Chinese herbal medicine for schizophrenia

John Rathbone; Lan Zhang; Mingming Zhang; Jun Xia; Xiehe Liu; Yanchun Yang

doi:10.1002/14651858.CD003444.pub2

Medicina herbaria china para la esquizofrenia

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Referencias

References to studies included in this review

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References to studies excluded from this review

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otras referencias

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References to studies awaiting assessment

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

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Chen 1997

Methods	Allocation: randomised. Blindness: single (assessors blinded). Duration: 6 months. Design: parallel group (without pattern differentiation).
Participants	Diagnosis: schizophrenia (CCMD‐2). N=120. Age: ˜27‐58 years. Sex: not reported. Setting: hospital. History: chronic illness, mean 17 years.
Interventions	1. Xingshen + antipsychotic: dose Xingshen 30ml/bid + antipsychotics (chlorpromazine n=16, clozapine n=38, sulpiride n=6) dosage ˜300‐700 mg/day. N=60. 2. Antipsychotics: dose chlorpromazine n=17, clozapine n=36, sulpiride n=7, dosage ˜250‐800 mg/day (no further details). N=60. Herbal formula ‐ Xingshen: Semen Cuscutae chinensis (Tu Si Zi) Cortex Cinnamomi cassiae (Rou Gui) Herba Epimedii (Yin Yang Huo) Rhizoma Curculiginis orchioidis (Xian mao) Radix Polygoni multiflori (He shou wu) Radix et Caulis jixueteng (Ji xue tang) Fructus Broussonetiae papyrifera (Chu shi zi) Grams not specified.
Outcomes	Leaving the study early. Mental state: SANS.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

Luo 1997 a

Methods	Allocation: randomised. Blindness: double. Duration: 16 weeks. Design: parallel groups (without pattern differentiation).
Participants	Diagnosis: schizophrenia (ICD 10 and CCMD‐2‐R). N=545. Age: 18‐60 years. Sex: 418M, 127F. Setting: hospital. History: not reported.
Interventions	1. Ginkgo biloba (EGb761) + maintenance antispychotics: dose EGb761, 120 mg/tds, antipsychotics. N=315. 2. Placebo + Antipsychotics: dose maintenance antipsychotics. N=230. Maintenance antipsychotics included clozapine, chlorpromazine, sulpiride, perphenazine and haloperidol. Doses and frequency not reported.
Outcomes	Leaving the study early. Mental state: BPRS, SANS. Unable to use ‐ Adverse effects: TESS (no usable data), SAS (data reported from subgroup), extrapyramidal symptoms (scale not stated).
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

Meng 1996

Methods	Allocation: randomised. Blindness: double. Duration: 8 weeks. Design: parallel groups (without pattern differentiation).
Participants	Diagnosis: schizophrenia (CCMD‐2). N=40. Age: 18‐60 years. Sex: male and female. Setting: hospital. History: not reported.
Interventions	1. Ginkgo biloba (EGb761) + antipsychotics: dose range EGb761, 120 mg/day first week, then 240 mg/day + continuation of antipsychotics (dosage not reported). N=21. 2. Placebo + Antipsychotics: dose (no further details). N=19.
Outcomes	Leaving the study early. Global state: CGI. Mental state: BPRS, SANS.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

