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BackgroundBackground Chinese herbal medicineChineseherbal medicine
has been usedto treat millions of peoplehas been usedtotreatmillions of people
with schizophrenia for thousands of years.with schizophrenia for thousands of years.
AimsAims To evaluate Chinese herbalTo evaluate Chinese herbal
medicine as a treatmentfor schizophrenia.medicine as a treatmentfor schizophrenia.
MethodMethod A systematic review ofA systematic review of
randomised controlled trials (RCTs).randomised controlled trials (RCTs).
ResultsResults Seventrials were included.Seventrialswere included.
Most studies evaluated Chinese herbalMost studies evaluated Chinese herbal
medicine in combination with Westernmedicine in combinationwithWestern
antipsychotic drugs; inthese trialsresultsantipsychotic drugs; inthese trials results
tended to favour combination treatmenttended to favour combinationtreatment
compared with antipsychotic alonecompared with antipsychotic alone
(Clinical Global Impressionnotimproved/(Clinical Global Impressionnotimproved/
worseworsenn123,RR123,RR0.19,95% CI 0.1^0.6,0.19,95% CI 0.1^0.6,
NNTNNT6,95 % CI 5^11;6,95% CI 5^11; nn109,Brief109,Brief
Psychiatric Rating Scalenotimproved/Psychiatric Rating Scalenot improved/
worseRRworseRR0.78,95% CI 0.5^1.2;0.78,95% CI 0.5^1.2; nn109,109,
Scale for the Assessment of NegativeScale for the Assessmentof Negative
Symptomsnotimproved/worseSymptomsnotimproved/worse
RRRR0.87,95% CI 0.7^1.2;0.87,95% CI 0.7^1.2; nn109, Scale for109, Scale for
the Assessmentof Positive Symptomsnotthe Assessmentof Positive Symptomsnot
improved/worseRRimproved/worseRR0.69,95% CI 0.5^0.69,95% CI 0.5^
1.0,NNT1.0,NNT6 95% CI 4^162).Medium-term6 95% CI 4^162).Medium-term
study attrition was significantlyless forstudy attritionwas significantlyless for
people allocated the herbal/antipsychoticpeople allocated the herbal/antipsychotic
mix (mix (nn897, four RCTs,RR897, four RCTs,RR0.34,95% CI0.34,95% CI
0.2^0.7,NNT0.2^0.7,NNT23,95% CI18^43).23,95% CI18^43).
ConclusionsConclusions Results suggestthatResults suggest that
combining Chinese herbal medicine withcombining Chinese herbal medicine with
antipsychotics is beneficial.antipsychotics is beneficial.
Declaration of interestDeclaration of interest None.None.
Chinese medicine, now commonly referredChinese medicine, now commonly referred
to as traditional Chinese medicine hasto as traditional Chinese medicine has
been used to treat schizophrenia-like illnessbeen used to treat schizophrenia-like illness
for over 2000 years (Ming, 2001).for over 2000 years (Ming, 2001).
Although antipsychotic drugs are the main-Although antipsychotic drugs are the main-
stay of treatment both in China and in thestay of treatment both in China and in the
West, they are associated with seriousWest, they are associated with serious
adverse effects such as tardive dyskinesiaadverse effects such as tardive dyskinesiaand tremor. In addition, about 20% of peo-and tremor. In addition, about 20% of peo-
ple do not respond adequately to treatmentple do not respond adequately to treatment
(Brenner(Brenner et alet al, 1990). Some earlier reports, 1990). Some earlier reports
have suggested that Chinese herbal medi-have suggested that Chinese herbal medi-
cine is effective for psychosis and that com-cine is effective for psychosis and that com-
bination treatments (drugs plus herbs) arebination treatments (drugs plus herbs) are
useful to enhance antipsychotic efficacy oruseful to enhance antipsychotic efficacy or
reduce the period of recovery and adversereduce the period of recovery and adverse
effects (Saku, 1991; Wang, 1998effects (Saku, 1991; Wang, 1998aa).).
