Interventions
Both group are monotherapy

Treatment: Dianxianning pill 4 g for adults and 2.5 g for children 3 times daily for 90 days
Control: valproate 0.4 g for adults and 0.2 g for children 3 times daily for 90 days
Outcomes
SEIZURE FREEDOM: treatment group seizure free (6), control group (0)
SEIZURE FREQUENCY (number of patients): treatment: 80% or greater reduction (82), 60% to 79%
reduction (12); control: 80% or greater reduction (30), 60% to 79% reduction (66)
IMPROVEMENT IN EEG: treatment: 100 (100%) obviously improved; control: 20 (40%) obviously
improved, 18 (36%) improved and 12 (24%) unchanged
ADVERSE EVENTS: treatment group had no obvious adverse events; control: 5 had gastrointestinal
reaction and 2 had fatigue and drowsiness
Notes
There was potential conflict of interest in the use of Dianxianning pill made by the authors hospital
Risk of bias
Item
Authors judgement
Description
Unclear
B - Unclear
Tian 2006
Methods

BLINDING: not used
DURATION OF FOLLOW UP: 90 days
Participants
COUNTRY AND SETTING: China; Shijiazhuang city, Hebei Province

NUMBER AND SEX: treatment group (males): 178 (87), Control: 156 (76)AGE: 4 to 70 years old.

13
Tian 2006
(Continued)
Treatment group: 4 to 10 years (39), 11 to 20 years (67), 21 to 30 years (51), 31 to 40 years (13), > 40
years (8). Control: 4 to 10 years (32), 11 to 20 years (54), 21 to 30 years (46), 31 to 40 years (19), > 40
years (5)
SEIZURE TYPES (number of patients): GTCS: treatment (91), control (82); absence: treatment (31),
control (40); simple partial seizure: treatment (34), control (23); complex partial seizure treatment (22),
control (11). Verified diagnosis of xian zheng in TCM, wind phlegm obstacle orifice types: treatment
(81), control (76); pyrophlegm intervene mind types: treatment (54), control (47); stagnant blood block
brain types: treatment (28), control (23); collateral and hepatic and renal yin deficiency types: treatment
(15), control (10)
BASELINE SEIZURE FREQUENCY: at least once a month and in total more than 3 times
TIME BETWEEN FIRST SEIZURE AND RANDOMISATION (number of patients): treatment: 0.3
to 5 years (85), 6 to 10 years (52), 11 to 20 years (30), 21 to 30 years (6), > 30 years (5); Control: 0.3 to
5 years (67), 6 to 10 years (46), 11 to 20 years (31), 21 to 30 years (9), > 30 years (3)
NUMBER AND TYPES OF AEDs TAKEN: most had monotherapy or biotherapy history including
VAL, CBZ, TPM etc
Interventions

Treatment group: Tianmadingxian capsule to be taken 3 times daily at age-dependent dosage: < 8 years
old (1.05 g), 8 to 12 years old (1.4 g), > 13 years old (2.1 g)
If the participants had ever taken AEDs, these should be decreased for 1 month, then Tianmadingxianling
taken separately for 90 days
Control group: phenytoin 0.15 g 3 times daily for adults and 3 to 8 mg/kg daily for children for 90 days
Outcomes
REDUCTION IN SEIZURE FREQUENCY (number of patients): 75% or greater reduction treatment

(125), control (46); 51% to 75% reduction treatment (44), control (62); 26% to 50% reduction treatment
(6), control group (21); less than 25% reduction treatment (3), control (27)
ADVERSE EVENTS: no mention
Notes
(1) There was potential conflict of interest in the use of Tianmadingxian capsule made by the authors
hospital
Risk of bias
Item
Authors judgement
Description
Unclear
B - Unclear
Xiang 1998
Methods

BLINDING: not used
DURATION OF FOLLOW UP: 60 days to 3 years
Participants
COUNTRY AND SETTING: China; Yongzhou city, Hunan Province

NUMBER AND SEX: treatment group (males): 100 (58); control: 100 (53).
AGE: treatment: 8 to 61 years old, mean 30.84 (SD 6.64) years; control: 9 to 53 years old, mean 28.82

14
Xiang 1998
(Continued)
(SD 6.52) years

SEIZURE TYPES: primary generalized tonic-clonic seizure and verified diagnosis of xian zheng in TCM
BASELINE SEIZURE FREQUENCY: at least once a month and in total more than 3 times
TIME BETWEEN FIRST SEIZURE AND RANDOMISATION: treatment: 0.3 to 25 years (mean 7.
66 +/-2.12 years); control: 0.4 to 21 years (mean 7.42 +/-1.84 years)
Interventions

