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Meta-Analysis
. 2010 Nov 10;2010(11):CD006633.
doi: 10.1002/14651858.CD006633.pub2.

Clozapine versus other atypical antipsychotics for schizophrenia

Claudia Asenjo Lobos  1 , Katja Komossa, Christine Rummel-Kluge, Heike Hunger, Franziska Schmid, Sandra Schwarz, Stefan Leucht
Affiliations
Meta-Analysis

Clozapine versus other atypical antipsychotics for schizophrenia

Claudia Asenjo Lobos et al. Cochrane Database Syst Rev. .

Abstract

Background: Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness.

Objectives: To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses.

Search strategy: We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies.

Selection criteria: All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders.

Data collection and analysis: We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model.

Main results: The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than olanzapine (9 RCTs, n=1674, RR 1.60 CI 1.07 to 2.40, NNT 25 CI 15 to 73) and risperidone (6 RCTs, n=627, RR 1.88 CI 1.11 to 3.21, NNT 16 CI 9 to 59). Fewer participants in the clozapine groups left the trials early due to inefficacy than risperidone (6 RCTs, n=627, RR 0.40 CI 0.23 to 0.70, NNT 11 CI 7 to 21), suggesting a certain higher efficacy of clozapine.Clozapine was more efficacious than zotepine in improving the participants general mental state (BPRS total score: 1 RCT, n=59, MD -6.00 CI -9.83 to -2.17), but not consistently more than olanzapine, quetiapine, risperidone and ziprasidone. There was no significant difference between clozapine and olanzapine or risperidone in terms of positive or negative symptoms of schizophrenia. According to two studies from China quetiapine was more efficacious for negative symptoms than clozapine (2 RCTs, n=142, MD 2.23 CI 0.99 to 3.48).Clozapine produced somewhat fewer extrapyramidal side-effects than risperidone (use of antiparkinson medication: 6 RCTs, n=304, RR 0.39 CI 0.22 to 0.68, NNT 7 CI 5 to 18) and zotepine (n=59, RR 0.05 CI 0.00 to 0.86, NNT 3 CI 2 to 5). More participants in the clozapine group showed decreased white blood cells than those taking olanzapine, more hypersalivation and sedation than those on olanzapine, risperidone and quetiapine and more seizures than people on olanzapine and risperidone. Also clozapine produced an important weight gain not seen with risperidone.Other differences in adverse effects were less documented and should be replicated, for example, clozapine did not alter prolactin levels whereas olanzapine, risperidone and zotepine did; compared with quetiapine, clozapine produced a higher incidence of electrocardiogram (ECG) alterations; and compared with quetiapine and risperidone clozapine produced a higher increase of triglyceride levels. Other findings that should be replicated were: clozapine improved social functioning less than risperidone and fewer participants in the clozapine group had to be hospitalised to avoid suicide attempts compared to olanzapine.Other important outcomes such as service use, cognitive functioning, satisfaction with care or quality of life were rarely reported.

Authors' conclusions: Clozapine may be a little more efficacious than zotepine and risperidone but further trials are required to confirm this finding. Clozapine differs more clearly in adverse effects from other second generation antipsychotics and the side-effect profile could be key in the selection of treatment depending on the clinical situation and a patient's preferences. Data on other important outcomes such as cognitive functioning, quality of life, death or service use are currently largely missing, making further large and well-designed trials necessary. It is also important to take into account that the large number of people leaving the studies early limits the validity and interpretation of our findings.