The methodology used in traditionalThe methodology used in traditional
Chinese medicine to diagnose and treatChinese medicine to diagnose and treat
schizophrenia differs from that used inschizophrenia differs from that used in
Western medicine. Traditional ChineseWestern medicine. Traditional Chinesemedicine differentiates cases of schizo-medicine differentiates cases of schizo-
phrenia into syndromes, and it is thesephrenia into syndromes, and it is these
syndromes rather than the disease labelsyndromes rather than the disease label
such as schizophrenia orsuch as schizophrenia or dian kuangdian kuang (with-(with-
drawal mania), that determine treatmentdrawal mania), that determine treatment
(Fig. 1). There are five main syndromes that(Fig. 1). There are five main syndromes that
fall within the disease category offall within the disease category of diandian
kuangkuangwhich may also include the Westernwhich may also include the Western
diagnosis of schizophrenia. The five typesdiagnosis of schizophrenia. The five types
are:are:
(a)(a) phlegm-fire;phlegm-fire;
(b)(b) phlegm-damp;phlegm-damp;(c)(c) qi stagnation with blood stasis;qi stagnation with blood stasis;
(d)(d) hyperactivity of fire due to yin defi-hyperactivity of fire due to yin defi-
ciency;ciency;
(e)(e) other miscellaneous types (Zhang,other miscellaneous types (Zhang,
1996).1996).
Each syndrome has a specific herbalEach syndrome has a specific herbal
formulation, but patients typically haveformulation, but patients typically have
mixed clinical presentations requiringmixed clinical presentations requiring
formulas to be adapted by adding or sub-formulas to be adapted by adding or sub-
tracting herbs. To complicate matters, intracting herbs. To complicate matters, in
China herbal medicines are sometimes usedChina herbal medicines are sometimes used
within the Western diagnostic paradigmwithin the Western diagnostic paradigmalone without incorporating traditionalalone without incorporating traditional
theory. Nevertheless, because of the enor-theory. Nevertheless, because of the enor-
mous population of China, even if herbalmous population of China, even if herbal
medicines are given to only a small propor-medicines are given to only a small propor-
tion of the estimated 13 million Chinesetion of the estimated 13 million Chinese
people with schizophrenia, these treatmentpeople with schizophrenia, these treatment
approaches could still be some of the mostapproaches could still be some of the most
prevalent used for this illness.prevalent used for this illness.
METHODMETHOD
Full details of all methods used and the pre-Full details of all methods used and the pre-
defined inclusion criteria are published else-defined inclusion criteria are published else-
where (Rathbonewhere (Rathbone et alet al, 2005). Randomised, 2005). Randomised
controlled trials were included if partici-controlled trials were included if partici-
pants had schizophrenia, schizophreniformpants had schizophrenia, schizophreniform
psychosis or a schizophrenia-like illness,psychosis or a schizophrenia-like illness,
diagnosed by any criteria. Interventionsdiagnosed by any criteria. Interventions
included Chinese herbal medicines (plant,included Chinese herbal medicines (plant,
animal or mineral) given in any dosage oranimal or mineral) given in any dosage orcombination, with or without a basis in tra-combination, with or without a basis in tra-
ditional Chinese medical theory, comparedditional Chinese medical theory, compared
with any other approach.with any other approach.
Studies were identified from searches ofStudies were identified from searches of
the Cochrane Schizophrenia Groups registerthe Cochrane Schizophrenia Groups register
of trials, which incorporates regular searchesof trials, which incorporates regular searches
of BIOSIS Inside, CENTRAL, CINAHL,of BIOSIS Inside, CENTRAL, CINAHL,
EMBASE, MEMBASE, MEDLINEEDLINE and PsycINFO; theand PsycINFO; the
hand-searching of relevant journals andhand-searching of relevant journals and
conference proceedings and searches ofconference proceedings and searches of
several grey literature sources. Additionalseveral grey literature sources. Additional
databases searched included the Traditionaldatabases searched included the Traditional
Chinese Medical Literature Analysis andChinese Medical Literature Analysis andRetrieval System, the Chinese BiomedicalRetrieval System, the Chinese Biomedical
Database, the China National KnowledgeDatabase, the China National Knowledge
Infrastructure database and the Allied andInfrastructure database and the Allied and
Complementary Medicine DatabaseComplementary Medicine Database
(AMED). Full details of the English and(AMED). Full details of the English and
Mandarin phrases used are reported else-Mandarin phrases used are reported else-
where (Rathbonewhere (Rathbone et alet al, 2005)., 2005).