Treatment group: Zhixian I mixture to be taken twice daily for 60 days.
Control group: phenytoin total 0.2 to 0.8g, 2 to 3 times a day for 60 days
Outcomes
REDUCTION IN SEIZURE FREQUENCY (number of patients): 75% or greater reduction: treatment

(88), control (62); 51% to 75% reduction treatment (9), control (12); 26% to 50% reduction treatment
(2), control (16); less than 25% reduction treatment (1), control (10)
IMPROVEMENT IN EEG (number of patients): treatment group: normal (23), borderline abnormal (2)
, abnormal (75) before treatment, normal (78), abnormal (8), improvement (14) after treatment; control:
normal (30), borderline abnormal (11), abnormal (59) before treatment, normal (40), abnormal (33),
improvement (25), aggravate (2) after treatment
RELAPSE RATE: participants who had more than 50% reduction in seizure frequency followed up for 3
years for observation of the relapse rate: treatment group 1 year (13/97, 13.4%), 2 years (20/97, 20.6%)
, 3 years (25/97, 25.8%); control group 1 year (25/74, 39.8%), 2 years (40/74, 20.6%), 3 years (51/74,
68.9%)
ADVERSE EVENTS: treatment group had gastrointestinal reaction (32) and no obvious effect on blood
routine examination, hepatic function and renal function.
Control group (number of participants): ataxia (30), gingival thickening (42), hirsuties (13), neuropathy
(11), gastrointestinal reaction (41), rash (18), hematopoietic system reaction (14)
Notes
(1) There was potential conflict of interest in the use of Zhixian I made by the authors hospital
(2) The baseline seizure frequency was not mentioned
Risk of bias
Item
Authors judgement
Description
Unclear
B - Unclear
Xin 1999
Methods

BLINDING: not used
Participants
COUNTRY AND SETTING: China; Beijing

NUMBER AND SEX: treatment group (males): 301(167);control group (males): 100 (59)
AGE: treatment: 3 to 13 years old (mean 6.98 years); control: 3 to 13 years old (mean 6.25 years)
SEIZURE TYPES (number of patients): primary generalized tonic-clonic seizure and partial secondary
tonic-clonic seizure and verified diagnosis of xian zheng in TCM. GTCS: treatment 244, control 76;

15
Xin 1999
(Continued)
STCS: treatment 57, control 24

BASELINE SEIZURE FREQUENCY in 3 months before inclusion: 1 to 2 times per month and in total
more than 3 times
Interventions

Treatment group: Antiepilepsy capsule to be taken 3 times daily at age-dependent dosage: 3 to 6 years
(2.5 g) and > 6 years (4 g). If the participants had ever taken AEDs for more than 1 month, Antiepilepsy
capsule was taken with AEDs for 1 month, then stopped taking AEDs and took separate Antiepilepsy
capsule for 90 days.
Control group: phenobarbital 1.5 to 2 mg/kg 3 times daily for 90 days
Outcomes
REDUCTION IN SEIZURE FREQUENCY (number of patients): 75% or greater reduction treatment

(180), control (41); 51% to 75% reduction treatment (42), control (20); no reduction treatment (79),
control (39)
IMPROVEMENT IN EEG (number of patients): treatment: obviously improved (113), improved (40)
and unchanged (86) ; control: obviously improved (37), improved (8) and unchanged (35)
ADVERSE EVENTS (number of patients): treatment group had gastrointestinal reaction such as poor
appetite (3), vomiting (2), bellyache (1) and diarrhoea (1); total adverse events incidence rate 2.33%,
no obvious effect on blood routine examination, hepatic function and renal function. Control group:
drowsiness (17), insomnia (1), slow reaction (3), vomiting (3), restlessness (2), dizziness and headache (1)
, rash (12); total adverse events incidence rate 37.0% and no obviously effect on blood routine, hepatic
function and renal function except 4 had lower haemoglobin
Notes
Risk of bias
Item
Authors judgement
Description
Unclear
B - Unclear
AED = antiepileptic drug

GTCS = generalised tonic-clonic seizure
STCS= secondary generalised tonic clonic seizure
VAL=valproate
CBZ=carbamazepine
TPM= topiramate
p.o. = orally
t.i.d. = three times daily