Zhang 1987

Methods	Allocation: 'divided into groups randomly'. Blindness: not reported. Duration: 20 days. Design: parallel groups (without pattern differentiation).
Participants	Diagnosis: schizophrenia. N=90. Age: 16‐51 years. Sex: not reported. Setting: hospital. History: mostly first admissions (n=82). Excluded: those who showed remission of symptoms on admission.
Interventions	1. Dang gui cheng qi tang: dose ˜ mean 50 ml/bid, max. 200 ml/day. N=45. 2. Chlorpromazine: any dose as required. N=45. Herbal formula ‐ Dang gui cheng qi tang: Radix Angelica sinensis (Dang Gui) 30g Radix et Rhizoma rhei (Da Huang) 30g Natrii sulfas (Mang xiao) 15g Fructus Poncirus trifoliate (Zhi shi) 12g Fructus trichosanthis (Gua Lou) 15g Additional herbs added as required for blood stagnation: Semen persicae (Tao ren) Radix Curcumae (Yu Jin) Radix Paeonia rubrae (Chi Shao Yao) Radix Bupleuri (Chai hu) Radix Scutellariae (Huang qin) Flos Carthami (Hong hua) Rhizoma Ligustici chuanxiong (Chuan xiong) Additional herbs added as required for hallucinations, restlessness and insomnia: Radix Stephaniae tetrandrae (Fang ji) Radix Ledebouriellae (Fang feng) Sclerotium Poriae cocos (Fu ling) Radix Polygalae (Yuan zhi) Fructus Ziziphi jujubae (Da zao) Radix rehmanniae (Sheng di huang) Rhizoma Acori graminei (Shi chang pu) Os draconis (Long gu) Concha ostreae (Mu li) Haematitum (Zhe shi) grams not specified.
Outcomes	Leaving the study early. Global state: not improved/worse.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

Zhang 1997

Methods	Allocation: randomised. Blindness: open label. Duration: 12 weeks. Design: randomised into 2 treatment groups, herbal medicine and control; herbal medicine group further divided, non‐randomly, into 2 groups based on pattern differentiation.
Participants	Diagnosis: schizophrenia (CCMD‐2) . N=123. Age: mean ˜ 32 years. Sex: male and female. Setting: hospital and community. History: mean length of illness 11 years.
Interventions	1. Herbal medicine: Dang gui cheng qi tang (those with yang syndrome), 100 ml 2‐3/day + antipsychotics (unclear which type or dosage, n=32); Xiao yao san (those with yin syndrome) 100ml 2‐3/day + antipsychotics (unclear which type or dosage, n=34). N=66. 2. Antipsychotics: dose and type not reported. N=57. Herbal formula ‐Dang gui cheng qi tang: Radix Angelica sinensis (Dang gui) 15g Fructus Immaturus (Zhi shi) 15g Radix et Rhizoma rhei (Da huang) 15g Fructus Lycii (Gou qi zi) 15g Natrii sulfas (Mang xiao) 15g Sclerotium Poriae cocos (Fu ling) 15g Rhizoma Atractylodis macrocephalae (Bai Zhu) 15g Herbal formula ‐ Xiao Yao san: Radix Angelica sinensis (Dang gui) 15g Radix Bupleuri (Chai hu) 15g Sclerotium Poriae cocos (Fu ling) 15g Radix Paeoniae lactiflorae (Bai Shao Yao) 15g Rhizoma Atractylodis macrocephalae (Bai Zhu) 15g Radix polygalae (Yuan zhi) 15g Aconiti Carmichaeli praeparata (Fu zi) 15g Radix Glycyrrhizae uralensis (Gan Cao) 15g Rhizoma Rheum palmatum (Da huang) 15g Radix Astragali membranacei (Huang Qi) 15g
Outcomes	Leaving the study early. Global state: not improved/worse. Mental state: BPRS.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

Zhang 2001

Methods	Allocation: randomised. Blindness: double. Duration: 12 weeks. Design: parallel groups (without pattern differentiation).
Participants	Diagnosis: schizophrenia (DSM III R). N=109. Age: 27‐61 years, mean ˜ 44 years. Sex: 63M, 46F. Setting: hospital. History: treatment resistant; average length of illness 21.5 years (minimum 5 years). Excluded: bipolar affective disorder, organic mental disorders, substance or alcohol abuse, brain damage, epilepsy, severe physical disease, pregnancy or breast feeding.
Interventions	1. Ginkgo biloba (EGb761) + antipsychotics: dose EGb761, 360 mg/day, + haloperidol 0.25 mg/kg/day. N=56. 2. Haloperidol: dose 0.25 mg/kg/day + placebo. N=53.
Outcomes	Leaving the study early. Mental state: BPRS, SAPS, SANS. Adverse effects: TESS.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