Data were not utilised from studies inData were not utilised from studies in
which more than 50% of participants inwhich more than 50% of participants in
any group were lost to follow-up (this doesany group were lost to follow-up (this does
not include the outcome of leaving thenot include the outcome of leaving the
study early). In studies with a less thanstudy early). In studies with a less than
50% withdrawal rate people leaving the50% withdrawal rate people leaving thestudy early were considered to have hadstudy early were considered to have had
the negative outcome, except for the eventthe negative outcome, except for the event
of adverse effects and death. For binaryof adverse effects and death. For binary
outcomes, the fixed-effects relative riskoutcomes, the fixed-effects relative risk
and its 95% confidence interval were calcu-and its 95% confidence interval were calcu-
lated. The numbers needed to treat/harmlated. The numbers needed to treat/harm
(NNT/NNH) were also calculated. An esti-(NNT/NNH) were also calculated. An esti-
mate of the weighted mean differencemate of the weighted mean difference
(WMD) between groups and its 95% confi-(WMD) between groups and its 95% confi-
dence interval were calculated for continu-dence interval were calculated for continu-
ous data. Data were not pooled if ous data. Data were not pooled if
standard deviations were too wide, suggest-standard deviations were too wide, suggest-
ing considerable skew (Altman & Bland,ing considerable skew (Altman & Bland,1996). Heterogeneity between studies was1996). Heterogeneity between studies was
3 7 93 7 9
B R I T I S H J O U R N A L O F P S Y C H I AT R YB R I T I S H J O U R N A L O F P S Y C H I AT R Y ( 2 0 0 7 ) , 1 9 0 , 3 7 9 ^ 3 8 4 . d o i : 1 0 . 1 1 9 2 / b j p . b p . 1 0 6 . 0 2 6 8 8 0( 2 0 0 7 ) , 1 9 0 , 3 7 9 ^ 3 8 4 . d o i : 1 0 . 1 1 9 2 / b j p . b p . 1 0 6 . 0 2 6 8 8 0 R E V I E W A R T I C L ER E V I E W A R T I C L E
Chinese herbal medicine for schizophreniaChinese herbal medicine for schizophrenia
Cochrane systematic review of randomised trialsCochrane systematic review of randomised trials
JOHN RATHBONE, L AN ZHANG, MINGMING ZHANG, JUN XIA ,JOHN RATHBONE, L AN ZHANG, MINGMING ZHANG, JUN XIA ,
XIEHE LIU, YANCHUN YANGXIEHE LIU, YANCHUN YANG andand CLIVE E. ADAMSCLIVE E. ADAMS
AUTHORS PROOFAUTHORS PROOF
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assessed by inspecting the relevant graph;assessed by inspecting the relevant graph;
this was supplemented using thethis was supplemented using the II22 statisticstatistic
(Higgins(Higgins et alet al, 2003). If inconsistency was, 2003). If inconsistency was
high (high (5575%), the data were not pooled75%), the data were not pooled
but were presented separately and thebut were presented separately and the
reasons for heterogeneity investigated.reasons for heterogeneity investigated.
Citations were inspected independentlyCitations were inspected independently
by at least two reviewers. The reliabilityby at least two reviewers. The reliability
of the data extraction was checked using aof the data extraction was checked using a10% sample. Full reports of studies of10% sample. Full reports of studies of
agreed relevance were obtained, quality-agreed relevance were obtained, quality-
rated (Aldersonrated (Alderson et alet al, 2004) and data ex-, 2004) and data ex-
tracted for details of methods, participants,tracted for details of methods, participants,
interventions and outcomes. Disagreementsinterventions and outcomes. Disagreements
between reviewers were discussed and ifbetween reviewers were discussed and if
they could not be resolved further infor-they could not be resolved further infor-
mation was sought from authors. Mainmation was sought from authors. Main
outcomes of interest were predefined asoutcomes of interest were predefined as
clinical response in global or mental state,clinical response in global or mental state,
adverse events including extrapyramidaladverse events including extrapyramidal
adverse effects, service use including hospi-adverse effects, service use including hospi-
talisation and relapse, quality of life, leav-talisation and relapse, quality of life, leav-ing the study early, death and economicing the study early, death and economic
evaluations.evaluations.
RESULTSRESULTS
Electronic searches resulted in over 640Electronic searches resulted in over 640
citations but most clearly did not meet thecitations but most clearly did not meet the
inclusion criteria. Full copies of only 14inclusion criteria. Full copies of only 14
studies were obtained, of which we couldstudies were obtained, of which we could
include 7 (Table 1). Of those we excluded,include 7 (Table 1). Of those we excluded,
three were not randomised (Cao & Wang,three were not randomised (Cao & Wang,
2000; Gong2000; Gong et alet al, 2000; Rong, 2001), three, 2000; Rong, 2001), three
did not report usable data (Zhaodid not report usable data (Zhao et alet al,,1997; Wang, 19981997; Wang, 1998bb; Han; Han et alet al, 2002) and, 2002) and
one study did not use Chinese herbal medi-one study did not use Chinese herbal medi-
cine (Zhen & Feng, 1992).cine (Zhen & Feng, 1992).