PubMed Disclaimer

Conflict of interest statement

Claudia Asenjo L: none known. Katja Komossa: participated in investigator meetings for clinical trials sponsored by Astra Zeneca, Pfizer, Sanofi Aventis, Servier. Christine Rummel: received lecture honoraria and travel grants to attend scientific meetings from AstraZeneca, Janssen‐Cilag, EliLilly and Pfizer. Heike Hunger: none Franziske Schmidt: none. Sandra Schwarz: none. Stefan Leucht: received speaker/consultancy honoraria from SanofiAventis, BMS, EliLilly, Janssen, Lundbeck and Pfizer. He received research support from SanofiAventis and EliLilly.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 1 Death.
1.2
1.2. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 2 Leaving the study early: 1. Any reason.
1.3
1.3. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 3 Leaving the study early: 2. Adverse effects.
1.4
1.4. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 4 Leaving the study early: 3. Inefficacy.
1.5
1.5. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 5 Global state.
1.6
1.6. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 6 Mental state: 1. No clinically important change ‐ various criteria.
1.7
1.7. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 7 Mental state: 2a. PANSS total score (high = poor).
1.8
1.8. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 8 Mental state: 2b. BPRS‐18 (1‐7) total score (high = poor).
1.9
1.9. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 9 Mental state: 2c. BPRS total score, various versions (high = poor).
1.10
1.10. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 10 Mental state: 3a. Positive symptoms: PANSS positive subscore (high = poor).
1.11
1.11. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 11 Mental state: 3b. Positive symptoms: SAPS ‐ short term (high = poor).
1.12
1.12. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 12 Mental state: 3c. Positive symptoms: BPRS positive subscore (high = poor).
1.13
1.13. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 13 Mental state: 4a. Negative symptoms: PANSS negative subscore (high = poor).
1.14
1.14. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 14 Mental state: 4b. Negative symptoms: SANS ‐ short term (high = poor).
1.15
1.15. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 15 Mental state: 4c. Negative symptoms: BPRS negative subscore ‐(high = poor).
1.16
1.16. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 16 Cognitive functioning: 1. No clinically important change ‐ less than 0.5 SD improved ‐ medium term.
1.17
1.17. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 17 Quality of Life: 1. SWN‐38 total score ‐ medium term (high= good).
1.18
1.18. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 18 Quality of Life: 2. MLDL total score ‐ medium term (high = good).
1.19
1.19. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 19 Service use: Hospital readmission ‐ long term.
1.20
1.20. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 20 Adverse effects: 1. At least one adverse effect.
1.21
1.21. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 21 Adverse effects: 2. Cardiac problems.
1.22
1.22. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 22 Adverse effects: 3a. Extrapyramidal: antiparkinson medication use.
1.23
1.23. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 23 Adverse effects: 3d. Extrapyramidal: SAS change or endpoint (high = poor).
1.24
1.24. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 24 Adverse effects: 3c. Extrapyramidal: ESRS score at endpoint ‐ medium term (high = poor).
1.25
1.25. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 25 Adverse effects: 3b. Extrapyramidal: various symptoms.
1.26
1.26. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 26 Adverse effects: 3e. Extrapyramidal: akathisia ‐ BARS change ‐ medium term (high = poor).
1.27
1.27. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 27 Adverse effects: 3f. Extrapyramidal: Hillside Akathisia Scale ‐ medium term (high=poor).
1.28
1.28. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 28 Adverse effects: 3g. Extrapyramidal: tardive dyskinesia ‐ AIMS change or endpoint ‐ (high = poor).
1.29
1.29. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 29 Adverse effects: 4a. Glucose: number of participants with significant increase ‐ long term.
1.30
1.30. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 30 Adverse effects: 4b. Glucose: average change or endpoint (high = poor).
1.31
1.31. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 31 Adverse effects: 5. Hypersalivation.
1.32
1.32. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 32 Adverse effects: 6a. Lipids: number of participants with significant increase.
1.33
1.33. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 33 Adverse effects: 6b. Lipids:average cholesterol change or endpoint (high = poor).
1.34
1.34. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 34 Adverse effects: 6c. Lipids: average triglyceride change ‐short term (high = poor).
1.35
1.35. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 35 Adverse effects: 7. Prolactin: average change or endpoint (high=poor).
1.36
1.36. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 36 Adverse effects: 8. Sedation.
1.37
1.37. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 37 Adverse effects: 9. Seizures.
1.38
1.38. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 38 Adverse effects: 10a. Weight: number of participants with weight gain.
1.39
1.39. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 39 Adverse effects: 10b. Weight: average weight change (high = poor).
1.40
1.40. Analysis
Comparison 1 CLOZAPINE versus OLANZAPINE, Outcome 40 Adverse effects: 11. White blood cell count: number of participants with a decrease.
2.1
2.1. Analysis
Comparison 2 CLOZAPINE versus OLANZAPINE ‐ Sensitivity Analysis, Outcome 1 Mental state: 1a. PANSS total score, excluding possibly skewed data (high = poor).
2.2
2.2. Analysis
Comparison 2 CLOZAPINE versus OLANZAPINE ‐ Sensitivity Analysis, Outcome 2 Mental state: 1b. BPRS‐18 (1‐7) total score, excluding possibly skewed data (high = poor).
2.3
2.3. Analysis
Comparison 2 CLOZAPINE versus OLANZAPINE ‐ Sensitivity Analysis, Outcome 3 Mental state: 2a. PANSS positive subscore, excluding possibly skewed data (high = poor).
2.4
2.4. Analysis
Comparison 2 CLOZAPINE versus OLANZAPINE ‐ Sensitivity Analysis, Outcome 4 Mental state: 2b. BPRS positive subscore, excluding possibly skewed data (high = poor).
2.5
2.5. Analysis
Comparison 2 CLOZAPINE versus OLANZAPINE ‐ Sensitivity Analysis, Outcome 5 Mental state: 3. SANS, excluding possibly skewed data (high=poor).
3.1
3.1. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 1 Leaving the study early ‐ short term.
3.2
3.2. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 2 Global state: No clinically important change ‐ less than "common criteria" ‐ short term.
3.3
3.3. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 3 Mental state: 1. No clinically important change ‐ less than 50% reduction PANSS total ‐ short term.
3.4
3.4. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 4 Mental state: 2a. PANSS total score ‐ short term (high = poor).
3.5
3.5. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 5 Mental state: 2b. BPRS‐18 (1‐7) total score ‐ short term (high = poor).
3.6
3.6. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 6 Mental state: 3. Positive symptoms: PANSS positive subscore ‐ short term (high = poor).
3.7
