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Quetiapine versus typical antipsychotic medications for schizophrenia

  1. Sirijit Suttajit1,*,
  2. Manit Srisurapanont1,
  3. Jun Xia2,
  4. Siritree Suttajit3,
  5. Benchalak Maneeton1,
  6. Narong Maneeton1

Editorial Group: Cochrane Schizophrenia Group

Published Online: 31 MAY 2013

Assessed as up-to-date: 28 MAR 2010

DOI: 10.1002/14651858.CD007815.pub2


How to Cite

Suttajit S, Srisurapanont M, Xia J, Suttajit S, Maneeton B, Maneeton N. Quetiapine versus typical antipsychotic medications for schizophrenia. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD007815. DOI: 10.1002/14651858.CD007815.pub2.

Author Information

  1. 1

    Chiang Mai University, Department of Psychiatry, Faculty of Medicine, Chiang Mai, Thailand

  2. 2

    The University of Nottingham, Cochrane Schizophrenia Group, Nottingham, UK

  3. 3

    Chiang Mai University, Faculty of Pharmacy, Chiang Mai, Thailand

*Sirijit Suttajit, Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. sirijits@gmail.com. ssuttaji@mail.med.cmu.ac.th.

Publication History

  1. Publication Status: New
  2. Published Online: 31 MAY 2013

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Characteristics of included studies [ordered by study ID]
vs CPZ - Ai 2007

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 12 weeks.
Setting: inpatients, Liaoning Renming Hospital, Liaoning Province, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 85.
Sex: male and female.
Age: mean 30 years, SD 11 years.
History: duration ill mean 5.8 years, SD 3.3 years.
Exclusion: severe physical illness.


Interventions1. Quetiapine: 400-750 mg/day. N = 43.
2. Chlorpromazine: 400-550 mg/day. N = 42.


OutcomesMental state: BPRS.

Global state: no clinical improvement*.

Adverse events.


Notes*BPRS decreased rate < 25%.

BPRS = Brief Psychiatric Rating Scale.

CCMD = Chinese Classification of Mental Disorders.
TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS measured, but not reported.

Other biasLow riskNone obvious.

vs CPZ - AstraZeneca 2005

MethodsAllocation: randomised, no further details.
Blinding: double, no further details.
Duration: 10 weeks, preceded by 4-week single-blind haloperidol treatment phase and a 1-week washout period.
Design: parallel, multicentre.
Setting: USA and Canada.


ParticipantsDiagnosis: schizophrenia (DSM-IV), resistant to treatment with standard antipsychotic agents.
N = 260*.
Sex: male 206, female 54.
Age: 18-65 years (mean 40.9 years).
History: receiving haloperidol 40 mg/day for ≧ 2 weeks, < 30% reduction in BPRS, either CGI-S ≧ 4 or BPRS ≧ 10.


Interventions1. Quetiapine: 600 mg/d. N = 130.

2. Chlorpromazine: 1200 mg/d. N = 130.


OutcomesLeaving the study early.
Global state: CGI-S.
Mental state: BPRS, Scale for the Assessment of Negative Symptoms (SANS).
Adverse effects: death, extrapyramidal side effects (AIMS, SAS).


Notes*7 patients were excluded from the ITT analysis due to protocol deviation (5 in quetiapine group, 2 in chlorpromazine group.)

BPRS = Brief Psychiatric Rating Scale.

CGI-S = Clinical Global Impression - Severity scale.

AIMS = Abnormal Involuntary Movement Scale.

SAS = Simpson Angus scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble blind, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available but total was high (31.5%).
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence for selective reporting was not found.

Other biasHigh riskSponsored by manufacturers of quetiapine.

vs CPZ - Bai 2005

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 8 weeks.
Setting: Shanghai mental health centre, China.


ParticipantsDiagnosis: schizophrenia (ICD-10).
N = 105.
Age: mean 33 years, SD 11years.
Sex: not stated.
History: duration ill mean 49 months, SD 66 months.
Exclusion: severe physical illness, drug/alcohol dependent, received depot antipsychotic within 2 weeks prior to the trial.


Interventions1. Quetiapine: dosage not stated. N = 45.
2. Chlorpromazine: dosage not stated. N = 46.


OutcomesCognitive functioning: WAIS, WCST, WMS.
Unable to use: leaving the study early - no n number reported for individual groups.


NotesICD-10 = International Classification of Diseases Version 10.
PANSS = Positive and Negative Syndrome Scale.
WAIS-R = Wechsler Adult Intelligence Scale-Revised.

WCST = Wisconsin Card Sorting Test.

WMS = Wechsler Memory Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskno details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskno details.

Incomplete outcome data (attrition bias)
All outcomes
High riskITT was not used.

Selective reporting (reporting bias)High riskPANSS was not reported.

Other biasLow riskNone obvious.

vs CPZ - Cao 2005

MethodsAllocation: randomised, no further details.
Blinding: open label.
Duration: 16 weeks.
Setting: Inpatients, Nanjing brain hospital, Nanjing city, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 100.
Age: 25-40 years.
Sex: male.
History: duration ill, age of onset: not reported.
Exclusion: having other mental health problems, other physical illness, drug/alcohol. dependent, abnormal lab test results, problematic marital relationships.


Interventions1. Quetiapine: dosage not stated. N = 25.
2. Chlorpromazine: dosage not stated. N = 25.


OutcomesLeaving the study early

Unable to use.
Adverse events - continuous data was reported, but the scale used was not clear.
Sexual arousal, and other sexual related outcomes that were measured using an invalidated scale.


NotesOnly male participants were included in the study; therefore, gender bias can
not be excluded.

CCMD = Chinese Classification of Mental Disorders.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
High riskOpen-label.

Incomplete outcome data (attrition bias)
All outcomes
High riskDrop outs were excluded from analysis.

Selective reporting (reporting bias)Low riskAll measured outcomes reported.

Other biasLow riskNone obvious.

vs CPZ - Chen 2001

MethodsAllocation: randomised using random number table.
Blinding: double, no further details.
Duration: 1 week wash out period + 8 weeks intervention.
Setting: inpatients, multi-centre, China.


ParticipantsDiagnosis: schizophrenia (CCMD-2-R).
N = 221.
Sex: male and female.
Age: 18-63 years.
History: duration ill, age of onset: not reported.
Exclusion: severe heart, renal, liver illness, nerve system illness, hypertension, blood illness, pregnant/lactating women, received ECT within 2 weeks prior to current study, suicidal patients, participated in other clinical trials within 1 month prior to current study.


Interventions1. Quetiapine: 200-800 mg/day. N = 114.
2. Chlorpromazine: 200-800 mg/day. N = 107.


OutcomesMental state: BPRS, PANSS.

Global state: no clinical improvement*.

Leaving the study early.
Adverse events.


Notes*PANSS decreased rate < 25%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

BPRS = Brief Psychiatric Rating Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using random number table.

Allocation concealment (selection bias)Low riskPharmacist produced identical pills, only they know which pill contains experimental drug.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble, no further details.

Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskITT was used.

Selective reporting (reporting bias)Low riskOutcomes reported as measured.

Other biasLow riskNone obvious.

vs CPZ - Chen 2007b

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 3 months.
Setting: inpatients and outpatients, Xuzhou, Jiangsu province, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 62.
Sex: male and female.
Age: 18-58 years.
History: duration ill: 6 months to 7 years.
Exclusion: severe physical illness, drug/alcohol dependent, pregnant/lactating women.


Interventions1. Quetiapine: 300.7 ± 100.3 mg/day. N = 32.
2. Chlorpromazine: 360.3 ± 82.5 mg/day. N = 30.


OutcomesMental state: PANSS, BPRS.

Adverse events.

Unable to use: GQOLI-74, only subscale scores available.


NotesCCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

BPRS = Brief Psychiatric Rating Scale.

GQOLI = General Quality Of Life Inventory.
TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation, no further details.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS was measured, but not reported.

Other biasLow riskNone obvious.

vs CPZ - Guo 2003

MethodsAllocation: randomised (by tossing a coin).
Blinding: not reported.
Duration: 8 weeks.
Setting: outpatients, Henan city, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
Sex: male and female.
Age: 18-55 years.
History: duration ill <1 year.
N = 148.
Exclusion: severe physical illness, drug/alcohol dependent.


Interventions1. Quetiapine: 450 ± 25 mg/day. N = 75.
2. Chlorpromazine: 600 ± 50 mg/day. N = 73.


OutcomesMental state: PANSS (total, positive and negative score).

Global state: no clinical improvement*

Adverse events.


Notes*PANSS decreased rate <25%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised by tossing a coin.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS scale score measured but not reported.

Other biasLow riskNone obvious.

vs CPZ - Guo 2007

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 8 weeks.
Setting: inpatients and outpatients, Kangning hospital, Guangzhou city, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 52.
Age: 18-40 years.
Sex: male and female.
History: duration ill 0.5-2 years.
Exclusion: severe physical illness, drug/alcohol dependent, pregnant/lactating women.


Interventions1. Quetiapine: 600-800 mg/day. N = 26.
2. Chlorpromazine: 300-500 mg/day. N = 26.


OutcomesMental state: PANSS.

Global state: CGI-S, CGI-I.

Adverse events


NotesCCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

CGI-S = Clinical Global Impression - Severity scale.

CGI-I = Clinical Global Impression - Improvement scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS was measured, but not reported.

Other biasLow riskNone obvious.

vs CPZ - He 2003

MethodsAllocation: randomised, no further details,
Blinding: open label.
Duration: 6 weeks.
Setting: Jiangsu City, China.


ParticipantsDiagnosis: schizophrenia (CCMD-2-R).
Sex: male and female.
Age: 18-50 years.
N = 40.
History: duration ill: 1 month - 10 years.
Exclusion criteria: severe physical illness, alcohol/drug abuse, pregnant/lactating women.


Interventions1. Quetiapine: 433 ± 19 mg/day. N = 20.
2. Chlorpromazine: 468 ± 39 mg/day. N = 20.


OutcomesMental state: PANSS endpoint score.
Global state: no clinical improvement*.
Adverse events.


Notes*PANSS decreased rate <40%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
High riskOpen label.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS score measured, but not reported.