We identified 16 citations dating fromWe identified 16 citations dating from
1987 to 2002 for the seven included stu-1987 to 2002 for the seven included stu-
dies. Overall, descriptions of studies weredies. Overall, descriptions of studies were
poorly reported. Two trials were availablepoorly reported. Two trials were available
in both Chinese and English (Luoin both Chinese and English (Luo et alet al,,
1997; Zhang1997; Zhang et alet al, 2001), four in Chinese, 2001), four in Chinese
only (Mengonly (Meng et alet al, 1996; Zhu, 1996; Zhu et alet al, 1996;, 1996;ChenChen et alet al, 1997; Zhang, 1997; Zhang et alet al, 1997) and, 1997) and
one in English only (Zhangone in English only (Zhang et alet al, 1987)., 1987).
All seven included studies were conductedAll seven included studies were conducted
in China and were described as beingin China and were described as being
randomised, but none gave a descriptionrandomised, but none gave a description
of the allocation procedure. Double-blindof the allocation procedure. Double-blind
methodology was used in three studies, allmethodology was used in three studies, all
of which usedof which used Ginkgo bilobaGinkgo biloba extractextract
(EGb761) combined with antipsychotics.(EGb761) combined with antipsychotics.
All trials included in this review containedAll trials included in this review contained
a moderate risk of bias (category B; Alder-a moderate risk of bias (category B; Alder-
sonson et alet al, 2004). Trials ranged in sample, 2004). Trials ranged in sample
size from 40 to 545 participants and lastedsize from 40 to 545 participants and lastedfrom 20 days to 6 months. Only one studyfrom 20 days to 6 months. Only one study
(Zhang(Zhang et alet al, 1997) attempted to allocate, 1997) attempted to allocate
treatment according to traditional Chinesetreatment according to traditional Chinese
medicine syndrome differentiation. Themedicine syndrome differentiation. The
other six studies employed Westernother six studies employed Western
diagnoses of schizophrenia with no furtherdiagnoses of schizophrenia with no further
differentiation into the traditional Chinesedifferentiation into the traditional Chinese
syndromes, and six used operational diag-syndromes, and six used operational diag-
nostic criteria. Three studies includednostic criteria. Three studies included
people with chronic schizophrenia (meanpeople with chronic schizophrenia (mean
duration 17 years), three did not reportduration 17 years), three did not report
participants history of illness and oneparticipants history of illness and one
study involved mostly people at firststudy involved mostly people at firstadmission to hospital.admission to hospital.
Herbal medicine aloneHerbal medicine alone
v.v. chlorpromazinechlorpromazine
Only one study (ZhangOnly one study (Zhang et alet al, 1987) gave, 1987) gave
the treatment group herbal medicinesthe treatment group herbal medicines
without the addition of an antipsychotic.without the addition of an antipsychotic.
Over a 20-day period, global state outcomeOver a 20-day period, global state outcome
not improved/worse significantly favourednot improved/worse significantly favoured
the control group receiving chlorpromazinethe control group receiving chlorpromazine
((nn90; RR90; RR1.88, 95% CI 1.2 to 2.9,1.88, 95% CI 1.2 to 2.9,
NNHNNH4, 95% CI 2 to 14). No participant4, 95% CI 2 to 14). No participant
left the study early.left the study early.
Herbal medicine plusHerbal medicine plus
antipsychoticsantipsychotics v.v. antipsychoticsantipsychotics
alonealone
Herbal medicines given according to tra-Herbal medicines given according to tra-
ditional Chinese medicine syndrome differ-ditional Chinese medicine syndrome differ-
entiation in only one study (Zhangentiation in only one study (Zhang et alet al,,
1997), using1997), using dang gui cheng qi tangdang gui cheng qi tang oror xiaoxiaoyao sanyao san when combined with anti- when combined with anti-
psychotic medication (unspecified) scoredpsychotic medication (unspecified) scored
significantly lower for the outcome ofsignificantly lower for the outcome of
global state not improved/worse than theglobal state not improved/worse than the
control group given unspecified antipsycho-control group given unspecified antipsycho-
tics (NNTtics (NNT6, 95% CI 5 to 11; Fig. 2(a)).6, 95% CI 5 to 11; Fig. 2(a)).
Further global state data from the ClinicalFurther global state data from the Clinical
Global Impression (CGI) scale MengGlobal Impression (CGI) scale Meng etet
alal (1996), unknown antipsychotic; Zhu(1996), unknown antipsychotic; Zhu etet
alal (1996), chlorpromazine also favoured(1996), chlorpromazine also favoured
the herbal medicine plus antipsychoticthe herbal medicine plus antipsychotic
group (Fig. 2(b)).group (Fig. 2(b)).