16
Characteristics of excluded studies [ordered by study ID]
Study
Reason for exclusion
Chen 1998
The diagnosis criteria for epilepsy were unclear
Chen 2000
Healthy volunteers as the control
Li 1997
Lin 1999
TCM (Ningxian capsule) combined with AEDs compared with AEDs
Liu 1994b
TCM (alkaline extract of Euphorbia fisheriana) combined with AEDs compared with AEDs
Cross-over design
Wang 2001
The participants did not accord with the diagnosis criteria of ILAE
Wu 2002
Healthy volunteers as the control
Xu 2005
Yin 2001
TCM (Ginkgo biloba extract) combined with AEDs compared with AEDs

ILAE = International League Against Epilepsy
TCM = traditional Chinese medicine
Characteristics of studies awaiting assessment [ordered by study ID]

Ma 2003a
Methods
DESIGN: unclear
BLINDING: not used
DURATION OF FOLLOW UP: 180 day
Participants
COUNTRY AND SETTING: China; Tianjin city

NUMBER AND SEX: xifeng capsule group (males): 200 (118); antiepilepsy capsule group: 100 (51); phenobarbital
group: 100 (59)
AGE (number of patients): xifeng capsule group: 2 to 6 years old (36), 6 to 10 years old (54), 11 to 14 years old
(110); antiepilepsy capsule group: 2 to 6 years old (21), 6 to 10 years old (40), 11 to 14 years old (39); phenobarbital
group: 2 to 6 years old (20), 6 to 10 years old (36), 11 to 14 years old (44)
SEIZURE TYPES: primary generalized tonic-clonic seizure
BASELINE SEIZURE FREQUENCY (number of patients): less than once a month: Xifeng group (113), antiepilepsy
capsule group (46), phenobarbital group (47); 1 to 3 times a month: Xifeng group (41), antiepilepsy capsule group
(24), phenobarbital group (30); more than 3 times a month: Xifeng group (46), antiepilepsy capsule group (30),

17
Ma 2003a
(Continued)
phenobarbital group (23)

TIME BETWEEN FIRST SEIZURE AND RANDOMISATION (number of patients): xifeng group: less than 1
year (84), 1 to 5 years (86), 6 to 10 years (27), 11 to 14 years (3); antiepilepsy capsule group: less than 1 year (36), 1
to 5 years (48), 6 to 10 years (16); phenobarbital group: less than 1 year (54), 1 to 5 years (37), 6 to 10 years (9)
Interventions
TREATMENT GROUP:
Xifeng capsule to be taken 3 times daily at age-dependent dosage: < 1 year 1 (1 capsule), 1 to 3 years (2 capsules), 3
to 7 years (5 capsules) and > 7 years (8 capsules)
Antiepilepsy capsule to be taken 3 times daily at age-dependent dosage: < 1 year 1 (1 capsule), 1 to 3 years (2
capsules), 3 to 7 years (5 capsules) and > 7 years (8 capsules)
Phenobarbital group: phenobarbital: 2 mg/kg 3 times daily for 180 days
Outcomes
REDUCTION IN SEIZURE FREQUENCY (number of patients)

Seizure freedom for at least 1 year
Xifeng group (49), antiepilepsy group (8), phenobarbital group (3)
75% or greater reduction
50% to 74% reduction
Less than 50% reduction
Notes
Ma 2003b
Methods

BLINDING: not used
Participants
COUNTRY AND SETTING: China; Tianjin city

NUMBER AND SEX: treatment group (males): 930 (518); control: 160 (95)
AGE: treatment: 1 to 5 years old (72), 5 to 10 years old (69), 10 to 14 years old (19), mean 22.8 years; control: 1 to
5 years old (320), 5 to 10 years old (444), 10 to 14 years old (166), mean 25.7 years
SEIZURE TYPES: classification of epilepsy in ILAE 1981
BASELINE SEIZURE FREQUENCY: more than 6 attacks within 6 months before treatment
TIME BETWEEN FIRST SEIZURE AND RANDOMISATION: unclear
Interventions
TREATMENT GROUP: Antiepilepsy capsule to be taken 3 times daily at age-dependent dosage: 1 to 5 years (1
to 5 capsules), 6 to 10 years (7 capsules) and 11 to 14 years (8 capsules). If the participants had ever taken AEDs for
more than 1 month, antiepilepsy capsule was taken with AEDs for 1 month, then AEDs were gradually decreased
from the second month, then stopped taking AEDs and took separate antiepilepsy capsule for 180 days
Control group: phenobarbital 1.5 to 2 mg/kg 3 times daily for 180 days
Outcomes
REDUCTION IN SEIZURE FREQUENCY (number of patients): 75% or greater reduction treatment (534),
control (64); 51% to 75% reduction treatment (241), control (19); 25% to 50% reduction treatment (96), control
(38); no reduction or aggravated treatment (13), control group (10)