Other biasLow riskNone obvious.

vs CPZ - Hu 2003

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 4 weeks.
Setting: inpatients, Mental health centre, Sichuan, China.


ParticipantsDiagnosis: schizophrenia (DSM-IV), first onset, inpatients.
N = 62.
Sex: male
Age: mean 26.94, SD 8.82
History: duration ill, age of onset: not reported.
Exclusion: severe physical illness, lactating/pregnant women.


Interventions1. Quetiapine: 410 ± 108.77 mg/d. N = 22.
2. Chlorpromazine: 350 ± 67.8 mg/d. N = 19.


OutcomesMental state: PANSS (positive, negative, general psychopathology subscale.)

Adverse events: TESS, RSESE.

Unable to use: GAF score - some data missing.


NotesPANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.

RSESE = Rating Scale for Extrapyramidal Side Effects.

GAF = Global Assessment of Functioning.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was no found.

Other biasLow riskNone obvious.

vs CPZ - Ji 2004

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 3 months.
Setting: inpatients, FuZhou mental illness prevention hospital, FuJian province, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 66.
Age: 18-45 years.
Sex: male and female.
History: duration ill mean 1.6 years, SD 0.5 years.
Exclusion: patients with severe physical illnesses, drug or alcohol dependency, pregnant or lactating women.


Interventions1. Quetiapine: dosage not stated. N = 33.
2. Chlorpromazine: dosage not stated. N = 33.


OutcomesLeaving the study early.

Mental state.
PANSS total, negative, positive, general psychopathology score
Quality of life GQOLI-74 score.

Adverse effect.


NotesCCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

GQOLI = General Quality Of Life Inventory.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
High riskDrop outs are excluded from analysis.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasLow riskNone obvious.

vs CPZ - Jiang 2006

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 8 weeks.
Setting: inpatients, Shanghai mental health centre, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 191.
Age: mean 34 years, SD 9.7 years.
Sex: not reported.
History: duration ill mean 58 months, SD 68 months.
Exclusion: severe physical illness, drug/alcohol dependent, received experimental drugs within 4 weeks prior to the trial.


Interventions1. Quetiapine: 100-800 mg/d. N = 94.
2. Chlorpromazine: 100-600 mg/d. N = 97.


OutcomesLeaving the study early.

Adverse events.


NotesCCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop outs were included in final analysis.

Selective reporting (reporting bias)High riskPANSS measured, but not reported.

Other biasLow riskNone obvious.

vs CPZ - Jin 2007

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 4 weeks.
Setting: outpatients and inpatients, Hebei province, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 60.
Sex: male and female.
Age: 18-60 years.
History: duration ill 1-24 months.
Exclusion: severe physical illness, drug abuse, pregnant/lactating women, allergic to either of the intervention drugs.


Interventions1. Quetiapine: 200-800 mg/day. N = 30.
2. Chlorpromazine: 200-600 mg/day. N = 30.


OutcomesMental state: PANSS score.

Global state: no clinical improvement*

Adverse events.


Notes*PANSS decreased rate <25%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS measured, but not reported.

Other biasLow riskNone obvious.

vs CPZ - Li 2003

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 6 months.
Setting: inpatients and outpatients, mental health centre, Shandong, China.


ParticipantsDiagnosis: schizophrenia (CCMD-2-R).
N = 103.
Sex: male and female.
Age: 18-56 years.
History: duration ill mean 1.2, SD 2.1 years.
Exclusion: severe physical illness, drug/alcohol dependent, pregnant/lactating women.


Interventions1. Quetiapine: 482 ± 124 mg/day. N = 52.
2. Chlorpromazine: 503 ± 134 mg/day. N = 51.


OutcomesLeaving the study early.

Mental state: PANSS scores.

Adverse effects: TESS scores.

Unable to use: WHO QOL-100 subscale scores.


NotesCCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.

WHO QOL = World Health Organization Quality of Life.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
High riskITT was not used.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasLow riskNone obvious.

vs CPZ - Link 1997

MethodsAllocation: randomised, no further details.
Blinding: investigator-blinded, no further details.
Duration: 6 weeks, preceded by 24 hours washout period.
Design: parallel, multicentre.
Setting: Belgium, UK, Spain, France, South Africa.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: schizophrenia, schizophreniform disorder (DSM-III-R).
N = 201.
Sex: male 129, female 72.
Age: 18 to 65 years.
History: BPRS ≧ 27, at least 3 on two or more of the BPRS positive symptom items 'conceptual disorganisation', 'suspiciousness', hallucinatory behaviour' and 'unusual thought content'; CGI-S ≧4.

Exclusion: medical condition or laboratory abnormality that might confound the trial results or put the patient at risk, receiving long-acting depot medication, participated in another investigational drug trial during the 4 weeks prior to randomisation, significant alcohol or other drug abuse within the previous 12 months.


Interventions1. Quetiapine: mean 407 mg/day; maximum 750 mg/day (but not more than 500 mg/day for more than 14 days). N = 101.

2. Chropromazine: mean 384 mg/day; maximum 750 mg/day. N = 100.


OutcomesLeaving the study early.
Global state: CGI (no SD).
Mental state: PANSS (no raw data), BPRS (no SD).
Adverse effects: extrapyramidal side effects (AIMS, BAS, SAS), haematology, liver function test, thyroid function tests, ECGs.


NotesPANSS = Positive and Negative Syndrome Scale.

BPRS = Brief Psychiatric Rating Scale.

CGI = Clinical Global Impression.

AIMS = Abnormal Involuntary Movement Scale.

BAS = Barnes Akathisia Scale.

SAS = Simpson Angus scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinded, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available.
ITT method was not used but overall discontinuation rate was low (2.5%).

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskSponsored by manufacturer of quetiapine.

vs CPZ - Mei 2007

MethodsAllocation: randomised, no further details..
Blinding: not reported.
Duration: 8 weeks.
Setting: inpatients, Rongjun hospital, Anhui, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 96.
Sex: male and female.
Age: 17-60 years.
History: duration ill 3 months to 12 years.
Exclusion: severe physical illness, drug/alcohol dependent, pregnant/lactating women.


Interventions1. Quetiapine: 600 ± 50 mg/day. N = 47.
2. Chlorpromazine: 425 ± 106 mg/day. N = 49.


OutcomesMental state: PANSS.

Global state: no clinical improvement*.

Adverse events.


Notes*PANSS decreased rate <25%

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.
TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS measured, but not reported.

Other biasLow riskNone obvious.

vs CPZ - Peng 2006

MethodsAllocation: randomised using random number table.
Blinding: double, no further details.
Duration: 42 days.
Setting: inpatients, West China Hospital, Sichuan, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 40.
Age: mean 30.6 years, SD 11.26 years.
Sex: male and female
History: duration ill mean 28.5 years, SD 6.45years
Exclusion: not stated.


Interventions1. Quetiapine: 555.56 ± 137.74 mg/day, N = 20.
2. Chlorpromazine: 473.61 ± 107.26 mg/day, N = 20


OutcomesLeaving the study early.

Unusable data:
PANSS, BPRS, TESS, RSESE scores - no SD reported.


NotesPANSS = Positive and Negative Syndrome Scale.

BPRS = Brief Psychiatric Rating Scale.

TESS = Treatment Emergent Symptom Scale.

RSESE = Rating Scale for Extrapyramidal Side Effects.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using random number table.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble blind, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear whether people dropped out are included in the analysis.

Selective reporting (reporting bias)Low riskNo evidence of selective reporting.

Other biasLow riskNone obvious.

vs CPZ - Tian 2006

MethodsAllocation: randomised, no further details..
Blinding: not reported.
Duration: 8 weeks.
Setting: inpatients and outpatients, Xiangfan No 1 people's hospital, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 92.
Sex: male and female.
Age: 18-61 years.
History: duration ill mean 6 years, SD 4 years.
Exclusion: severe physical illness, drug/alcohol dependent, pregnant/lactating women, aggressive and suicidal patients.


Interventions1. Quetiapine: 421±18 mg/day. N = 46.
2. Chlorpromazine: 420±67.2 mg/day. N = 46.


OutcomesMental state: PANSS scores.

Global state: no clinical improvement.

Adverse events.


NotesCCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasLow riskNone obvious.

vs CPZ - Wang 2004

MethodsAllocation: randomised, no further details.
Blinding: no details.
Duration: 6 weeks.
Setting: inpatients, Guangzhou Mental Health Hospital, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 96.
Sex: male and female.
Age: 19-58 years.
History: duration ill 2 months - 14 years.
Exclusion criteria: pregnant/lactating women, drug/alcohol dependent patients, severe physical illness, took quetiapine or chlorpromazine within 4 weeks prior to the study, suicidal, allergic to any of the intervention drugs, participated in other clinical trials within 30days prior to the current study.


Interventions1. Quetiapine: 300-750 mg/day. N = 48.
2. Chlorpromazine: 300-750 mg/day. N = 48.


OutcomesLeaving the study early.

Mental state: PANSS (total, positive, negative,general psychopathology subscale).

Global state: CGI endpoint total improvement score, illness severity score, no clinical improvement*.

Adverse events


Notes*PANSS decreased rate < 30%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

CGI = Clinical Global Impression.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskITT was used.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasLow riskNone obvious.

vs CPZ - Wang 2005

MethodsAllocation: randomised,no further details..
Blinding: open label.
Duration: 8 weeks.
Setting: inpatients, Shanghai mental health centre, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 105.
Age: mean 33 years, SD 11 years.
Sex: not stated.
History:duration ill mean 65 days, SD 8 days.
Exclusion: drug/alcohol dependent patients, severe physical illness, took quetiapine or chlorpromazine within 4 weeks prior to the study.


Interventions1. Quetiapine: 400-750 mg/day. N = 48.
2. Chlorpromazine: 100-600 mg/day. N = 57.


OutcomesLeaving study early.

Mental state: PANSS scores.

Global state: no clinical improvement*.

Adverse effect.


Notes*PANSS decreased rate <25%

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
High riskopen label.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo details.

Selective reporting (reporting bias)High riskTESS score measured not reported.