ZhangZhang et alet al (2001) found Brief Psychi-(2001) found Brief Psychi-atric Rating Scale (BPRS) scores dichoto-atric Rating Scale (BPRS) scores dichoto-
mised to not improved/worse weremised to not improved/worse were
equivocal (equivocal (nn109, RR109, RR0.78, 95% CI 0.50.78, 95% CI 0.5
to 1.2) whento 1.2) when Ginkgo bilobaGinkgo biloba plus haloperi-plus haloperi-
dol were compared with haloperidol, asdol were compared with haloperidol, as
were data from the Scale for the Assessmentwere data from the Scale for the Assessment
of Negative Symptoms (SANS) (of Negative Symptoms (SANS) (nn109,109,
RRRR0.87, 95% CI 0.7 to 1.2). However,0.87, 95% CI 0.7 to 1.2). However,
the Scale for the Assessment of Positivethe Scale for the Assessment of Positive
Symptoms (SAPS) did slightly favour theSymptoms (SAPS) did slightly favour the
herbal medicine plus haloperidol combina-herbal medicine plus haloperidol combina-
tion (tion (nn109, RR109, RR0.69, 95% CI 0.5 to0.69, 95% CI 0.5 to
1.0; NNT1.0; NNT6, 95% CI 4 to 162). Continu-6, 95% CI 4 to 162). Continu-ous short-term BPRS data Mengous short-term BPRS data Meng et alet al
(1996), unknown antipsychotic; Zhu(1996), unknown antipsychotic; Zhu et alet al
(1996), chlorpromazine significantly(1996), chlorpromazine significantly
favoured the herbal medicine plus antipsy-favoured the herbal medicine plus antipsy-
chotic combination (Fig. 2(c)), but datachotic combination (Fig. 2(c)), but data
were heterogeneous (were heterogeneous (II2281%). Medium-81%). Medium-
term BPRS data (Fig. 2(c)) also favouredterm BPRS data (Fig. 2(c)) also favoured
the herbal medicine plus antipsychoticthe herbal medicine plus antipsychotic
combination: Luocombination: Luo et alet al (1997), antipsy-(1997), antipsy-
chotics clozapine, chlorpromazine, sul-chotics clozapine, chlorpromazine, sul-
piride, perphenazine and haloperidol; andpiride, perphenazine and haloperidol; and
ZhangZhang et alet al (2001), haloperidol ((2001), haloperidol (nn621,621,
WMDWMD77
4.17, 95% CI4.17, 95% CI77
5.5 to5.5 to77
2.8).2.8).Medium-term SANS scores (Fig. 2(d))Medium-term SANS scores (Fig. 2(d))
3 8 03 8 0
AUTHORS PROOFAUTHORS PROOF
Fig. 1Fig.1 Diagnosis and treatment plan for schizophrenia in Western and traditional Chinese medicine.Diagnosis and treatment plan for schizophrenia in Western and traditional Chinese medicine.
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Fig. 2Fig. 2 Comparison of herbal medicine + antipsychoticComparison of herbal medicine + antipsychotic vv. antipsychotic ( BPRS, Brief Psychiatric Rating Scale; NNT, number needed to treat; RR, relative risk; SANS,. antipsychotic (BPRS, Brief Psychiatric Rating Scale; NNT, number needed to treat; RR, relative risk; SANS,
Scale for the Assessment of Negative Symptoms; WMD, weightedmean difference).Scale for the Assessment of Negative Symptoms; WMD, weightedmean difference).
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significantly favoured the herbal medicinesignificantly favoured the herbal medicine
plus antipsychotic group.plus antipsychotic group.
Adverse events are associated with anti-Adverse events are associated with anti-
psychotic medication, and combining her-psychotic medication, and combining her-
bal medicines with chlorpromazine (Zhubal medicines with chlorpromazine (Zhu
et alet al, 1996) did not mitigate extrapyrami-, 1996) did not mitigate extrapyrami-
dal adverse effects, with both groups beingdal adverse effects, with both groups beingequivocal. Constipation, however, wasequivocal. Constipation, however, was
significantly lower in the herbal plussignificantly lower in the herbal plus
antipsychotic combination group (0/32)antipsychotic combination group (0/32)
despite patients receiving the constipatingdespite patients receiving the constipating
antipsychotic chlorpromazine (antipsychotic chlorpromazine (nn67;67;
RRRR0.03, 95% CI 0.0 to 0.5; NNH0.03, 95% CI 0.0 to 0.5; NNH2,2,
95% CI 2 to 4); the comparison group95% CI 2 to 4); the comparison group
(chlorpromazine alone) fared less well (19/(chlorpromazine alone) fared less well (19/
35). Medium-term studies found signifi-35). Medium-term studies found signifi-
cantly fewer patients leaving the study earlycantly fewer patients leaving the study early
(Fig. 2(e)) in the herbal plus antipsychotic(Fig. 2(e)) in the herbal plus antipsychotic
group (group (nn897, four RCTs, RR897, four RCTs, RR0.34,0.34,
95% CI 0.2 to 0.7; NNT95% CI 0.2 to 0.7; NNT23, 95% CI 1823, 95% CI 18to 43).to 43).
