Intervention Review

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Quetiapine versus other atypical antipsychotics for schizophrenia

  1. Laila Asmal1,*,
  2. Srnka J Flegar1,
  3. Jikun Wang2,
  4. Christine Rummel-Kluge3,
  5. Katja Komossa4,
  6. Stefan Leucht5

Editorial Group: Cochrane Schizophrenia Group

Published Online: 18 NOV 2013

Assessed as up-to-date: 7 MAY 2010

DOI: 10.1002/14651858.CD006625.pub3


How to Cite

Asmal L, Flegar SJ, Wang J, Rummel-Kluge C, Komossa K, Leucht S. Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD006625. DOI: 10.1002/14651858.CD006625.pub3.

Author Information

  1. 1

    University of Stellenbosch, Department of Psychiatry, Tygerberg, South Africa

  2. 2

    East China Normal University, School of Psychology and Cognitive Science, Shanghai, China

  3. 3

    University of Leipzig, Clinic and Outpatient Clinic of Psychiatry and Psychotherapy, Leipzig, Saxony, Germany

  4. 4

    University Hospital of Zurich, Department of Psychiatry and Psychotherapy, Zurich, Switzerland

  5. 5

    Technische Universität München Klinikum rechts der Isar, Klinik und Poliklinik für Psychiatrie und Psychotherapie, München, Germany

*Laila Asmal, Department of Psychiatry, University of Stellenbosch, Faculty of Medicine and Health Sciences, PO Box 19063, Tygerberg, 7505, South Africa. laila@sun.ac.za.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 18 NOV 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Astrazeneca 1998

MethodsAllocation: random.

Blindness: double-blind.

Duration: 10 weeks.

Design: parallel.

Location: multi-centre.


ParticipantsDiagnosis: schizophrenia (DSM IV).

N = 408.

Gender: quetiapine: 129 M, 71 F. risperidone: 127 M, 80 F.

Age: 18 - 65 years, quetiapine 35 years, risperidone 37 years.

History:  duration ill not reported, age at onset not reported.

Setting: not reported.


Interventions1. Quetiapine: flexible dose 300mg/day up to week 4, then increased to 600mg if poor response. Mean dose not reported. N = 200.

2. Risperidone: flexible dose 6mg/day up to week 4, then increased to 10mg/day if poor response. Mean dose not reported. N = 208.


OutcomesMental state: PANSS total score.
Leaving the study early: any reason, inefficacy.
Adverse effects: total numbers.

Data not available:

Global state: Global State: CGI.

Mental State: PANSS general subscore, positive subscore, negative subscore, BPRS total score, BPRS positive subscore, BPRS negative subscore.

Adverse effects: Barnes Global Akathisia scale, Simpson Scale and Abnormal Involuntary Movement Scale (AIMS). Prolactin increase, white cell count.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble-blind. Whether blinding was successful has not been examined, but the compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Unclear riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High risk36% attrition, early leavers not adequately accounted for.

Selective reporting (reporting bias)High riskNot all pre-defined outcomes were described, including CGI scores, PANSS subscales and adverse event rating scales.

Other biasUnclear riskStudy sponsored by manufacturer of quetiapine.

Atmaca 2003

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 6 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (DSM IV).
N = 56.
Gender: 24 M, 29 F.
Age: 19 - 46 years (mean clozapine 31.3 years, mean olanzapine 29.6 years, mean quetiapine 30.1 years, mean risperidone 27.9 years, mean control group 32.1 years).
History: duration ill: mean clozapine 6.6 years, mean olanzapine 6.3 years, mean quetiapine 5.9 years, mean risperidone 5.6. Age at onset not reported.


Interventions1. Clozapine: flexible dose. Allowed dose range: not reported. Mean dose: 207.1 mg/day. N = 14.

2. Olanzapine: flexible dose. Allowed dose range: not reported. Mean dose: 15.7 mg/day. N = 14.

3. Quetiapine: flexible dose. Allowed dose range: not reported. Mean dose: 535.7 mg/day. N = 14.

4. Risperidone: flexible dose. Allowed dose range: not reported. Mean dose: 6.7 mg/day. N = 14.


OutcomesLeaving the study early: any reason.
Mental state: PANSS total score.
Adverse effects: EPS (use of antiparkinson medication), weight gain (BMI), laboratory (serum leptin, triglyceride levels).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but the compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall attrition was low (5.4%). Reasons for leaving early were not assessed; only completer data were presented. Because of the very low rate of attrition, we do not think that a risk of bias was present.

Selective reporting (reporting bias)Low riskProbably free of bias. The study focused on serum leptin and triglyceride levels, which were adequately described.

Other biasUnclear riskData on the allowed dose range have not been presented. Furthermore, the pre-study treatment was heterogeneous, as 19 participants had never taken any psychotropic drugs, but most other participants had a long history of previous treatment.

Byerly 2008

MethodsAllocation: random, no further details.
Blindness: double.
Duration: 6 weeks.
Design: parallel.
Location: multi-centre.


ParticipantsDiagnosis: schizophrenia (DSM IV ), (N = 28) or schizoaffective disorder (N = 14), moderate sexual dysfunction (ASEX score 15 or more), on risperidone 4mg or less as only antipsychotic treatment.

N = 42.

Gender: 22 M, 20 F.

Age:18 years or older (mean risperidone 41.2 years, mean quetiapine 43.5 years).

History: duration ill not reported, age at onset not reported.

Setting: outpatient.


Interventions1. Quetiapine: flexible dose.  Allowed dose range up to 800mg/day. N = 20.

2. Risperidone: flexible dose. Maintained on pre-trial dose of 4mg or less. N = 22.


OutcomesMental State: PANSS total score.

Adverse events: prolactin, sexual dysfunction.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskWhether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo discussion of participants leaving the study early or of missing data. 100% retention with no missing data is unusual for this type of study.

Selective reporting (reporting bias)Low riskWe did not find evidence for selective reporting.

Other biasUnclear riskNo washout period was provided, and a one-week overlap of risperidone in the quetiapine group was described.

Canuso 2008

MethodsAllocation: randomised.

Blindness: double-blinded.

Duration: 2 weeks.

Design: parallel.

Location: multisite, in-patient,


ParticipantsDiagnosis: schizophrenia (DSM-IV) , acute exacerbation.
N = 399 (placebo arm not included in review).
Gender: quetiapine 105 M 52 F, paliperidone 107 M 50 F.
Age: mean quetiapine 36.9 years, mean paliperidone 35.7 years.
History: duration ill not reported. Age at onset: quetiapine 25.2, paliperidone 23.2.


Interventions1. Quetiapine: flexible dose, mean dose 690.9. N = 159.

2. Paliperidone: flexible dose, mean dose 10.4. N = 160.

3. Placebo N = 80.


OutcomesMental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.

Adverse effects: weight gain, gastrointestinal disorders, insomnia, sedation, headache, Simpson-Angus Rating Scale, the Barnes Rating Scale for Drug-Induced Akathisia, and the Abnormal Involuntary Movement Scale.
Data not available:
Treatment satisfaction: Medication satisfaction questionnaire.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskStratified according to site but method unclear, likely adequate.

Allocation concealment (selection bias)Low riskVoice response system.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, identical capsules. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskRelatively low attrition (15%) for monotherapy phase of study. Difference of 5 participants between randomly assigned and ITT population that are unaccounted for Unlikely to affect final data.

Selective reporting (reporting bias)High riskNot all pre-defined adverse effects were reported.

Other biasHigh riskThe study was sponsored by the manufacturer of paliperidone.

Conley 2005

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 12 weeks.
Design: parallel.
Location: not reported.


ParticipantsDiagnosis: schizophrenia (DSM-IV), treatment resistance, persistent positive psychotic symptoms, BPRS total score of 35 or more plus CGI score of 4 or more.
N = 38.
Gender: 30 M, 8 F.
Age: 18 - 65 years (mean fluphenazine 44.2 years, mean quetiapine = 43.7 years, mean risperidone 46.3 years).
History: duration ill not reported, age at onset not reported.
Setting: inpatient.


Interventions1. Fluphenazine: flexible dose. Allowed dose range: 10 - 15 mg/day. Mean dose: 13.2 mg/day. N = 13.

2. Quetiapine: flexible dose. Allowed dose range: 300 - 500 mg/day, Mean dose: 463.6 mg/day. N = 12.

3. Risperidone: flexible dose. Allowed dose range: 3 - 5 mg/day. Mean dose: 4.31 mg/day. N = 13.


OutcomesGlobal State: CGI.

Leaving the study early: any reason, adverse events, inefficacy.
Mental State: BPRS total score, BPRS positive subscore, BPRS negative subscore.
Cognitive functioning: Neuropsychological testing.
Quality of life: QLS.
Adverse effects: open interviews, EPS (use of antiparkinson medication, SAS), prolactin increase, sexual dysfunction, sedation, weight gain, laboratory (thyroidal hormones).

Unable to use -
Prolactin increase: no useable data.
Sexual dysfunction: no useable data.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, no further details. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was moderate at 36%. The analysis was based on mixed-effect models. It is unclear whether this statistical method can account for such a relatively high attrition rate.

Selective reporting (reporting bias)High riskNot all pre-defined adverse effects were reported.

Other biasUnclear riskA slight baseline imbalance was noted in terms of mean age and mean number of previous hospitalisations (14 in the risperidone group and 9.7 in the quetiapine group).

Deberdt 2008

MethodsAllocation: randomised.

Blindness: double-blind.

Duration: 24 weeks.

Design: parallel.

Location: multi-site.


ParticipantsDiagnosis: schizophrenia (DSM-IV) or schizoaffective (DSM IV).

N = 133.

Gender: not reported.

Age: 18 - 75 years, quetiapine mean 42.5 years, olanzapine mean 45.4 years.

History: duration ill not reported, age at onset not reported.

Setting: not reported.


Interventions1. Quetiapine: flexible dose between 300 - 800 mg/day, mean modal dose: 439.7 mg/day. N = 65.

2. Olanzapine: flexible dose between 7.5 - 20mg/day, mean modal dose: 16.9 mg/day. N = 68.


OutcomesLeaving the study early.
Relapse.
Service use: number of patients re-hospitalised.
Adverse effects: laboratory (prolactin, lipids, glucose), weight gain.

Unable to use -
Global state: CGI (no usable data).
Mental state: PANSS score (no usable data).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation method not reported, statistically significant baseline differences in mean PANSS total and BMI between groups.

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, no further details. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was very high (57%). The last-observation-carried-forward method was used to account for people leaving the study early. It assumes that a participant who discontinued the study would not have had a change in his condition if he had remained in the study. This assumption obviously can be wrong.

Selective reporting (reporting bias)High riskNot all pre-defined outcomes were described, including PANSS scores.

Other biasHigh riskThe study was sponsored by the manufacturers of olanzapine. Mean modal dose rather than mean dose reported. Study inadequately powered for primary outcome because of recruitment difficulties.

Eerdekens 2007

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 12 days.
Design: parallel.
Location: multi-site.


ParticipantsDiagnosis: schizophrenia (DSM IV) or schizoaffective (DSM IV), normal ECG.

N = 110*.

Gender: 67 M, 20 F.

Age: quetiapine mean 35 years, paliperidone mean 37 years

History:duration ill not reported. Age at onset: quetiapine 24 years, paliperidone 23 years.

Setting: not reported.


Interventions1. Quetiapine: fixed dose of 400mg bd from Day 5 after initial titration. N = 43.

2. Paliperidone: fixed dose of 12mg/d D2 - 6, 15mg/d on D7 and 18mg/d D8 - 11. N = 44.

3. Placebo: N = 22.


OutcomesLeaving study early

Adverse effect: various side effects, QTc interval


Notes * Assigned 2:2:1 to quetiapine, paliperidone and placebo. Placebo arm not included in review. One participant discontinued prior to double-blind treatment.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer randomisation with block permutation.

Allocation concealment (selection bias)Low riskCentral call centre.

Blinding (performance bias and detection bias)
Subjective outcomes
Low riskUnlikely that ECG interpretation could have been unblinded. No other subjective outcomes. All medication was identical over encapsulated.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskUnlikely that ECG interpretation could have been unblinded.

Incomplete outcome data (attrition bias)
All outcomes
High risk17.2% attrition in treatment groups. Only completer data were assessed for cardiac effects.

Selective reporting (reporting bias)Unclear riskDetails for concomitant medication prescription in each treatment arm not mentioned.

Other biasUnclear riskStudy sponsored by the manufacturer of paliperidone.

Hatta 2009

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 8 weeks.
Design: parallel.
Location: multi-centre.


ParticipantsDiagnosis: schizophrenia (ICD-10) and schizoaffective disorder.
N = 80.
Gender: 33 M, 47 F.
Age: mean age olanzapine 39.8 years, mean risperidone 41.1 years, mean aripiprazole 42.1 years, mean quetiapine 39.8 years.
History: duration ill not reported, age at onset not reported.
Setting: in-patient.


Interventions1. Risperidone: flexible dose. Initial dose 3mg/day. Allowed dose range: 3 - 12mg/day. Mean dose: 7.2mg/day. N = 20.

2. Olanzapine: flexible dose. Initial dose 10mg/day. Allowed dose range: 10 - 20mg/day. Mean dose: 17.4mg/day. N = 17.

4. Aripiprazole: Flexible dose. Inital dose 12mg/day. Allowed dose range: 12 - 30mg/day. Mean 23.6mg/day.N = 21.

2. Quetiapine: flexible dose. Initial dose 300mg/day. Allowed dose range: 300 - 750mg/day. Mean dose: 570.mg/day. N = 20.


OutcomesLeaving the study early: any reason, adverse events, inefficacy, non-adherence.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
General functioning: GAF

Service use: admission
Adverse effects: extrapyramidal side-effects, sedation, weight gain, cholesterol change, fasting glucose change, sexual side-effects.


NotesIntramuscular haloperidol allowed. The significance of this additive antipsychotic is not explored in the results.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskImplied but not stated.

Allocation concealment (selection bias)Low riskSealed envelopes.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater blinded. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskHow attrition was accounted for is not described. Half of the participants in the aripiprazole and quetiapine groups dropped out of the study.

Selective reporting (reporting bias)Low riskPre-stipulated outcomes are reported.

Other biasHigh riskStudy was powered for discontinuation of treatment only. Not powered for any other outcomes.

Hu 2008

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 8 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (CCMD-3), first episode, PANSS ≥ 60.
N = 68.
Gender: 38 M, 30 F.
Age: mean age risperidone 30.25 years, mean quetiapine 28.96 years.
History: duration ill: mean risperidone 1.08 years, mean quetiapine 0.96 years.
Setting: not reported.


Interventions1. Risperidone: flexible dose. Allowed dose range: 3 - 6mg/day. Mean dose: 4.8mg/day. N = 33.

2. Quetiapine: flexible dose. Allowed dose range: 400 - 800mg/day. Mean dose: 672.5mg/day. N = 35.


OutcomesGlobal state.
Mental state: PANSS total, Postive, Negative, General subscore

Extrapyramidal side effects. ECG changes.

Adverse effects (at least one).

Unable to use -
Leaving the study early: due to specific reasons (not reported).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater blinded. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

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

Selective reporting (reporting bias)Unclear riskNot all pre-defined adverse effects were reported.

Other biasUnclear riskNo dropouts were reported. Funding source was not reported.

Kinon 2006b

MethodsAllocation: random, computer-generated randomisation.
Blindness: double, identical capsules.
Duration: 26 weeks.
Design: parallel.
Location: multicentre.


ParticipantsDiagnosis:) schizophrenia (DSM-IV), (n = 230), schizoaffective disorder (n = 116), prominent negative symptoms.
N = 346.
Gender: 228 M, 118 F.
Age: mean olanzapine 41.67 years, mean quetiapine 40.45 years.
History: duration ill: mean olanzapine 17.57 years, quetiapine 17.78 years. Age at onset: mean olanzapine 24.16 years, quetiapine 22.59 years.
Setting: outpatient.


Interventions1. Olanzapine flexible dose. Allowed dose range: 10 - 20 mg/day. Mean dose: 15.6 mg/day. N = 171.