Other biasLow riskNone obvious.

vs CPZ - Zhang 2002

MethodsAllocation: randomised (by tossing a coin).
Blinding: double blind, no further details.
Duration: 8 weeks.
Setting: inpatients, RiZhao mental health centre, Shandong Province, China.


ParticipantsDiagnosis: schizophrenia (CCMD-2-R).

N = 117.
Sex: male and female.
Age: mean age 24 years, SD 5 years.
History: duration ill mean 3.8 years, SD 1.1 years.
Exclusion criteria: length of illness > 5 years, with severe physical or neurological illness, pregnant or lactating women.


Interventions1. Quetiapine: 300 mg-550 mg/day. N = 60.
2. Chlorpromazine: 300 mg-550 mg/day. N = 57.


OutcomesMental state: PANSS positive, negative, general psychopathology and endpoint score and change score.
Global state: no clinical improvement*.
Adverse event: TESS endpoint and change score.

Unusable data:
Leaving the study early, no 'n' number reported.


Notes* PANSS decreased rate < 25%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised by tossing a coin.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble blind, no further details.

Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasLow riskNone obvious.

vs CPZ - Zhang 2003

MethodsAllocation: randomised using computer generated random number.
Blinding: double, no further details.
Duration: 1 week wash out period + 6 weeks of intervention + 1 week with reduced dose of medication to help patients to withdraw from the interventions.
Setting: inpatients, multicentre, China.


ParticipantsDiagnosis: schizophrenia (CCMD-2-R).
N = 237.
Sex: male and female.
Age: mean age 32 years, SD 11.
History: duration ill: mean Quetiapine 7.0 ± 7.3 years, mean Chlorpromazine 5.9±7.2 years.
Exclusion criteria: patients with neurological, heart, liver, renal or other severe physical illnesses; pregnant or lactating women; alcohol or drug dependent patients; patients who received quetiapine or chlorpromazine 4 weeks prior to the study; patients with allergy of quetiapine and chlorpromazine; patients who participated in other clinical drug trials within the last 30 days of this study.


Interventions1.Quetiapine: first week 75mg-300 mg/day, second week onwards 300mg-750 mg/day. N = 119.
2.Chlorpromazine:first week 75mg-300 mg/day, second week onwards 300mg-750 mg/day. N = 118.


OutcomesLeaving the study early.
Mental state, PANSS end point score and PANSS score decreased rate.

Unusable data:
CGI score measured, but data not reported.
No clinical improvement: no n number reported.
Adverse effect measured, but 'n' numbers were not reported.


NotesCCMD = Chinese Classification of Mental Disorders.

CGI =

PANSS = Positive and Negative Syndrome Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using computer-generated random number.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble blind, no further details.

Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskITT was used.

Selective reporting (reporting bias)High riskCGI and adverse events were measured, but data not reported.

Other biasLow riskNone obvious.

vs CPZ - Zhong 2005

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 12 weeks.
Setting: inpatients, Beijing hospital, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 84.
Sex: not stated.
Age: 16-60 years.
Exclusion: patients with severe physical illness, or drug/alcohol dependent.


Interventions1.Quetiapine: 400-900 mg/day. N = 42.
2.Chlorpromazine: 300-800 mg/day. N = 42.


OutcomesMental state: PANSS negative, positive, general psychopathology, total score.
Global state: SF-36 total score.

Adverse events.


NotesCCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

SF-36 = Short Form (36) Health Survey.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS measured, but not reported.

Other biasLow riskNone obvious.

vs CPZ - Zhou 2003

MethodsAllocation: randomised, using random number table.
Blinding: assessors are blinded, unclear if the patients are.
Duration: 6 weeks.
Setting: inpatients, Mental health centre, Sichuan, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3), inpatients.
N = 40.
Sex: male and female.
Age: mean˜28, SD˜10 years.
History: duration ill mean˜25, SD˜6 years.
Exclusion: not described.


Interventions1. Quetiapine: dosage not stated. N = 20.
2. Chlorpromazine: dosage not stated. N = 20.


OutcomesLeaving study early.

Unable to use: WCST subscale scores,


NotesCCMD = Chinese Classification of Mental Disorders.

WCST = Wisconsin Card Sorting Test.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using random number table.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding, but unclear whether single or double blind (assessors are blinded anyway).

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasLow riskNone obvious.

vs CPZ - Zhou 2004

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 12 weeks.
Setting: inpatients, Jinan psychiatric hospital, Shandong province, China.


ParticipantsDiagnosis: schizophrenia (ICD-10, CCMD-3).
N = 83.
Age: 17-51 years old.
Sex: male and female.
History: duration ill 4 months to 21 years.
Exclusion criteria: not stated.


Interventions1. Quetiapine: 300-400 mg/d. N = 42.
2. Chlorpromazine: 200-600 mg/d. N = 41.


OutcomesLeaving the study early.

Mental state: PANSS positive, negative, general psychopathology, total score.

Global state: no clinical improvement*

Quality of life: GQOLI score.

Adverse events: TESS score.


Notes*PANSS decreased rate <25%

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

GQOLI = General Quality Of Life Inventory.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo n number reported, so not clear what happened to people who dropped out.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not clear.

Other biasLow riskNone obvious.

vs CPZ - Zou 2006

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 8 weeks.
Setting: Community and hospital, Zhejiang, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 86.
Age: 17-56 year.
Sex: male and female.
History: duration ill <10 years.
Exclusion: severe physical illness, drug/alcohol dependent, pregnant/lactating women, allergic to experimental drugs.


Interventions1. Quetiapine: 483.1 ± 25.5 mg/day. N = 43.
2. Chlorpromazine: 450.2 ± 30.2 mg/day. N = 43.


OutcomesMental state: PANSS scores.

Global state: no clinical improvement*.

Adverse events.


Notes*PANSS decreased rate <25%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS scores measured, but not reported.

Other biasLow riskNone obvious.

vs FLUPHEN - Conley 2005

MethodsAllocation: randomised, no further details.
Blinding: double, no further details.
Duration: 12 weeks, preceded by 4-6 weeks of open-label trial with olanzapine or typical antipsychotic other than fluphenazine.
Design: parallel.
Setting: inpatients, USA.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: schizophrenia (DSM-IV).
N = 52.*
Sex: male 44, female 8.
Age: 18-65 years (mean 44 years).
History: BPRS ≧ 4 on 2 of 4 psychosis items, BPRS total ≧ 45, CGI ≧ 4, 2 prior failed treatment with 2 antipsychotics, no stable period of good social/occupational functioning within 5 years.


Interventions1. Quetiapine: 300-500 mg/d. N = 12.

2. Fluphenazine: 10-15 mg/d. N = 13.


OutcomesGlobal state: CGI-S, quality of life.

Mental state: BPRS.

Adverse effects: Extrapyramidal side effects (SAS, AIMS), Barnes Akathisia Scale.


NotesBPRS = Brief Psychiatric Rating Scale.

CGI-S = Clinical Global Impression - Severity scale.

AIMS = Abnormal Involuntary Movement Scale.

SAS = Simpson Angus scale.

*Thirteen participants were randomly assigned to risperidone.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
High riskData for leaving study early were available but total was high (47%).
Last-observation-carried-forward method was not used.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskSponsored by manufacturers of quetiapine and risperidone.

vs HLP - Arvanitis 1997

MethodsAllocation: randomised, no further details.
Blinding: double, no further details.
Duration: 6 weeks, preceded by 7 days washout period.*
Design: parallel, multicentre.
Setting: inpatients, USA and Canada.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: schizophrenia (DSM-III-R).
N = 361.
Sex: male 274, female 87.
Age: 18-65 years (mean = 37 years).
History: BPRS ≧ 27, 3 on two or more of the BPRS positive symptom items 'conceptual disorganisation', 'suspiciousness', hallucinatory behaviour' and 'unusual thought content'; CGI-S ≧ 4.

Exclusion: concurrent Axis I DSM-III-R diagnoses; history of seizure disorder; clinically significant medical condition; participation in another investigational drug trial within 30 days of trial entry; use of depot antipsychotics within one dosing interval; pregnancy.


Interventions1. Quetiapine: 75 mg/day. N = 53.

2. Quetiapine: 150 mg/day. N = 48.

3. Quetiapine: 300 mg/day. N = 52.

4. Quetiapine: 600 mg/day. N = 51.

5. Quetiapine: 750 mg/day. N = 54.

2. Haloperidol:12 mg/day. N = 52.


OutcomesLeaving the study early.
Global state: CGI.
Mental state: BPRS, Modified Scale for the Assessment of Negative Symptoms (SANS).
Adverse effects: extrapyramidal side effects (AIMS, SAS), haematology, liver function test, serum prolactin (no SD), thyroid function tests, weight, ECGs.


Notes*After the 7-day, single blind, placebo washout phase, patients with a 20% or greater decrease in BPRS total score or a greater than 1-point decrease in CGI-S was considered placebo responders and were withdrawn.

BPRS = Brief Psychiatric Rating Scale.

AIMS = Abnormal Involuntary Movement Scale.

SAS = Simpson Angus scale.

ECG = electrocardiogram.

CGI-S = Clinical Global Impression - Severity scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available but total was high (59%).
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence for selective reporting was not found.

Other biasHigh riskSponsored by manufacturers of quetiapine.

vs HLP - Atmaca 2002

MethodsAllocation: randomised, no further details.
Blinding: open label.
Duration: 6 weeks, preceded by 14 days washout period.
Design: single centre.
Setting: inpatient and outpatient, Turkey.

Consent: obtained.

Loss: described (all participants completed the study.)


ParticipantsDiagnosis: schizophrenia (DSM-IV).
N = 35.
Sex: female 35.
Age: 18-45 years (mean quetiapine = 27.62 years and mean haloperidol = 29.44 years).
History: duration ill and age of onset: not reported.

Exclusion: severe physical illness, history of alcohol and substance abuse or dependence, presence of any endocrinology state, taking oral contraceptives.


Interventions1. Quetiapine: 600 mg/day. N = 18.

2. Haloperidol: 10 mg/day. N = 17.


OutcomesLeaving the study early: any cause, lack of efficacy, intolerability, patient's decision.
Mental state: PANSS, BPRS.
Adverse effects: extrapyramidal side effects (ESRS), prolactin level.