Zhu 1996

Methods	Allocation: randomised. Blindness: open label. Duration: 30 days. Design: parallel groups (without pattern differentiation).
Participants	Diagnosis: schizophrenia (CCMD‐2). N=67. Age: 17‐53 years. Sex: female. Setting: hospital. History: not reported.
Interventions	1. Hirudo seu Whitmania (Shui zhi) and Rhizoma Rheum palmatum (Da huang) (doses not specified) + chlorpromazine =/<300 mg/day). N=32. 2. Chlorpromazine: dose =/<400 mg/day. N=35.
Outcomes	Leaving the study early. Global state: CGI. Mental state: BPRS. Adverse effects: extrapyramidal, gastrointestinal. Unable to use ‐ Adverse effects: haematology (no usable data).
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear

DSM ‐ Diagnostic and Statistical Manual
ICD 10 ‐ International Classification of Diseases
CCMD ‐2‐R ‐ Chinese Classification of Mental Disorders Second Edition Revised

Global state:
CGI ‐ Clinical Global Impression

Mental state:
BPRS ‐ Brief Psychiatric Rating Scale
SANS ‐ Scale for the Assessment of Negative Symptoms
SAPS ‐ Scale for the Assessment of Positive Symptoms

Adverse effects:
TESS ‐Treatment Emergent Symptom Scale

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos
estudios a la espera de clasificación

Study	Reason for exclusion
Cao 2000	Allocation: not randomised.
Gong 2000	Allocation: not randomised.
Han 2002	Allocation: not reported, double blind (wrote to authors, no reply). Participants: people with schizophrenia. Interventions: chinese medicine versus clozapine. Outcomes: no usable data.
Rong 2001	Allocation: not randomised.
Wang 1998 a	Allocation: randomised. Participants: peole with schizophrenia. Intervention: Chinese herbal medicine versus antispychotics. Outcomes: no time points reported (authors contacted, no reply).
Zhao 1997	Allocation: randomised. Participants: people with schizophrenia. Interventions: Ginkgo biloba + antipsychotics versus antipsychotics +placebo. Outcomes: no usable data.
Zhen 1992	Allocation: randomised. Participants: people with schizophrenia. Interventions: haloperidol decanoate versus pipothiazine palmitate.

Characteristics of studies awaiting assessment [ordered by study ID]

Ir a:

estudios incluidos
estudios excluidos

Chen 2008

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Chen 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Chiu 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Hung 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Mei 2005

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Miyaoka 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Mundewadi 2008

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

NCT01045720

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Sanchez 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Tang 2005

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Wang 2005

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Xiao 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Yan 2005

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Zhang 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Zhou 1989

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

于瑞丽, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

孟彬, 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

尹道亮 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

左潇, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

庞铁良, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

张子梅, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

彭东阳 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

易世国, 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

林升 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

林虹, 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

柳贵明, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

段武钢, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

段武钢, 2010a

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

汪艳, 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

洪娜 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

王鹤秋, 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

石建喜, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

罗世芳, 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

翁深宏, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

肖世富, 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

胡海燕, 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

胥德广, 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

解克平 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

解克平, 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

邓方渝 2010

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

郝广义, 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

鄢爱平, 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

陈克彦 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

马俊国, 2009

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

黄平, 2011

Methods
Participants
Interventions
Outcomes
Notes	To be assessed.

Data and analyses

Open in table viewer

Comparison 1. HERBAL MEDICINE versus ANTIPSYCHOTICS

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: Not improved/worse ‐ short term Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	1.88 [1.24, 2.86]
Open in figure viewer Analysis 1.1 Comparison 1 HERBAL MEDICINE versus ANTIPSYCHOTICS, Outcome 1 Global state: Not improved/worse ‐ short term.
2 Behaviour: Leaving the study early ‐ short term Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
Open in figure viewer Analysis 1.2 Comparison 1 HERBAL MEDICINE versus ANTIPSYCHOTICS, Outcome 2 Behaviour: Leaving the study early ‐ short term.