2. Quetiapine flexible dose. Allowed dose range: 300 - 700 mg/day. Mean dose: 455.8 mg/day. N = 175.


OutcomesLeaving the study early: any reason, adverse events, inefficacy.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore, SANS total score.
General functioning: GAF.
Quality of life: QLS total score.
Adverse effects: Sedation, weight gain.

Unable to use -
Adverse effect: Leukopenia (no useable data), use of antiparkinson medication (no data).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom, computer-generated randomisation.

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, identical capsules. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was very high (54.9%). The last-observation-carried-forward method was used to account for people leaving the study early. It assumes that a participant who discontinued the study would not have had a change in his condition if he had remained in the study. This assumption obviously can be wrong.

Selective reporting (reporting bias)High riskThe numbers of participants who received antiparkinson medication or who had leukopaenia were not indicated.

Other biasHigh riskThe study was sponsored by the manufacturer of olanzapine.

Li 2005

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 12 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (CCMD-3) .
N = 67.
Gender: not reported.
Age: mean 26.18 years.
History: duration ill: mean clozapine 0.49 years, mean quetiapine 0.5 years. Age at onset not reported.
Setting: inpatient.


Interventions1. Clozapine: flexible dose. Allowed dose range: 100 - 550 mg/day. Mean dose: 255.96 mg/day. N = 34.

2. Quetiapine: flexible dose. Allowed dose range: 150 - 650 mg/day. Mean dose: 362.09 mg/day. N = 33.


OutcomesLeaving the study early: any reason.
Mental State: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Unable to use -
Extrapyramidal symptoms: no data.
Sedation: no data.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, no further details. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was 9.1%. Numbers leaving early were reported only for any reason. Only completer data were assessed.

Selective reporting (reporting bias)High riskNo reporting of adverse effects was provided.

Other biasUnclear riskBaseline characteristics have not been presented for both groups separately. Therefore, baseline imbalance cannot be excluded. Furthermore, no washout period was provided.

Li 2002

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 8 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia, (CCMD-3).
N = 63.
Gender: not reported.
Age: mean clozapine 30 years, mean quetiapine 28 years.
History: duration ill: mean clozapine 0.63 years, mean quetiapine 0.65 years. Age at onset not reported.
Setting: in- and outpatient.


Interventions1. Clozapine: flexible dose. Allowed dose range: 25 - 750 mg/day. Mean dose: 270.5 mg/day. N = 31.

2. Quetiapine: flexible dose. Allowed dose range: 25 - 750 mg/day. Mean dose: 478.5 mg/day. N = 32.


OutcomesLeaving the study early: any reason.
Global State: CGI.
Mental State: PANSS total score.
Adverse effects: cardiac effects (palpitation), EPS (akathisia, rigor, tremor), sedation, weight gain, laboratory (white blood cell count).

Unable to use -
Leaving the study early: due to adverse events (not fully reported).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, probably identical capsules. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskTwo participants left the study early as the result of adverse events in the clozapine group. Some doubt continues about whether all data on leaving the study early have been presented.

Selective reporting (reporting bias)Low riskWe did not find evidence of selective reporting.

Other biasUnclear riskNo data on pre-study medication were provided; therefore baseline imbalance cannot be excluded.

Li 2003

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 8 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia, (CCMD-2).
N = 76.
Gender: not reported.
Age: mean clozapine 36.2 years, mean quetiapine 34.7 years.
History: duration ill: mean clozapine 6.12 years, mean quetiapine 5.71 years. Age at onset not reported.
Setting: inpatient.


Interventions1. Clozapine: fixed/flexible dose: not reported.

Allowed dose range: start with 25 mg, after two weeks the target should be reached, but which dose this was was not reported. Mean dose: 325 mg/day. N = 38.

2. Quetiapine: fixed/flexible dose: not reported. Allowed dose range: start with 25 mg, after two weeks the target should be reached, but which dose this was was not reported. Mean dose: 375 mg/day. N = 38.


OutcomesGlobal state.
Leaving the study early.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.

Unable to use -
Leaving the study early: not fully reported.

Adverse events - treatment emergent symptom scale: not fully reported.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOne participant in the quetiapine group left the study early because of inefficacy. This participant was not included in the analysis. Some doubt continues about whether all data on leaving the study early have been presented.

Selective reporting (reporting bias)High riskThe study duration was eight weeks, but only outcomes at four weeks were available.

Other biasUnclear riskThe allowed dose range was not indicated.

Lieberman 2005

MethodsAllocation: random, no further details.
Blindness: double, identical capsules.
Duration: 78 weeks.
Design: parallel.
Location: multicentre.


ParticipantsDiagnosis: schizophrenia (DSM-IV), previously more than one schizophrenic episode, responder. N = 1493.
Gender: 1080 M, 380 F.
Age: 18 - 65 years (mean = 40.6 years).
History: duration ill not reported, age at onset not reported.
Setting: in- and outpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 7.5 - 30 mg/day, mean dose 20.1 mg/day. N = 336.

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

3. Quetiapine: flexible dose. Allowed dose range: 200 - 800 mg/day, mean dose 543.4 mg/day. N = 337.

4. Risperidone: flexible dose. Allowed dose range: 1.5 - 6.0 mg/day, mean dose 3.9 mg/day. N = 341.

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


OutcomesGlobal state: CGI-S.

Leaving the study early: any reason, adverse events, inefficacy.
Mental state: PANSS total score.
Service use: number of patients re-hospitalised.
Adverse effects: Death (suicide attempt), EPS (use of antiparkinson medication, akathisia), cardiac effects (ECG), prolactin-associated side-effects, sedation, weight gain, laboratory (prolactin, lipids, glucose).

Unable to use -
Leaving the study early: specific reason - data on patients leaving the study early specifically due to extrapyramidal effects were not reported.


Notes33 participants were excluded from the analysis.


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, identical capsules. Whether blinding was successful has not been examined, but the examined compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskThe attrition rate was very high (75%). Continuous outcomes were evaluated on the basis of a mixed-effects model. It is unclear whether any statistical method can account for such a high attrition rate.

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

Other biasUnclear riskDose ranges were very different; the upper dose range of olanzapine was 30 mg, whereas risperidone could be titrated only up to 6 mg/d. No washout period was provided. An overlap in the administration of formerly given antipsychotics was permitted for the first four weeks after randomisation.
Allocation to ziprasidone treatment was not possible from the start of the study because of later availability of ziprasidone.

Liu 2004

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 12 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia, (CCMD-3).
N = 72.
Gender: not reported.
Age: mean clozapine 37.44 years, mean quetiapine 36.86 years.
History: duration ill: mean clozapine 9.36 years, mean quetiapine 8.64 years. Age at onset not reported.
Setting: inpatient.


Interventions1. Clozapine: flexible dose. Allowed dose range: initial dose: 50 mg/day, after 10 days: 400 - 600 mg/day. Mean dose: not reported N = 36.

2. Quetiapine: flexible dose. Allowed dose range: initial dose: 100 mg/day, after 10 days: 400 - 700 mg/day. Mean dose: not reported, N = 36.


OutcomesLeaving the study early: adverse events, inefficacy.
Global state.
Mental state: BPRS total, SANS total.
Adverse effects: open interviews, cardiac effects (ECG) EPS (akathisia, tremor), sedation, dry mouth, hypersalivation, hypotonia, liver function, dizziness, hyperemesis, maldigestion, weight gain.

Unable to use -
Leaving the study early: due to any reason (not fully reported).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskFive participants left the study early: three because of adverse events in the clozapine group and two for unclear reasons in the quetiapine group. These five participants were not included in the analysis. Some doubt continues about whether all data on leaving the study early have been presented.

Selective reporting (reporting bias)High riskMean doses of the medications used were not indicated.

Other biasHigh riskClozapine was titrated to 400 mg/d within 10 days. Such a fast dose increase can be accompanied by a higher rate of adverse effects.

Lu 2006

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 6 months.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (CCMD-3) .
N = 96.
Gender: 53 M, 43 F.
Age: mean overall 30.2 years, mean risperidone and mean quetiapine age not reported.
History: duration ill: overall mean 12.6 months. Mean risperidone and mean quetiapine duration ill not reported. Age at onset: 27.8 years.
Setting: not reported.


Interventions1. Risperidone: flexible dose. Allowed dose range: 2 - 6mg/day. Mean dose: not reported N = 33.

2. Quetiapine: flexible dose. Allowed dose range: 50 - 100mg/day. Mean dose: not reported, N = 31.


OutcomesLeaving the study early: any reason.
Global State.
Mental State: PANSS Total, Postive, Negative, General subscore

Quality of Life Scale.

Unable to use -
Leaving the study early: due to specific reasons (not reported).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom, no further details.

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Unclear riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk96 participants were recruited, but data are available on only 64 participants. How these missing data were addressed statistically is not stated.

Selective reporting (reporting bias)Unclear riskMean doses of the medications used were not indicated.

Other biasUnclear riskQuetiapine dose range was below therapeutic range.

Luo Xin 2008

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 8 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (CCMD-3), first episode, PANSS of 60 or more.
N = 70.
Gender: 37 M, 33 F.
Age: mean aripiprazole 28.5 years, mean quetiapine 27.1 years.
History: duration ill: mean aripiprazole 1.2 years, mean quetiapine 1.2 years. Age at onset not reported.
Setting: inpatient.


Interventions1. Aripiprazole: flexible dose. Allowed dose range: initial dose: 5 mg/day, after 1 week: 10 - 25 mg/day. Mean dose: not reported N = 35.

2. Quetiapine: flexible dose. Allowed dose range: initial dose: 200 mg/day, after 1 week: 400 - 800 mg/day. Mean dose: not reported, N = 35.


OutcomesLeaving the study early: any reason.
Mental state: PANSS total score, positive subscore, negative subscore
Adverse effects: leaving the study early (any reason), number of participants with at least one adverse event, akathisia, tremor, weight gain.

Unable to use -
ECG changes, all other EPSE data besides akathisia and tremor, reasons for leaving study early.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo leaving early reported. This is unusual for this type of study.

Selective reporting (reporting bias)High riskPANSS scores and akathisia were the only outcomes reported. No other adverse events mentioned.

Other biasUnclear riskFunding source is unclear.

McEvoy 2006

MethodsAllocation: random, no further details.
Blindness: double, identical capsules.
Duration: 52 weeks (26 weeks observed, because of small group sizes).
Design: parallel.
Location: multicentre.


ParticipantsDiagnosis: schizophrenia (DSM-IV) , inadequate efficacy in previous study, clozapine treatment (n = 49) was open-label.
N = 99 (observed N = 50).
Gender: 80 M, 19 F.
Age: 18 - 65 years (mean 39.7 years).
History: duration ill not reported, age at onset not reported.
Setting: in- and outpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 7.5 - 30 mg/day. Mean dose: 23.4 mg/day. N = 19.

2. Quetiapine: flexible dose. Allowed dose range: 200 - 800 mg/day. Mean dose: 642.9 mg/day. N = 15.

3. Risperidone: flexible dose. Allowed dose range: 1.5 - 6 mg/day. Mean dose: 4.8 mg/day. N = 16.


OutcomesLeaving the study early: any reason, adverse events, inefficacy.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Adverse effects: open interviews, amenorrhoea, galactorrhoea, sexual dysfunction, sedation, laboratory (lipids, glucose, prolactin), weight gain.

Unable to use -
Global state: CGI (no data).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, identical capsules. Whether blinding was successful has not been examined, but the compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was extremely high (74%). We doubt that the validity of the findings was not affected by this high number.

Selective reporting (reporting bias)High riskBecause of small numbers and the very high attrition, only data on 26 weeks of treatment (rather than the full duration of 52 weeks) were presented.

Other biasUnclear riskThe dose ranges were very different, and the upper dose range of olanzapine was 30 mg/d, whereas risperidone could be given only in a maximum dose of 6 mg/d. Participants had a history of former inefficacy of one of the medications. It was excluded that the same medication could be given again, but still this might implicate a risk of bias due to baseline imbalance in terms of former treatment. No washout phase was provided.

McEvoy 2007

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 52 weeks.
Design: parallel.
Location: multicentre.


ParticipantsDiagnosis: schizophrenia (DSM-IV) (n = 231), schizophreniform disorder (n = 115) or schizoaffective disorder (n = 54), first episode, psychotic symptoms for 1 month to 5 years, PANSS psychosis and CGI-S score of 4 or more. N = 400.
Gender: 292 M, 108 F.
Age: 16 - 40 years (mean 24.5 years).
History: duration ill: mean 1.08 years. Age at onset 23.5 years.
Setting: in- and outpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 2.5 - 20 mg/day. Mean dose: 11.7 mg/day. N = 133.

2. Quetiapine: flexible dose. Allowed dose range: 100 - 800 mg/day. Mean dose: 506 mg/day. N = 134.

3. Risperidone: flexible dose. Allowed dose range: 0.5 - 4 mg/day. Mean dose: 2.4 mg/day. N = 133.


OutcomesLeaving the study early: any reason, adverse events, inefficacy.
Global State: CGI.
Mental State: PANSS total, PANSS positive subscore, PANSS negative subscore, depression Calgary depression scale.
Adverse effects: open interviews, death (suicide attempt, suicide, EPS (akathisia, akinesia, use of antiparkinson medication, laboratory (cholesterol, fasting glucose, prolactin), prolactin associated side effects (amenorrhoea, galactorrhoea, gynaecomastia, sexual dysfunction), sedation, weight gain.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, no further details. Whether blinding was successful has not been examined, but the compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was high (70.3%). The primary analysis was based on a mixed-effects model; secondary outcomes used the last-observation-carried forward approach and included only study completers. Nevertheless, it is unclear whether any statistical method can account for such high attrition.

Selective reporting (reporting bias)High riskAdverse events were presented only in cases of moderate or worse severity.

Other biasHigh riskThe study was sponsored by the manufacturer of quetiapine.

Mori 2004

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 8 weeks (last 4 weeks observed).
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia disorganised (DSM-IV, (n = 23), paranoid (n = 10), undifferentiated (n = 34). N = 77.
Gender: 39 M, 38 F.
Age: 28 - 84 years (mean = 59.9 years).
History: duration ill: mean 34.51 years. Age at onset: not reported.
Setting: inpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 2.5 - 20 mg/day. Mean dose: 16.5 mg/day. N = 20.

2. Perospirone: flexible dose. Allowed dose range: 4 - 48 mg/day. Mean dose: 37.3 mg/day. N = 18.

3. Quetiapine: flexible dose. Allowed dose range: 50 - 750 mg/day. Mean dose: 432.5 mg/day. N = 20.

4. Risperidone: flexible dose. Allowed dose range: 1 - 12 mg/day. Mean dose: 7.37 mg/day. N = 19.


OutcomesMental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Unable to use -
Cognitive functioning: composite data unavailable.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, no further details. Whether blinding was successful has not been examined, but the compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskData on leaving the study early have not been presented.

Selective reporting (reporting bias)High riskAdverse events were not reported. Numbers on use of antiparkinson medication have not been presented.

Other biasHigh riskNo washout period was provided. The previous antipsychotic treatment was gradually tapered over four weeks. Thus, during a period of 4 weeks, participants were taking two drugs.

Ozguven 2004

MethodsAllocation: random, no further details.
Blindness: single, no further details.
Duration: 6 weeks.
Design: parallel.
Location: not reported.


ParticipantsDiagnosis: schizophrenia (DSM-IV).
N = 30.
Gender: 8 M, 22 F.
Age: mean = 35.3 years.
History: duration ill not reported, age at onset not reported.
Setting: not reported.


Interventions1. Olanzapine: flexible dose. Allowed dose range: mean dose: 23.0 mg/day. N = 15.

2. Quetiapine: flexible dose. Allowed dose range: mean dose: 826.67 mg/day. N = 15.


OutcomesLeaving the study early: any reason, adverse events, inefficacy.
Global state: CGI.
Mental state: SAPS total score, SANS total score.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater blind. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe overall attrition rate was 13%. The method used to address incomplete outcomes has not been presented. Nevertheless, because of the low attrition rate, we consider the risk to be low.