NotesPANSS = Positive and Negative Syndrome Scale.

BPRS = Brief Psychiatric Rating Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
High riskOpen label; however, some outcome measures such as prolactin level are unlikely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants completed the study.

Selective reporting (reporting bias)Low riskEvidence for selective reporting was not found.

Other biasHigh riskOnly female participants could be included in the study; therefore, gender bias can not be excluded.

vs HLP - Copolov 2000

MethodsAllocation: randomised, no further details.
Blinding: double, no further details.
Duration: 6 weeks, preceded by 48 hours washout period.
Design: parallel, multicentre.
Setting: inpatient, 14 countries.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: Schizophrenia (DSM-III-R).
N = 448.
Sex: male 305, female 143.
Age: 18 years or over (mean quetiapine 37 years, mean haloperidol 37 years).
History: acute exacerbation of chronic or subchronic schizophrenia; CGI-S ≧ 4; PANSS ≧ 60, at least 4 on two or more of the PANSS items 'delusions', 'conceptual disorganization', 'hallucinatory behaviour', and 'suspiciousness/persecution'.

Exclusion: significant clinical disorders or laboratory or ECG findings, epilepsy, low WBC count; pregnant or lactating women, or women of reproductive age not using adequate contraception; treatment with a long-acting depot medication less than one dosing period; participation in any other investigational drug trial during 4 weeks prior to randomisation.


Interventions1. Quetiapine: range 300-600 mg/day, maximum 800 mg/day. N = 221.

2. Haloperidol: range 6-12 mg/day, maximum 16 mg/day. N = 227.


OutcomesLeaving the study early.
Global state: CGI.
Mental state: PANSS.
Adverse effects: extrapyramidal side effects (AIMS, SAS), haematology, liver function test, serum prolactin, thyroid function tests, weight.


NotesPANSS = Positive and Negative Syndrome Scale.

CGI = Clinical Global Impression.

AIMS = Abnormal Involuntary Movement Scale.

SAS = Simpson Angus scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available but total was high (33%).
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskSponsored by manufacturers of quetiapine.

vs HLP - Emsley 1999

MethodsAllocation: randomised, no further details.
Blinding: double, no further details.
Duration: 8 weeks, preceded by 4 weeks fluphenazine run-in phase.
Design: parallel, multicentre.
Setting: Europe and South Africa.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: Schizophrenia (DSM-IV).
N = 365*.
Sex: male 203, female 85.
Age: 18 years or over.
History:persistent positive symptoms while taking antipsychotics; positive scale of PANSS ≧ 15, at least 4 on two or more of the PANSS items 'delusions', 'conceptual disorganization', 'hallucinatory behaviour', and 'suspiciousness/persecution'; CGI-S ≧ 3.

Exclusion: clozapine non-responders; acute exacerbation of schizophrenia within the previous 3 months; known sensitivity to drugs evaluated in the trial or history of idiopathic or drug-induced agranulocytosis.


Interventions1. Quetiapine: 600 mg/day. N = 143.

2. Haloperidol: 20 mg/day. N = 145.


OutcomesLeaving the study early (death, adverse event, non-compliance with protocol, deterioration of condition, informed consent withdrawn, patient lost to follow-up).

Unusable data:

Global state: CGI (no SD).
Mental state: PANSS (positive, negative, general psychopathology subscale) (no SD), BPRS (total, positive subscale, mood cluster) (no SD).
Adverse effects: extrapyramidal side effects (SAS), haematology, serum prolactin (no SD).


Notes*After 4 weeks run-in phase, 288 participants were included and randomised.

PANSS = Positive and Negative Syndrome Scale.

BPRS = Brief Psychiatric Rating Scale.

CGI = Clinical Global Impression.

SAS = Simpson Angus scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble blind, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available.
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskSponsored by manufacturers of quetiapine.

vs HLP - Emsley 2004

MethodsAllocation: randomised, no further details.
Blinding: investigator-blinded, no further details.
Duration: 50 weeks, preceded by 2 weeks washout period.
Design: parallel, single centre.
Setting: inpatients and outpatients, South Africa.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: Schizophrenia, schizoaffective disorder (DSM-IV).
N = 47*.
Sex: male 29, female 16.
Age: 18 to 65 years (mean quetiapine 49.2 years, mean haloperidol 50.1 years)
History:diagnosis of tardive dyskinesia (Schooler and Kane criteria).

Exclusion: resistant to standard antipsychotic medication; clozapine non-responders; acute exacerbation of schizophrenia within the previous 3 months; known sensitivity to drugs evaluated in the trial or history of idiopathic or drug-induced agranulocytosis.


Interventions1. Quetiapine: 100 mg/day for 2 days, 200 mg/day for 2 days, 300 mg/day for 2 days, 400 mg/day from day 7 onwards; maximum 800 mg/day. N = 22.

2. Haloperidol: 5 mg/day for 4 days, 10 mg/day for 3 days and onwards; maximum 20 mg/day. N = 23.


OutcomesMental state: PANSS (positive, negative, general psychopathology subscale).
Adverse effects: dyskinesia (ESRS dyskinesia subscale), weight, BMI, serum prolactin, glycosylated haemoglobin.


Notes*Two were excluded (1 withdrew before reaching the target dose, 1 had unrelated medical illness).

PANSS = Positive and Negative Syndrome Scale.

ESRS = Extrapyramidal Symptom Rating Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskSingle-blinded (investigator-blinded), no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available but total was high (38%).
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskESRS dyskinesia subscale and CGI dyskinesia scores were not shown in the result.

Sponsored by manufacturer of quetiapine.

vs HLP - Fl'hacker 2005

MethodsAllocation: randomised, web-based online system.
Blinding: open label.
Duration: 12 months.
Design: parallel, multicentre.
Setting: 13 European countries and Israel.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: schizophrenia, schizoaffective disorder, schizophreniform disorder (DSM-IV).
N = 498.
Sex: male 298, female 200.
Age: 18 to 40 years (mean quetiapine 26.4 years, mean haloperidol 25.4 years).
History: duration of illness less than 2 years; exposure to antipsychotic treatment not more than 2 weeks in the year preceding study entry or 6 weeks in lifetime.

Exclusion: known to be intolerance to one of the study drugs; met any of the contraindications for any of the study drugs.


Interventions1. Quetiapine: range 200-750 mg/day. N = 104.

2. Haloperidol: range 1-4 mg/day. N = 103.

3. Olanzapine: range 5-20 mg/day. N = 105.

4. Ziprasidone: range 40-160 mg/day. N = 82.

5. Amisulpride: range 200-800 mg/day. N = 104.


OutcomesLeaving the study early.

Global state: CGI, GAF.

Mental state: PANSS (positive, negative, general psychopathology subscale), CDSS.

Quality of life: Manchester short assessment of quality of life scale (MANSA)

Cognition: Composite score from Rey Auditory Verbal Learning test, Trail Making Test, WAIS Digit Symbol Test and Purdue Pegboard Test.
Adverse effects: Extrapiramidal side effect (ST. Hans rating scale; SHRS), dyskinesia (ESRS dyskinesia subscale), sexual dysfunction (selected items from the Udvalg for Kliniske Undersøgelser; UKU), weight, BMI, serum prolactin, glycosylated haemoglobin, ECG.


NotesCGI = Clinical Global Impression.

GAF = Global Assessment of Functioning.

PANSS = Positive and Negative Syndrome Scale.

CDSS = Calgary Depression Scale for Schizophrenia.

WAIS = Wechsler Adult Intelligence Scale.

ESRS = Extrapyramidal Symptom Rating Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised, web-based online system.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
High riskOpen label.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available but total was high (42%).
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskSponsored by manufacturer of quetiapine and other drug companies.

vs HLP - Huang 2007

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 18 months.
Setting: inpatients and outpatients, Guangzhou mental health hospital, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 128.
Age: 18-60 years.
Sex: male and female.
History: duration ill mean 5.6 years, SD 3 years.
Exclusion: severe physical illness, children, pregnant/lactating women, drug/alcohol dependent, suicidal, aggressive and agitated, allergic to intervention drugs, taking antipsychotic medication within 1 week prior to the trial.


Interventions1. Quetiapine: 400-700 mg/day. N = 64.
2. Haloperidol: 4-40 mg/day. N = 64.


OutcomesMental state: PANSS score.

Global state: no clinical improvement*

Adverse events.


Notes*PANSS decreased rate <25%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete outcome data.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasLow riskNone obvious.

vs HLP - McCue 2006

MethodsAllocation: randomised, using randomisation website.
Blinding: open trial.
Duration: 3 weeks.
Design: single centre.
Setting: inpatients, USA.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: Schizophrenia, schizoaffective disorder, schizophreniform disorder (DSM-IV).
N = 327*.
Sex: male 198, female 121.
Age: 18 years and older.
History: duration ill: mean quetiapine 14.5 years, mean haloperidol 12.2 years.

Exclusion: pregnant or lactating; medical condition in which pharmacotherapy would prove a risk; history of response or lack of response to a particular antipsychotic drug; psychiatrist judged that would best not entered into the study; diagnosis of bipolar disorder, major depressive disorder, substance-induced psychotic disorder.


Interventions1. Quetiapine: range 50-1200 mg/day; mean 652.5 mg/day. N = 50.

2. Haloperidol: range 4-30 mg/day; mean 16.0 mg/day. N = 57.

3. Aripiprazole: range 10-45 mg/day; mean 21.8 mg/day. N = 53.

4. Olanzapine: range 5-40 mg/day; mean 19.1 mg/day. N = 52.

5. Risperisdone: range 2-9 mg/day; mean 5.2 mg/day. N = 57.

6. Ziprasidone: range 40-240 mg/day; mean 151.2 mg/day. N = 50.


OutcomesEffectiveness defined as no longer required acute in-patient care.

Mental state: BPRS.


Notes*Eight participants were withdrawn for reasons unrelated to antipsychotic treatment and were not included in the analysis.

BPRS = Brief Psychiatric Rating Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRamdomised, using computer random number generator.

Allocation concealment (selection bias)Low riskStaff and patients did not have assess to the list.