Sensitivity analysis:Sensitivity analysis: Ginkgo bilobaGinkgo biloba
alone or plus antipsychoticsalone or plus antipsychotics v.v.
antipsychoticsantipsychotics
Studies ofStudies of Ginkgo bilobaGinkgo biloba were tested in awere tested in a
sensitivity analysis by comparing them withsensitivity analysis by comparing them with
the original pooled data (the original pooled data (Ginkgo bilobaGinkgo biloba
data pooled with other herbs). Effect sizesdata pooled with other herbs). Effect sizes
for CGI and BPRS scores were increasedfor CGI and BPRS scores were increased
forfor Ginkgo bilobaGinkgo biloba when analysed sepa-when analysed sepa-
rately, although these differences were notrately, although these differences were not
statistically significant.statistically significant.
DISCUSSIONDISCUSSION
Six of the seven studies evaluated the use ofSix of the seven studies evaluated the use of
Chinese herbs for schizophrenia rather thanChinese herbs for schizophrenia rather than
traditional Chinese herbal medicine fortraditional Chinese herbal medicine for
schizophrenia, i.e. treatment was allocatedschizophrenia, i.e. treatment was allocated
according to a diagnosis of schizophreniaaccording to a diagnosis of schizophrenia
without further differentiation accordingwithout further differentiation according
to traditional Chinese methodology. Studyto traditional Chinese methodology. Study
sizes were generally small and pooled datasizes were generally small and pooled datawere typically derived from one or twowere typically derived from one or two
studies. All outcomes, therefore, werestudies. All outcomes, therefore, were
underpowered. The one study that incorpo-underpowered. The one study that incorpo-
rated traditional Chinese medical theoryrated traditional Chinese medical theory
did show significant improvement in globaldid show significant improvement in global
state but was limited by lack of blinding.state but was limited by lack of blinding.
There were no descriptions of allocationThere were no descriptions of allocation
concealment and no assurances that blind-concealment and no assurances that blind-
ing was maintained. The type of anti-ing was maintained. The type of anti-
psychotic used and the dosages were oftenpsychotic used and the dosages were often
poorly reported, although three studiespoorly reported, although three studies
used the same herbal intervention used the same herbal intervention GinkgoGinkgo
bilobabiloba (EGb761). The remainder, however,(EGb761). The remainder, however,used different herbal medicines, andused different herbal medicines, and
unfortunately all threeunfortunately all three Ginkgo bilobaGinkgo biloba studiesstudies
used different antipsychotic medications.used different antipsychotic medications.
Herbal medicine aloneHerbal medicine alone v.v.
antipsychoticsantipsychotics
Global state measured as not improved/Global state measured as not improved/
worse favoured the chlorpromazine groupworse favoured the chlorpromazine group
(NNT with chlorpromazine 4, 95% CI 2(NNT with chlorpromazine 4, 95% CI 2
to 14) when compared with the treatmentto 14) when compared with the treatment
group receivinggroup receiving dang gui cheng qi tangdang gui cheng qi tang..
This NNT concurs with findings whenThis NNT concurs with findings when
chlorpromazine is compared with placebochlorpromazine is compared with placebo
(Adams(Adams et alet al, 2007); however, this is based, 2007); however, this is based
on a single study (on a single study (nn90; Zhang90; Zhang et alet al, 1987), 1987)
lasting 20 days with participants given Chi-lasting 20 days with participants given Chi-
nese herbs according to a diagnosis ofnese herbs according to a diagnosis of
schizophrenia without using traditionalschizophrenia without using traditional
Chinese medicine differentiation. ResultsChinese medicine differentiation. Results
must therefore be interpreted with cautionmust therefore be interpreted with caution
given the design limitations, but neverthe-given the design limitations, but neverthe-
less do not supportless do not support dang gui cheng qi tangdang gui cheng qi tang
as a sole treatment for schizophrenia.as a sole treatment for schizophrenia.