Selective reporting (reporting bias)High riskThe study has been published only as an abstract. Efficacy data have been presented only as percentage change from baseline.

Other biasUnclear riskOnly female participants could be included, so a possible gender bias cannot be excluded.

Peng 2007

MethodsAllocation: random, no further details.
Blindness: single, rater blinded.
Duration: 8 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: first episode schizophrenia (CCMD-3), treatment naive. Duration of untreated psychosis <3 months.
N = 85.
Gender: 45 M, 40 F.
Age: aripiprazole 31.7 years, quetiapine 29.5 years.
History: duration ill: mean aripiprazole 0.23 years, mean quetiapine 0.23 years. Age at onset not reported.
Setting: inpatient.


Interventions1. Aripiprazole: flexible dose. Allowed dose range: 5 - 25 mg/day. Mean dose: not reported. N = 41.

2. Quetiapine: flexible dose. Allowed dose range: 100 - 600 mg/day. Mean dose: not reported. N = 44.


OutcomesLeaving the study early: any reason.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Adverse effects: akathisia, dystonia, parkinsonism, weight gain, cardiac effects (ECG changes).
Unable to use -
Adveres effects: extrapyramidal symptoms limited data on specific side effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater blinded. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskDropouts not reported.

Selective reporting (reporting bias)Unclear riskNumber on parkinsonian medication not reported.

Other biasUnclear riskFunding source unclear.

Potkin 2006

MethodsAllocation:random, no further details.
Blindness: double, identical capsules.
Duration: 6 weeks (2 weeks observed).
Design: parallel.
Location: multicentre.


ParticipantsDiagnosis: schizophrenia (DSM-IV), (n = 341) disorganised, paranoid or undifferentiated or schizoaffective disorder (n = 30) plus (n = 11), CGI-S of 5 or more, recent exacerbation.
N = 382.
Gender: 251 M, 131 F.
Age: 18 - 65 years (mean 34.8 years).
History: duration ill not reported, age at onset not reported.
Setting: inpatient.


Interventions1. Quetiapine: flexible dose. Allowed dose range: 50 - 800 mg/day. Mean dose: 523.8 mg/day (after 2 weeks), 579.5 mg/day (after 6 weeks). N = 156.

2. Risperidone: flexible dose. Allowed dose range: 1 - 6 mg/day. Mean dose: 4.32 mg/day (after 2 weeks), 4.7 mg/day (after 6 weeks). N = 153.

3. Placebo: N = 73*.


OutcomesLeaving the study early: any reason.
Global state: CGI.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore, Depression Hamilton Rating Scale for Depression, Readiness for Discharge Questionnaire.
Satisfaction of treatment: Study Medication Satisfaction.
Adverse effects: open interviews, death (natural cause), cardiac effects (ECG), EPS (akathisia, rigor, AIMS, SAS),
prolactin associated side effects (amenorrhoea, decreased libido), sedation, laboratory (prolactin).

Unable to use -
BAS: no data.
Cardiac effects: QTc-prolongation: no data.


Notes* data not analysed from placebo group.


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Low riskParticipants were assigned using a centralised interactive voice response system. Probably a correct method.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, identical capsules. Whether blinding was successful has not been examined, but both compounds differsubstantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall attrition was 12%. The last-observation-carried-forward method was used to account for people leaving the study early. It assumes that a participant who discontinued the study would not have had a change in his condition if he had remained in the study. This assumption obviously can be wrong. Nevertheless, because of the overall low attrition, it is unlikely that the results have been affected.

Selective reporting (reporting bias)High riskData on some adverse effects were not available. Side effects had to occur in at least 10% to be reported. Important side effects may have been missed by this procedure.

Other biasHigh riskThis study was sponsored by the manufacturer of risperidone.

Riedel 2005

MethodsAllocation: random, no further details.
Blindness: double, identical capsules.
Duration: 12 weeks.
Design: parallel.
Location: not reported.


ParticipantsDiagnosis: schizophrenia (DSM-IV or ICD-10), predominant negative symptoms, CGI of 4 or more, PANSS negative subscore of 21 or more.
N = 44.
Gender: 27 M, 17 F.
Age: mean quetiapine 30.6 years, mean risperidone 39.3 years.
History: duration ill: mean quetiapine 5.4 years, mean risperidone 2.5 years. Age at onset mean quetiapine 25.3 years, mean risperidone 36.9 years.
Setting: partially in- and outpatient.


Interventions1. Quetiapine: flexible dose. Allowed dose range: 50 - 800 mg/day, Mean dose: 589.7 mg/day. N = 22.

2. Risperidone: flexible dose. Allowed dose range: 2 - 8 mg/day. Mean dose: 4.9 mg/day. N = 22.


OutcomesLeaving the study early: any reason, adverse events, inefficacy.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore, SANS total score.
Adverse effects: open interviews, cardiac effects (ECG), EPS (akathisia, parkinsonism, use of antiparkinson medication, SAS), sedation, headache, nausea, insomnia, dizziness, weight gain, laboratory (prolactin).

Unable to use -
Adverse effects: SANS total score, prolactin change from baseline in ng/ml, cardiac effects (no data).

Cognitive functioning: composite data not available.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, identical capsules. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was considerable (45.2%). The data were analysed using last-observation-carried-forward and a completer analysis. Nevertheless, it is questionable whether any statistical method can account for such high attrition.

Selective reporting (reporting bias)High riskData on negative symptoms (SANS) and some adverse effects were not available.

Other biasHigh riskThe study was sponsored by the manufacturer of quetiapine.

Riedel 2007

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 8 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (DSM-IV), acute episode, CGI of more than 4, PANSS total score of more than 60.
N = 52.
Gender: 21 M, 12 F (of completers, here defined as those who completed cognitive assessments at two or more time points out of three (baseline, week 4, weeks 8)).
Age: 18 - 65 years (mean olanzapine 34.47 years, mean quetiapine 36.69 years, of completers).
History: duration ill: mean olanzapine 4.71 years, mean quetiapine 8.44 years (of completers). Age at onset mean olanzapine 29.76 years, mean quetiapine 28.25 years (of completers).
Setting: inpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 10 - 20 mg/day. Mean dose: 15.82 mg/day. N = 26.

2. Quetiapine: flexible dose. Allowed dose range: 400 - 800 mg/day. Mean dose: 586.86 mg/day. N = 26.


OutcomesLeaving the study early: any reason, adverse events.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Adverse effects: open interviews, UKU EPS (akathisia, use of antiparkinson medication, ESRS), sedation, headache, dizziness, obstipation, weight gain.

Unable to use -
Global state: no data.
BAS: no data.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, no further details. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was very high at 61.5%.The last-observation-carried-forward method was used to account for people leaving the study early. It assumes that a participant who discontinued the study would not have had a change in his condition if he had remained in the study. This assumptionobviously can be wrong.

Selective reporting (reporting bias)High riskData on global state have not been presented.

Other biasHigh riskThe study was sponsored by the manufacturer of olanzapine.

Sacchetti 2004

MethodsAllocation: random, no further details.
Blindness: single (rater-blinded).
Duration: 16 weeks (8 weeks observed).
Design: parallel.
Location: multicentre.


ParticipantsDiagnosis: schizophrenia (DSM-IV), PANSS total score ≥ 70, PANSS positive subscore ≥ 4 on at least 2 items.
N = 75.
Gender: not reported.
Age: 18 - 65 years.
History: duration ill not reported, age at onset not reported.
Setting: inpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 10 - 20 mg/day. Mean dose: 14.6 mg/day. N = 25.

2. Quetiapine: flexible dose. Allowed dose range: 400 - 800 mg/day. Mean dose: 602.4 mg/day. N = 25.

3. Risperidone: flexible dose. Allowed dose range: 4 - 8 mg/day. Mean dose: 4.3 mg/day. N = 25.


OutcomesLeaving the study early: any reason.
Mental State: BPRS hostility cluster score.
Adverse effects: EPS (BAS, SAS), weight gain.

Unable to use -
Mental State: PANSS total score, PANSS positive subscore, PANSS negative subscore (no usable data).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but the compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskSingle, rater-blind. Objective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe attrition rate was 18.6%. The last-observation-carried-forward method was used to account for people leaving the study early. It assumes that a participant who discontinued the study would not have had a change in his condition if he had remained in the study. This assumption obviously can be wrong.

Selective reporting (reporting bias)High riskEfficacy data (PANSS) were presented only as percentage change, without indications of standard deviations, standard errors, P values or ranges. Only interim data after half of the participants had been recruited have been presented.

Other biasHigh riskThe study was sponsored by the manufacturer of quetiapine.

Sirota 2006

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 12 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (DSM-IV), PANSS negative subscore > 15, SANS total score > 60.
N = 40.
Gender: 32 M, 8 F.
Age: 21 - 64 years (mean olanzapine 36.2 years, mean quetiapine 38.3 years).
History: duration ill: mean olanzapine 13.3 years, mean quetiapine 15.9 years. Age at onset not reported.
Setting: inpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 5 - 20 mg/day. Mean dose: 16.0 mg/day. N = 21.

2. Quetiapine: flexible dose. Allowed dose range: 200 - 800 mg/day. Mean dose: 637.2 mg/day. N = 19.


OutcomesLeaving the study early: any reason, adverse events, inefficacy.
Adverse effects: open interviews, cardiac effects (ECG), EPS (akathisia, parkinsonism, use of antiparkinson medication, SAS, AIMS, BAS), sedation, seizures, weight gain.

Unable to use -
Mental State: PANSS total score, negative symptoms SANS (median change).
EPS scales: no data.
Cardiac effects: no data.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall attrition was low (12%). The last-observation-carried-forward method was used to account for people leaving the study early. It assumes that a participant who discontinued the study would not have had a change in his condition if he had remained in the study. This assumption obviously can be wrong. Nevertheless, because of the low attrition, we do not think that this led to bias.

Selective reporting (reporting bias)High riskEfficacy data (PANSS, SANS) have been presented only as median change. No data on extrapyramidal side effects and cardiac effects were provided.

Other biasHigh riskThis study was sponsored by the manufacturer of quetiapine.

Song 2008

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 12 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (CCMD-3rd) , PANSS of 60 or more.
N = 66.
Gender: 31 M, 35 F.
Age: mean quetiapine 35.9 years, mean risperidone 36.7 years).
History: duration ill: mean quetiapine 9.4 years, mean risperidone 8.8 years. Age at onset not reported.
Setting: inpatient.


Interventions1. Risperidone: flexible dose. Initial dose 1mg/day titrated after 2 weeks to allowed dose range: 4 - 6 mg/day. Mean dose: not reported. N = 32.

2. Quetiapine: flexible dose. Initial dose 100mg/day titrated after 2 weeks to allowed dose range: 200 - 800 mg/day. Mean dose: not reported mg/day. N = 32.


OutcomesMental state: PANSS total score, positive subscore, negative subscore.

WHO Quality of Life Scale
Adverse effects: EPS (TESS).

Unable to use -
Mental State:
EPS scales: no data except regarding tremor.
Cardiac effects and weight gain: no data.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but the compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo dropouts were reported. This is unusual for this type of study.

Selective reporting (reporting bias)Unclear riskNot all stipulated outcome measures were reported, including adverse events, weight and ECG changes.

Other biasHigh riskWhether informed consent was obtained is unclear, and the funding source was not stated.

Stroup 2006

MethodsAllocation: random, 2 steps of randomisation before and after availability of ziprasidone, subjects received other medication than in previous phase 1 treatment. Re-randomised.
Blindness: double, identical capsules.
Duration: 26 weeks.
Design: parallel.
Location: not reported.


ParticipantsDiagnosis: chronic schizophrenia, (DSM-IV).
N = 444.
Gender: 308 M, 136 F.
Age: 18 - 65 years (mean olanzapine 40.0 years, mean quetiapine 40.1 years, mean risperidone 41.8 years, mean ziprasidone 41.3 years).
History: duration ill not reported, age at onset not reported.
Setting: in- and outpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 7.5 - 30 mg/day, mean dose = 20.5 mg/day. N = 108.

2. Quetiapine: flexible dose. Allowed dose range: 200 - 800 mg/day, mean dose = 565.2 mg/day. N = 95.

3. Risperidone: flexible dose. Allowed dose range: 1.5 - 6.0 mg/day, mean dose = 4.1 mg/day. N = 104.

4. Ziprasidone: flexible dose. Allowed dose range: 40 - 160 mg/day, mean dose = 115.9 mg/day. N = 137.


OutcomesLeaving the study early: any reason, adverse events, inefficacy.
Global state: CGI.
Mental state: PANSS total score.
Adverse effects: death (suicide), EPS (akathisia), cardiac effects (ECG), prolactin-associated side effects, weight gain, laboratory results (prolactin, glucose, cholesterol).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandom; two steps of randomisation before and after availability of ziprasidone; subjects received other medication than in previous phase 1 treatment. Re-randomised.

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, identical capsules. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskThe attrition rate was very high (72.5%). Continuous data were analysed on the basis of mixed-effects models. It is unclear whether any statistical method can account for such high rates of leaving the study early.

Selective reporting (reporting bias)High riskUse of antiparkinson medication was permitted, but data on this outcome have not been presented.

Other biasUnclear riskParticipants had a history of former intolerance to atypical antipsychotic treatment, but baseline data on this were not provided.

Svestka 2003b

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 6 weeks.
Design: parallel.
Location: not reported.


ParticipantsDiagnosis: acute schizophrenia, (ICD-10), (n = 32), schizoaffective disorder (n = 10).
N = 42.
Gender: 42 F.
Age: mean 35.78 years.
History: duration ill: mean 7.05 years. Age at onset not reported.
Setting: inpatient.


Interventions1. Olanzapine: flexible dose. Allowed dose range: 10 - 20 mg/day. Mean dose: 19.5 mg/day. N = 20.

2. Quetiapine: flexible dose. Allowed dose range: 50 - 700 mg/day. Mean dose: 677.3 mg/day. N = 22.


OutcomesLeaving the study early: inefficacy.
Global state: CGI.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Adverse effects: Cardiac effects (QTc), EPS (akathisia, dystonia, extrapyramidal symptoms, tremor), weight gain, laboratory (prolactin)

Unable to use -
Cholesterol: no data.
Glucose: no data.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, no further details. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskData on the overall attrition rate were not available.

Selective reporting (reporting bias)High riskFor some metabolic parameters, no data were available.

Other biasUnclear riskA slight baseline imbalance in mean age was described as non-significant.

Voruganti 2007

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 52 weeks.
Design: parallel.
Location: not reported.


ParticipantsDiagnosis: schizophrenia.
N = 86.
Gender: not reported.
Age: not reported.
History: duration ill not reported, age at onset not reported.
Setting: not reported.


Interventions1. Olanzapine: fixed/flexible dose: not reported Allowed dose range: not reported. Mean dose: 17.2 mg/day. N = 42.

2. Quetiapine: fixed/flexible dose. Allowed dose range: not reported. Mean dose: 612.8 mg/day. N = 43.


OutcomesMental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
General functioning: GAF.
Adverse effects: EPS (SAS, AIMS, BAS), weight gain, number of dysglycaemic individuals.

Unable to use

Cognitive functioning: composite score not available.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskA discrepancy has been noted between the abstract and the text. According to the abstract, fewer participants left the study early; however, this finding was no longer mentioned in the text, according to which the overall attrition was only 1.2%.

Selective reporting (reporting bias)High riskUse of antiparkinson medication was permitted, but the numbers have not been presented.

Other biasHigh riskThe study was sponsored by the manufacturer of quetiapine.No washout period was provided.

Wang 2006

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.
Duration: 8 weeks.
Design: parallel.
Location: single site.


ParticipantsDiagnosis: schizophrenia (CCMD- 3rd), PANSS of 60 or more.
N = 60.
Gender: 27 M, 33 F.
Age: mean quetiapine 31.8 years, mean risperidone 32.1 years
History: duration ill not reported. Age at onset not reported.
Setting: not reported.