3.7. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 7 Mental state: 4 No clinically important change ‐ less than 50% reduction SANS ‐ short term.
3.8
3.8. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 8 Mental state: 5a. Negative symptoms: PANSS negative subscore ‐ short term (high = poor).
3.9
3.9. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 9 Mental state: 5b. Negative symptoms: SANS ‐ short term (high = poor).
3.10
3.10. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 10 Adverse effects: 1. At least one adverse effect ‐ short term.
3.11
3.11. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 11 Adverse effects: 2. Cardiac problems ‐ short term.
3.12
3.12. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 12 Adverse effects: 3a. Extrapyramidal: antiparkinson medication use ‐ short term.
3.13
3.13. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 13 Adverse effects: 3b. Extrapyramidal: various symptoms ‐ short term.
3.14
3.14. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 14 Adverse effects: 4. Hypersalivation ‐ short term.
3.15
3.15. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 15 Adverse effects: 5. Lipids: average triglyceride change ‐ short term (high = poor).
3.16
3.16. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 16 Adverse effects: 6. Sedation ‐ short term.
3.17
3.17. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 17 Adverse effects: 7a. Weight: number of participant with weight gain ‐ short term.
3.18
3.18. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 18 Adverse effects: 7b. Weight: average weight change ‐ short term (high = poor).
3.19
3.19. Analysis
Comparison 3 CLOZAPINE versus QUETIAPINE, Outcome 19 Adverse effects: 8. White blood cell count: number of participant with a decrease ‐ short term.
4.1
4.1. Analysis
Comparison 4 CLOZAPINE versus QUETIAPINE ‐ Sensitivity Analysis, Outcome 1 Mental state: 1. PANSS total score ‐ excluding possibly skewed data ‐ short term (high = poor).
5.1
5.1. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 1 Death ‐ short term.
5.2
5.2. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 2 Leaving the study early: 1. Any reason.
5.3
5.3. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 3 Leaving the study early: 2. Adverse effects.
5.4
5.4. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 4 Leaving the study early: 3. Inefficacy.
5.5
5.5. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 5 Global state: No clinically important change ‐ less than much improved on CGI ‐ short term.
5.6
5.6. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 6 Mental state: 1. No clinically important change ‐ various criteria.
5.7
5.7. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 7 Mental state: 2a. PANSS total score (high = poor).
5.8
5.8. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 8 Mental state: 2b. BPRS‐18 (1‐7) total score ‐ short term (high = poor).
5.9
5.9. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 9 Mental state: 3a. Positive symptoms: PANSS positive subscore (high = poor).
5.10
5.10. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 10 Mental state: 3b. Positive symptoms: BPRS‐18 (1‐7) positive subscore ‐ short term (high = poor).
5.11
5.11. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 11 Mental state: 4a. Negative symptoms: PANSS negative subscore (high = poor).
5.12
5.12. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 12 Mental state: 4b. Negative symptoms: SANS ‐ short term (high = poor).
5.13
5.13. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 13 General functioning: GAF score ‐ short term (high = good).
5.14
5.14. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 14 Social functioning: SFS score ‐ short term (high = good).
5.15
5.15. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 15 Treatment satisfaction: DAI score ‐ short term (high = good).
5.16
5.16. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 16 Cognitive functioning: No clinically important change ‐ less than 0.5 SD improved ‐ medium term.
5.17
5.17. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 17 Adverse effects: 1. At least one adverse effect ‐ short term.
5.18
5.18. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 18 Adverse effects: 2. Cardiac problems.
5.19
5.19. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 19 Adverse effects: 3a. Extrapyramidal: antiparkinson medication use.
5.20
5.20. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 20 Adverse effects: 3b. Extrapyramidal: various symptoms ‐ short term.
5.21
5.21. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 21 Adverse effects: 3c. Extrapyramidal: symptom scales (high = poor).
5.22
5.22. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 22 Adverse effects: 4. Glucose: average change ‐ medium term (high = poor).
5.23
5.23. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 23 Adverse effects: 5. Hypersalivation ‐short term.
5.24
5.24. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 24 Adverse effects: 6. Lipids: average change (high = poor).
5.25
5.25. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 25 Adverse effects: 7a. Prolactin: associated side effects ‐ short term.
5.26
5.26. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 26 Adverse effects: 7b. Prolactin: average at endpoint (high = poor).
5.27
5.27. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 27 Adverse effects: 8. Sedation ‐ short term.
5.28
5.28. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 28 Adverse effects: 9. Seizures.
5.29
5.29. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 29 Adverse effects: 10a. Weight: number of participants with weight gain.
5.30
5.30. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 30 Adverse effects: 10b. Weight: average weight change (high=poor).
5.31
5.31. Analysis
Comparison 5 CLOZAPINE versus RISPERIDONE, Outcome 31 Adverse effects: 11. White blood cell count: number of participants with a decrease.
6.1
6.1. Analysis
Comparison 6 CLOZAPINE vs. RISPERIDONE ‐ Sensitivity Analysis, Outcome 1 Mental state: 1. BPRS‐18 (1‐7) total score, excluding possibly skewed data (high = poor).
6.2
6.2. Analysis
Comparison 6 CLOZAPINE vs. RISPERIDONE ‐ Sensitivity Analysis, Outcome 2 Mental state: 2. PANSS positive subscore, excluding possibly skewed data (high = poor).
6.3
6.3. Analysis
Comparison 6 CLOZAPINE vs. RISPERIDONE ‐ Sensitivity Analysis, Outcome 3 Mental state: 3. PANSS negative subscore, excluding possibly skewed data (high = poor).
7.1
7.1. Analysis
Comparison 7 CLOZAPINE versus ZIPRASIDONE, Outcome 1 Leaving the study early: any reason ‐ medium term.
7.2
7.2. Analysis
Comparison 7 CLOZAPINE versus ZIPRASIDONE, Outcome 2 Mental state: PANSS total score ‐ medium term (high = poor).
7.3
7.3. Analysis
Comparison 7 CLOZAPINE versus ZIPRASIDONE, Outcome 3 Adverse effects: 1. Cardiac problems.
8.1
8.1. Analysis
Comparison 8 CLOZAPINE versus ZOTEPINE, Outcome 1 Leaving the study early: any reason.
8.2
8.2. Analysis
Comparison 8 CLOZAPINE versus ZOTEPINE, Outcome 2 Global state: no clinically important change ‐ less than successfully and no increase on CGI‐S ‐ short term.
8.3
8.3. Analysis
Comparison 8 CLOZAPINE versus ZOTEPINE, Outcome 3 Mental state: BPRS‐18 total score ‐ short term (high=poor).
8.4
8.4. Analysis
Comparison 8 CLOZAPINE versus ZOTEPINE, Outcome 4 Adverse effects: 1. Extrapyramidal: antiparkinson medication use ‐ short term.
8.5
8.5. Analysis
Comparison 8 CLOZAPINE versus ZOTEPINE, Outcome 5 Adverse effects: 2. Prolactin: average change ‐ short term (high=poor).
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Comment in