Open in table viewer

Comparison 2. HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Not improved/worse ‐ medium term Show forest plot

1

123

Risk Ratio (M‐H, Fixed, 95% CI)

0.19 [0.06, 0.61]

Analysis 2.1

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 1 Global state: 1. Not improved/worse ‐ medium term.

2 Global state: 2. Average score ‐ short term (CGI endpoint , high score=worse) Show forest plot

2

103

Mean Difference (IV, Fixed, 95% CI)

‐0.46 [‐0.86, ‐0.06]

Analysis 2.2

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 2 Global state: 2. Average score ‐ short term (CGI endpoint , high score=worse).

3 Mental state: 1. Not improved ‐ various measures ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.3

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 3 Mental state: 1. Not improved ‐ various measures ‐ medium term.

3.1 overall ‐ BPRS

1

109

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.52, 1.16]

3.2 negative symptoms ‐ SANS

1

109

Risk Ratio (M‐H, Fixed, 95% CI)

0.87 [0.66, 1.15]

3.3 positive symptoms ‐ SAPS

1

109

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.48, 0.99]

4 Mental state: 2. Average score (BPRS endpoint, high score=worse) Show forest plot

4

724

Mean Difference (IV, Fixed, 95% CI)

‐3.33 [‐4.32, ‐2.34]

Analysis 2.4

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 4 Mental state: 2. Average score (BPRS endpoint, high score=worse).

4.1 short term

2

103

Mean Difference (IV, Fixed, 95% CI)

‐2.41 [‐3.85, ‐0.97]

4.2 medium term

2

621

Mean Difference (IV, Fixed, 95% CI)

‐4.17 [‐5.54, ‐2.79]

5 Mental state: 3. Average scores ‐ various scales (endpoint, high score=worse, skewed data) Show forest plot

Other data

No numeric data

Analysis 2.5


Study	Intervention	mean	SD	N
overall ‐ medium term ‐ BPRS
Zhang 1997	Herbal medicine + antipsychotics	13.4	6.7	66
Zhang 1997	Antipsychotics	26.6	15.2	57
negative symptoms ‐ short term ‐ SANS
Meng 1996	Ginkgo (EGb61)	37.1	16.0	21
Meng 1996	Antipsychotics	46.6	30.0	15
positive symptoms ‐ medium term ‐ SAPS
Zhang 2001	Ginkgo biloba (EGb) + haloperidol	7.1	8.4	56
Zhang 2001	Haloperidol	11	10.5	53

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 5 Mental state: 3. Average scores ‐ various scales (endpoint, high score=worse, skewed data).

5.1 overall ‐ medium term ‐ BPRS

Other data

No numeric data

5.2 negative symptoms ‐ short term ‐ SANS

Other data

No numeric data

5.3 positive symptoms ‐ medium term ‐ SAPS

Other data

No numeric data

6 Mental state: 4. Average score ‐ negative symptoms ‐ medium term (SANS endpoint, high score=worse) Show forest plot

3

741

Mean Difference (IV, Fixed, 95% CI)

‐9.15 [‐12.10, ‐6.20]

Analysis 2.6

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 6 Mental state: 4. Average score ‐ negative symptoms ‐ medium term (SANS endpoint, high score=worse).

7 Behaviour: Leaving the study early Show forest plot

6

1004

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.16, 0.58]

Analysis 2.7

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 7 Behaviour: Leaving the study early.

7.1 short term

2

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.01, 1.76]

7.2 medium term

4

897

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.17, 0.65]

8 Adverse effects: 1. Various symptoms ‐ short term Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 2.8

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 8 Adverse effects: 1. Various symptoms ‐ short term.

8.1 extrapyramidal

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.18, 1.64]

8.2 gastrointestinal ‐ constipation

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.03 [0.00, 0.45]

9 Adverse effects: 2. Average score ‐ short term (TESS endpoint, high score=worse, skewed data) Show forest plot

Other data

No numeric data

Analysis 2.9


Study	Intervention	mean	SD	N
Zhang 2001	Ginkgo biloba (EGb) + haloperidol	1.8	2.8	56
Zhang 2001	Haloperidol	2.7	4.6	53

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 9 Adverse effects: 2. Average score ‐ short term (TESS endpoint, high score=worse, skewed data).