Interventions1. Risperidone: Flexible dose: 0.5 - 1mg/day, titrated up to allowed dose range of 4 - 6mg after one week. Mean dose: not reported. N = 30.

2. Quetiapine: Flexible dose: 50 - 100mg/day, titrated up to allowed dose range of 400 - 600mg/day. Mean dose: not reported. N = 30.


OutcomesMental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Adverse effects: EPS, tachycardia, weight gain.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number table.

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater-blind. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

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

Selective reporting (reporting bias)Unclear riskECG changes not reported.

Other biasUnclear riskFunding source is unclear. Ethics approval and informed consent not stated.

Wei 2006a

MethodsAllocation: random, no further details.
Blindness: single, rater blinded.
Duration: 6 months.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (CCMD-3rd), first-episode, treatment naive, PANSS of 60 or more.
N = 58.
Gender: 23 M, 35 F.
Age: 18 - 60 years.
History: duration ill: mean quetiapine 37.44 months, mean risperidone = 37.8 months. Age at onset: (mean quetiapine 28.32 years, mean risperidone 29.04 years).
Setting: in- and outpatient, initially inpatient.


Interventions1. Quetiapine:flexible dose. Allowed dose range: 200 - 800 mg/day. Mean dose: 525 mg/day. N = 338.

2. Risperidone: flexible dose. Allowed dose range: 2 - 8 mg/day. Mean dose: 5.2 mg/day. N = 335.


OutcomesLeaving the study early: any reason, adverse events, inefficacy
Global state: CGI.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Adverse effects: cardiac effects (QTc), death (natural causes, suicide), EPS (akathisia, dystonia, parkinsonism, use of antiparkinson medication, AIMS, BAS, SAS), sedation, prolactin-associated side effects (dysmenorrhoea, galactorrhoea, sexual dysfunction) weight gain, laboratory results (cholesterol, glucose, prolactin, white blood cell count).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskSingle, rater blinded.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk12.1% attrition. How this attrition was accounted for statistically is unclear.

Selective reporting (reporting bias)High riskUse of antiparkinson medication was permitted, but numbers have not been presented. Adverse events not described.

Other biasUnclear riskEthics approval unclear.

Wei 2006b

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 8 weeks.
Design: parallel.
Location: single centre.


ParticipantsDiagnosis: schizophrenia (CCMD-3), PANSS ≥ 60. CGI ≥ 4.
N = 108.
Gender: all female.
Age: 18 - 60 years.
History: duration ill: mean aripiprazole 15.33 months, mean quetiapine 14.16 months. Age at onset not reported.
Setting: inpatient.


Interventions1. Aripiprazole: flexible dose. Allowed dose range: 5 - 20 mg/day. Mean dose: not reported. N = 50.

2. Quetiapine: flexible dose. Allowed dose range: 100 - 400 mg/day. Mean dose: Not reported. N = 51.


OutcomesLeaving the study early: any reason.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.

Adverse effects: at least one adverse events (any reason).

Unable to use
Adverse effects: extrapyramidal symptoms: no data.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskNo further details. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Unclear riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskSeven participants left the study early s the result of adverse events (4 in quetiapine group and 3 in aripiprazole group). Intention-to-treat analysis not done.

Selective reporting (reporting bias)High riskPANSS positive and negative scores only reported. Details on adverse events not provided

Other biasUnclear riskNo data on pre-study medication; therefore, baseline imbalance cannot be excluded. Funding source unclear.

Zhong 2006

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 8 weeks.
Design: parallel.
Location: multicentre.


ParticipantsDiagnosis: schizophrenia (DSM-IV), PANSS ≥ 60, CGI-S ≥ 4
N = 673.
Gender: 510 M, 163 F.
Age: 18 - 65 years (mean quetiapine 40.2 years, mean risperidone 39.6 years).
History: duration ill not reported, age at onset not reported.
Setting: in- and outpatient, initially inpatient.


Interventions1. Quetiapine:flexible dose. Allowed dose range: 200 - 800 mg/day. Mean dose: 525 mg/day. N = 338.

2. Risperidone: flexible dose. Allowed dose range: 2 - 8 mg/day. Mean dose: 5.2 mg/day. N = 335.


OutcomesGlobal state: CGI.

Leaving the study early: any reason, adverse events, inefficacy
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore.
Adverse effects: cardiac effects (QTc), death (natural causes, suicide), EPS (akathisia, dystonia, parkinsonism, use of antiparkinson medication, AIMS, BAS, SAS), sedation, prolactin-associated side effects (dysmenorrhoea, galactorrhoea, sexual dysfunction), weight gain, laboratory results (cholesterol, glucose, prolactin, white blood cell count).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

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

Allocation concealment (selection bias)Unclear riskNo further details.

Blinding (performance bias and detection bias)
Subjective outcomes
Unclear riskDouble, no further details. Whether blinding was successful has not been examined, but both compounds differ substantially in terms of side effects. This can be a problem for blinding.

Blinding (performance bias and detection bias)
Objective outcomes
Low riskObjective outcomes such as laboratory measures or death are unlikely to have been much affected by problems of blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall attrition was high (52.1%). The last-observation-carried-forward method was used to account for people leaving the study early. It assumes that a participant who discontinued the study would not have had a change in his condition if he had remained in the study. This assumption obviously can be wrong. Data on study completers were also available. Nevertheless, it is unclear whether any statistical method can account for such a degree of attrition.

Selective reporting (reporting bias)High riskAdverse events were presented only with an incidence of at least 5% among participants; therefore, important side effects may have been missed by this procedure.

Other biasHigh riskThe study was sponsored by the manufacturer of quetiapine.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

An 2003Allocation: randomised.
Blindness: open-label.

An 2006Allocation: randomised.
Blindness: open-label.

An 2006aAllocation: not randomised.

Antonova 2005Allocation: randomised.
Blindness: single-blind (rater-blind).
Participants: people with schizophrenia.
Interventions: olanzapine, risperidone and quetiapine versus conventional antipsychotics.
Outcomes: no usable data.

Arango 2009Allocation: randomised.
Blindness: open-label.

Ascher-Svanum 2006Allocation: not randomised, cohort study.

Baloescu 2006Allocation: not randomised, controlled clinical trial.

Ban 2008Allocation: randomised.

Blindness: not reported.

Beuzen 2005Allocation: randomised.
Blindness: open-label.

Boter 2005Allocation: randomised.
Blindness: open-label.

Brecher 2007Allocation: randomised.
Blindness: open-label.

Byerly 1999Allocation: not reported.
Blindness: not reported.
Participants: people with schizophrenia.
Interventions: clozapine versus quetiapine.
Outcomes: no usable data.

Byerly 2006Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus risperidone.
Outcomes: no usable data.

Cai 2005Allocation: randomised.
Blindness: open-label.

Canas 2006Allocation: not randomised, controlled clinical trial.

Cao 2005Allocation: randomised.
Blindness: open-label.

Cao 2005 aAllocation: randomised.
Blindness: open-label.

Cao 2006aAllocation: randomised.
Blindness: open-label.

Cao 2006dAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus chlorpramazine.

Chang 2007Allocation: randomised.
Blindness: open-label.

Chang 2008Allocation: randomised.

Blindness: not reported.

Chaudhry 2006Allocation: randomised.
Blindness: open-label.

Chen 2006aAllocation: randomised.
Blindness: open-label

Chen 2006kAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus perphenazine.

Chen 2007aAllocation: randomised.
Blindness: open-label.

Chen 2007bAllocation: randomised.
Blindness: open-label.

Chen 2007cAllocation: randomised.

Blindness: not reported.

Chen 2008Allocation: randomised.

Blindness: not reported.

Chu 2006Allocation: not randomised.

Cortese 2008Allocation: randomised.
Blindness: open-label.

Dai 2004Allocation: randomised.
Blindness: open-label.

Dai 2005Allocation: randomised.
Blindness: open-label.

Dai 2008Allocation: not randomised.

Davies 2007Allocation: randomised.
Blindness: single-blind (rater-blind).
Participants: people with schizophrenia.
Interventions: clozapine versus second generation antipsychotics.
Outcomes: no usable data.

Ding 2004Allocation: randomised.
Blindness: open-label.

Dong 2008Allocation: not randomised.

Dossenbach 2005Allocation: not randomised, cohort study.

Du 2003Allocation: randomised.
Blindness: open-label.

Emsley 2005Allocation: randomised.
Blindness: investigator-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus haloperidol.

Fan 2005Allocation: randomised.
Blindness: open-label.

Fan 2008Allocation: not randomised.

Fleischhacker 2005Allocation: randomised.
Blindness: open-label.

Fu 2005Allocation: randomised.
Blindness: open-label.

Fu 2005aAllocation: randomised.
Blindness: open-label.

Gao 2003Allocation: randomised.
Blindness: open-label.

García 2006Allocation: not randomised, case series.

Guo 2008Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus chlorpramazine.

Hao 2007Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: Imported quetiapine vs domestic quetiapine.

Harrigan 2004Allocation: randomised.
Blindness: open-label.

He 2003Allocation: randomised.
Blindness: open-label.

Horacek 2004Allocation: randomised.
Blindness: open-label.

Huang 2003Allocation: randomised.
Blindness: open-label.

Huang 2006Allocation: not randomised.

Huber 2004Allocation: not randomised.
Blindness: open label.

Jiang 2006Allocation: randomised.

Blindness: not reported.

Karow 2002Allocation: not randomised, review.

Keks 2006Allocation: randomised.
Blindness: open-label.

Kelemen 2006Allocation: not randomised, controlled clinical trial.

Kim 2004Allocation: not randomised, controlled clinical trial.

Knegtering 2004Allocation: randomised.
Blindness: open-label.

Kolotkin 2008Allocation: randomised.
Blindness: open-label.

Koponen 2008Allocation: randomised.
Blindness: open-label.

Kuang 2007Allocation: non-randomised.

L'Italien 2007Allocation: randomised.
Blindness: open-label

Lan 2006Allocation: non-randomised.

Li 2001Allocation: randomised.
Blindness: open-label.

Li 2002aAllocation: not randomised.

Li 2003aAllocation: randomised.
Blindness: open-label.

Li 2003bAllocation: randomised.
Blindness: open-label.

Li 2005aAllocation: randomised.
Blindness: open-label.

Li 2005bAllocation: randomised.
Blindness: open-label.

Li 2007aAllocation: randomised.
Blindness: open-label.

Li 2007hAllocation: randomised.
Blindness: open-label.

Li 2008aAllocation: randomised.
Blindness: open-label.

Li 2008bAllocation: not randomised.

Li 2008cAllocation: randomised.
Blindness: open-label.

Li 2008dAllocation: randomised.
Blindness: open-label.

Liang 2008Allocation: not randomised.

Lin 2005Allocation: randomised.
Blindness: open-label.

Lin 2007Allocation: randomised.

Blindness: not reported.

Liu 2003Allocation: randomised.
Blindness: open-label.

Liu 2003aAllocation: randomised.
Blindness: open-label.

Liu 2004aAllocation: randomised.
Blindness: open-label.

Liu 2004bAllocation: randomised.
Blindness: open-label.

Liu 2005Allocation: randomised.
Blindness: open-label.

Liu 2005aAllocation: randomised.
Blindness: open-label.

Liu 2006Allocation: randomised.
Blindness: open-label.

Liu 2007Allocation: not randomised.

Liu 2008Allocation: not randomised.

Lu 2005Allocation: randomised.
Blindness: open-label.

Luo 2005Allocation: randomised.
Blindness: open-label.

Lv 2008Allocation: randomised.
Blindness: open-label.

Mei 2006Allocation: not randomised.

Mintzer 2004Allocation: randomised.
Blindness: open-label.

Mullen 2001Allocation: randomised.
Blindness: open-label

Musil 2006Allocation: not randomised, cohort study.

Nai 2007Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus chlorpramazine.

Pan 2004Allocation: randomised.
Blindness: open-label.

Pan 2004aAllocation: randomised.
Blindness: open-label.

Pan 2004bAllocation: randomised.
Blindness: open-label.

Pan 2008Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: ziprasidone versus chlorpromazine.

Pang 2002Allocation: randomised.
Blindness: open-label.

Peng 2004Allocation: randomised.
Blindness: not mentioned.
Participants: people with schizophrenia.
Interventions: quetiapine versus chlorpramazine.

Petty 2005Allocation: randomised.
Blindness: open-label.

Pfizer 2005Allocation: randomised.
Blindness: open-label.

Qi 2004Allocation: randomised.
Blindness: open-label.

Qian 2004Allocation: randomised.
Blindness: open-label.

Reznik 2004Allocation: randomised.
Blindness: open-label.

Riera 2004Allocation: randomised.
Blindness: open-label.

Ruan 2005Allocation: randomised.
Blindness: open-label.

Ryu 2006Allocation: not randomised, controlled clinical trial.

Sajatovic 2002Allocation: randomised.
Blindness: open-label.

Sarma 2008aAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: lurasidone versus quetiapine.

Outcomes: no usable data.

Sheng 2006Allocation: not randomised.

Song 2006Allocation: randomised.
Blindness: open-label.

Song 2008aAllocation: not randomised, controlled clinical trial.

Song 2008bAllocation: not randomised, controlled clinical trial.

Sun 2006aAllocation: not randomised.

Sun 2006eAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus chlorpromazine.

Sun 2007aAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: ziprasidone versus risperidone.

Sun 2007bAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus perphenazine.

Sun 2007cAllocation: not randomised.

Sun 2008Allocation: not randomised.

Swadi 2010Allocation: randomised.
Blindness: outcome assessors blinded.
Participants: first episode mood and psychotic disorder.

Swanson 2006Allocation: randomised.
Blindness: open-label.

Tang 2003Allocation: randomised.
Blindness: open-label.

Tang 2005Allocation: randomised.
Blindness: open-label.

Tao 2008Allocation: non-randomised.

Tian 2006Allocation: randomised.
Blindness: open-label.

Tian 2007Allocation: not randomised.

Tian 2008Allocation: not randomised.

Wang 2000Allocation: randomised.
Blindness: open-label.

Wang 2004Allocation: randomised.
Blindness: open-label.

Wang 2004aAllocation: not randomised.

Wang 2005Allocation: randomised.
Blindness: open-label.

Wang 2005aAllocation: randomised.
Blindness: open-label.

Wang 2005bAllocation: randomised.
Blindness: open-label.

Wang 2005cAllocation: randomised.
Blindness: open-label.

Wang 2005dAllocation: randomised.
Blindness: open-label.

Wang 2006aAllocation: not randomised.

Wang 2006bAllocation: randomised.
Blindness: open-label.

Wang 2007Allocation: not randomised.

Wang 2007aAllocation: not randomised.

Wang 2007bAllocation: not randomised.

Wang 2008Allocation: not randomised.

Wang 2008aAllocation: not randomised.

Wang 2008bAllocation: not randomised.

Wang 2008cAllocation: not randomised.

Wei 2006Allocation: randomised.
Blindness: open-label.

Wei 2006cAllocation: not randomised (sequential allocation).
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus clozapine.

Weickert 2003Allocation: randomised.
Participants: people with schizophrenia.
Interventions: Within-subject comparison of placebo versus atypical antipsychotics.

Wen 2005Allocation: randomised.
Blindness: open-label.

Wu 2005Allocation: randomised.
Blindness: open-label.

Xiang 2005Allocation: randomised.
Blindness: open-label.

Xu 2002Allocation: randomised.
Blindness: open-label.

Xu 2003Allocation: randomised.
Blindness: open-label.

Xu 2005Allocation: randomised.
Blindness: open-label.

Xu 2006Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus chlorpromazine.

Yamashita 2005Allocation: not randomised, case series.

Yang 2004Allocation: randomised.
Blindness: open-label.

Yang 2005Allocation: randomised.
Blindness: open-label.

Yang 2005aAllocation: randomised.
Blindness: open-label.

Yang 2006Allocation: randomised.
Blindness: open-label.

Yang 2006aAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus haloperidol.

Yang 2006bAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus haloperidol.

Yang 2007Allocation: not randomised.

Yang 2007aAllocation: not randomised.

Yu 2003Allocation: randomised.
Blindness: open-label.