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    1. Kelly DL, Conley RR, Richardson CM, Tamminga CA, Carpenter Jr WT. Adverse effects and laboratory parameters of high‐dose olanzapine vs. clozapine in treatment‐resistant schizophrenia. Annals of Clinical Psychiatry 2003;15(3‐4):181‐6. - PubMed
Heinrich 1994 {published data only}
    1. Heinrich K. Risperidone versus clozapine in acute schizophrenia. Proceedings of the 1st International Risperidone Investigators' Meeting; 1992 Mar 9‐10; Paris, France. 1992:27‐28.
    1. Heinrich K, Klieser E, Lehmann E, Kinzler E. Experimental comparison of the efficacy and compatibility of clozapine and risperidone in acute schizophrenia. Clinical Neuropharmacology 1992;15(Suppl 1 (Pt B)):375B.
    1. Heinrich K, Klieser E, Lehmann E, Kinzler E. Experimental comparison of the efficacy and compatibility of risperidone and clozapine in acute schizophrenia. Proceedings of the 17th Collegium Internationale Neuro‐Psychopharmacologicum Congress; 1990 Sep 10‐14; Kyoto, Japan. 1991:37‐9.
    1. Heinrich K, Klieser E, Lehmann E, Kinzler E, Hruschka H. Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial. Progress in Neuropsychopharmacology and Biological Psychiatry 1994;18(1):129‐37. - PubMed
    1. Klieser E, Kinzler E. Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double‐blind, randomised trial. Clinical report 1991. - PubMed
Krakowski 2006 {published data only}
    1. Krakowski MI. Clozapine and olanzapine in violent schizophrenics. CRISP database (https://www‐commons.cit.nih.gov/crisp/index.html) (accessed 19th February 2001).
    1. Krakowski MI, Czobor P, Citrome L, Bark N, Cooper TB. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Archives of General Psychiatry 2006;63(6):622‐9. - PubMed
Kumra 2008 {published and unpublished data}
    1. Kumra S, Kranzler H, Gerbino‐Rosen G, Kester HM, DeThomas C, Kafantaris V, Correl CU, Kane JM. Clozapine and "high‐dose" olanzapine in refractory early‐onset schizophrenia: a 12 weeks randomized and double‐blind comparison. Biological Psychiatry 2008;63(5):524‐29. - PubMed
Li 2002 {published data only}
    1. Li Yan, Wang CH, Zhang DH. A study of quetiapine and clozapine in treatment of the first episode schizophrenia. Chinese Journal of Nervous and Mental Diseases 2002;28(3):219‐20.
Li 2003 {published data only}
    1. Li CH. A study of quetiapine and clozapine in treatment of schizophrenia. Chinese Journal of Nervous and Mental Diseases 2003;29(4):306‐07.
Li 2005 {published data only}
    1. Li Y‐F, Feng Y‐G. A double blind comparing study between the effects of quetiapine and clozapine on the life quality of the patients with schizophrenia. Medical Journal of Chinese People Health 2005;17(6):262‐4.
Lin 2003 {published data only}
    1. Lin C‐C, Bai Y‐M, Chen J‐Y, Wang Y‐C, Liou Y‐J, Chao C‐H, Lai I‐C, Tsai K‐Y, Chiu H‐J. Switching from clozapine to zotepine in schizophrenic patients: a randomized, single‐blind controlled study. Journal of the European College of Neuropsychopharmacology 2003;13(4):S318.
    1. Lin CC, Chen JY, Bai YM, Chen TT, Wang YC, Liou YJ, Lin WK. Remission of tardive dyskinesia following the switch from clozapine to zotepine: 2‐year follow‐up. Journal of the European College of Neuropsychopharmacology 2006;16(Suppl 4):S410.
    1. Lin CC, Chen JY, Bai YM, Wang YC, Liou YJ, Lin WK, Chen TT. Long‐term outcome of switching from clozapine to zotepine in refractory schizophrenia: a 2‐year follow‐up study. Journal of the European College of Neuropsychopharmacology 2005;15(Suppl 3):S500.
Lindenberg 1997 {published data only}
    1. Gallhofer B, Gruppe H, Bauer U. Zotepine versus clozapine: A comparison of the impact on the cognitive dysfunction syndrome in schizophrenia (a double blind trial). Pharmacopsychiatry 1995;28:179.
    1. Gallhofer B, Ulferts J, Bauer U, Gruppe H. Cognitive dysfunction in schizophrenia: a comparison of the impact of zotepine versus clozapine on the syndrome (a double blind trial). Schizophrenia Research 1996;18(2‐3):220.
    1. Meyer‐Lindenberg A, Bauer U, Lis S, Krieger S, Gallhofer B. Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: Results from a double blind trial. Pharmacopsychiatry 1997;30(2):35‐42. - PubMed
Liu 2004 {published data only}
    1. Liu Y, Xu M, Chen X. A controlled study of quetiapine and clozapine in the treatment of schizophrenia with predominantly negative symptoms. Shandong Archives of Psychiatry 2004;17(1):6‐8.
McGurk 2005 {published data only}
    1. Bellack AS, Schooler NR, Marder SR, Kane JM, Brown CH, Yang Y. Do clozapine and risperidone affect social competence and problem solving?. American Journal of Psychiatry 2004;161(2):364‐7. - PubMed
    1. Marder SR, Schooler NR, Kane JM, Petrides G, Chengappa KN, Wirshing WC, Wirshing DA, Umbricht D, Parapelli H. Tolerability of clozapine and risperidone during a twenty nine week trial. Schizophrenia Research 2003;60(1):293‐4.
    1. McGurk SR, Carter C, Goldman R, Green MF, Marder SR, Xie H, Schooler NR, Kane JM. The effects of clozapine and risperidone on spatial working memory in schizophrenia. American Journal of Psychiatry 2005;162(5):1013‐6. - PubMed
    1. McGurk SR, Goldman RS, Carter C, Green MF, Schooler N, Marder SR, Kane J. A double‐blind comparison of clozapine and risperidone on spatial working memory in treatment‐resistant schizophrenia.. Proceedings of the 39th Annual Meeting of the American College of Neuropsychopharmacology; 2000 Dec 10‐14; San Juan, Puerto Rico. 2000.
    1. McGurk SR, Goldman RS, Carter C, Green MF, Schooler R, Marder SR, Kane JM. A double‐blind comparison of clozapine and risperidone on spatial working memory in treatment resistant schizophrenia. Schizophrenia Research 2001;49(1‐2 Suppl):238.
Meltzer 2003 {published data only}
    1. Alphs L, Anand R, Islam MZ, Meltzer HY, Kane JM, Krishnan R, Green AI, Potkin S, Chouinard G, Lindenmayer JP, Kerwin R. The International Suicide Prevention Trial (InterSePT): Rationale and design of a trial comparing the relative ability of clozapine and olanzapine to reduce suicidal behavior in schizophrenia and schizoaffective patients. Schizophrenia Bulletin 2004;30(3):577‐86. - PubMed
    1. Bourgeois M, Swendsen J, Young F, Amador X, Pini S, Cassano GB, Lindenmayer JP, Hsu C, Alphs L, Meltzer HY, InterSePT Study Group. Awareness of disorder and suicide risk in the treatment of schizophrenia: results of the international suicide prevention trial. American Journal of Psychiatry 2004;161(8):1494‐6. - PubMed
    1. Glick ID, Zaninelli R, Hsu C, Young FK, Weiss L, Gunay I, Kumar V. Patterns of concomitant psychotropic medication use during a 2‐year study comparing clozapine and olanzapine for the prevention of suicidal behavior. Journal of Clinical Psychiatry 2004;65(5):679‐85. - PubMed
    1. Kane J, Alphs LD, Meltzer HY, Green AI, Hsu C, Anand R, Young F, Fahy T. The relationship between clinical response and changes in weight for clozapine and olanzapine‐treated patients. International Journal of Neuropsychopharmacology 2002;5(Suppl 1):S171.
    1. Meltzer H. Decreasing suicide in schizophrenia: the intersept study. European Psychiatry 2002;17(Suppl 1):26.