Herbal medicine plusHerbal medicine plus
antipsychoticsantipsychotics v.v. antipsychoticsantipsychotics
The herbal medicine group receiving eitherThe herbal medicine group receiving either
dang gui cheng qi tangdang gui cheng qi tangoror xiao yao sanxiao yao san plusplus
antipsychotics were significantly less likelyantipsychotics were significantly less likely
to have an outcome of no change or worseto have an outcome of no change or worse
compared with participants receiving onlycompared with participants receiving only
antipsychotics, measured using the Clinicalantipsychotics, measured using the Clinical
Global Impression scale (NNTGlobal Impression scale (NNT6, 95% CI6, 95% CI5 to 11). This could be an important finding5 to 11). This could be an important finding
and does fit with the CGI continuousand does fit with the CGI continuous
scores. These results are broadly encoura-scores. These results are broadly encoura-
ging and suggest that combining herbalging and suggest that combining herbal
medicines with antipsychotics might bemedicines with antipsychotics might be
beneficial, although results are only basedbeneficial, although results are only based
on two small studies (totalon two small studies (total nn103). These103). These
vaguely positive finding also apply to men-vaguely positive finding also apply to men-
tal state outcomes. The dichotomised BPRStal state outcomes. The dichotomised BPRS
and SANS measures reported by Zhangand SANS measures reported by Zhang etet
alal (2001);(2001); nn109) were equivocal, but109) were equivocal, but
SAPS scores again showed borderline sig-SAPS scores again showed borderline sig-
nificance in favour of the herbal medicinenificance in favour of the herbal medicineplus antipsychotic combination. Medium-plus antipsychotic combination. Medium-
term continuous SANS data, however, pro-term continuous SANS data, however, pro-
vided more robust results, with threevided more robust results, with three
studies (studies (nn741) favouring the herbal plus741) favouring the herbal plus
antipsychotic combination group. The ex-antipsychotic combination group. The ex-
perimental group had, on average, nineperimental group had, on average, nine
points less on this scale than those allocatedpoints less on this scale than those allocated
to antipsychotic drugs alone. In our opi-to antipsychotic drugs alone. In our opi-
nion, in this group of chronically unwellnion, in this group of chronically unwell
people such an average difference wouldpeople such an average difference would
be noticeable and clinically meaningful.be noticeable and clinically meaningful.
Further supporting this improvement, bothFurther supporting this improvement, both
short-term and medium-term BPRS scoresshort-term and medium-term BPRS scoreswere significantly better for those receivingwere significantly better for those receiving
herbal medicines plus antipsychotics com-herbal medicines plus antipsychotics com-
pared with those receiving antipsychoticpared with those receiving antipsychotic
drugs alone, although there was heteroge-drugs alone, although there was heteroge-
neity in these results. The latter might haveneity in these results. The latter might have
been due to the use of different anti-been due to the use of different anti-
psychotic drugs between trials.psychotic drugs between trials.
Adverse effect Treatment EmergentAdverse effect Treatment EmergentSigns and Symptoms scores were reportedSigns and Symptoms scores were reported
by Zhangby Zhang et alet al (2001), but standard devia-(2001), but standard devia-
tions were wide and no conclusion can betions were wide and no conclusion can be
made with confidence. Only one studymade with confidence. Only one study
(Zhu(Zhu et alet al, 1996;, 1996; nn67) reported extra-67) reported extra-
pyramidal symptoms, and these were notpyramidal symptoms, and these were not
significantly different between groups. Insignificantly different between groups. In
one trial in which both groups were givenone trial in which both groups were given
chlorpromazine, constipation was signifi-chlorpromazine, constipation was signifi-
cantly more frequent in the control groupcantly more frequent in the control group
(NNH(NNH2). In this trial the herb used was2). In this trial the herb used was
a purgative used also in Western medicinea purgative used also in Western medicine
Rhizoma rhei palmatumRhizoma rhei palmatum (rhubarb).(rhubarb).Numbers of participants leaving theNumbers of participants leaving the
study early in the short term were similarstudy early in the short term were similar
for both groups. Medium-term datafor both groups. Medium-term data
showed significantly fewer left early in theshowed significantly fewer left early in the
herbal medicine plus antipsychotic groupherbal medicine plus antipsychotic group
compared with people receiving only anti-compared with people receiving only anti-
psychotics (psychotics (nn897; 2%897; 2% v.v. 7%). In the con-7%). In the con-
text of these studies, the addition of herbaltext of these studies, the addition of herbal
medicine did not worsen treatment compli-medicine did not worsen treatment compli-
ance and there is the suggestion that theance and there is the suggestion that the
addition of the herbal medicine made itaddition of the herbal medicine made it
easier for participants to take standardeasier for participants to take standard
antipsychotics.antipsychotics.We did aWe did a post hoc post hoc sensitivity analysissensitivity analysis
for the single herbfor the single herb Ginkgo bilobaGinkgo biloba, used, used
outside the traditional Chinese medicineoutside the traditional Chinese medicine
approach within a Western model ofapproach within a Western model of
schizophrenia. We found no evidence thatschizophrenia. We found no evidence that
this particular herb had remarkable effects.this particular herb had remarkable effects.