Yu 2005Allocation: randomised.
Blindness: open-label.

Yu 2006Allocation: randomised.
Blindness: open-label.

Yuan 2005Allocation: randomised.
Blindness: open-label.

Zeng 2006Allocation: not randomised.

Zhang 2003Allocation: randomised.
Blindness: open-label.

Zhang 2005Allocation: randomised.
Blindness: open-label.

Zhang 2005aAllocation: randomised.
Blindness: open-label.

Zhang 2005bAllocation: randomised.
Blindness: open-label.

Zhang 2005cAllocation: randomised.
Blindness: open-label.

Zhang 2005dAllocation: randomised.
Blindness: open-label.

Zhang 2006Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus chlorpromazine

Zhang 2006aAllocation: randomised.
Blindness: open-label.

Zhang 2007Allocation: not randomised.

Zhang 2007aAllocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus chlorpromazine.

Zhang 2009bAllocation: randomised.

Blinding: participant blinded.

Intervention: quetiapine versus haloperidol.

Zhao 2004Allocation: randomised.
Blindness: open-label.

Zhao 2005Allocation: randomised.
Blindness: open-label.

Zhao 2005aAllocation: randomised.
Blindness: open-label.

Zhao 2007Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus sulpiride.

Zheng 2007Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine + clozapine vs quetiapine alone.

Zhong 2006aAllocation: randomised.
Blindness: open-label.

Zhou 2003Allocation: randomised.
Blindness: open-label.

Zhou 2003aAllocation: randomised.
Blindness: open-label.

Zhou 2006Allocation: randomised.
Blindness: double-blind.
Participants: people with schizophrenia.
Interventions: quetiapine versus sulpiride.

Zhou 2007Allocation: not randomised.

Zhu 2006Allocation: not randomised.

Zhu 2008Allocation: not randomised.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Gafoor 2005

MethodsAllocation: randomised.

ParticipantsDiagnosis: schizophrenia.

Interventions1. Quetiapine.

2. Risperidone.

OutcomesLeaving the study early: any reason, adverse events, inefficacy.
Mental state: PANSS total score, PANSS positive subscore, PANSS negative subscore, SANS total score, depression (Calgary Depression Scale).
General functioning: GAF.
Quality of life: QLS total score.
Adverse effects: sedation, libidinal dysfunction, BMI change, weight gain.

NotesNot all participants accounted for in intention-to-treat analysis.

 
Characteristics of ongoing studies [ordered by study ID]
Eli Lilly 2004b

Trial name or titleTrial 8894
F1D-US-HGLR.

MethodsAllocation: random, no further details.
Blindness: double, no further details.
Duration: 26 weeks.
Design: parallel.
Location: not reported.

ParticipantsDiagnosis: schizophrenia or schizoaffective disorder.
N = not reported.
Gender: not reported.
Age: 18 - 75 years.
History: duration ill not reported, age at onset not reported.
Setting: not reported.

Interventions1. Olanzapine: flexible dose. Allowed dose range: 7.5-20 mg/day, mean dose: not reported. N = not reported.

2. Quetiapine: flexible dose. Allowed dose range: 300-800 mg/day, mean dose: not reported, N = not reported.

OutcomesGlobal state: CGI, PG-I, response to treatment.

Leaving the study early: any reason, lack of efficacy or worsening of psychiatric syndromes.
Mental state: PANSS, depression, MADRS.
General functioning: DAI-10, GAF.
Quality of life: SF-36.
Adverse effects: EPS (SAS, BAS, AIMS), vital signs, weight (waist circumference, BMI, appetite, metabolic syndrome), laboratory results (fasting glucose, haemoglobin A1c, lipids, insulin).

Starting dateJuly 2004.

Contact informationEli Lilly and Company.

Notes

Li 2009b

Trial name or titleStudy NCT00817648: A Study to Evaluate the Efficacy and Safety of Seroquel in Chinese Han Patients With Schizophrenia.

MethodsAllocation: random, no further details.
Blindness: Single, rater-blinded.

ParticipantsOutpatients or inpatients with schizophrenia from the Chinese Han race.

InterventionsQuetiapine 600 to 750 mg/d, risperidone 3 to 6 mg/d.

OutcomesGlobal state: CGI.

Mental state: change in PANSS total score, depression (CDSS).
Adverse effects: EPSE (AIMS, SAS).

Starting dateDecember 2008.

Contact informationHuafang LI, MD, PhD, 86-21-64387250 ext 3128, lhlh5@yahoo.com.cn

Yan LI, MD, 86-21-64387250 ext 3122, liyan7721@yeah.net

Notes

Ratna 2003

Trial name or titleImproved Response in Schizophrenia IRIS.

MethodsAllocation: random, no further details.
Blindness: double, no further details.

ParticipantsDiagnosis: schizophrenia.

Interventions1. Quetiapine: dose: not reported.

2. Risperidone: dose: not reported.

OutcomesGlobal state: CGI-S.
Mental state: PANSS, GAS, HAM-D scores.
Quality of life SQLS and care-giving inventory scores.
Health economics.
Adverse effects: EPS (AIMS, SAS, BAS).

Starting date1 October 2002

Contact informationDr Lawrence Ratna
Barnet Hospital
Wellhouse Lane
Barnet
EN5 3DJ
UK
Telephone: 020 8216 4617
Fax: 020 8216 4595

Notes

Reynolds 2001

Trial name or titleA Six-Month, Rater-Blind Comparison of Quetiapine and Risperidone in the Treatment of Tardive Dyskinesia in People With Schizophrenia.

MethodsAllocation: random, no further details.
Blindness: single, rater-blinded.

ParticipantsDiagnosis: schizophrenia.
N = 30.

Interventions1. Quetiapine: dose: not reported.

2. Risperidone: dose not reported.

OutcomesNot known.

Starting dateNot known.

Contact informationNot known.

Notes

 
Comparison 1. QUETIAPINE versus ARIPIPRAZOLE

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

 1 Leaving the study early2149Risk Ratio (M-H, Random, 95% CI)1.00 [0.59, 1.70]

    1.1 any reason
2149Risk Ratio (M-H, Random, 95% CI)1.00 [0.59, 1.70]

 2 Mental state: 1. General - average endpoint score (PANSS total, high=poor)4297Mean Difference (IV, Random, 95% CI)1.62 [-0.89, 4.14]

    2.1 short term
4297Mean Difference (IV, Random, 95% CI)1.62 [-0.89, 4.14]

 3 Mental state: 2. Positive symptoms - average endpoint score (PANSS positive subscore, high=poor)4297Mean Difference (IV, Random, 95% CI)0.62 [-1.13, 2.38]

    3.1 short term
4297Mean Difference (IV, Random, 95% CI)0.62 [-1.13, 2.38]

 4 Mental state: 3. Negative symptoms - average endpoint score (PANSS negative subscore, high=poor)4297Mean Difference (IV, Random, 95% CI)1.00 [-0.25, 2.25]

    4.1 short term
4297Mean Difference (IV, Random, 95% CI)1.00 [-0.25, 2.25]

 5 General functioning: General - average endpoint score - medium term (GAF total score, high=poor141Mean Difference (IV, Random, 95% CI)-1.20 [-14.43, 12.03]

 6 Adverse effects: 1. General - at least one adverse effect3215Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.71, 1.17]

 7 Adverse effects: 2a. Cardiac effects - QTc prolongation185Risk Ratio (M-H, Random, 95% CI)3.21 [0.13, 76.74]

 8 Adverse effects: 2b. Cardiac effects - Tachycardia185Risk Ratio (M-H, Random, 95% CI)7.50 [0.40, 140.91]

 9 Adverse effects: 3a. Extrapyramidal effects3599Risk Ratio (M-H, Random, 95% CI)0.90 [0.45, 1.82]

    9.1 akathisia
3196Risk Ratio (M-H, Random, 95% CI)0.57 [0.08, 4.02]

    9.2 dyskinesia
141Risk Ratio (M-H, Random, 95% CI)3.14 [0.14, 72.92]

    9.3 dystonia
2126Risk Ratio (M-H, Random, 95% CI)1.42 [0.10, 20.77]

    9.4 parkinsonism
141Risk Ratio (M-H, Random, 95% CI)0.75 [0.28, 1.98]

    9.5 tremor
2155Risk Ratio (M-H, Random, 95% CI)1.68 [0.08, 35.92]

    9.6 use of antiparkinson medication
140Risk Ratio (M-H, Random, 95% CI)0.67 [0.12, 3.57]

 10 Adverse effects: 4a. Prolactin associated side effects185Risk Ratio (M-H, Random, 95% CI)3.21 [0.13, 76.74]

    10.1 galactorrhea
185Risk Ratio (M-H, Random, 95% CI)3.21 [0.13, 76.74]

 11 Adverse effects: 5a. Metabolic - weight gain of 7% or more of total body weight2155Risk Ratio (M-H, Random, 95% CI)0.52 [0.10, 2.74]

 12 Adverse effects. 5b. Metabolic - weight gain - change from baseline in kg141Mean Difference (IV, Random, 95% CI)1.7 [-0.14, 3.54]

 13 Adverse effects: 5c. Metabolic - cholesterol - change from baseline in mg/dl141Mean Difference (IV, Random, 95% CI)8.2 [-12.24, 28.64]

 14 Adverse effects: 5d. Metabolic - glucose - change from baseline in mg/dl141Mean Difference (IV, Random, 95% CI)-9.4 [-17.90, -0.90]

 15 Adverse effects: 6. Death  174Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    15.1 natural causes
137Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    15.2 suicide
137Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. QUETIAPINE versus CLOZAPINE - all data short term

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

 1 Leaving the study early3Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 any reason
295Risk Ratio (M-H, Random, 95% CI)0.67 [0.18, 2.43]

    1.2 due to adverse events
172Risk Ratio (M-H, Random, 95% CI)0.14 [0.01, 2.67]

    1.3 due to inefficacy
172Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 2 Global state: 1a. No clinically significant response (as defined by original studies)172Risk Ratio (M-H, Random, 95% CI)0.94 [0.78, 1.13]

 3 Global state: 1b. No clinically important change - short term (as measured by CGI)176Risk Ratio (M-H, Random, 95% CI)0.94 [0.74, 1.18]

 4 Mental state: 1a. General - no clinically important change - short term (less than 50% PANSS total score reduction)163Risk Ratio (M-H, Random, 95% CI)1.07 [0.53, 2.14]

 5 Mental state: 1b. General - average endpoint score - short term (PANSS total, high=poor)4232Mean Difference (IV, Random, 95% CI)-0.50 [-2.85, 1.86]

 6 Mental state: 1c. General - average endpoint score - short term (BPRS total, high=poor)167Mean Difference (IV, Random, 95% CI)-0.89 [-3.20, 1.42]

 7 Mental state: 2. Positive symptoms - average endpoint score (PANSS positive subscore, high=poor)2142Mean Difference (IV, Random, 95% CI)-0.70 [-2.07, 0.68]

 8 Mental state: 3a. Negative symptoms - average endpoint score - short term (PANSS negative subscore, high=poor)2142Mean Difference (IV, Random, 95% CI)-2.23 [-3.48, -0.99]

 9 Mental state: 3b. Negative symptoms - no clinically important change - short term (less than 50% SANS total score reduction)172Risk Ratio (M-H, Random, 95% CI)0.94 [0.78, 1.13]

 10 Mental state: 3c. Negative symptoms - average endpoint score - short term (SANS total, high=poor)167Mean Difference (IV, Random, 95% CI)-1.64 [-8.17, 4.89]

 11 Adverse effects: 1. General - at least one adverse effect163Risk Ratio (M-H, Random, 95% CI)0.42 [0.26, 0.66]

 12 Adverse effects: 2. Cardiac effects: ECG abnormalities172Risk Ratio (M-H, Random, 95% CI)0.13 [0.02, 0.95]

 13 Adverse effects: 3. Central nervous system - sedation2135Risk Ratio (M-H, Random, 95% CI)0.22 [0.11, 0.47]

 14 Adverse effects: 4. Extrapyramidal effects3Risk Ratio (M-H, Random, 95% CI)Subtotals only

    14.1 akathisia
2135Risk Ratio (M-H, Random, 95% CI)0.40 [0.08, 1.99]

    14.2 rigor
163Risk Ratio (M-H, Random, 95% CI)1.94 [0.18, 20.30]

    14.3 tremor
2135Risk Ratio (M-H, Random, 95% CI)0.99 [0.29, 3.34]

    14.4 use of antiparkinson medication
128Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 15 Adverse effects: 5. Haematological: Important decline in white blood cells163Risk Ratio (M-H, Random, 95% CI)0.19 [0.01, 3.88]

 16 Adverse effects: 6a. Metabolic - weight - gain2135Risk Ratio (M-H, Random, 95% CI)0.53 [0.25, 1.11]

 17 Adverse effects: 6b. Metabolic - weight - change from baseline (kg)127Mean Difference (IV, Random, 95% CI)-2.11 [-4.30, 0.08]

 
Comparison 3. QUETIAPINE versus OLANZAPINE

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

 1 Leaving the study early13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 any reason
121821Risk Ratio (M-H, Random, 95% CI)1.26 [1.12, 1.42]

    1.2 due to adverse events
91610Risk Ratio (M-H, Random, 95% CI)0.90 [0.69, 1.18]

    1.3 due to inefficacy
91600Risk Ratio (M-H, Random, 95% CI)1.83 [1.42, 2.36]

 2 Global state: 1a. No clinically significant response (as defined by the original studies)3339Risk Ratio (M-H, Random, 95% CI)1.11 [0.86, 1.43]

 3 Global state: 1b. No clinically important change (as measured by CGI)2309Risk Ratio (M-H, Random, 95% CI)1.18 [0.89, 1.57]

    3.1 short term
142Risk Ratio (M-H, Random, 95% CI)1.36 [0.59, 3.15]

    3.2 long term
1267Risk Ratio (M-H, Random, 95% CI)1.16 [0.86, 1.57]

 4 Mental state: 1a. General - no clinically important change - short term (less than 50% PANSS total score reduction)142Risk Ratio (M-H, Random, 95% CI)0.91 [0.54, 1.53]

 5 Mental state: 1b. General - average endpoint score (PANSS total, high=poor)111486Mean Difference (IV, Random, 95% CI)3.67 [1.95, 5.39]

    5.1 short term
5179Mean Difference (IV, Random, 95% CI)2.29 [-1.30, 5.87]

    5.2 medium term
3482Mean Difference (IV, Random, 95% CI)5.57 [1.97, 9.17]

    5.3 long term
3825Mean Difference (IV, Random, 95% CI)3.40 [0.91, 5.88]

 6 Mental state: 2a. Positive symptoms - no clinically important change - short term (less than 20% SAPS total score reduction)130Risk Ratio (M-H, Random, 95% CI)15.0 [0.93, 241.20]

 7 Mental state: 2b. Positive symptoms - average endpoint score (PANSS positive subscore, high=poor)9801Mean Difference (IV, Random, 95% CI)1.02 [-0.81, 2.85]

    7.1 short term
4152Mean Difference (IV, Random, 95% CI)1.24 [-0.48, 2.96]

    7.2 medium term
3483Mean Difference (IV, Random, 95% CI)2.21 [0.90, 3.52]

    7.3 long term
2166Mean Difference (IV, Random, 95% CI)-1.25 [-7.28, 4.79]

 8 Mental state: 2c. Positive symptoms - SAPS total score - percent change - short term (high=poor)130Mean Difference (IV, Random, 95% CI)40.84 [23.97, 57.71]

 9 Mental state: 3a. Negative symptoms - no clinically important change - short term (less than 20% SANS total score reduction)130Risk Ratio (M-H, Random, 95% CI)1.5 [0.53, 4.26]

 10 Mental state: 3b. Negative symptoms - average endpoint score (PANSS negative subscore, high=poor)9801Mean Difference (IV, Random, 95% CI)0.86 [-0.32, 2.03]

    10.1 short term
4152Mean Difference (IV, Random, 95% CI)-0.07 [-1.70, 1.56]

    10.2 medium term
3483Mean Difference (IV, Random, 95% CI)0.40 [-0.67, 1.47]