Blinding (performance bias and detection bias)
All outcomes
High riskOpen label.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available.
ITT method was not used but overall discontinuation rate was low (5.6%).

Selective reporting (reporting bias)Low riskNo evidence of selective reporting was found.

Other biasLow riskNone obvious.

vs HLP - Murasaki 1999

MethodsAllocation: randomised, no further details.
Blinding: double, no further details.
Duration: 8 weeks.
Design: parallel, multicentre.
Setting: inpatient and outpatient, Japan.

Loss: described.


ParticipantsDiagnosis: Schizophrenia (ICD-10).
N = 197.
Sex: male 129, female 68.
Age: 18-65 years.
History: duration ill: mean quetiapine 17.5 years, mean haloperidol 16.9 years.

Exclusion: significant deterioration of personality, receiving high-dose antipsychotics, severe endocrinological disease, epilepsy or convulsive disorders, Parkinson's disease, organic cerebral disorder.


Interventions1. Quetiapine: range 150-600 mg/day, mean 226 mg/day. N = 100.

2. Haloperidol: range 4.5-18 mg/day, mean 6.7 mg/day. N = 97.


OutcomesLeaving the study early.
Global state: Global Improvement Rating (GIR).
Mental state: PANSS (total, positive, negative and general psychopathology), BPRS.
Adverse effects: reported EPS, Overall Safety Rating (OSR), Global Usefulness Rating (GUR).


NotesPANSS = Positive and Negative Syndrome Scale.

BPRS = Brief Psychiatric Rating Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
High riskData for leaving study early were available but total was high (39%).
ITT method was not used.

Selective reporting (reporting bias)Low riskNo evidence of selective reporting was found.

Other biasHigh riskSponsored by manufacturer of quetiapine.

vs HLP - Purdon 2001

MethodsAllocation: randomised, no further details.
Blinding: Single-blinded (investigator-blinded), no further details.
Duration: 6 months, preceded by 2 days washout period.
Design: multicentre.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: schizophrenia (DSM-IV).
N = 25.
Sex: male 20, female 5.
Age: mean 33.9 (SD 7.3) years.
History: duration ill and age of onset: not reported.

Exclusion: history of a serious medical disease or neurological disorder (including serious head injury); active substance abuse in the 30-day period before enrolment.


Interventions1. Quetiapine: range 300-600 mg/day. N = 13.

2. Haloperidol: range 10-20 mg/day. N = 12.


OutcomesMental state: PANSS (positive, negative, general psychopathology subscale); CDS; BDI.

Cognition: Battery of tests used to determine functioning in 6 domains (motor skill, attention span, verbal fluency and reasoning, visuospatial fluency and construction) consists of finger tapping test, grooved pegboard test, Wechsler memory scale-revised, controlled oral word association test, WAIS-R similarities, design fluency, visual organisation test, complex figure copy test, trailmaking part B WAIS-R digit symbol test, Wisconsin card sorting test, Ray and Crawfoord auditory verbal learning tests, serial design learning tests, story recall test, Wechsler memory scale visual reproduction test, Reay and Taylor complex figure immediate recall test.

Adverse effects: EPS (AIMS, SAS).


NotesPANSS = Positive and Negative Syndrome Scale.

CDS = Calgary Depression Scale.

BDI = Beck Depression Inventory.

WAIS-R = Wechsler Adult Intelligence Scale -Revised.

AIMS = Abnormal Involuntary Movement Scale.

SAS = Simpson Angus scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blinded, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available but total was high (48%).
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskSponsored by manufacturer of quetiapine.

vs HLP - Taneli 2003

MethodsAllocation: randomised, no further details.
Blinding: open label.
Duration: 12 weeks.
Design: parallel, multicentre.
Setting: outpatient, Turkey.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: schizophrenia (DSM-IV).
N = 79.
Sex: male 68, female 11.
Age: 18-65 years.
History: exacerbation of schizophrenia with PANSS ≧ 60; CGI-S ≧ 3.

Exclusion: no detail.


Interventions1. Quetiapine: range 400-750 mg/day. N = 45.

2. Haloperidol: range 5-20 mg/day. N = 34.


OutcomesLeaving the study early.

Global state: CGI-S.

Mental state: PANSS (positive, negative, general psychopathology subscale).

Adverse effects: extrapyramidal side effects (AIMS, SAS,ASC-SR).


NotesPANSS = Positive and Negative Syndrome Scale.

CGI = Clinical Global Impression.

AIMS = Abnormal Involuntary Movement Scale.

SAS = Simpson Angus scale.

ASC-SR = Approaches to Schizophrenia Communication Self-Report.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
High riskOpen label.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available.
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskSponsored by manufacturer of quetiapine.

vs HLP - Velligan 2002

MethodsAllocation: randomised, no further details.
Blinding: Double-blinded, no further details.
Duration: 24 weeks.
Design: multicentre.
Setting: outpatient.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: Schizophrenia (DSM-III-R).
N = 116*.
Sex: male 43, female 15.
Age: mean 39.5 years.
History: conventional antipsychotic doses equivalent to 30 mg/day or less of haloperidol; in full or partial remission; BPRS no more than 3 for items assessing 'conceptual disorganisation', 'suspiciousness', hallucinatory behaviour' and 'unusual thought content'; CGI-S no more than 4.

Exclusion:physical disorder or laboratory finding that made it inappropriate to receive study medication.


Interventions1. Quetiapine: 300 mg/day. N = 41.

2. Quetiapine: 600 mg/day. N = 52.

2. Haloperidol: 12 mg/day. N = 23.


OutcomesLeaving the study early.

Mental state: BPRS.

Cognition: Cognitive summary score (Stroop-Color-Word, Hopkins Verbal Learning, Symbol Digit Substitution, Trials A and B, Paragraph Recall, Verbal Fluency, Pattern Memory and Paced Serial Addition.)


Notes*The participants were a sub-sample form 301 participants and only 58 participants were included in the analysis.

BPRS = Brief Psychiatric Rating Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble blind, no further details.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
High riskData for leaving study early were available but total was high (50%).
ITT was not used.

Selective reporting (reporting bias)Low riskEvidence of selective reporting was not found.

Other biasHigh riskSponsored by manufacturers of quetiapine.

vs HLP - Zou 2007

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 8 weeks.
Setting: inpatients, Leshan mental health hospital, Sichuang, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 72.
Age: 18-60 years.
Sex: male and female.
History: duration ill mean 4.2 years, SD 2 years.
Exclusion: severe physical illness, delayed/impaired mental development, pregnant, abnormal lab test results, received depot antipsychotics within 1 month prior to the trial.


Interventions1. Quetiapine: 400-800 mg/day. N = 36.
2. Haloperidol: 8-32 mg/day. N = 36.


OutcomesMental state: PANSS scores.

Global state: no clinical improvement*.

Adverse events.


Notes*PANSS decreased rate < 25%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS scores, and some of the PANSS outcomes measured, but not reported, even though these are subscale scores.

Other biasLow riskNone obvious.

vs PERPHEN - Chen 2007a

MethodsAllocation: randomised, no further details.
Blinding: not reported.
Duration: 10 weeks.
Setting: inpatients and outpatients, Chaoyang district mental health centre, Beijing, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).

N = 61.
Age: > 60years.
Sex: male and female.
History: duration ill: 15-30 years.
Exclusion: severe physical illness.


Interventions1. Quetiapine: 422.6 ± 108.4 mg/day. N = 31.
2. Perphenazine: 21.0 ± 16.4 mg/day. N = 30.


OutcomesMental state: PANSS.

Global state: No clinical improvement*.
Adverse events.

Unable to use: medication compliance, no n number reported.


Notes*PANSS decreased rate <40%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS was measured, but not reported.

Other biasLow riskNone obvious.

vs PERPHEN - L'rman 2005

MethodsAllocation: randomised, no further details.
Blinding: double, identical-appearing capsules.
Duration: 18 months.
Design: parallel, multicentre (57 US. sites).
Setting: inpatient and outpatient, USA.

Consent: obtained.

Loss: described.


ParticipantsDiagnosis: Schizophrenia (DSM-IV).
N = 1,493**.
Sex: male 1080, female 380.
Age: 18-65 years (mean Quetiapine = 40.9 years, mean Perphenazine = 40.0 years).
History: duration ill, age of onset: not reported.

Exclusion: diagnosis of schizoaffective disorder, mental retardation, or other cognitive disorders; history of serious adverse reactions to the proposed treatments; one schizophrenic episode; history of treatment resistance; pregnant or breastfeeding; serious and unstable medical condition.


Interventions1. Quetiapine: range 200-800 mg/day, mean 543.4 mg/day. N = 337.

2. Perphenazine: range 8-32 mg/day, mean 20.8 mg/day. N = 261.

3. Olanzapine: range 7.5-30 mg/day, mean 20.1 mg/day. N = 336.

4. Riperidone: range 1.5-6.0 mg/day, mean 3.9 mg/day. N = 341.

5. Ziprasidone*: range 40-160 mg/day, mean 112.8 mg/day. N = 185.


OutcomesLeaving the study early: any cause, lack of efficacy, intolerability, patient's decision.
Global state: CGI.
Mental state: PANSS (total, positive, negative sub-score).

Cognitive***: Compostite score (processing speed, reasoning, working memory, verbal memory, vigilance)
Adverse effects: any serious adverse event, suicidal attempt, suicidal ideation, extrapyramidal side effects (AIMS, BAS, SAS), weight change, prolactin level.


Notes* Ziprasidone was included after its approval by the US FDA.

**Only 1,460 participants were randomised.

*** The composite score consisted of five neurocognitive domains scores which were calculated from controlled oral word, category instances, grooved pegboard, Wechsler adult intelligence-revised, Wisconsin card sorting test, Wechsler intelligence scale for children-third edition mazes, Hopkins verbal learning test, computerized test of visuospatial working memory, letter-number sequencing test and continuous performance test.

PANSS = Positive and Negative Syndrome Scale.

CGI = Clinical Global Impression.

AIMS = Abnormal Involuntary Movement Scale.

BAS = Barnes Akathisia Scale.

SAS = Simpson Angus scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble blind, identical-appearing capsules.
Whether blinding was successful was not examined.