18
Ma 2003b
(Continued)
Notes

19
DATA AND ANALYSES
Comparison 1. One formula of TCMH versus single Western medication
Outcome or subgroup title

1 Xiaxingci granule versus
phenytoin
1.1 Seizure freedom
1.2 75% or greater reduction
in seizure duration
in seizure frequency
2 Dianxianning pill versus
valproate
2.1 Seizure freedom
3 Tianmadingxian capsule
in seizure duration
4 Zhixian I versus phenytoin
5 Antiepilepsy capsule versus
phenobarbital
in seizure duration
in seizure duration
6 Incidence of adverse or harmful
effects
6.1 Antiepilepsy capsule
versus phenobarbital
No. of
studies
No. of
participants
Statistical method
Effect size
Risk Ratio (M-H, Fixed, 95% CI)
Subtotals only
1
1
40
40

1.0 [0.07, 14.90]

1.5 [0.28, 8.04]
40
1.0 [0.81, 1.23]
Subtotals only
1
1
1
200
200

13.0 [0.74, 227.72]

2.73 [2.00, 3.74]
200
0.98 [0.92, 1.04]
1
1
334

Subtotals only
1.37 [1.23, 1.53]
334
2.38 [1.83, 3.09]
334
1.19 [1.10, 1.28]
1
1
200

Subtotals only
1.31 [1.16, 1.48]
200
1.42 [1.20, 1.68]
200
1.1 [1.03, 1.18]
Subtotals only
1
1
401
1.21 [1.02, 1.43]
401
1.46 [1.13, 1.88]
401
1.29 [0.98, 1.69]
401
1.25 [1.05, 1.48]
Odds Ratio (Peto, Fixed, 99% CI)
Subtotals only
Odds Ratio (Peto, Fixed, 99% CI)
0.04 [0.01, 0.12]
1
1
401

20
Analysis 1.1. Comparison 1 One formula of TCMH versus single Western medication, Outcome 1 Xiaxingci
granule versus phenytoin.
Review:
Comparison: 1 One formula of TCMH versus single Western medication

Outcome: 1 Xiaxingci granule versus phenytoin
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
1/20
1/20
100.0 %
1.00 [ 0.07, 14.90 ]
20
20
100.0 %
1.00 [ 0.07, 14.90 ]
3/20
2/20
100.0 %
1.50 [ 0.28, 8.04 ]
20
20
100.0 %
1.50 [ 0.28, 8.04 ]
18/20
18/20
100.0 %
1.00 [ 0.81, 1.23 ]
20
20
100.0 %
1.00 [ 0.81, 1.23 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
1 Seizure freedom
Liu 1994a
Subtotal (95% CI)

Total events: 1 (Treatment), 1 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P = 1.0)
2 75% or greater reduction in seizure duration

Liu 1994a
Subtotal (95% CI)

3 25% or greater reduction in seizure frequency

Liu 1994a
Subtotal (95% CI)

0.01
0.1
Favours experimental
10
100
Favours control

21
Analysis 1.2. Comparison 1 One formula of TCMH versus single Western medication, Outcome 2
Dianxianning pill versus valproate.
Review:

Outcome: 2 Dianxianning pill versus valproate
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
6/100
0/100
100.0 %
13.00 [ 0.74, 227.72 ]
100
100
100.0 %
13.00 [ 0.74, 227.72 ]
82/100
30/100
100.0 %
2.73 [ 2.00, 3.74 ]
100
100
100.0 %
2.73 [ 2.00, 3.74 ]
94/100
96/100
100.0 %
0.98 [ 0.92, 1.04 ]
100
100
100.0 %
0.98 [ 0.92, 1.04 ]
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI
1 Seizure freedom
Song 2001
Subtotal (95% CI)


Song 2001
Subtotal (95% CI)

Test for overall effect: Z = 6.29 (P < 0.00001)
Song 2001
Subtotal (95% CI)