    10.3 long term
2166Mean Difference (IV, Random, 95% CI)2.64 [-1.29, 6.56]

 11 Mental state: 3c. Negative symptoms - average endpoint score - medium term (SANS, high=poor)1335Mean Difference (IV, Random, 95% CI)3.70 [-0.48, 7.88]

 12 Mental state: 3d. Negative symptoms - average change in endpoint score - short term (SANS, high=poor)130Mean Difference (IV, Random, 95% CI)2.46 [-31.90, 36.82]

 13 General functioning: General - average endpoint score - medium term (GAF total score, low=poor)3400Mean Difference (IV, Random, 95% CI)2.55 [0.33, 4.76]

 14 Quality of life: General - average change in endpoint score - medium term (QLS total score, low=poor)1286Mean Difference (IV, Random, 95% CI)1.80 [-2.42, 6.02]

 15 Service use: 1. Number of participants re-hospitalised31009Risk Ratio (M-H, Random, 95% CI)1.83 [1.33, 2.52]

    15.1 medium term
2336Risk Ratio (M-H, Random, 95% CI)1.98 [1.05, 3.75]

    15.2 long term
1673Risk Ratio (M-H, Random, 95% CI)1.78 [1.24, 2.58]

 16 Adverse effects: 1. General - at least one adverse effect71306Risk Ratio (M-H, Random, 95% CI)0.96 [0.88, 1.05]

 17 Adverse effects: 2. Death41450Risk Ratio (M-H, Random, 95% CI)0.74 [0.13, 4.23]

    17.1 suicide attempt
2940Risk Ratio (M-H, Random, 95% CI)0.35 [0.05, 2.29]

    17.2 suicide
3510Risk Ratio (M-H, Random, 95% CI)4.96 [0.24, 102.41]

 18 Adverse effects: 3a. Cardiac effects - QTc prolongation1673Risk Ratio (M-H, Random, 95% CI)12.96 [0.73, 229.17]

 19 Adverse effects: 3b. Cardiac effects - QTc abnormalities - change from baseline in ms3643Mean Difference (IV, Random, 95% CI)4.81 [0.34, 9.28]

 20 Adverse effects: 4a. Central nervous system - sedation71615Odds Ratio (M-H, Fixed, 95% CI)0.97 [0.78, 1.20]

 21 Adverse effects: 4b. Central nervous system - seizures140Risk Ratio (M-H, Random, 95% CI)3.3 [0.14, 76.46]

 22 Adverse effects: 5a. Extrapyramidal effects9Risk Ratio (M-H, Random, 95% CI)Subtotals only

    22.1 akathisia
71314Risk Ratio (M-H, Random, 95% CI)0.97 [0.68, 1.38]

    22.2 akinesia
1267Risk Ratio (M-H, Random, 95% CI)1.02 [0.67, 1.56]

    22.3 dyskinesia
137Risk Ratio (M-H, Random, 95% CI)2.57 [0.11, 59.30]

    22.4 dystonia
3752Risk Ratio (M-H, Random, 95% CI)1.13 [0.21, 6.23]

    22.5 extrapyramidal symptoms
2245Risk Ratio (M-H, Random, 95% CI)1.62 [0.72, 3.67]

    22.6 parkinsonism
277Risk Ratio (M-H, Random, 95% CI)0.77 [0.34, 1.74]

    22.7 tremor
142Risk Ratio (M-H, Random, 95% CI)0.39 [0.12, 1.31]

    22.8 use of antiparkinson medication
71127Risk Ratio (M-H, Random, 95% CI)0.51 [0.32, 0.81]

 23 Adverse effects: 5b. Extrapyramidal effects - scale measured3Mean Difference (IV, Random, 95% CI)Subtotals only

    23.1 akathisia: Barnes Akathisia Scale (high=poor)
2135Mean Difference (IV, Random, 95% CI)0.06 [-0.10, 0.22]

    23.2 extrapyramidal symptoms: ESRS total score (high=poor)
133Mean Difference (IV, Random, 95% CI)0.0 [-2.68, 2.68]

    23.3 extrapyramidal symptoms: Simpson-Angus Scale (high=poor)
2135Mean Difference (IV, Random, 95% CI)-0.06 [-0.57, 0.44]

    23.4 extrapyramidal symptoms: Abnormal Involuntary Movement Scale (AIMS, high=poor)
185Mean Difference (IV, Random, 95% CI)0.17 [-0.38, 0.72]

 24 Adverse effects: 6a. Prolactin associated side effects5Risk Ratio (M-H, Random, 95% CI)Subtotals only

    24.1 abnormally high prolactin value
142Risk Ratio (M-H, Random, 95% CI)0.10 [0.01, 1.77]

    24.2 amenorrhea
3252Risk Ratio (M-H, Random, 95% CI)0.66 [0.36, 1.21]

    24.3 galactorrhea
41025Risk Ratio (M-H, Random, 95% CI)0.66 [0.25, 1.73]

    24.4 gynecomastia
1267Risk Ratio (M-H, Random, 95% CI)0.33 [0.09, 1.20]

    24.5 sexual dysfunction
41177Risk Ratio (M-H, Random, 95% CI)0.80 [0.64, 0.99]

 25 Adverse effects: 6b. Prolactin - change from baseline in ng/ml51021Mean Difference (IV, Random, 95% CI)-5.89 [-11.62, -0.16]

 26 Adverse effects: 7a. Metabolic - cholesterol - significant cholesterol increase1267Risk Ratio (M-H, Random, 95% CI)0.99 [0.59, 1.68]

 27 Adverse effects: 7b. Metabolic - cholesterol - change from baseline in mg/dl61156Mean Difference (IV, Random, 95% CI)-2.73 [-8.05, 2.59]

 28 Adverse effects: 7c. Metabolic - glucose - abnormally high fasting glucose value31025Risk Ratio (M-H, Random, 95% CI)0.47 [0.21, 1.02]

 29 Adverse effects: 7d. Metabolic - glucose - change from baseline in mg/dl61156Mean Difference (IV, Random, 95% CI)-4.67 [-9.41, 0.07]

 30 Adverse effects: 7e. Metabolic - weight - gain81667Risk Ratio (M-H, Random, 95% CI)0.68 [0.51, 0.92]

    30.1 significant weight gain (as defined by the original studies)
71321Risk Ratio (M-H, Random, 95% CI)0.69 [0.51, 0.95]

    30.2 as "weight gain" reported adverse events
1346Risk Ratio (M-H, Random, 95% CI)0.49 [0.04, 5.34]

 31 Adverse effects: 7f. Metabolic - weight - change from baseline in kg101428Mean Difference (IV, Random, 95% CI)-2.54 [-3.82, -1.26]

 
Comparison 4. QUETIAPINE versus PALIPERIDONE

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

 1 Leaving the study early21131Risk Ratio (M-H, Random, 95% CI)1.07 [0.70, 1.62]

    1.1 any reason
2406Risk Ratio (M-H, Random, 95% CI)1.03 [0.61, 1.73]

    1.2 due to adverse events
2406Risk Ratio (M-H, Random, 95% CI)0.90 [0.37, 2.17]

    1.3 due to inefficacy
1319Risk Ratio (M-H, Random, 95% CI)4.97 [0.59, 42.05]

 2 Mental state: 1. General - average endpoint score (PANSS total, high=poor)1Mean Difference (Random, 95% CI)6.3 [2.77, 9.83]

    2.1 short term
1Mean Difference (Random, 95% CI)6.3 [2.77, 9.83]

 3 Mental state: 2. Positive symptoms - average endpoint score (PANSS positive subscore, high=poor)1Mean Difference (Random, 95% CI)1.6 [0.42, 2.78]

    3.1 short term
1Mean Difference (Random, 95% CI)1.6 [0.42, 2.78]

 4 Mental state: 3. Negative symptoms - average endpoint score (PANSS negative subscore, high=poor)1Mean Difference (Random, 95% CI)1.30 [0.52, 2.08]

    4.1 short term
1Mean Difference (Random, 95% CI)1.30 [0.52, 2.08]

 5 Adverse effects: 1. General - at least one adverse effect187Risk Ratio (M-H, Random, 95% CI)1.27 [1.06, 1.53]

 6 Adverse effects: 2a. Cardiac effects - QTc prolongation1319Risk Difference (M-H, Random, 95% CI)0.0 [-0.01, 0.01]

 7 Adverse effects: 2b. Cardiac effects - QTc abnormalities - change from baseline in ms187Mean Difference (IV, Random, 95% CI)2.3 [-2.50, 7.10]

 8 Adverse effects: 3a. Extrapyramidal effects21537Risk Ratio (M-H, Random, 95% CI)0.61 [0.42, 0.89]

    8.1 akathisia
2406Risk Ratio (M-H, Random, 95% CI)1.35 [0.55, 3.34]

    8.2 dystonia
187Risk Ratio (M-H, Random, 95% CI)1.02 [0.15, 6.94]

    8.3 rigidity
2406Risk Ratio (M-H, Random, 95% CI)0.34 [0.12, 0.92]

    8.4 tremor
1319Risk Ratio (M-H, Random, 95% CI)0.37 [0.17, 0.80]

    8.5 use of antiparkinson medication
1319Risk Ratio (M-H, Random, 95% CI)0.64 [0.45, 0.91]

 9 Adverse effects: 3b. Extrapyramidal effects - scale measured1Mean Difference (Random, 95% CI)0.45 [-0.43, 1.33]

    9.1 abnormal involuntary movement: AIMS (high=poor)
1Mean Difference (Random, 95% CI)0.0 [-0.39, 0.39]

    9.2 extrapyramidal symptoms: Simpson-Angus Scale (high=poor)
1Mean Difference (Random, 95% CI)0.9 [0.51, 1.29]

 10 Adverse effects: 4a. Prolactin associated effects1317Risk Ratio (M-H, Random, 95% CI)0.20 [0.01, 4.16]

    10.1 sexual dysfunction
1317Risk Ratio (M-H, Random, 95% CI)0.20 [0.01, 4.16]

 11 Adverse effects: 4b. Prolactin - change from baseline in ng/ml1317Mean Difference (IV, Random, 95% CI)-49.3 [-57.80, -40.80]

 12 Adverse effects: 5a. Metabolic - weight gain - change from baseline in kg1Mean Difference (Random, 95% CI)0.40 [0.20, 0.60]

 13 Adverse effects: 5b. Metabolic - weight gain of 7% or more of total body weight1319Risk Ratio (M-H, Random, 95% CI)2.52 [0.50, 12.78]

 
Comparison 5. QUETIAPINE versus RISPERIDONE

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

 1 Leaving the study early13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 any reason
132784Risk Ratio (M-H, Random, 95% CI)1.09 [1.00, 1.19]

    1.2 due to adverse events
92299Risk Ratio (M-H, Random, 95% CI)1.12 [0.80, 1.57]

    1.3 due to inefficacy
81891Risk Ratio (M-H, Random, 95% CI)1.32 [1.02, 1.71]

 2 Global state: 1a. No clinically significant response (as defined by the original studies)41274Risk Ratio (M-H, Random, 95% CI)1.07 [0.95, 1.22]

 3 Global state: 1b. No clinically important change (as measured by CGI)51342Risk Ratio (M-H, Random, 95% CI)1.10 [0.98, 1.25]

    3.1 short term
41075Risk Ratio (M-H, Random, 95% CI)1.09 [0.95, 1.26]

    3.2 long term
1267Risk Ratio (M-H, Random, 95% CI)1.18 [0.87, 1.60]

 4 Mental state: 1a General - no clinically important change - short term (less than 30% PANSS total score reduction)2982Risk Ratio (M-H, Random, 95% CI)1.11 [0.87, 1.42]

 5 Mental state: 1b. General - no clinically important change - short term (less than 20% BPRS total score reduction)125Risk Ratio (M-H, Random, 95% CI)0.98 [0.63, 1.52]

 6 Mental state: 1c. General -average endpoint score (PANSS total score, high=poor)142302Mean Difference (IV, Random, 95% CI)1.67 [0.39, 2.96]

    6.1 short term
81232Mean Difference (IV, Random, 95% CI)1.37 [-0.28, 3.01]

    6.2 medium term
5327Mean Difference (IV, Random, 95% CI)1.93 [-1.56, 5.42]

    6.3 long term
2743Mean Difference (IV, Random, 95% CI)3.11 [0.40, 5.82]

 7 Mental state: 1d. General - average endpoint score - short term (BPRS total score, high=poor)125Mean Difference (IV, Random, 95% CI)1.68 [-8.33, 11.69]

 8 Mental state: 2a. Positive symptoms - no clinically important change - short term (less than 40% PANSS positive reduction)1673Risk Ratio (M-H, Random, 95% CI)1.00 [0.90, 1.12]

 9 Mental state: 2b. Positive symptoms - average endpoint score - (PANSS positive subscore, high=poor)121639Mean Difference (IV, Random, 95% CI)1.22 [0.51, 1.94]

    9.1 short term
71231Mean Difference (IV, Random, 95% CI)1.29 [0.28, 2.29]

    9.2 medium term
5327Mean Difference (IV, Random, 95% CI)1.21 [-0.21, 2.63]

    9.3 long term
181Mean Difference (IV, Random, 95% CI)1.30 [-0.13, 2.73]

 10 Mental state: 2c. Positive symptoms - average change in endpoint score - short term (BPRS positive subscore, high=poor)125Mean Difference (IV, Random, 95% CI)1.1 [0.18, 2.02]

 11 Mental state: 3a. Negative symptoms - no clinically important change - short term (less than 40% PANSS negative reduction)1673Risk Ratio (M-H, Random, 95% CI)0.98 [0.93, 1.04]

 12 Mental state: 3b. Negative symptoms -average endpoint score - (PANSS negative subscore, high=poor)111514Mean Difference (IV, Random, 95% CI)0.70 [0.13, 1.26]

    12.1 short term
61106Mean Difference (IV, Random, 95% CI)0.55 [-0.25, 1.34]

    12.2 medium term
5327Mean Difference (IV, Random, 95% CI)1.05 [-0.24, 2.34]

    12.3 long term
181Mean Difference (IV, Random, 95% CI)0.80 [-0.64, 2.24]

 13 Mental state: 3c. Negative symptoms - average change in endpoint score - (BPRS negative subscore, high=poor)125Mean Difference (IV, Random, 95% CI)0.57 [0.17, 0.97]

 14 Quality of life: General - average endpoint score - (QLS total score, low=poor)3152Mean Difference (IV, Random, 95% CI)-3.44 [-4.46, -2.43]

    14.1 short term
122Mean Difference (IV, Random, 95% CI)-0.5 [-13.87, 12.87]

    14.2 medium term
2130Mean Difference (IV, Random, 95% CI)-3.46 [-4.48, -2.45]

 15 Service use: number of participants re-hospitalised2877Risk Ratio (M-H, Random, 95% CI)1.34 [1.00, 1.79]

    15.1 medium term
1199Risk Ratio (M-H, Random, 95% CI)1.3 [0.71, 2.38]

    15.2 long term
1678Risk Ratio (M-H, Random, 95% CI)1.35 [0.97, 1.88]

 16 Adverse effects: 1. General - at least one adverse effect132868Risk Ratio (M-H, Random, 95% CI)1.01 [0.91, 1.13]

 17 Adverse effects: 2. Death63146Risk Ratio (M-H, Random, 95% CI)0.73 [0.17, 3.09]

    17.1 natural causes
31022Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    17.2 suicide attempt
2945Risk Ratio (M-H, Random, 95% CI)0.43 [0.06, 2.95]

    17.3 suicide
41179Risk Ratio (M-H, Random, 95% CI)1.41 [0.11, 18.32]

 18 Adverse effects: 3a. Cardiac effects - QTc prolongation31419Risk Ratio (M-H, Random, 95% CI)1.34 [0.36, 5.04]

 19 Adverse effects: 3b. Cardiac effects - QTc abnormalities - change from baseline in ms3940Mean Difference (IV, Random, 95% CI)2.21 [-5.05, 9.48]