Moresco 2004 {published data only}
    1. Moresco RM, Cavallaro R, Messa C, Bravi D, Gobbo C, Galli LLG, Colombo C, Rizzo G, Velona I, Smeraldi E, Fazio F. Cerebral D2 and 5‐HT2 receptor occupancy in schizophrenic patients treated with olanzapine or clozapine. Journal of Psychopharmacology 2004;18(3):355‐65. - PubMed
Naber 2005 {published data only}
    1. Bender S, Dittmann‐Balcar A, Schall U, Klimke A, Riedel M, Vorbach U, Kuehn KU, Lambert M, Dittmann RW, Naber D. Effects of olanzapine versus clozapine on executive functions in schizophrenia. Schizophrenia Research 2002;53(3 Suppl 1):194.
    1. Bender S, Dittmann‐Balcar A, Schall U, Wolstein J, Klimke A, Riedel M, Vorbach E‐U, Kuhn K‐U, Lambert M, Dittmann RW, Naber D. Influence of atypical neuroleptics on executive functioning in patients with schizophrenia: a randomized, double‐blind comparison of olanzapine vs clozapine. International Journal of Neuropsychopharmacology 2006;9(2):135‐45. - PubMed
    1. Dittmann‐Balcar A, Bender S, Schall U, Klimke A, Mueller N, Vorbach U, Kuehn KU, Dittmann RW, Naber D. Effects of olanzapine versus clozapine on executive functions in schizophrenia. Schizophrenia Research 2003;60(1):131.
    1. Naber D, Bandelow B, Bender S, Klimke A, Kuehn K, Lambert M, Lemmer W, Dittmann M, Riedel ER. Subjective well‐being under neuroleptic treatment with olanzapine versus clozapine: first results from a double‐blind clinical trial using the SWN self‐rating scale. Schizophrenia Research 2001;49(1, 2):240.
    1. Naber D, Degner D, Bender S, Klimke A, Kuhn KU, Lambert M, Lemmer W, Riedel M, Vorbach EU, Dittmann RW. Olanzapine vs. clozapine: findings on subjective well‐being from a double‐blind clinical trial. Schizophrenia Research 2002;53(3 Suppl 1):176.
Ren 2002 {published data only}
    1. Ren Q, Lu Y. Comparison of quality of life of schizophrenic outpatients treated with risperdal or clozapine. Chinese Mental Health Journal 2002;16(3):198‐9.
Sacchetti 2006 {published data only}
    1. Sacchetti E, Galluzzo A, Valsecchi P, Romeo F, Gorini B, Warrington L. Efficacy and safety of ziprasidone and clozapine in treatment refractory schizophrenic patients: results of a randomized, double‐blind, 18‐week trial. Journal of the European College of Neuropsychopharmacology 2006;16(Suppl 4):S374.
Shaw 2006 {published data only}
    1. Shaw P, Sporn A, Gogtay N, Overman GP, Greenstein D, Gochman P, Tossell JW, Lenane M, Rapoport JL. Childhood‐onset schizophrenia: a double blind, randomized clozapine‐olanzapine comparison. Archives of General Psychiatry 2006;63(7):721‐30. - PubMed
Tollefson 2001 {published data only}
    1. Beasley CM, Beuzen JN, Birkett MA. Olanzapine versus clozapine: an international double‐blind study in the treatment of patients with treatment‐resistant schizophrenia. Proceedings of the 39th Annual Meeting of the New Clinical Drug Evaluation Unit; 1999 Jun 1‐4; Boca Raton, Florida, USA. 1999.
    1. Beasley CM, Beuzen JN, Birkett MA, Kiesler GM, Tollefson GD, Wood AJ. Olanzapine versus clozapine: an international double‐blind study of the treatment of resistant schizophrenia. Proceedings of the 152nd Annual Meeting of the American Psychiatric Association; 1999 May 15‐20; Washington DC, USA 1999.
    1. Beuzen JN, Birkett M, Kiesler G, Wood A. Olanzapine vs. clozapine in resistant schizophrenic patients ‐ results of an international double‐ blind randomised clinical trial. Proceedings of the 21st Collegium Internationale Neuro‐Psychopharmacologicum Congress; 1998 Jul 12‐16; Glasgow, UK. 1998.
    1. Beuzen JN, Birkett MA, Kiesler GM. An investigation of subgroup effects in a study of olanzapine versus clozapine in the treatment of resistant schizophrenic patients. Proceedings of the 11th European College of Neuropsychopharmacology Congress; 1998 Oct 31 ‐ Nov 4; Paris, France. 1998.
    1. Beuzen JN, Wood AJ, Kiesler GM, Birkett M, Tollefson GD. Olanzapine vs. Clozapine: an international double‐blind study in the treatment of patients with treatment‐resistant schizophrenia. Proceedings of the 11th World Congress of Psychiatry; 1999 Aug 6‐11; Hamburg, Germany. 1999.
Volavka 2002 {published data only}
    1. Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, Lindenmayer J‐P, Citrome L, McEvoy J, Kunz M, Chakos M, Lieberman JA. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol on treatment‐resistant patients with schizophrenia and schizoaffective disorder. Schizophrenia Research 2002;53(3 Suppl 1):194. - PubMed
    1. Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, Lindenmayer JP, Citrome L, McEvoy J, Kunz M, Chakos M, Cooper TB, Horowitz TL, Lieberman JA. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. American Journal of Psychiatry 2002;159(6):1018‐28. - PubMed
    1. Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, Lindenmayer JP, Citrome L, McEvoy J, Kunz M, Chakos M, Lieberman JA. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol on treatment‐resistant patients with schizophrenia and schizoaffective disorder. European Neuropsychopharmacology 2001;11(3):256.
    1. Citrome L, Volavka J, Czobor P, Sheitman B, Lindenmayer J‐P, McEvoy J, Cooper TB, Chakos M, Lieberman JA. Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Psychiatric Services 2001;52(11):1510‐4. - PubMed
    1. Citrome LL, Volavka J, Czobor P, Nolan K, Lieberman JA, Lindenmayer J‐P, Sheitman BB. Overt aggression and psychotic symptoms in patients with schizophrenia treated with clozapine, olanzapine, risperidone, or haloperidol. Proceedings of the 156th Annual Meeting of the American Psychiatric Association; 2003 May 17‐22; San Francisco, California, USA. 2003.
Wahlbeck 2000 {published data only}
    1. Cheine MV, Wahlbeck K, Tuisku K, Joffe G. Risperidone versus clozapine in the treatment of neuroleptic‐refractory/intolerant schizophrenia patients: a single‐blind randomized trial: Preliminary report of an on‐going study. Nordic Journal of Psychiatry. 1997; Vol. 51:99.
    1. Wahlbeck K, Cheine M, Tuisku K, Ahokas A, Joffe G, Rimon R. Risperidone versus clozapine in treatment‐resistant schizophrenia: a randomized pilot study. Progress in Neuropsychopharmacology and Biological Psychiatry 2000;24(6):911‐22. - PubMed
    1. Wahlbeck K, Cheine M, Tuisku K, Ahokas A, Joffe G, Rimón R. Risperidone versus clozapine in treatment‐resistant schizophrenia: a randomized pilot study. International Journal of Neuropsychopharmacology 2000;3(Suppl 1):S122. - PubMed
    1. Wahlbeck K, Cheine M, Tuisku K, Joffe G. Risperidone versus clozapine in treatment resistant schizophrenia: a randomised pilot trial. Schizophrenia Research 2000;41(1):197. - PubMed
Wang 2002 {published data only}
    1. Wang C, Feng Y, Wang L. A double‐blind randomized controlled study of olanzapine and clozapine on treatment of schizophrenia. Shanghai Archives of Psychiatry 2002;14(3):143‐5.
Zhou 2000 {published data only}
    1. Zhou Z, Shu Z, Yu Y. A control study of risperidone and clozapine in the treatment of the negative symptoms of schizophrenia. Aerospace Medicine 2000;11(2):69‐71.