0.01
0.1
10
100
Favours control

22
Tianmadingxian capsule.
Review:

Outcome: 3 Tianmadingxian capsule
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

Tian 2006
Subtotal (95% CI)
169/178
108/156
100.0 %
1.37 [ 1.23, 1.53 ]
178
156
100.0 %
1.37 [ 1.23, 1.53 ]
125/178
46/156
100.0 %
2.38 [ 1.83, 3.09 ]
178
156
100.0 %
2.38 [ 1.83, 3.09 ]
175/178
129/156
100.0 %
1.19 [ 1.10, 1.28 ]
178
156
100.0 %
1.19 [ 1.10, 1.28 ]

Tian 2006
Subtotal (95% CI)

Tian 2006
Subtotal (95% CI)

0.01
0.1
10
100
Favours control

23
Analysis 1.4. Comparison 1 One formula of TCMH versus single Western medication, Outcome 4 Zhixian I
versus phenytoin.
Review:

Outcome: 4 Zhixian I versus phenytoin
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

Xiang 1998
Subtotal (95% CI)
97/100
74/100
100.0 %
1.31 [ 1.16, 1.48 ]
100
100
100.0 %
1.31 [ 1.16, 1.48 ]
88/100
62/100
100.0 %
1.42 [ 1.20, 1.68 ]
100
100
100.0 %
1.42 [ 1.20, 1.68 ]
99/100
90/100
100.0 %
1.10 [ 1.03, 1.18 ]
100
100
100.0 %
1.10 [ 1.03, 1.18 ]

Xiang 1998
Subtotal (95% CI)

Xiang 1998
Subtotal (95% CI)

0.01
0.1
10
100
Favours control

24
Antiepilepsy capsule versus phenobarbital.
Review:

Outcome: 5 Antiepilepsy capsule versus phenobarbital
Study or subgroup
Treatment
Control
n/N
n/N
Risk Ratio
Weight
M-H,Fixed,95% CI
Risk Ratio
M-H,Fixed,95% CI

Xin 1999
Subtotal (95% CI)
222/301
61/100
100.0 %
1.21 [ 1.02, 1.43 ]
301
100
100.0 %
1.21 [ 1.02, 1.43 ]
180/301
41/100
100.0 %
1.46 [ 1.13, 1.88 ]
301
100
100.0 %
1.46 [ 1.13, 1.88 ]
147/301
38/100
100.0 %
1.29 [ 0.98, 1.69 ]
301
100
100.0 %
1.29 [ 0.98, 1.69 ]
225/301
60/100
100.0 %
1.25 [ 1.05, 1.48 ]
301
100
100.0 %
1.25 [ 1.05, 1.48 ]

Xin 1999
Subtotal (95% CI)

Xin 1999
Subtotal (95% CI)

Xin 1999
Subtotal (95% CI)

0.01
0.1
10
100
Favours control

25
Analysis 1.6. Comparison 1 One formula of TCMH versus single Western medication, Outcome 6 Incidence
of adverse or harmful effects.
Review:

Outcome: 6 Incidence of adverse or harmful effects
Study or subgroup
Treatment
Control
Odds Ratio
n/N
n/N
Peto,Fixed,99% CI
Weight
Odds Ratio
Peto,Fixed,99% CI
1 Antiepilepsy capsule versus phenobarbital

Xin 1999
7/301
37/100
100.0 %
0.04 [ 0.01, 0.12 ]
301
100
100.0 %
0.04 [ 0.01, 0.12 ]
Subtotal (99% CI)


Test for subgroup differences: Not applicable
0.01
0.1
10
100
Favours control
ADDITIONAL TABLES
Table 1. The preparation and composition of the herbal medicines in the included trials
Name of tested herb
Preparation
Composition
Xiaxingci granule
Granule
A formula composed of banxia (Rhizoma Liu 1994a

pinelliae), dannanxing (Arisaema cum bile),
fuling (Poria), zuru (Bambusae caulis im taeniam), gandilong (Allolobophora caliginosa
trapezoides), cishi (magnetitum), etc.
Dianxianning pill
Pill
A formula composed of dannanxing Song 2001

(Arisaema cum bile), banxia (Rhizoma pinelliae), changpu (Acori graminei rhizoma),
yuanzhi (Polygala), quanxie (Scorpio), wugong (centipede), suanzaoren (jujube seed)
, gouteng (Rhynchophylla), tianzuhuang
(concretio silicea bambusae), lingyangjiao
(cornu antelopes), gouqi (Lycium chinense Mill.), huangjing (Polygonati rhizoma)
, shanzhuyu (asiatic cornelian cherry fruit),
hupofen (succinum)