Open in table viewer

Comparison 3. SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: Average score ‐ short term (CGI endpoint , high score=worse) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.1 Comparison 3 SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS, Outcome 1 Global state: Average score ‐ short term (CGI endpoint , high score=worse).
1.1 ginkgo biloba alone	1	36	Mean Difference (IV, Fixed, 95% CI)	‐1.30 [‐2.29, ‐0.31]
1.2 other herbs combined	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.46 [‐0.86, ‐0.06]
2 Mental state: 1. Average score (BPRS endpoint, high score=worse) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.2 Comparison 3 SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS, Outcome 2 Mental state: 1. Average score (BPRS endpoint, high score=worse).
2.1 ginkgo biloba alone	1	36	Mean Difference (IV, Fixed, 95% CI)	‐4.0 [‐5.97, ‐2.03]
2.2 other herbs combined	2	103	Mean Difference (IV, Fixed, 95% CI)	‐2.41 [‐3.85, ‐0.97]
3 Mental state: 2. Average score ‐ negative symptoms ‐ medium term (SANS endpoint, high score=worse) Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.3 Comparison 3 SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS, Outcome 3 Mental state: 2. Average score ‐ negative symptoms ‐ medium term (SANS endpoint, high score=worse).
3.1 ginkgo biloba alone	2	621	Mean Difference (IV, Fixed, 95% CI)	‐9.16 [‐12.52, ‐5.79]
3.2 other herbs combined	3	741	Mean Difference (IV, Fixed, 95% CI)	‐9.15 [‐12.10, ‐6.20]
4 Behaviour: Leaving the study early Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.4 Comparison 3 SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS, Outcome 4 Behaviour: Leaving the study early.
4.1 short term ‐ ginkgo biloba alone	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.76]
4.2 short term ‐ other herbs combined	2	107	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.76]
4.3 medium term ‐ ginkgo biloba alone	2	654	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.17, 0.65]
4.4 medium term ‐ other herbs combined	4	897	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.17, 0.65]

Figure 1

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Analysis 1.1

Comparison 1 HERBAL MEDICINE versus ANTIPSYCHOTICS, Outcome 1 Global state: Not improved/worse ‐ short term.

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Analysis 1.2

Comparison 1 HERBAL MEDICINE versus ANTIPSYCHOTICS, Outcome 2 Behaviour: Leaving the study early ‐ short term.

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Analysis 2.1

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 1 Global state: 1. Not improved/worse ‐ medium term.

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Analysis 2.2

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 2 Global state: 2. Average score ‐ short term (CGI endpoint , high score=worse).

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Analysis 2.3

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 3 Mental state: 1. Not improved ‐ various measures ‐ medium term.

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Analysis 2.4

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 4 Mental state: 2. Average score (BPRS endpoint, high score=worse).

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Study	Intervention	mean	SD	N
overall ‐ medium term ‐ BPRS
Zhang 1997	Herbal medicine + antipsychotics	13.4	6.7	66
Zhang 1997	Antipsychotics	26.6	15.2	57
negative symptoms ‐ short term ‐ SANS
Meng 1996	Ginkgo (EGb61)	37.1	16.0	21
Meng 1996	Antipsychotics	46.6	30.0	15
positive symptoms ‐ medium term ‐ SAPS
Zhang 2001	Ginkgo biloba (EGb) + haloperidol	7.1	8.4	56
Zhang 2001	Haloperidol	11	10.5	53

Analysis 2.5

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 5 Mental state: 3. Average scores ‐ various scales (endpoint, high score=worse, skewed data).

Ir a la figura de la revisión

Analysis 2.6

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 6 Mental state: 4. Average score ‐ negative symptoms ‐ medium term (SANS endpoint, high score=worse).

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Analysis 2.7

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 7 Behaviour: Leaving the study early.