The application of traditional ChineseThe application of traditional Chinese
herbal medicine is fundamentally inter-herbal medicine is fundamentally inter-
woven with syndrome differentiation.woven with syndrome differentiation.
Failure to apply syndrome differentiationFailure to apply syndrome differentiation
may result in treatments being ineffectivemay result in treatments being ineffective
or even harmful. Despite this, there is someor even harmful. Despite this, there is some
evidence that these Chinese herbal medi-evidence that these Chinese herbal medi-cines, combined with antipsychotics andcines, combined with antipsychotics and
given in a way that is not in keeping withgiven in a way that is not in keeping with
their normal use within traditional Chinesetheir normal use within traditional Chinese
medicine, may be beneficial for people withmedicine, may be beneficial for people with
schizophrenia across a range of outcomes.schizophrenia across a range of outcomes.
If these medicines are used within theirIf these medicines are used within their
usual context the positive effects could beusual context the positive effects could be
greater. Even the gains seen in this reviewgreater. Even the gains seen in this review
would still be important for the millionswould still be important for the millions
for whom these treatments are used. Bothfor whom these treatments are used. Both
West and East need well-reported (MoherWest and East need well-reported (Moher
et alet al, 2001) randomised trials that are, 2001) randomised trials that are
adequately powered, blinded and of suffi-adequately powered, blinded and of suffi-cient duration so we can detect meaningfulcient duration so we can detect meaningful
3 8 33 8 3
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treatment effects with high levels of confi-treatment effects with high levels of confi-
dence.dence.
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3 8 43 8 4
AUTHORS PROOFAUTHORS PROOF
JOHNRATHBONE, MPhil, Cochrane Schizophrenia Group, Academic Department of PsychiatryJOHN RATHBONE, MPhil, Cochrane Schizophrenia Group, Academic Department of Psychiatry
and B ehavioural Sciences,University of Leeds UK; LAN ZHANG,MD, Institute of Mental Health, MINGMINGand Behavioural Sciences,University of Leeds UK; LAN ZHANG, MD, Institute of Mental Health,MINGMING
ZHANG,MSc, Chinese Cochrane Centre,West China Hospital of Sichuan University,Chengdu,China; JUN XIA,ZHANG,MSc, Chinese Cochrane Centre,West China Hospital of Sichuan University,Chengdu,China; JUN XIA,
BSc,Cochrane Schizophrenia Group, Academic Department of Psychiatry and Behavioural Sciences,UniversityBSc, Cochrane Schizophrenia Group, Academic Department of Psychiatry and Behavioural Sciences,University
of Leeds, UK; XIEHE LIU, MD,YANCHUN YANG,MD, Institute of Mental Health,West China Hospital ofof Leeds, UK; XIEHE LIU, MD,YANCHUN YANG, MD, Institute of Mental Health,West China Hospital of
Sichuan University, Chengdu,China; CLIVE ELLIOTT ADAMS, MD, Cochrane Schizophrenia Group, AcademicSichuan University, Chengdu,China; CLIVE ELLIOTT ADAMS, MD, Cochrane Schizophrenia Group, Academic
Department of Psychiatry and Behavioural Sciences,University of Leeds,UKDepartment of Psychiatry and Behavioural Sciences,University of Leeds,UK
Correspondence:John Rathbone, Cochrane Schizophrenia Group,Academic Depar tmentof PsychiatryCorrespondence:John Rathbone, Cochrane Schizophrenia Group, Academic Department of Psychiatry
and B ehavioural Sciences,University of Leeds, 15 HydeTerrace, Leeds LS2 9LT,UK.Tel: +4 4 ( 0)113 343and B ehavioural Sciences,University of Leeds, 15 HydeTerrace,Lee ds LS2 9LT,UK.Tel: +4 4 ( 0)113 343
1897; fax: +44 (0)113 3432723; email: jrathbone1897; fax: +44 (0)113 3432723; email: jrathbone@@cochrane-sz.orgcochrane-sz.org
(First received 31May 20 06, final revision 8 September 2 00 6, accepted 16 January 2 007)(First received 31 May 20 06, final revision 8 September 200 6, accepted 16 January 2 007)
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