Study ID
26
Table 1. The preparation and composition of the herbal medicines in the included trials
(Continued)
Tianmadingxian capsule
Capsule
A formula composed of tianma (Gastrodia Tian 2006

rhizome), fuling (Poria), yuanzhi (Polygala)
, wugong (centipede), quanxie (Scorpio),
changpu (Acori graminei, rhizome), danshen
(Salvia miltiorrhiza), honghua (Carthamus
tinctorius), bingpian (Borneo camphor), etc.
Zhixian I
Decotion
A formula composed of banxia (Rhizoma Xiang 1998

pinelliae), fuling (Poria), changpu (Acori
graminei, rhizome), tianma (Gastrodia rhizome), quancxie (Scorpio), yuanzhi (Polygala), chuanxiong (Ligustici rhizome), danggui (Angelica), danshen (Salvia miltiorrhiza)
, jiangcan (Bombyx Batryticatus), suanzaoren
(jujube seed), gancao (Radix glycyrrhizae)
Antiepilepsy capsule
Capsule
A
formula
composed
of
dan- Xin 1999
naxing (Arisaema cum bile), tianma (Gastrodia rhizome), banxia (Rhizoma pinelliae)
, changpu (Acori graminei, rhizome), fuling
(Poria), taizishen (heterophylly falsestarwort
root), chuanxiong (Ligustici rhizome), etc.
APPENDICES
Appendix 1. MEDLINE search strategy
The following search was used in MEDLINE and adapted for use in other databases:
1. exp Epilepsy/
2. epilep$.tw.
3. exp Seizures/
4. seizure$.tw.
5. convuls$.tw.
6. Lennox Gastaut.tw.
7. West$ syndrome.tw.
8. infant$ spasm.tw.
9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
10. exp Medicine, Herbal/
11. exp Plants, Medicinal/
12. exp Medicine, Traditional/
13. exp Drugs, Chinese Herbal/
14. herb$.tw.
15. (plant or plants).tw.
16. exp Medicine, Oriental Traditional/
17. (Chinese adj medicine).tw.
27
18. (traditional adj Chinese).tw.

19. (traditional adj medicine).tw.
20. (Chinese adj1 drug$).tw.
21. 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20
22. 9 and 21
23. randomized controlled trial.pt.
24. controlled clinical trial.pt.
25. exp Randomized Controlled Trials/
26. exp Random Allocation/
27. exp Double-Blind Method/
28. exp Single-Blind Method/
29. clinical trial.pt.
30. exp Clinical Trials/
31. (clin$ adj trial$).ab,ti.
32. ((singl$ or doubl$ or trebl$ or tripl$) adj (blind$ or mask$)).ab,ti.
33. exp PLACEBOS/
34. placebo$.ab,ti.
35. random$.ab,ti.
36. exp Research Design/
37. or/23-36
38. (animals not humans).sh.
39. 37 not 38
40. 39 and 22
HISTORY
Protocol first published: Issue 2, 2007
Review first published: Issue 3, 2009
Date
Event
Description
23 May 2008
Amended
Converted to new review format.
CONTRIBUTIONS OF AUTHORS
Dr Qifu Li performed the bibliographic searches, identified the studies, assessed their methodological quality, extracted the data, and
produced the first draft of the review. Dr Xiaoyan Chen and Dr Li He performed the bibliographic searches, identified the studies and
extracted the data. Dr Dong Zhou assessed the methodological quality of the studies, checked the extracted data, and commented on
all the draft manuscripts.

28
DECLARATIONS OF INTEREST
None known.
SOURCES OF SUPPORT
Internal sources
Department of Neurology, West China Hospital, China.
Chinese Cochrane Center, China.
External sources
No sources of support supplied
INDEX TERMS
Medical Subject Headings (MeSH)
Anticonvulsants [therapeutic use]; Drugs, Chinese Herbal [ therapeutic use]; Epilepsy [ drug therapy]; Epilepsy, Tonic-Clonic [drug
therapy]; Medicine, Chinese Traditional [methods]; Phenobarbital [therapeutic use]; Phenytoin [therapeutic use]; Randomized Controlled Trials as Topic; Valproic Acid [therapeutic use]
MeSH check words

Humans

29

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