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Analysis 2.8

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 8 Adverse effects: 1. Various symptoms ‐ short term.

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Study	Intervention	mean	SD	N
Zhang 2001	Ginkgo biloba (EGb) + haloperidol	1.8	2.8	56
Zhang 2001	Haloperidol	2.7	4.6	53

Analysis 2.9

Comparison 2 HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS, Outcome 9 Adverse effects: 2. Average score ‐ short term (TESS endpoint, high score=worse, skewed data).

Ir a la figura de la revisión

Analysis 3.1

Comparison 3 SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS, Outcome 1 Global state: Average score ‐ short term (CGI endpoint , high score=worse).

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Analysis 3.2

Comparison 3 SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS, Outcome 2 Mental state: 1. Average score (BPRS endpoint, high score=worse).

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Analysis 3.3

Comparison 3 SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS, Outcome 3 Mental state: 2. Average score ‐ negative symptoms ‐ medium term (SANS endpoint, high score=worse).

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Analysis 3.4

Comparison 3 SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS, Outcome 4 Behaviour: Leaving the study early.

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Comparison 1. HERBAL MEDICINE versus ANTIPSYCHOTICS

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: Not improved/worse ‐ short term Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	1.88 [1.24, 2.86]

2 Behaviour: Leaving the study early ‐ short term Show forest plot	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. HERBAL MEDICINE versus ANTIPSYCHOTICS

Ir a la tabla de la revisión

Comparison 2. HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: 1. Not improved/worse ‐ medium term Show forest plot	1	123	Risk Ratio (M‐H, Fixed, 95% CI)	0.19 [0.06, 0.61]

2 Global state: 2. Average score ‐ short term (CGI endpoint , high score=worse) Show forest plot	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.46 [‐0.86, ‐0.06]

3 Mental state: 1. Not improved ‐ various measures ‐ medium term Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 overall ‐ BPRS	1	109	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.52, 1.16]
3.2 negative symptoms ‐ SANS	1	109	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.66, 1.15]
3.3 positive symptoms ‐ SAPS	1	109	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.48, 0.99]
4 Mental state: 2. Average score (BPRS endpoint, high score=worse) Show forest plot	4	724	Mean Difference (IV, Fixed, 95% CI)	‐3.33 [‐4.32, ‐2.34]

4.1 short term	2	103	Mean Difference (IV, Fixed, 95% CI)	‐2.41 [‐3.85, ‐0.97]
4.2 medium term	2	621	Mean Difference (IV, Fixed, 95% CI)	‐4.17 [‐5.54, ‐2.79]
5 Mental state: 3. Average scores ‐ various scales (endpoint, high score=worse, skewed data) Show forest plot			Other data	No numeric data

5.1 overall ‐ medium term ‐ BPRS			Other data	No numeric data
5.2 negative symptoms ‐ short term ‐ SANS			Other data	No numeric data
5.3 positive symptoms ‐ medium term ‐ SAPS			Other data	No numeric data
6 Mental state: 4. Average score ‐ negative symptoms ‐ medium term (SANS endpoint, high score=worse) Show forest plot	3	741	Mean Difference (IV, Fixed, 95% CI)	‐9.15 [‐12.10, ‐6.20]

7 Behaviour: Leaving the study early Show forest plot	6	1004	Risk Ratio (M‐H, Fixed, 95% CI)	0.30 [0.16, 0.58]

7.1 short term	2	107	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.76]
7.2 medium term	4	897	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.17, 0.65]
8 Adverse effects: 1. Various symptoms ‐ short term Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 extrapyramidal	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	0.55 [0.18, 1.64]
8.2 gastrointestinal ‐ constipation	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	0.03 [0.00, 0.45]
9 Adverse effects: 2. Average score ‐ short term (TESS endpoint, high score=worse, skewed data) Show forest plot			Other data	No numeric data