References to studies excluded from this review

Agelink 2001 {published data only}
    1. Agelink MW, Majewski T, Wurthmann C, Lukas K, Ullrich H, Linka T, Klieser E. Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine. Journal of Clinical Psychopharmacology 2001;21(1):8‐13. - PubMed
Allison 2001 {published data only}
    1. Allison D, Cavazzoni P, Beasley C, Holcombe J, Buse J. Analysis of random glucose concentration data from patients with schizophrenia treated with typical and atypical agents during double‐blind, randomized, controlled clinical trials. Proceedings of the 7th World Congress of Biological Psychiatry; 2001 Jul 1‐6; Berlin, Germany. 2001, issue Suppl 1.
    1. Allison DB, Cavazzoni P, Beasley Jr CM, Berg PH, Mukhopadhyay N, Mallinckrodt C, Baker RW, Holcombe J, Taylor CC, Breier A, Buse JB. Random blood glucose levels in patients with schizophrenia treated with typical and atypical antipsychotic agents: an analysis of data from double‐blind, randomized, controlled clinical trial. European Neuropsychopharmacology 2001;11(3):280.
Altamura 1999 {published data only}
    1. Altamura AC, Cao A, Croce ML, Serri L, Soddu A, Laddomada A, Percudani M. Are atypical antipsychotics less depressogenic than typical compounds?. Journal of the European College of Neuropsychopharmacology 1999;9:S168.
Anonymous 1994 {published data only}
    1. Anonymous. Risperidone vs clozapine. Biological Therapies in Psychiatry 1994;17(12):47‐8.
Ascher‐Svanum 2006 {published data only}
    1. Ascher‐Svanum H, Zhu B, Faries D, Landbloom R, Swartz M, Swanson J. Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia. BMC Psychiatry 2006;6:8. - PMC - PubMed
Baumann 1993 {published data only}
    1. Baumann P, Billeter U, Kasas A, Blajev B, Juvet P, Souche A, Bondolfi G, Meylan C, Dufour H. Pharmacogenetic investigations about risperidone and clozapine in schizophrenic patients. Proceedings of the 9th World Congress of Psychiatry; 1993 Jun 6‐12; Rio de Janeiro, Brazil. Switzerland, 1993:76.
Beasley 2001 {published data only}
    1. Beasley CM, Berg PH, Dananberg J, Kwong KC, Taylor CCM, Breier A. Treatment emergent potential impaired glucose tolerance and potential diabetes with olanzapine compared to other antipsychotic agents and placebo. emergent potential impaired glucose tolerance and potential diabetes with olanzapine compared to other antipsychotic agents and placebo emergent potential impaired glucose tolerance and potential diabetes with olanzapine compared to other antipsychotic agents and placebo. Biological Psychiatry 2001;49(8):121S.
Bondolfi 1996 {published data only}
    1. Bondolfi G, Baumann P, Dufour H. Treatment‐resistant schizophrenia ‐ clinical experience with new antipsychotics. European Neuropsychopharmacology 1996;6(Suppl 2):S21‐5. - PubMed
Cai 2000 {published data only}
    1. Cai C, Wan C, Cheng F. The controlled investigation of risperidone and clozapine in the treatment of schizophrenia. Health Psychology Journal 2000;8(2):152‐4.
CATIE {published data only}
    1. Lieberman JA, Schneider LS, McEvoy J, Pariot P, Stroup S, Adiao J, Lebowitz BD. Effectiveness trials of antipsychotic drugs. Proceedings of the 154th Annual Meeting of the American Psychiatric Association; 2001 May 5‐10; New Orleans, Louisiana, USA. Marathon Multimedia, 2001.
    1. Lieberman JA, Schneider LS, McEvoy J, Pariot P, Stroup S, Adiao J, Lebowitz BD. Effectiveness trials of antipsychotic drugs. Proceedings of the 155th Annual Meeting of the American Psychiatric Association; 2002 May 18‐23; Philadelphia, Pennsylvania, USA. 2002.
    1. Lieberman JA, Stroup S. Schizophrenia, VI. The CATIE Project Protocol. American Journal of Psychiatry 2003;160(10):1748. - PubMed
    1. McEvoy JP. Comparison of clozapine versus other atypical drugs in prospectively defined, unresponsive patients. Proceedings of the 159th Annual Meeting of the American Psychiatric Association; 2006 May 20‐25, Toronto, Canada. 2006.
    1. McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. American Journal of Psychiatry 2006;163(4):600‐10. - PubMed
Cavazzoni 2002 {published data only}
    1. Cavazzoni P, Berg PH, Millikan M, Carlson C, Beasley CM. An integrated analysis of treatment‐emergent extrapyramidal syndrome in schizophrenic patients during olanzapine clinical trials versus placebo, haloperidol, risperidone or clozapine. International Journal of Neuropsychopharmacology 2002;5(Suppl 1):S164.
    1. Cavazzoni P, Berg PH, Millikan M, Carlson C, Beasley CM. An integrated analysis of treatment‐emergent extrapyramidal syndrome in schizophrenic patients during olanzapine clinical trials versus placebo, haloperidol, risperidone or clozapine. Schizophrenia Research 2002;53(3 Suppl 1):171. - PubMed
Cha 2002 {published data only}
    1. Cha A, Xu Y, Zhu XH. The curative effect comparison of risperidone and clozapine to treat recurrent schizophrenia. Chinese Medical Journal of Metallurgical Industry 2002;19(3):143‐4.
Chen 2002 {published data only}
    1. Chen SZ, Chi XZ, Li QH, Jiang YQ. A study of risperidone and clozapine in treatment of resistant schizophrenia. Heath Psychology Journal 2002;10(1):44‐46.
Chen 2003 {published data only}
    1. Chen F, Liang L, Zhu XH. A control study of elderly patients with schizophrenia treated with olanzapine or clozapine. Journal of Clinical Psychological Medicine 2003;13(5):298‐99.
Chen 2003b {published data only}
    1. Chen CQ. A study of risperidone and clozapine in treatment of first episode schizophrenia. HuaXia Medicine 2003;27:578‐79.
Chen 2004 {published data only}
    1. Chen YH, Li YM. A study of risperidone with haloperidol and clozapine in treatment of positive symptoms in schizophrenia. Suzhou University Journal of Medical Science 2004;24(6):912‐17.
Chen 2005 {published data only}
    1. Chen J, Li Z. A controlled study of olanzapine versus clozapine in schizophrenia. Journal of Clinical Psychosomatic Diseases 2005;11(3):217‐8.
Chen 2005b {published data only}
    1. Chen B, Liu X, Zhang X. A study of risperidone combination with clozapine in the treatment of the schizophrenia. Health Psychology Journal 2005;13(2):116‐7.
Cheng 2004 {published data only}
    1. Cheng Q, Huang CF. The influence of risperidone and clozapine in the quality of life of schizophrenia. Chinese Journal of Clinical Rehabilitation 2004;8(18):3640‐41.
Chou 1999 {published data only}
    1. Chou X, Chen Q, Li J. A clinical controlled study between risperidone and clozapine in the treatment of chronic schizophrenia. Sichuan Mental Health 1999;12(4):244‐6.
Chouinard 1994 {published data only}
    1. Chouinard G, Vainer JL, Belanger MC, Turnier L, Beaudry P, Roy JY, Miller R. Risperidone and clozapine in the treatment of drug‐resistant schizophrenia and neuroleptic‐induced supersensitivity psychosis. Progress in Neuropsychopharmacology and Biological Psychiatry 1994;18(7):1129‐41. - PubMed
Conley 1999a {published data only}
    1. Conley J, Goldman RS, Bilder RM, Bates J, Reiter G, Pappadopulos E, Robinson D, Alvir JMA, Lieberman J, Schooler N. A comparison of the neurocognitive effects of treatment with typical and atypical neuroleptics in first‐episode schizophrenia. Schizophrenia Research 1999;36(1‐3):128.