 20 Adverse effects: 4. Central nervous system - sedation82226Risk Ratio (M-H, Fixed, 95% CI)1.21 [1.06, 1.38]

 21 Adverse effects: 5a. Extrapyramidal effects13Risk Ratio (M-H, Random, 95% CI)Subtotals only

    21.1 akathisia
82270Risk Ratio (M-H, Random, 95% CI)0.55 [0.32, 0.95]

    21.2 akinesia
1267Risk Ratio (M-H, Random, 95% CI)0.91 [0.61, 1.37]

    21.3 dyskinesia
140Risk Ratio (M-H, Random, 95% CI)1.0 [0.07, 14.90]

    21.4 dystonia
41451Risk Ratio (M-H, Random, 95% CI)0.13 [0.04, 0.43]

    21.5 extrapyramidal symptoms
2872Risk Ratio (M-H, Random, 95% CI)0.59 [0.43, 0.81]

    21.6 parkinsonism
4825Risk Ratio (M-H, Random, 95% CI)0.39 [0.19, 0.78]

    21.7 rigor
1309Risk Ratio (M-H, Random, 95% CI)0.45 [0.16, 1.25]

    21.8 tremor
2126Risk Ratio (M-H, Random, 95% CI)1.10 [0.04, 27.67]

    21.9 use of antiparkinson medication
82163Risk Ratio (M-H, Random, 95% CI)0.50 [0.36, 0.69]

 22 Adverse effects: 5b. Extrapyramidal effects - scale measured - endpoint/ change to endpoint score5Mean Difference (IV, Random, 95% CI)Subtotals only

    22.1 abnormal involuntary movement: AIMS (high=poor)
2958Mean Difference (IV, Random, 95% CI)-0.34 [-0.76, 0.08]

    22.2 akathisia: Barnes Akathisia Scale (high=poor)
2700Mean Difference (IV, Random, 95% CI)-0.73 [-2.00, 0.54]

    22.3 extrapyramidal symptoms: Simpson-Angus Scale (high=poor)
51077Mean Difference (IV, Random, 95% CI)-0.59 [-1.16, -0.02]

 23 Adverse effects: 6. Haematological: important decline in white blood cells1673Risk Ratio (M-H, Random, 95% CI)2.97 [0.12, 72.73]

 24 Adverse effects: 7a. Prolactin associated side effects7Risk Ratio (M-H, Random, 95% CI)Subtotals only

    24.1 amenorrhea
5427Risk Ratio (M-H, Random, 95% CI)0.55 [0.32, 0.96]

    24.2 dysmenorrhea
1163Risk Ratio (M-H, Random, 95% CI)0.45 [0.08, 2.38]

    24.3 galactorrhea
51188Risk Ratio (M-H, Random, 95% CI)0.37 [0.16, 0.85]

    24.4 gynecomastia
1267Risk Ratio (M-H, Random, 95% CI)0.23 [0.07, 0.79]

    24.5 sexual dysfunction
62157Risk Ratio (M-H, Random, 95% CI)0.70 [0.48, 1.01]

 25 Adverse effects: 7b. Prolactin - change from baseline in mg/dl71773Mean Difference (IV, Random, 95% CI)-35.25 [-43.59, -26.91]

 26 Adverse effects: 8a. Metabolic - cholesterol - significant cholesterol increase2940Risk Ratio (M-H, Random, 95% CI)1.27 [0.72, 2.24]

 27 Adverse effects: 8b. Metabolic - cholesterol - change from baseline in mg/dl61473Mean Difference (IV, Random, 95% CI)8.57 [4.85, 12.29]

 28 Adverse effects: 8c. Metabolic - glucose - abnormally high fasting glucose value31618Risk Ratio (M-H, Random, 95% CI)0.89 [0.47, 1.69]

 29 Adverse effects: 8d. Metabolic - glucose - change from baseline in mg/dl61476Mean Difference (IV, Random, 95% CI)0.30 [-2.45, 3.05]

 30 Adverse effects: 8e. Metabolic - weight gain of 7% or more of total body weight92070Risk Ratio (M-H, Random, 95% CI)0.96 [0.82, 1.14]

 31 Adverse effects: 8f. Metabolic - weight gain - change from baseline in kg81486Mean Difference (IV, Random, 95% CI)0.94 [-0.59, 2.46]

 
Comparison 6. QUETIAPINE versus ZIPRASIDONE

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

 1 Leaving the study early2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 any reason
2722Risk Ratio (M-H, Random, 95% CI)1.05 [0.97, 1.13]

    1.2 adverse events
2722Risk Ratio (M-H, Random, 95% CI)1.04 [0.72, 1.49]

    1.3 inefficacy
2722Risk Ratio (M-H, Random, 95% CI)1.14 [0.89, 1.47]

 2 Mental state: 1. General - average endpoint score (PANSS total score, high=poor)2710Mean Difference (IV, Random, 95% CI)-0.11 [-6.36, 6.14]

    2.1 medium term
1198Mean Difference (IV, Random, 95% CI)3.70 [-2.97, 10.37]

    2.2 long term
1512Mean Difference (IV, Random, 95% CI)-2.78 [-6.81, 1.25]

 3 Mental state: 2. Positive symptoms - average endpoint score - medium term (PANSS positive subscore, high=poor)1198Mean Difference (IV, Random, 95% CI)0.0 [-2.18, 2.18]

 4 Mental state: 3. Negative symptoms - average endpoint score - medium term (PANSS negative subscore, high=poor)1198Mean Difference (IV, Random, 95% CI)1.60 [-0.34, 3.54]

 5 Service use: number of participants re-hospitalised2754Risk Ratio (M-H, Random, 95% CI)1.17 [0.85, 1.59]

    5.1 medium term
1232Risk Ratio (M-H, Random, 95% CI)1.25 [0.71, 2.17]

    5.2 long term
1522Risk Ratio (M-H, Random, 95% CI)1.13 [0.78, 1.65]

 6 Adverse effects: 1. General - at least one adverse effect2754Risk Ratio (M-H, Random, 95% CI)1.03 [0.91, 1.17]

 7 Adverse effects: 2. Death2754Risk Ratio (M-H, Random, 95% CI)0.41 [0.05, 3.15]

    7.1 suicide attempt
1522Risk Ratio (M-H, Random, 95% CI)0.55 [0.03, 8.73]

    7.2 suicide
1232Risk Ratio (M-H, Random, 95% CI)0.29 [0.01, 5.92]

 8 Adverse effects: 3a. Cardiac effects - QTc prolongation1522Risk Ratio (M-H, Random, 95% CI)1.65 [0.34, 8.08]

 9 Adverse effects: 3b. Cardiac effects - QTc abnormalities - change from baseline in ms2549Mean Difference (IV, Random, 95% CI)3.41 [-1.37, 8.18]

 10 Adverse effects: 4. Central nervous system - sedation2754Risk Ratio (M-H, Random, 95% CI)1.36 [1.03, 1.81]

 11 Adverse effects: 5. Extrapyramidal effects2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    11.1 akathisia
2754Risk Ratio (M-H, Random, 95% CI)0.78 [0.42, 1.45]

    11.2 dystonia
1522Risk Ratio (M-H, Random, 95% CI)0.18 [0.02, 1.75]

    11.3 extrapyramidal symptoms
1232Risk Ratio (M-H, Random, 95% CI)2.02 [0.66, 6.17]

    11.4 use of antiparkinson medication
1522Risk Ratio (M-H, Random, 95% CI)0.43 [0.20, 0.93]

 12 Adverse effects: 6a. Prolactin associated effects2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    12.1 amenorrhea
1138Risk Ratio (M-H, Random, 95% CI)0.43 [0.15, 1.24]

    12.2 galactorrhea
2572Risk Ratio (M-H, Random, 95% CI)0.55 [0.18, 1.68]

    12.3 sexual dysfunction
2754Risk Ratio (M-H, Random, 95% CI)0.96 [0.64, 1.42]

 13 Adverse effects: 6b. Prolactin - change from baseline in ng/ml2754Mean Difference (IV, Random, 95% CI)-4.77 [-8.16, -1.37]

 14 Adverse effects: 7a. Metabolic - cholesterol - change from baseline in mg/dl2754Mean Difference (IV, Random, 95% CI)16.01 [8.57, 23.46]

 15 Adverse effects: 7b. Metabolic - glucose- change from baseline in mg/dl2754Mean Difference (IV, Random, 95% CI)3.10 [-3.99, 10.19]

 16 Adverse effects: 7c. Metabolic - glucose - abnormally high fasting glucose value1522Risk Ratio (M-H, Random, 95% CI)0.64 [0.30, 1.36]

 17 Adverse effects: 7d. Metabolic - weight gain of 7% or more of total body weight2754Risk Ratio (M-H, Random, 95% CI)2.22 [1.35, 3.63]

 18 Adverse effects: 7e. Metabolic - weight gain - change from baseline in kg1466Mean Difference (IV, Random, 95% CI)1.2 [-0.05, 2.45]

 
Comparison 7. QUETIAPINE versus ARIPIPRAZOLE - sensitivity analyses (skewed data excluded)

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

 1 Mental state: 1. General - average endpoint score - short term (PANSS total, high=poor)2142Mean Difference (IV, Random, 95% CI)1.24 [-1.91, 4.39]

 
Comparison 8. QUETIAPINE versus CLOZAPINE- sensitivity analysis (skewed data excluded)

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

 1 Mental state: 1. General - average endpoint score - short term (PANSS total, high=poor)127Mean Difference (IV, Random, 95% CI)0.18 [-4.11, 4.47]

    1.1 short term
127Mean Difference (IV, Random, 95% CI)0.18 [-4.11, 4.47]

 
Comparison 9. QUETIAPINE versus OLANZAPINE- sensitivity analysis (skewed data excluded)

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

 1 Mental state: 1. General - average endpoint score (PANSS total subscore, high=poor)101401Mean Difference (IV, Random, 95% CI)4.10 [2.25, 5.95]

    1.1 short term
5179Mean Difference (IV, Random, 95% CI)2.29 [-1.30, 5.87]

    1.2 medium term
3482Mean Difference (IV, Random, 95% CI)5.57 [1.97, 9.17]

    1.3 long term
2740Mean Difference (IV, Random, 95% CI)4.31 [1.60, 7.01]

 2 Mental state: 2. Positive symptoms - average endpoint score (PANSS positive subscore, high=poor)7676Mean Difference (IV, Random, 95% CI)1.84 [1.02, 2.67]

    2.1 short term
3112Mean Difference (IV, Random, 95% CI)0.69 [-1.87, 3.24]

    2.2 medium term
3483Mean Difference (IV, Random, 95% CI)2.21 [0.90, 3.52]

    2.3 long term
181Mean Difference (IV, Random, 95% CI)1.80 [0.39, 3.21]

 3 Mental state: 3. Negative symptoms - average endpoint score (PANSS negative subscore, high=poor)8716Mean Difference (IV, Random, 95% CI)0.38 [-0.37, 1.14]

    3.1 short term
4152Mean Difference (IV, Random, 95% CI)-0.07 [-1.70, 1.56]

    3.2 medium term
3483Mean Difference (IV, Random, 95% CI)0.40 [-0.67, 1.47]

    3.3 long term
181Mean Difference (IV, Random, 95% CI)0.70 [-0.73, 2.13]

 
Comparison 10. QUETIAPINE versus RISPERIDONE- sensitivity analysis (skewed data excluded)

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

 1 Global state: 1a. No clinically significant response (as defined by the original studies)3965Risk Ratio (M-H, Random, 95% CI)1.01 [0.93, 1.09]

 2 Mental state: 1. General - average endpoint score - (PANSS total score, high=poor)91986Mean Difference (IV, Random, 95% CI)3.10 [1.49, 4.71]

    2.1 short term
51097Mean Difference (IV, Random, 95% CI)2.77 [0.50, 5.03]

    2.2 medium term
2146Mean Difference (IV, Random, 95% CI)6.27 [-3.94, 16.48]

    2.3 long term
2743Mean Difference (IV, Random, 95% CI)3.11 [0.40, 5.82]

 3 Mental state: 6. Positive symptoms - average endpoint score - (PANSS positive subscore, high=poor)61225Mean Difference (IV, Random, 95% CI)1.76 [1.04, 2.48]

    3.1 short term
3998Mean Difference (IV, Random, 95% CI)2.08 [0.60, 3.56]

    3.2 medium term
2146Mean Difference (IV, Random, 95% CI)2.15 [-0.01, 4.31]

    3.3 long term
181Mean Difference (IV, Random, 95% CI)1.30 [-0.13, 2.73]

 4 Mental state: 6. Negative symptoms - average endpoint score - (PANSS negative subscore, high=poor)61139Mean Difference (IV, Random, 95% CI)0.79 [0.04, 1.54]

    4.1 short term
3912Mean Difference (IV, Random, 95% CI)0.53 [-0.82, 1.88]

    4.2 medium term
2146Mean Difference (IV, Random, 95% CI)1.30 [-0.75, 3.35]

    4.3 long term
181Mean Difference (IV, Random, 95% CI)0.80 [-0.64, 2.24]

 5 Adverse effects: 1. Extrapyramidal effects - Simpson-Angus Scale (high=poor)41033Mean Difference (IV, Random, 95% CI)-0.82 [-1.95, 0.31]

 
Summary of findings for the main comparison. QUETIAPINE versus ARIPIPRAZOLE for schizophrenia

QUETIAPINE versus ARIPIPRAZOLE for schizophrenia

Patient or population: participants with schizophrenia
Settings:
Intervention: QUETIAPINE versus ARIPIPRAZOLE

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

Assumed riskCorresponding risk

ControlQUETIAPINE versus ARIPIPRAZOLE

Mental state: 1. General - average endpoint score
PANSS total
Mean mental state: 1. General - average endpoint score in the intervention groups was
1.62 higher
(0.89 lower to 4.14 higher)
297
(4 studies)
⊕⊕⊝⊝
low1,2,3

Mental state: 2. Positive symptoms average endpoint score
PANSS positive subscore
Mean mental state: 2. Positive symptoms - average endpoint score in the intervention groups was
0.62 higher
(1.13 lower to 2.38 higher)
297
(4 studies)
⊕⊕⊝⊝
low1,2,3

Mental state: 3. Negative symptoms - average endpoint score (PANSS negative subscore, high = poor)Mean mental state: 3. Negative symptoms - average endpoint score (PANSS negative subscore, high = poor) in the intervention groups was
1 higher
(0.25 lower to 2.25 higher)
297
(4 studies)
⊕⊕⊝⊝
low1,2,3

Quality of life: substantial improvementSee commentSee commentNot estimable0
(0)
See commentNo study reported this outcome in any form

Adverse effects: 1. SedationSee commentSee commentNot estimable0
(0)
See commentNo study reported this outcome in any form

Adverse effects: 2. Extrapyramidal effects - use of antiparkinson medicationLow4 RR 0.67
(0.12 to 3.57)
40
(1 study)
⊕⊕⊝⊝
low5,6,7

50 per 100034 per 1000
(6 to 178)

Moderate4

150 per 1000101 per 1000
(18 to 535)

High4

250 per 1000168 per 1000
(30 to 892)

Adverse effects: 3. Metabolic - weight gain7% of total body weightLow4 RR 0.52
(0.1 to 2.74)
155
(2 studies)
⊕⊕⊝⊝
low8,9

10 per 10005 per 1000
(1 to 27)

Moderate4

50 per 100026 per 1000
(5 to 137)

High4

100 per 100052 per 1000
(10 to 274)

*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 Risk of bias: rated serious - only one study adequately described appropriate allocation concealment methods (but not sequence generation). All other studies did not adequately describe sequence generation and allocation concealment.
2 Inconsistency: rated 'no' the P value for heterogeneity not statistically significant and I2 < 50%.
3 Imprecise data: rated serious - only a few studies contributed to this outcome and confidence interval was wide.
4 Moderate risk equates to that found within study.
5 Risk of bias: rated serious - the one study that contributed to this outcome adequately described appropriate allocation concealment methods but not sequence generation.
6 Imprecise data: rated serious - only one study with a wide confidence interval reported this outcome.
7 Publication bias: rated no - only one study reported this outcome making publication bias difficult to assess
8 Risk of bias: rated serious - neither of the two studies reporting this outcome adequately described appropriate allocation concealment and sequence generation methods.
9 Imprecise data: rated serious - only two studies reported this outcome, both with wide confidence intervals crossing the line of no effect.
 