Comparison 2. HERBAL MEDICINE + ANTIPSYCHOTCS versus ANTIPSYCHOTICS

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Comparison 3. SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: Average score ‐ short term (CGI endpoint , high score=worse) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 ginkgo biloba alone	1	36	Mean Difference (IV, Fixed, 95% CI)	‐1.30 [‐2.29, ‐0.31]
1.2 other herbs combined	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.46 [‐0.86, ‐0.06]
2 Mental state: 1. Average score (BPRS endpoint, high score=worse) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 ginkgo biloba alone	1	36	Mean Difference (IV, Fixed, 95% CI)	‐4.0 [‐5.97, ‐2.03]
2.2 other herbs combined	2	103	Mean Difference (IV, Fixed, 95% CI)	‐2.41 [‐3.85, ‐0.97]
3 Mental state: 2. Average score ‐ negative symptoms ‐ medium term (SANS endpoint, high score=worse) Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

3.1 ginkgo biloba alone	2	621	Mean Difference (IV, Fixed, 95% CI)	‐9.16 [‐12.52, ‐5.79]
3.2 other herbs combined	3	741	Mean Difference (IV, Fixed, 95% CI)	‐9.15 [‐12.10, ‐6.20]
4 Behaviour: Leaving the study early Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 short term ‐ ginkgo biloba alone	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.76]
4.2 short term ‐ other herbs combined	2	107	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.76]
4.3 medium term ‐ ginkgo biloba alone	2	654	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.17, 0.65]
4.4 medium term ‐ other herbs combined	4	897	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.17, 0.65]

Comparison 3. SENSITIVITY ANALYSIS ‐ GINKGO BILOBA ALONE/NOT ALONE + ANTIPSYCHOTICS versus ANTIPSYCHOTICS

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Referencias

References to studies included in this review

Chen 1997 {published data only}

Luo 1997 a {published data only}

Meng 1996 {published data only}

Zhang 1987 {published data only}

Zhang 1997 {published data only}

Zhang 2001 {published data only}

Zhu 1996 {published data only}

References to studies excluded from this review

Cao 2000 {published data only}

Gong 2000 {published data only}

Han 2002 {published data only}

Rong 2001 {published data only}

Wang 1998 a {published data only}

Zhao 1997 {published data only}

Zhen 1992 {published data only}

References to studies awaiting assessment

Chen 2008 {published data only}

Chen 2009 {published data only}

Chiu 2010 {published data only}

Hung 2011 {published data only}

Mei 2005 {published data only}

Miyaoka 2009 {published data only}

Mundewadi 2008 {published data only}

NCT01045720 {published data only}

Sanchez 2011 {published data only}

Tang 2005 {published data only}

Wang 2005 {published data only}

Xiao 2011 {published data only}

Yan 2005 {published data only}

Zhang 2011 {published data only}

Zhou 1989 {published data only}

于瑞丽, 2010 {published data only}

孟彬, 2009 {published data only}

尹道亮 2011 {published data only}

左潇, 2010 {published data only}

庞铁良, 2010 {published data only}

张子梅, 2010 {published data only}

彭东阳 2010 {published data only}

易世国, 2009 {published data only}

林升 2010 {published data only}

林虹, 2011 {published data only}

柳贵明, 2010 {published data only}

段武钢, 2010 {published data only}

段武钢, 2010a {published data only}

汪艳, 2011 {published data only}

洪娜 2010 {published data only}

王鹤秋, 2009 {published data only}

石建喜, 2010 {published data only}

罗世芳, 2011 {published data only}

翁深宏, 2010 {published data only}

肖世富, 2011 {published data only}

胡海燕, 2010 {published data only}

胥德广, 2011 {published data only}

解克平, 2009 {published data only}

解克平 2010 {published data only}

邓方渝 2010 {published data only}

郝广义, 2009 {published data only}

鄢爱平, 2009 {published data only}

陈克彦 2009 {published data only}

马俊国, 2009 {published data only}

黄平, 2011 {published data only}

Additional references

Alderson 2004

Altman 1996

Andreasen 1983

Bland 1997

Divine 1992

Donner 2002

Egger 1997

Gulliford 1999

Guy 1970

Guy 1976

Higgins 2003

Li 2002

Luo 1997

Marshall 2000