Incomplete outcome data (attrition bias)
All outcomes
Low riskData for leaving study early were available but total was high (74%).
Last-observation-carried-forward method used (assumes that participants who discontinue remain stable).

Selective reporting (reporting bias)Low riskEvidence for selective reporting was not found.

Other biasUnclear riskDose ranges of each antipsychotic drugs were quite different.

Allocation to ziprasidone treatment was not possible from the start.

vs PERPHEN - Yi 2006

MethodsAllocation: randomised, no further details.
Blinding: not stated.
Duration: 12 weeks.
Setting: community and hospital, Sichuang, China.


ParticipantsDiagnosis: schizophrenia (CCMD-3).
N = 81.
Age: mean˜11.4 years, SD˜3 years.
Sex: male and female.
History: duration ill 1-14months.
Exclusion: severe physical illness, abnormal lab test results.


Interventions1. Quetiapine: 560 ± 50 mg/day. N = 41.
2. Perphenazine: 7.55 ± 3.28 mg/day. N = 40.


OutcomesMental state: PANSS scores.

Global state: no clinical improvement*.

Adverse events.


Notes*PANSS decreased rate =/<25%.

CCMD = Chinese Classification of Mental Disorders.

PANSS = Positive and Negative Syndrome Scale.

TESS = Treatment Emergent Symptom Scale.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, no further details.

Allocation concealment (selection bias)Unclear riskNo details.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo details.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data.

Selective reporting (reporting bias)High riskTESS scores measured, but not reported.

Other biasLow riskNone obvious.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Buckley 2001Allocation: randomised.

Participants: schizophrenia.

Intervention: quetiapine vs haloperidol.

Outcome: no usable data.

Cheng 2003Allocation: randomised.

Participants: schizophrenia.

Intervention: quetiapine + routine antipsychotics vs chlorpromazine + routine antipsychotics.

Du 2004Allocation: quasi randomisation - according to hospital admission order.

Participants: schizophrenia.

Interventions: quetiapine vs chlorpromazine.

Glick 2005Allocation: randomised.

Participants: schizophrenia.

Intervention: quetiapine vs haloperidol decanoate.

Incomplete outcome data: data for leaving study early were available but total was high (37%) and Intention-to-treat was not used.

Sponsored by manufacturers of quetiapine.

Goldstein 1999Allocation: randomised.

Participants: schizophrenia.

Intervention: quetiapine vs haloperidol.

Outcome: no usable data.

Grecu 2006Allocation: randomised.
Participants: schizophrenia.

Intervention: quetiapine vs haloperidol.
Outcome: no usable data (data reported in graph).

Guo 2006Allocation: randomised.
Participants: schizophrenia.
Intervention: quetiapine vs chlorpromazine.
Outcome: no usable data (only blood sugar level, TC, TG, GLU were reported).

Hammond 2001Allocation: unclear.
Participants: schizophrenia, schizoaffective disorder, schizophreniform disorder.

Intervention: quetiapine vs haloperidol.
Outcome: no usable data.

Jones 2006Allocation: randomised.
Participants: schizophrenia, schizoaffective disorder or delusional disorder.
Interventions: first-generation antipsychotic drugs vs second-generation antipsychotic drugs as group, no usable data.

Keleman 2006Allocation: unclear.
Participants: schizophrenia.

Intervention: quetiapine vs haloperidol.
Outcome: no usable data.

Kelly 2005Allocation: randomised.
Participants: schizophrenia.

Intervention: quetiapine vs fluphenazine.
Outcome: no usable data (only thyroid functions were reported).

Kelly 2006Allocation: randomised.
Participants: schizophrenia.

Intervention: quetiapine vs fluphenazine.
Outcome: no usable data (data reported in graph).

Kong 2003Allocation: randomised.
Participants: schizophrenia (CCMD-3).
Intervention: quetiapine vs chlorpromazine.
Outcome: no usable data (only blood serum concentration was reported).

Lee 2001Post-hoc analysis of pooled data from 3 RCT's.

Loza 2001Allocation: randomised.
Participants: schizophrenia.

Intervention: quetiapine vs perphenazine.
Outcome: abstract with no usable data.

Ma 2004Allocation: controlled clinical trial, not randomised.

Nai 2007Allocation: randomised.
Participants: schizophrenia.
Intervention: quetiapine vs chlorpromazine.
Outcome: no usable data (WCST subscale scores).

Qiu 2003Allocation: controlled clinical trial, not randomised.
Participants: schizophrenia.
Intervention: quetiapine vs haloperidol.
Outcome: PANSS.

Reveley 2001Allocation: randomised.
Participants: schizophrenia.

Intervention: quetiapine vs chlorpromazine.
Outcome: not available.

Richardson 2005Allocation: randomised.
Participants: schizophrenia.

Intervention: quetiapine vs chlorpromazine.
Outcome: abstract with no usable data.

Sharma 2002Allocation: randomised.
Participants: schizophrenia.

Intervention: quetiapine vs haloperidol.
Outcome: not available.

Zhang 2007Allocation: quasi randomisation - randomised according to hospital admission number.

 
Comparison 1. QUETIAPINE versus TYPICAL ANTIPSYCHOTICS

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Global state: 1. No clinical improvement151607Risk Ratio (IV, Random, 95% CI)0.96 [0.75, 1.23]

    1.1 short term
151479Risk Ratio (IV, Random, 95% CI)1.05 [0.81, 1.35]

    1.2 medium term
1128Risk Ratio (IV, Random, 95% CI)0.16 [0.05, 0.51]

 2 Global state: 2a. CGI: Average CGI-S (high = poor)81253Mean Difference (IV, Random, 95% CI)0.20 [0.06, 0.33]

    2.1 short term - endpoint score
5347Mean Difference (IV, Random, 95% CI)0.22 [-0.04, 0.49]

    2.2 short term - change score
2699Mean Difference (IV, Random, 95% CI)0.20 [0.04, 0.36]

    2.3 long term - endpoint score
1207Mean Difference (IV, Random, 95% CI)-0.10 [-0.93, 0.73]

 3 Global state: 2b. CGI: Average endpoint CGI-I (high = poor)5507Mean Difference (IV, Random, 95% CI)0.38 [0.28, 0.47]

    3.1 short term
4496Mean Difference (IV, Random, 95% CI)0.39 [0.30, 0.47]

    3.2 medium term
111Mean Difference (IV, Random, 95% CI)-0.20 [-1.08, 0.68]

 4 Leaving the study early: 1. Any reason233576Risk Ratio (IV, Random, 95% CI)0.91 [0.81, 1.01]

    4.1 short term
172535Risk Ratio (IV, Random, 95% CI)0.88 [0.78, 1.00]

    4.2 medium term
3203Risk Ratio (IV, Random, 95% CI)0.72 [0.52, 0.99]

    4.3 long term
3838Risk Ratio (IV, Random, 95% CI)0.99 [0.77, 1.28]

 5 Leaving the study early: 2. Adverse events153010Risk Ratio (IV, Random, 95% CI)0.48 [0.30, 0.77]

    5.1 short term
112044Risk Ratio (IV, Random, 95% CI)0.51 [0.31, 0.84]

    5.2 medium term
1128Risk Ratio (IV, Random, 95% CI)0.03 [0.00, 0.53]

    5.3 long term
3838Risk Ratio (IV, Random, 95% CI)0.46 [0.12, 1.78]

 6 Leaving the study early: 3. Inefficacy92063Risk Ratio (IV, Random, 95% CI)1.24 [1.00, 1.54]

    6.1 short term
3842Risk Ratio (IV, Random, 95% CI)1.20 [0.87, 1.66]

    6.2 long term
61221Risk Ratio (IV, Random, 95% CI)1.41 [0.94, 2.11]

 7 Mental state: 1a. General - average score (PANSS total, high = poor)273052Mean Difference (IV, Random, 95% CI)0.09 [-2.14, 2.31]

    7.1 short term - endpoint score
212055Mean Difference (IV, Random, 95% CI)0.84 [-1.46, 3.15]

    7.2 short term - change score
2565Mean Difference (IV, Random, 95% CI)3.59 [0.09, 7.10]

    7.3 medium term - endpoint score
3180Mean Difference (IV, Random, 95% CI)-7.77 [-15.69, 0.14]

    7.4 long term - endpoint score
2252Mean Difference (IV, Random, 95% CI)-0.90 [-4.94, 3.15]

 8 Mental state: 1b. General - average score -short term (BPRS total, high = poor)81025Mean Difference (IV, Random, 95% CI)0.71 [-0.77, 2.20]

    8.1 endpoint score
6666Mean Difference (IV, Random, 95% CI)-0.24 [-1.66, 1.17]

    8.2 change score
2359Mean Difference (IV, Random, 95% CI)3.49 [0.90, 6.08]

 9 Mental state: 2a. Positive symptoms - average endpoint score (PANSS positive subscore, high = poor)221934Mean Difference (IV, Random, 95% CI)0.02 [-0.39, 0.43]

    9.1 short term
191801Mean Difference (IV, Random, 95% CI)0.19 [-0.25, 0.62]

    9.2 medium term
288Mean Difference (IV, Random, 95% CI)-1.57 [-3.41, 0.26]

    9.3 long term
145Mean Difference (IV, Random, 95% CI)-1.30 [-3.12, 0.52]

 10 Mental state: 2b. Positive symptoms - average score - short term (BPRS positive subscore, high = poor)3381Mean Difference (IV, Random, 95% CI)0.63 [-0.37, 1.62]

    10.1 endpoint score
2128Mean Difference (IV, Random, 95% CI)0.12 [-0.42, 0.65]

    10.2 change score
1253Mean Difference (IV, Random, 95% CI)1.34 [0.27, 2.41]

 11 Mental state: 3a. Negative symptoms - average endpoint score (PANSS negative subscore, high = poor)221934Mean Difference (IV, Random, 95% CI)-0.82 [-1.59, -0.04]

    11.1 short term
191801Mean Difference (IV, Random, 95% CI)-0.81 [-1.63, 0.01]

    11.2 medium term
288Mean Difference (IV, Random, 95% CI)-2.45 [-4.64, -0.27]

    11.3 long term
145Mean Difference (IV, Random, 95% CI)1.20 [-2.09, 4.49]