Summary of findings 2. QUETIAPINE versus CLOZAPINE - all data short term for schizophrenia

QUETIAPINE versus CLOZAPINE all data short term for schizophrenia

Patient or population: participants with schizophrenia
Settings:
Intervention: QUETIAPINE versus CLOZAPINE all data short term

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

Assumed riskCorresponding risk

ControlQUETIAPINE versus CLOZAPINE all data short term

Mental state: 1. General - average endpoint score short term (PANSS total, high = poor)Mental state: 1. General - average endpoint score short term (PANSS total, high = poor) in the intervention groups was
0.5 lower
(2.85 lower to 1.86 higher)
232
(4 studies)
⊕⊕⊝⊝
low1,2,3

Mental state: 2. Positive symptoms - average endpoint score
PANSS positive subscore
Mean mental state: 2. Positive symptoms - average endpoint score in the intervention groups was
0.7 lower
(2.07 lower to 0.68 higher)
142
(2 studies)
⊕⊕⊝⊝
low1,2,4

Mental state: 3. Negative symptoms - average endpoint score short term
PANSS negative subscore
Mental state: 3. Negative symptoms - average endpoint score short term in the intervention groups was
2.23 lower
(3.48 to 0.99 lower)
142
(2 studies)
⊕⊕⊝⊝
low1,2,4

Quality of life: substantial improvementSee commentSee commentNot estimable0
(0)
See commentNo study reported this outcome in any form

Adverse effects: 1. SedationLow5 RR 0.22
(0.11 to 0.47)
135
(2 studies)
⊕⊕⊕⊝
moderate1,2

200 per 100044 per 1000
(22 to 94)

Moderate5

500 per 1000110 per 1000
(55 to 235)

High5

800 per 1000176 per 1000
(88 to 376)

Adverse effects: 2. Extrapyramidal effects - use of antiparkinson medicationModerateSee comment28
(1 study)
⊕⊕⊝⊝
low1,6
Risks were calculated from pooled risk differences. No events in either group (RD 0.0 CI -0.13 to 0.13)

0 per 10000 per 1000
(0 to 0)

Adverse effects: 3. Metabolic - weight gainLow5 RR 0.53
(0.25 to 1.11)
135
(2 studies)
⊕⊕⊝⊝
low1,2,3

100 per 100053 per 1000
(25 to 111)

Moderate5

250 per 1000132 per 1000
(62 to 278)

High5

400 per 1000212 per 1000
(100 to 444)

*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.

 1Risk of bias: rated serious none of the studies adequately described sequence generation and allocation concealment.
2Inconsistency: rated 'no' the P value for heterogeneity not statistically significant and I2 < 50%.
3Imprecise data: rated serious wide confidence intervals for all individual studies, all crossing the line of no effect.
4Imprecise data: rated serious only two studies, both with wide confidence intervals.
5Moderate risk equates to that within trials.
6Imprecise data: rated serious one small study. No events.
 
Summary of findings 3. QUETIAPINE versus OLANZAPINE for schizophrenia

QUETIAPINE versus OLANZAPINE for schizophrenia

Patient or population: participants with schizophrenia
Settings:
Intervention: QUETIAPINE versus OLANZAPINE

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

Assumed riskCorresponding risk

ControlQUETIAPINE versus OLANZAPINE

Mental state: 1. General - average endpoint score (PANSS total, high = poor)Mental state: 1. General - average endpoint score (PANSS total, high = poor) in the intervention groups was
3.67 higher
(1.95 to 5.39 higher)
1486
(11 studies)
⊕⊕⊝⊝
low1,2

Mental state: 2. Positive symptoms - average endpoint score
PANSS positive subscore
Mental state: 2. Positive symptoms - average endpoint score in the intervention groups was
1.02 higher
(0.81 lower to 2.85 higher)
801
(9 studies)
⊕⊕⊕⊝
moderate3,4,5

Mental state: 3. Negative symptoms - endpoint score
PANSS negative subscore
Mental state: 3. Negative symptoms - average endpoint score in the intervention groups was
0.86 higher
(0.32 lower to 2.03 higher)
801
(9 studies)
⊕⊕⊕⊝
moderate3,4

Quality of life: general - average change in endpoint score medium term
QLS total score
Mean quality of life: general - average change in endpoint score medium term in the intervention groups was
1.8 higher
(2.42 lower to 6.02 higher)
286
(1 study)
⊕⊕⊕⊝
moderate4,6

Adverse effects: 1. SedationLow7 RR 0.98
(0.84 to 1.13)
1615
(7 studies)
⊕⊕⊕⊝
moderate6

100 per 100098 per 1000
(84 to 113)

Moderate7

300 per 1000294 per 1000
(252 to 339)

High7

500 per 1000490 per 1000
(420 to 565)

Adverse effects: 2. Extrapyramidal effects - use of antiparkinson medicationLow7 See comment1127
(7 studies)
⊕⊕⊕⊝
moderate6
Risks were calculated from pooled risk differences

50 per 100028 per 1000
(10 to 44)

Moderate7

100 per 100055 per 1000
(21 to 89)

High7

150 per 100082 per 1000
(31 to 133)

Adverse effects: 3. Metabolic - weight significant gainLow7 RR 0.69
(0.51 to 0.95)
1321
(7 studies)
⊕⊕⊕⊝
moderate6

200 per 1000138 per 1000
(102 to 190)

Moderate7

400 per 1000276 per 1000
(204 to 380)

High7

600 per 1000414 per 1000
(306 to 570)

*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.

 1Risk of bias: rated serious no studies adequately described sequence generation and allocation concealment.
2Imprecision: rated ’very serious’ only few studies contribute data to this event and the CI was quite wide.
3Risk of bias: rated serious one study adequately described appropriate allocation concealment methods but not sequence generation, and another study adequately described sequence generation but not allocation concealment. All other studies did not adequately describe sequence generation and allocation concealment.
4Inconsistency: rated ’no’ although the P value for heterogeneity was statistically significant and the I2 > 50%, the direction of the effect of almost all studies was the same. Exclusion of one outlier (Voruganti 2007) rendered the heterogeneity not statistically significant and I2 < 50%. Therefore, this inconsistency does not challenge the overall results.
5Imprecision: rated 'no' exclusion of potentially skewed data (Mori 2004; Voruganti 2007) revealed an overall significant difference in favour of olanzapine.
6Risk of bias: rated serious no studies adequately described sequence generation and allocation concealment.
7Moderate risk equates to that of studies.
 
Summary of findings 4. QUETIAPINE versus PALIPERIDONE for schizophrenia

QUETIAPINE versus PALIPERIDONE for schizophrenia

Patient or population: participants with schizophrenia
Settings:
Intervention: QUETIAPINE versus PALIPERIDONE

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

Assumed riskCorresponding risk

ControlQUETIAPINE versus PALIPERIDONE

Mental state: 1. General - average endpoint score
PANSS total
Mental state: 1. General - average endpoint score in the intervention groups was
6.3 higher
(2.77 to 9.83 higher)1
319
(1 study)
⊕⊕⊕⊝
moderate2

Mental state: 2. Positive symptoms - average endpoint score
PANSS positive subscore
Mental state: 2. Positive symptoms average endpoint score in the intervention groups was
1.60 higher
(0.42 to 2.78 higher)1
319
(1 study)
⊕⊕⊕⊝
moderate2

Mental state: 3. Negative symptoms - average endpoint score
PANSS negative subscore
Mental state: 3. Negative symptoms - average endpoint score in the intervention groups was
1.3 higher
(0.52 to 2.08 higher)
319
(1 study)
⊕⊕⊕⊝
moderate2

Quality of life: substantial improvementSee commentSee commentNot estimable0
(0)
See commentNo trial reported this outcome in any form

Adverse effects: 1. SedationSee commentSee commentNot estimable0
(0)
See commentNo trial reported this outcome in any form

Adverse effects: 2. Extrapyramidal effects use of antiparkinson medicationLow3 RR 0.64
(0.45 to 0.91)
319
(1 study)
⊕⊕⊕⊝
moderate2

200 per 1000128 per 1000
(90 to 182)

Moderate3

400 per 1000256 per 1000
(180 to 364)

High3

600 per 1000384 per 1000
(270 to 546)

Adverse effects: 3. Metabolic weight gain7% of total body weightModerate3 RR 2.52
(0.5 to 12.78)
319
(1 study)
⊕⊕⊕⊝
moderate2

10 per 100025 per 1000
(5 to 128)

High3

100 per 1000252 per 1000
(50 to 1000)

*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.

 1Calculated using generic inverse variance.
2Imprecision: rated ’serious’ only one study contributes data to outcome and the CI was quite wide.
3Moderate risk equates to that within the trial.
 
Summary of findings 5. QUETIAPINE versus RISPERIDONE for schizophrenia

QUETIAPINE versus RISPERIDONE for schizophrenia

Patient or population: participants with schizophrenia
Settings:
Intervention: QUETIAPINE versus RISPERIDONE

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

Assumed riskCorresponding risk

ControlQUETIAPINE versus RISPERIDONE

Mental state: 1. General - average endpoint score
PANSS total score
Mental state: 1. General - average endpoint score in the intervention groups was
1.74 higher
(0.19 to 3.29 higher)
2155
(13 studies)
⊕⊕⊕⊝
moderate1,2

Mental state: 2. Positive symptoms - average endpoint score
PANSS positive subscore
Mental state: 2. Positive symptoms - average endpoint score in the intervention groups was
1.38 higher
(0.51 to 2.24 higher)
1492
(11 studies)
⊕⊕⊕⊝
moderate1,2

Mental state: 3. Negative symptoms - average endpoint score
PANSS negative subscore
Mean mental state: 3. Negative symptoms - average endpoint score in the intervention groups was
0.69 higher
(0.02 lower to 1.41 higher)
1367
(10 studies)
⊕⊕⊝⊝
low3,4

Quality of life: general average endpoint score
QLS total score
Mean quality of life: general average endpoint score in the intervention groups was
3.44 lower
(4.46 to 2.43 lower)
152
(3 studies)
⊕⊕⊝⊝
low4,5

Adverse effects: 1. SedationStudy populationRR 1.21
(1.06 to 1.38)
2226
(8)

246 per 1000298 per 1000
(261 to 340)

Moderate

239 per 1000289 per 1000
(253 to 330)

Adverse effects: 2. Extrapyramidal effects - use of antiparkinson medicationLow6 RR 0.5
(0.36 to 0.69)
2163
(8 studies)
⊕⊕⊕⊝
moderate1

50 per 100025 per 1000
(18 to 34)

Moderate6

150 per 100075 per 1000
(54 to 103)

High6

250 per 1000125 per 1000
(90 to 172)

Adverse effects: 3. Metabolic weight gain7% of total body weightLow6 RR 0.96
(0.82 to 1.14)
2070
(9 studies)
⊕⊕⊕⊝
moderate3

100 per 100096 per 1000
(82 to 114)

Moderate6

200 per 1000192 per 1000
(164 to 228)

High6

300 per 1000288 per 1000
(246 to 342)

*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.

 1Risk of bias: rated serious overall inadequate description of sequence generation and allocation concealment. Only two studies adequately described sequence generation.
2Inconsistency: rated ’no’ although the P value for heterogeneity was statistically significant and the I2 > 50%, the direction of the effect of almost all studies was the same. Therefore, this inconsistency does not challenge the overall results.
3Risk of bias: rated serious overall inadequate description of sequence generation and allocation concealment. One study adequately described sequence generation and one study sequence generation.
4Imprecision: rated serious most studies comprised small samples sizes with wide confidence intervals.
5Risk of bias: rated serious overall inadequate description of sequence generation and allocation concealment. One study adequately described sequence generation and two studies sequence generation.
6Moderate risk equates to that within trials.
 
Summary of findings 6. QUETIAPINE versus ZIPRASIDONE for schizophrenia

QUETIAPINE versus ZIPRASIDONE for schizophrenia

Patient or population: participants with schizophrenia
Settings:
Intervention: QUETIAPINE versus ZIPRASIDONE

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

Assumed riskCorresponding risk

ControlQUETIAPINE versus ZIPRASIDONE

Mental state: 1. General - average endpoint score
PANSS total score
Mental state: 1. General - average endpoint score in the intervention groups was
3.7 higher
(2.97 lower to 10.37 higher)
198
(1 study)
⊕⊕⊝⊝
low1,2

Mental state: 2. Positive symptoms - average endpoint score medium term
PANSS positive subscore
Mental state: 2. Positive symptoms - average endpoint score medium term in the intervention groups was
0 higher
(2.18 lower to 2.18 higher)
198
(1 study)
⊕⊕⊝⊝
low1,2

Mental state: 3. Negative symptoms - average endpoint score medium term
PANSS negative subscore
Mental state: 3. Negative symptoms - average endpoint score medium term in the intervention groups was
1.6 higher
(0.34 lower to 3.54 higher)
198
(1 study)
⊕⊕⊝⊝
low1,2

Quality of life: substantial improvementSee commentSee commentNot estimable0
(0)
See commentNo trial reported this outcome in any form

Adverse effects: 1. SedationLow3 RR 1.36
(1.03 to 1.81)
754
(2 studies)
⊕⊕⊝⊝
low1,2

100 per 1000136 per 1000
(103 to 181)

Moderate3

200 per 1000272 per 1000
(206 to 362)

High3

300 per 1000408 per 1000
(309 to 543)

Adverse effects: 2. Extrapyramidal effects - use of antiparkinson medicationLow3 RR 0.43
(0.2 to 0.93)
522
(1 study)
⊕⊕⊝⊝
low1,2

50 per 100022 per 1000
(10 to 47)

Moderate3

100 per 100043 per 1000
(20 to 93)

High3

150 per 100065 per 1000
(30 to 140)

Adverse effects: 3. Metabolic weight gain7% of total body weightLow3 RR 2.22
(1.35 to 3.63)
754
(2 studies)
⊕⊕⊕⊝
moderate1

10 per 100022 per 1000
(14 to 36)

Moderate3

50 per 1000111 per 1000
(68 to 182)

High3

100 per 1000222 per 1000
(135 to 363)

*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.

 1Risk of bias: rated serious - inadequately described sequence generation and allocation concealment.
2Imprecision: rated serious - only one study contributed to this important outcome and the confidence interval was large.
3Moderate risk equates to that within trials.
 
Table 2. Excluded studies relevant to other quetiapine comparisons

Excluded studyComparison

Zheng 2007quetiapine versus quetiapine + clozapine

Cao 2006d; Guo 2008; Nai 2007; Zhang 2006; Sun 2006e; Xu 2006; Zhang 2007aquetiapine versus chlorpramazine

Yang 2006a; Yang 2006bquetiapine versus haloperidol

Chen 2006k; Sun 2007bquetiapine versus perphenazine

Zhao 2007; Zhou 2006quetiapine versus sulpiride

Hao 2007quetiapine from non-domestic source vs domestic quetiapine

 
Table 3. 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 (operational criteria).
N = 3000*.
Age: any.
Gender: both.
History: any.

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

2. Amisulpride: dose ˜ 400-800 mg/day. N=300.

3. Aripiprazole: dose ˜ 10-30 mg/day. N=300.

4. Clozapine: dose ˜ 300-800 mg/day. N=300.

5. Olanzapine: dose ˜ 10-20 mg/day. N=300.

6. Ziprasidone: dose ˜ 120-160 mg/day. N=300.

7. Risperidone: dose ˜ 4-8 mg/day. N=300.

8. Sertindole: dose ˜ 12-24 mg/day. N=300.

9. Zotepine: dose ˜ 100-300 mg/day. N=300.

10. Paliperidone: dose˜ 6-12 mg/day. N=300.

OutcomesGlobal state: CGI**, relapse.

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

 *Power calculation suggested 300/group would allow good chance of showing a 10% difference between groups for primary outcome.

**Primary outcome.