Cui 2002 {published data only}
    1. Cui B, Shen J, Tian H, Wang Y, Guo X. A comparative study of the effects of risperidone, chlorpromazine and clozapine to patients with schizophrenia by the electrocardiograms. Tianjin Pharmacy 2002;3:54‐5.
CUTLASS {published data only}
    1. Brownlee MM. The CUTLASS study: a multi‐centre randomised controlled trial of atypical anti‐psychotic drugs in severe schizophrenia. National Research Register 2000.
    1. Jones PB. Cost utility of the latest antipsychotics in severe schizophrenia (CUtlASS). National Research Register 2001; Vol. 3.
    1. Kerwin R. Cost utility of the latest antipsychotics in severe schizophrenia (CUTLASS) ‐ a multi‐centre, randomised controlled trial. National Research Register 2000.
    1. Lewis S. Cost utility of the latest antipsychotics in severe schizophrenia (CUTLASS): a multi‐centre, randomised, controlled trial. National Research Register 2000.
    1. Lewis S. The CUTLASS study: a multi‐centre randomised controlled trial of atypical anti‐psychotic drugs in severe schizophrenia. National Research Register 2000.
Dai 2004 {published data only}
    1. Dai J‐P, Zhao Z‐H, Mai G‐Y. Comparative study on the influence of olanzapine and clozapine on efficacy and quality of life in schizophrenia. Chinese Journal of Behavioral Medical Science 2004;13(4):396‐98.
David 1999 {published data only}
    1. David SR, Meehan KM, Sutton VK, Taylor CC. Treatment of negative symptoms with olanzapine in comparison with other novel antipsychotic agents. International Journal of Neuropsychopharmacology 2000;3(Suppl 1):s140.
    1. David SR, Meehan KM, Sutton VK, Taylor CC. Treatment of negative symptoms with olanzapine in comparison with other novel antipsychotic agents. Journal of the European College of Neuropsychopharmacology 1999;9:S292.
Deng 2000 {published data only}
    1. Deng H, Zheng H, He Z. A comparative trial of olanzapine versus clozapine in the treatment of schizophrenia. Shanghai Archives of Psychiatry 2000;12(3):143‐45.
Ding 2005 {published data only}
    1. Ding Z, Yu Z, Xu G. Control studies of increase of blood sugar induced by neo‐antipsychotics. Journal of Clinical Psychosomatic Diseases 2005;11(4):309‐10.
Du 2003 {published data only}
    1. Du JF, Zhou T, Xiong LH, Tian DF. A study of quetiapine and clozapine in treatment of chronic schizophrenia. Journal of Luzhou Medical College 2003;26(6):511‐12.
Du 2003b {published data only}
    1. Du WJ, Yu JL, Zhen HB, Zhong XQ, Ma C. The influence of chlorpromazine, clozapine and risperidone on the cognitive function of schizophrenia. International Medicine & Health Guidance News 2003;9(16):86‐8.
Du 2004 {published data only}
    1. Du Z‐H. A study on the change of serum thyroxin treated with Risperdal or clozapine. Journal of Practical Medical Techniques 2004;11(68):1020‐21.
Du 2005 {published data only}
    1. Du Z, Wu H. Effects of clozapine and risperidone on the glucose metabolism in schizophrenic patients. Qilu Journal of Medical laboratory Sciences 2005;16(1):8‐9.
Earnst 1999 {published data only}
    1. Earnst KS, Taylor SF, Smet IC, Goldman RS, Tandon R, Berent S. The effects of typical antipsychotics, clozapine, and risperidone on neuropsychological test performance in schizophrenia. Schizophrenia Research 1999;40(3):255‐6. - PubMed
Ellis 2000 {published data only}
    1. Ellis T, Cudkowicz ME, Sexton PM, Growdon JH. Clozapine and risperidone treatment of psychosis in parkinson's disease. Journal of Neuropsychiatry and Clinical Neurosciences 2000;12(3):364‐9. - PubMed
Fan 2003 {published data only}
    1. Fan C, Leiying, Wang K. The effect of clozapine and risperidone on blood sugar of patients with schizophrenia. Shandong Archives of Psychiatry 2003;16(3):131‐2.
Fang 2005 {published data only}
    1. Fang JH, Li WJ. A study of quetiapine in treatment of the dominant negative symptoms in schizophrenia. Sichuan Mental Health 2005;18(3):178.
Feng 2004 {published data only}
    1. Feng Y. The influence of clozapine and risperidone on the weight. Journal of Clinical Psychological Medicine 2004;14(2):101.
Fleming 1999 {published data only}
    1. Fleming K, Potkin SG, Alva G, Carreon D. Dissociation of improvement in neurocognition and negative symptomatology with olanzapine and clozapine conference abstract. Schizophrenia Research 1999;1, 2 & 3:279.
Flynn 1997 {published data only}
    1. Flynn SW, MacEwan GW, Altman S, Kopala LC, Smith GN, Honer WG. A comparison of two atypical antipsychotics in treatment resistant schizophrenia. Schizophrenia Research 1997;24(1, 2):185.
Fu 2005 {published data only}
    1. Fu H, Yu H, Huo J. A comparative study of quetiapine vs clozapine in the treatment of schizophrenia. Journal of Clinical Psychosomatic Diseases 2005;11(4):313‐4.
Gaertner 1999 {published data only}
    1. Gaertner I, Gaertner HJ, Lampe D. Therapeutic drug monitoring of clozapine and olanzapine. Similarities and differences. Psychopharmakotherapie 1999;6(3):105‐9.
Gallhofer 1995 {published data only}
    1. Gallhofer B, Gruppe H, Bauer U. Zotepine versus clozapine: A comparison of the impact on the cognitive dysfunction syndrome in schizophrenia (a double blind trial). Pharmacopsychiatry 1995;28:179.
Gallhofer 1996 {published data only}
    1. Gallhofer B, Bauer U, Lis S, Krieger S, Gruppe H. Cognitive dysfunction in schizophrenia: comparison of treatment with atypical antipsychotic agents and conventional neuroleptic drugs. European Neuropsychopharmacology 1996;6(Suppl 2):S13‐20. - PubMed
Ganguli 2005 {published data only}
    1. Ganguli R, Brar JS. Prevention of weight gain, by behavioral interventions, in patients starting novel antipsychotics. Schizophrenia Bulletin 2005;31:561‐62.
Gao 2003 {published data only}
    1. Gao CZ, Gao Z. A study of quetiapine in the treatment of first‐onset schizophrenia. Journal of Clinical Psychological Medicine 2003;13(4):221‐2.
Goldberg 2000 {published data only}
    1. Goldberg TE, Dodge M, Aloia M, Egan MF, Weinberger DR. Effects of neuroleptic medications on speech disorganization in schizophrenia: biasing associative networks towards meaning. Psychological Medicine 2000;30(5):1123‐30. - PubMed
Green 2001 {published data only}
    1. Green AI. Cannabis and schizophrenia‐clozapine vs risperidone. CRISP database (https://www‐commons.cit.nih.gov/crisp/index.html) (accessed 19th February 2001)..
Guan 2005 {published data only}
    1. Guan D‐H, Song H‐F. A control study of social function improvement in schizophrenia patients with risperdal and clozapine. Medical Journal of Chinese People Health 2005;17(9):506‐7.
Guo 2001 {published data only}
    1. Guo HR, Zhang SR, Sun FG. Clinical controlled study of risperidone and clozapine in treatment of schizophrenia. Journal of Xinxiang Medical College 2001;18(3):174‐6.
Guo 2003 {published data only}
    1. Guo S, Lu L, Cheng W. Effect of clozapine and risperidone on interleukin‐2 on schizophrenia. Shanghai Archives of Psychiatry 2003;15(1):35‐8.
Han 2005 {published data only}
    1. Han Z‐Y, Wang L‐J, Wang J. Analysis of risperidone, clonazepam in treatment of positive symptoms in schizophrenia. Ningxia Medical Journal 2005;27(9):631‐2.