 12 Mental state: 3b. Negative symptoms - average score - short term (BPRS negative subscore, high = poor))2278Mean Difference (IV, Random, 95% CI)-0.67 [-1.31, -0.04]

    12.1 endpoint score
125Mean Difference (IV, Random, 95% CI)0.11 [-2.01, 2.23]

    12.2 change score
1253Mean Difference (IV, Random, 95% CI)-0.75 [-1.42, -0.08]

 13 Mental state: 3c. Negative symptoms - average score - short term (SANS total, high = poor)2331Mean Difference (IV, Random, 95% CI)0.66 [-1.35, 2.66]

    13.1 endpoint score
1103Mean Difference (IV, Random, 95% CI)1.80 [0.24, 3.36]

    13.2 change score
1228Mean Difference (IV, Random, 95% CI)-0.26 [-1.08, 0.56]

 14 Mental state: 4. General psychopathology - average endpoint score (PANSS general psychopathology subscore, high = poor)181569Mean Difference (IV, Random, 95% CI)-0.20 [-0.83, 0.42]

    14.1 short term
151472Mean Difference (IV, Random, 95% CI)-0.17 [-0.81, 0.47]

    14.2 medium term
252Mean Difference (IV, Random, 95% CI)0.47 [-3.30, 4.24]

    14.3 long term
145Mean Difference (IV, Random, 95% CI)-2.20 [-6.02, 1.62]

 15 General functioning: General - average endpoint score - long term (GAF total score, low = poor)1207Mean Difference (IV, Random, 95% CI)-0.10 [-9.80, 9.60]

 16 Quality of life: 1a. General - average endpoint score -short term (SF-36, low = poor)184Mean Difference (IV, Random, 95% CI)13.76 [5.95, 21.57]

 17 Quality of life: 1b. General - average endpoint score - long term (MANSA total score, low = poor)1207Mean Difference (IV, Random, 95% CI)0.0 [-1.38, 1.38]

 18 Quality of life: 1c. General - average change score - long term (QLS, high = poor)1156Mean Difference (IV, Random, 95% CI)0.1 [-0.23, 0.43]

 19 Cognitive function: 1a. General - average change score - long term (Composite score, high = poor)2407Mean Difference (IV, Random, 95% CI)0.00 [-0.19, 0.20]

 20 Cognitive function: 1b. General - average endpoint scores as defined by the original studies (low = poor)3142Mean Difference (IV, Random, 95% CI)1.55 [-0.62, 3.72]

    20.1 short term
191Mean Difference (IV, Random, 95% CI)8.30 [1.64, 14.96]

    20.2 long term
251Mean Difference (IV, Random, 95% CI)0.82 [-0.77, 2.41]

 21 Service use: number of participants re-hospitalised - long term2722Risk Ratio (IV, Random, 95% CI)1.23 [0.90, 1.68]

 22 Adverse effects: 1. General - at least one adverse effect91985Risk Ratio (IV, Random, 95% CI)0.76 [0.64, 0.90]

    22.1 short term
71180Risk Ratio (IV, Random, 95% CI)0.75 [0.62, 0.91]

    22.2 long term
2805Risk Ratio (IV, Random, 95% CI)0.82 [0.52, 1.29]

 23 Adverse effects: 2. Death21456Risk Ratio (IV, Random, 95% CI)0.78 [0.20, 3.04]

    23.1 suicide attempt - long term
1598Risk Ratio (IV, Random, 95% CI)0.77 [0.05, 12.32]

    23.2 suicide - long term
1598Risk Ratio (IV, Random, 95% CI)0.52 [0.09, 3.07]

    23.3 death - short term
1260Risk Ratio (IV, Random, 95% CI)3.0 [0.12, 72.97]

 24 Adverse effects: 3a. Cardiac effects - QTc prolongation - long term141Risk Ratio (IV, Random, 95% CI)1.73 [0.17, 17.59]

 25 Adverse effects: 3b. Cardiac effects - abnormal ECG - short term2165Risk Ratio (IV, Random, 95% CI)0.38 [0.16, 0.92]

 26 Adverse effects: 3c. Cardiac effects - orthostatic hypotension51393Risk Ratio (IV, Random, 95% CI)0.61 [0.28, 1.35]

    26.1 short term
4795Risk Ratio (IV, Random, 95% CI)0.45 [0.13, 1.54]

    26.2 long term
1598Risk Ratio (IV, Random, 95% CI)1.01 [0.64, 1.60]

 27 Adverse effects: 3d. Cardiac effects - low blood pressure - short term6572Risk Ratio (IV, Random, 95% CI)0.69 [0.41, 1.18]

 28 Adverse effects: 3e. Cardiac effects - tachycardia - short term8814Risk Ratio (IV, Random, 95% CI)0.70 [0.36, 1.34]

 29 Adverse effects: 4. Central nervous system - sedation142298Risk Ratio (IV, Random, 95% CI)0.70 [0.43, 1.16]

    29.1 short term
131700Risk Ratio (IV, Random, 95% CI)0.69 [0.37, 1.30]

    29.2 long term
1598Risk Ratio (IV, Random, 95% CI)1.08 [0.84, 1.39]

 30 Adverse effects: 5a. Extrapyramidal effects - overall - short term81095Risk Ratio (IV, Random, 95% CI)0.17 [0.09, 0.32]

 31 Adverse effects: 5b. Extrapyramidal effects - akathisia162217Risk Ratio (IV, Random, 95% CI)0.27 [0.18, 0.39]

    31.1 short term
152059Risk Ratio (IV, Random, 95% CI)0.24 [0.17, 0.35]

    31.2 long term
1158Risk Ratio (IV, Random, 95% CI)0.50 [0.25, 0.98]

 32 Adverse effects: 5c. Extrapyramidal effects - parkinsonism3343Risk Ratio (IV, Random, 95% CI)0.26 [0.14, 0.47]

    32.1 short term
2185Risk Ratio (IV, Random, 95% CI)0.13 [0.04, 0.48]

    32.2 long term
1158Risk Ratio (IV, Random, 95% CI)0.31 [0.15, 0.62]

 33 Adverse effects: 5d. Extrapyramidal effects - dystonia5992Risk Ratio (IV, Random, 95% CI)0.19 [0.06, 0.64]

    33.1 short term
4834Risk Ratio (IV, Random, 95% CI)0.13 [0.04, 0.51]

    33.2 long term
1158Risk Ratio (IV, Random, 95% CI)0.86 [0.05, 13.49]

 34 Adverse effects: 5e. Extrapyramidal effects - tremor - short term121641Risk Ratio (IV, Random, 95% CI)0.33 [0.23, 0.47]

 35 Adverse effects: 5f. Extrapyramidal effects - scale measured (dichotomous data) - long term1Risk Ratio (IV, Random, 95% CI)Subtotals only

    35.1 extrapyramidal symptoms: Simpson-Angus Scale (SAS >/=1)
1541Risk Ratio (IV, Random, 95% CI)0.65 [0.31, 1.37]

    35.2 abnormal movement: Abnormal Involuntary Movement Scale (AIMS>/=2)
1473Risk Ratio (IV, Random, 95% CI)0.73 [0.48, 1.14]

    35.3 akathisia: Barnes Akathisia Scale (BARS >/=3)
1546Risk Ratio (IV, Random, 95% CI)0.79 [0.40, 1.55]

 36 Adverse effects: 5g. Extrapyramidal effects - scale measured (continuous data, high=poor)5373Mean Difference (IV, Random, 95% CI)-1.24 [-2.54, 0.05]

    36.1 average endpoint score - Extrapyramidal symptoms (ESRS) - short term
135Mean Difference (IV, Random, 95% CI)-4.55 [-6.58, -2.52]

    36.2 average endpoint score - Abnormal Involuntary Movement Scale ( AIMS) - medium term
111Mean Difference (IV, Random, 95% CI)0.30 [-0.83, 1.43]

    36.3 average endpoint score - Simpson-Angus Scale (SAS) - medium term
111Mean Difference (IV, Random, 95% CI)1.10 [-1.94, 4.14]

    36.4 average endpoint score - Treatment Emergent Symptom Scale (TESS) - short term
2158Mean Difference (IV, Random, 95% CI)-1.09 [-2.51, 0.33]

    36.5 average change score - Treatment Emergent Symptom Scale (TESS) - short term
1117Mean Difference (IV, Random, 95% CI)-1.03 [-2.49, 0.43]

    36.6 average endpoint score - Treatment Emergent Symptom Scale (TESS) - medium term
141Mean Difference (IV, Random, 95% CI)-2.1 [-4.55, 0.35]

 37 Adverse effects: 6a. Prolactin associated side effects11196Risk Ratio (IV, Random, 95% CI)0.77 [0.33, 1.79]

    37.1 gynaecomastia, galactorrhoea - long term
1598Risk Ratio (IV, Random, 95% CI)1.16 [0.33, 4.07]

    37.2 menstrual irregularities - long term
1598Risk Ratio (IV, Random, 95% CI)0.55 [0.18, 1.72]

 38 Adverse effects: 6b. Prolactin - Hyperprolactinemia3229Risk Ratio (IV, Random, 95% CI)0.27 [0.04, 1.92]

    38.1 short term
2165Risk Ratio (IV, Random, 95% CI)0.08 [0.01, 0.60]

    38.2 long term
164Risk Ratio (IV, Random, 95% CI)0.91 [0.51, 1.62]

 39 Adverse effects: 6c. Prolactin level - average level in ng/mL41034Mean Difference (IV, Random, 95% CI)-16.20 [-23.34, -9.07]

    39.1 short term - endpoint level
135Mean Difference (IV, Random, 95% CI)-15.67 [-21.00, -10.34]

    39.2 short term - change level
1356Mean Difference (IV, Random, 95% CI)-22.43 [-23.20, -21.66]

    39.3 long term - endpoint level
145Mean Difference (IV, Random, 95% CI)-16.4 [-23.83, -8.97]

    39.4 long term - change level
1598Mean Difference (IV, Random, 95% CI)-9.70 [-14.02, -5.38]

 40 Adverse effects: 7a. Weight gain (as defined by the original studies)111512Risk Ratio (IV, Random, 95% CI)0.68 [0.44, 1.04]

