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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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R A T H B O N E E T A LR A T H B O N E E T A L

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


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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3 8 23 8 2

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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C H I N E S E M E D I C I N E I N S C H I Z O P H R E N I AC H I N E S E M E D I C I N E I N S C H I Z O P H R E N I A

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



6/6


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


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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