    40.1 short term
9866Risk Ratio (IV, Random, 95% CI)0.52 [0.34, 0.80]

    40.2 long term
2646Risk Ratio (IV, Random, 95% CI)1.27 [0.97, 1.66]

 41 Adverse effects: 7b. Weight gain - average weight in kg.3168Mean Difference (IV, Random, 95% CI)3.35 [0.29, 6.40]

    41.1 short term - change weight
125Mean Difference (IV, Random, 95% CI)1.40 [-5.66, 8.46]

    41.2 long term - endpoint weight
145Mean Difference (IV, Random, 95% CI)4.30 [-0.31, 8.91]

    41.3 long term - change weight
198Mean Difference (IV, Random, 95% CI)3.2 [-1.79, 8.19]

 42 Adverse effects: 8. decreased white blood cell count - short term140Risk Ratio (IV, Random, 95% CI)0.33 [0.01, 7.72]

 43 Sensitivity analysis (skewed data excluded), Mental state: 1. General - average endpoint score (PANSS total, high = poor)3172Mean Difference (IV, Random, 95% CI)-2.25 [-5.35, 0.85]

    43.1 short term
295Mean Difference (IV, Random, 95% CI)-0.88 [-3.63, 1.88]

    43.2 medium term
177Mean Difference (IV, Random, 95% CI)-4.90 [-8.06, -1.74]

 44 Sensitivity analysis (skewed data excluded), Mental state: 2. Negative symptoms - average endpoint score (PANSS negative subscore, high=poor) - medium term177Mean Difference (IV, Random, 95% CI)-2.70 [-4.96, -0.44]

 45 Sensitivity analysis (inappropriate comparator doses excluded), Mental state: 1: General- average endpoint score (PANSS total, high=poor)171835Mean Difference (IV, Random, 95% CI)1.55 [-1.38, 4.49]

    45.1 short term - endpoint
131173Mean Difference (IV, Random, 95% CI)2.04 [-1.67, 5.74]

    45.2 short term - change
2565Mean Difference (IV, Random, 95% CI)3.59 [0.09, 7.10]

    45.3 medium term - endpoint
252Mean Difference (IV, Random, 95% CI)-4.72 [-7.85, -1.59]

    45.4 long term - endpoint
145Mean Difference (IV, Random, 95% CI)-2.30 [-10.22, 5.62]

 46 Sensitivity analysis (inappropriate comparator doses excluded), Mental state: 2: Positive symptoms- average endpoint score (PANSS positive subscore, high = poor)131011Mean Difference (IV, Random, 95% CI)0.02 [-0.58, 0.62]

 47 Sensitivity analysis (inappropriate comparator doses excluded), Mental state: 3: Negative symptoms- average endpoint score (PANSS negative subscore, high = poor)131011Mean Difference (IV, Random, 95% CI)-0.98 [-2.09, 0.14]

    47.1 short term
10878Mean Difference (IV, Random, 95% CI)-0.99 [-2.26, 0.28]

    47.2 medium term
288Mean Difference (IV, Random, 95% CI)-2.45 [-4.64, -0.27]

    47.3 long term
145Mean Difference (IV, Random, 95% CI)1.20 [-2.09, 4.49]

 48 Senstivity analysis (high attrition rate data excluded), Mental state: 1: General - average score (PANSS total, high = poor)252834Mean Difference (IV, Random, 95% CI)0.08 [-2.26, 2.42]

    48.1 short term - endpoint score
212055Mean Difference (IV, Random, 95% CI)0.84 [-1.46, 3.15]

    48.2 short term - change score
2565Mean Difference (IV, Random, 95% CI)3.59 [0.09, 7.10]

    48.3 medium term - endpoint score
2169Mean Difference (IV, Random, 95% CI)-9.11 [-17.54, -0.68]

    48.4 long term - endpoint score
145Mean Difference (IV, Random, 95% CI)-2.30 [-10.22, 5.62]

 49 Sensitivity analysis (high attrition rate data excluded), Mental state: 2. Positive symptoms - average endpoint score (PANSS positive subscore, high = poor)211923Mean Difference (IV, Random, 95% CI)0.02 [-0.39, 0.43]

    49.1 short term
191801Mean Difference (IV, Random, 95% CI)0.19 [-0.25, 0.62]

    49.2 medium term
177Mean Difference (IV, Random, 95% CI)-1.80 [-3.70, 0.10]

    49.3 long term
145Mean Difference (IV, Random, 95% CI)-1.30 [-3.12, 0.52]

 50 Sensitivity analysis (high attrition rate data excluded), Mental state: 3. Negative symptoms - average endpoint score (PANSS negative subscore, high = poor)211923Mean Difference (IV, Random, 95% CI)-0.83 [-1.62, -0.04]

    50.1 short term
191801Mean Difference (IV, Random, 95% CI)-0.81 [-1.63, 0.01]

    50.2 medium term
177Mean Difference (IV, Random, 95% CI)-2.70 [-4.96, -0.44]

    50.3 long term
145Mean Difference (IV, Random, 95% CI)1.20 [-2.09, 4.49]

 51 Senstivity analysis (completer data only), Mental state: 1: General - average score (PANSS total, high=poor)181628Mean Difference (IV, Random, 95% CI)-0.41 [-3.32, 2.51]

    51.1 short term - endpoint score
161342Mean Difference (IV, Random, 95% CI)0.55 [-2.27, 3.38]

    51.2 short term - change score
1117Mean Difference (IV, Random, 95% CI)3.88 [-1.68, 9.44]

    51.3 medium term - endpoint score
2169Mean Difference (IV, Random, 95% CI)-9.11 [-17.54, -0.68]

 52 Sensitivity analysis (completer data only), Mental state: 2. Positive symptoms - average endpoint score (PANSS positive subscore, high = poor)161385Mean Difference (IV, Random, 95% CI)0.00 [-0.46, 0.46]

    52.1 short term
151308Mean Difference (IV, Random, 95% CI)0.11 [-0.36, 0.59]

    52.2 medium term
177Mean Difference (IV, Random, 95% CI)-1.80 [-3.70, 0.10]

 53 Sensitivity analysis (completer data only), Mental state: 3. Negative symptoms - average endpoint score (PANSS negative subscore, high = poor)161385Mean Difference (IV, Random, 95% CI)-1.16 [-2.08, -0.25]

    53.1 short term
151308Mean Difference (IV, Random, 95% CI)-1.06 [-2.01, -0.12]

    53.2 medium term
177Mean Difference (IV, Random, 95% CI)-2.70 [-4.96, -0.44]

 
Summary of findings for the main comparison. Quetiapine compared to Typical antipsychotics for schizophrenia

Quetiapine compared to Typical antipsychotics for schizophrenia

Patient or population: patients with schizophrenia
Settings:
Intervention: Quetiapine
Comparison: Typical antipsychotics

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Typical antipsychoticsQuetiapine

Global state
No clinical significant response as defined by the individual studies
Study populationRR 0.96
(0.75 to 1.23)
1607
(16 studies)
⊕⊕⊕⊝
moderate1

145 per 1000139 per 1000
(109 to 178)

Moderate


Leaving the study early due to any reasonStudy populationRR 0.91
(0.81 to 1.01)
3576
(23 studies)
⊕⊕⊕⊝
moderate1

369 per 1000336 per 1000
(299 to 373)

Moderate


Positive symptoms
PANSS positive subscore
The mean positive symptoms in the intervention groups was
0.02 higher
(0.39 lower to 0.43 higher)
1934
(22 studies)
⊕⊕⊕⊝
moderate1

Negative symptoms
PANSS negative subscore
The mean negative symptoms in the intervention groups was
0.82 lower
(1.59 to 0.04 lower)
1934
(22 studies)
⊕⊕⊕⊝
moderate1

Cognitive function
Average endpoint scores as defined by the original studies
The mean cognitive function in the intervention groups was
1.55 higher
(0.62 lower to 3.72 higher)
142
(3 studies)
⊕⊝⊝⊝
very low1,2,3

Extrapyramidal effectsStudy populationRR 0.17
(0.09 to 0.32)
1095
(8 studies)
⊕⊕⊕⊝
moderate1

548 per 100093 per 1000
(49 to 175)

Moderate


Prolactin level
Average level in ng/mL
The mean prolactin level in the intervention groups was
16.20 lower
(23.34 to 9.07 lower)
1034
(4 studies)
⊕⊕⊕⊝
moderate1

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Limitations in design - rated 'serious' : poor description of randomisation, no details about blinding, no details about concealment.
2 Inconsistency -rated 'serious' : the measurement of cognitive function were various.
3 Imprecision - rated 'serious' : number of participants was very small.
PANSS: Positive and Negative Syndrome Scale
 
Table 1. Suggested design of future study

MethodsAllocation: randomised - clearly described generation of sequence and concealment of allocation.
Blindness.: double - described and tested.
Duration: 6 months minimum.

ParticipantsDiagnosis: schizophrenia.
N = 1800.*
Age: any.
Sex: both.
History: any.

Interventions1. Quetiapine: dose 300-800 mg/day. N = 300.

2. Typical antipsychotic medications.

2a. Chlorpromazine: dose 300-1000 mg/day. N = 300.**

2b. Fluphenazine: dose 5-20 mg/day.N = 300.

2c. Perphenazine: dose 16-64 mg/day. N = 300.

2d. Trifluoperazine: dose 15-50 mg/day. N = 300.

2e. Haloperidol: dose 5-20 mg/day. N = 300.

OutcomesGlobal impression: CGI***, relapse.

Leaving study early (any reason, adverse events, inefficacy).
Service outcomes: hospitalised, time in hospital, attending out patient clinics.
Mental state: PANSS.
Adverse events.

Functioning: employment, living independently, functioning improved to an important extent.

Quality of life: improved to an important extent.

Economics: direct and indirect costs.

 * Power calculation suggested 300/group would allow good chance of showing a 10% difference between groups for primary outcome.
** Of the many possible comparisons we would probably choose chlorpromazine or perphenazine.

*** Primary outcome.
CGI: Clinical Global Impression Scale
PANSS: Positive and Negative Syndrome Scale