Hang 2000 {published data only}
    1. Hang P. A study of risperidone and clozapine in treatment of resistant schizophrenia. Journal of Jining Medical College 2000;23(3):75.
He 2005 {published data only}
    1. He Y‐Q, Ma S‐H, Du J. A controlled study on hostility and side effects in clozapine and risperidone for treatment of patients with schizophrenia. Journal of Xinxiang Medical College 2005;22(2):118‐20.
Hu 2000 {published data only}
    1. Hu X‐C, Tao R‐F. A study of risperidone and clozapine in treatment of schizophrenia. Journal of Handan Medical College 2000;13(2):91.
Hu 2005 {published data only}
    1. Hu T‐S. A study of risperidone in treatment of dominant positive symptoms in schizophrenia. Chinese Journal of Behavioral Medical Science 2005;14(5):428.
Huang 2001 {published data only}
    1. Huang QM, Li J, Zhu XW, Mel QY. A study of risperidone and clozapine in treatment of the behaviours in schizophrenia. Shanghai Archives of Psychiatry 2001;13(3):152‐4.
Huang 2003 {published data only}
    1. Huang S‐P, Ma Z‐W, Guo B‐Y. Effectiveness of quetiapine vs clozapine in the treatment of schizophrenia. Journal of Clinical Psychosomatic Diseases 2003;9(4):206‐7.
Kelemen 2006 {published data only}
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Kong 2001 {published data only}
    1. Kong Q‐R, Yang R‐X, Li S‐C, Lu Z‐S, Li J‐Y, Chen X. A study of clozapine with risperidone and clozapine with sulpiride in treatment of resistant schizophrenia. Shandong Archives of Psychiatry 2001;14(2):119‐20.
Konrad 1996 {published data only}
    1. Konrad C, Schormair C, Eikelmann B, Berger K, Rottmann P. Clozapine and risperidone in the treatment of therapy‐resistant schizophrenia: a preliminary report on two ongoing clinical trials. Proceedings of the 8th Congress of the Association of European Psychiatrists; 1996 Jul 7‐12; London, UK. 1996.
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Kufferle 1997 {published data only}
    1. Kufferle B, Tauscher J, Asenbaum S, Vesely C, Podreka I, Brucke T, Kasper S. IBZM SPECT imaging of striatal dopamine‐2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol. Psychopharmacology 1997;133:323‐28. - PubMed
Lee 1995 {published data only}
    1. Lee MS, Jung IK, Kwak DI. Clinical efficacy of clozapine in treatment‐refractory schizophrenic patients. Proceedings of the 8th European College of Neuropsychopharmacology Congress; 1995 Sep 30 ‐ Oct 4; Venice, Italy. 1995.
Lei 2002 {published data only}
    1. Lei X, Liang T, Zhang X. A controlled study on risperidone and clozapine in treatment of schizophrenia. China Pharmacist 2002;5(3):169‐71.
Lei G 2004 {published data only}
    1. Lei G‐W, Hen A‐P, Qi L, Liu G‐X. The influence of atypical antipsychotics on glucose, triglycerides and total cholesterol. Chinese Journal of Misdiagnostics 2004;4(10):1665.
Li 2003b {published data only}
    1. Li T, Xue XM, Gong CF. A comparison study on the efficacy of risperidone vs clozapin in cognition of schizophrenia. Medical Journal of Chinese People Health 2003;15(11):653‐6.
Li 2001 {published data only}
    1. Li J, Dai X. A comparative study of risperidone and sulpiride in treating schizophrenia. Medical Journal of Chinese Civil Administration 2001;13(3):136‐8.
Li 2003 {published data only}
    1. Li C‐M, Guo L. A comparison of cognitive function in the first‐onset schizophrenia treated with quetiapine and clozapine. Medical Journal of Chinese People Health 2003;15(12):718‐21.
Li 2004 {published data only}
    1. Li Z. A comparative study of clozapine and risperidone lead to putting on weight. Heath Psychology Journal 2004;12(5):396‐97.
Liang 2002 {published data only}
    1. Liang S, Yu G, Ding G. Controlled study of olanzapine and clozapine in the treatment of schizophrenia. Shandong Archives of Psychiatry 2002;15(4):193‐94.
Liang 2005 {published data only}
    1. Liang Z‐Y, Huang X‐S. A study of risperidone and clozapine in treatment of first episode schizophrenia. Medical Journal of Chinese People Health 2005;17(9):509‐10.
Lindenmayer 1996 {published data only}
    1. Lindenmayer JP, Iskander A, Apergi FS, Park M. Cognitive profile and soft signs in clozapine versus risperidone treatment. Proceedings of the 150th Annual Meeting of the American Psychiatric Association; 1997 May 17‐22; San Diego, California, USA. 1997.
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Liu 1999 {published data only}
    1. Liu Q, Man C, Li X. A control study of risperidone and clozapine to treating the positive symptoms of schizophrenia. Sichuan Mental Health 1999;12(2):98‐100.
Liu 2001 {published data only}
    1. Liu Q, Li X. A comparative study on the efficacy of combining risperidone and clozapine in the treatment of schizophrenia. Shandong Archives of Psychiatry 2001;14(1):28‐30.
Liu 2003 {published data only}
    1. Liu X, Cheng J. A comparative study between quetiapine and clozapine in the treatment of schizophrenia and the relation with the plasma levels of il‐2, sil‐2r. an Baofu. Sichuan Mental Health 2003;16(3):152‐4.
Liu 2003b {published data only}
    1. Liu F, Dai M. The effects of risperidone and clozapine to patients with schizophrenia's life quality. Sichuan Mental Health 2003;16(4):203‐4.
Liu 2004 {published data only}
    1. Liu W, Li H, Zheng L. A controlled study on olanzapine and clozapine in the treatment of the acute phase of schizophrenia. Shanghai Archives of Psychiatry 2004;16(5):282‐84.
Liu 2004b {published data only}
    1. Liu J‐B, Wu J‐H. The influence of clozapine, risperidone and chlorpromazine on the glucose, triglycerides, total cholesterol and the weight in first episode schizophrenia. Chinese Journal of Nervous and Mental Diseases 2004;30(4):293‐95.
Liu 2004c {published data only}
    1. Liu N‐H, Zhang J‐Y. A study of risperidone with clonazepam in treatment of schizophrenia. Journal of Hainan Medical College 2004;10(6):394‐95.
Liu 2005 {published data only}
    1. Liu Y. A comparative study of risperidone and clozapine in the treatment of refractory schizophrenia. Journal of Heze Medical College 2005;17(1):13‐4.
Liu 2005b {published data only}
    1. Liu C‐X, Liu S‐H, Tu Z‐M, Liu B. A study of quetiapine with small dose of clozapine in treatment of resistant schizophrenia. Medical Journal of Chinese People Health 2005;17(12):748‐9.
Liu 2005c {published data only}
    1. Liu GF, Zhou JS. The influence of risperidone and clozapine in the quality of life of schizophrenia. Medical Journal of Chinese People Health 2005;17(6):289‐90.
Louwerens 1996 {published data only}
    1. Louwerens JW, Slooff CJ, Korf J, Coppens HJ, Paans AMJ. Dopamine2‐ and serotonine2‐receptor‐antagonism by antipsychotics in man. Schizophrenia Research 1996;18(2):141.
Lu 2002 {published data only}
    1. Lu Y, Ren Q, Tian M. A comparison of cognitive function in the first‐onset schizophrenia treated with risperidone and clozapine. Shandong Archives of Psychiatry 2002;15(4):206‐7.
Lu 2005 {published data only}
    1. Lu S, Zhang S‐A, Ren Y. Comparative study on the psychopathology and the quality of life of schizophrenia treated with risperidone, clozapine and quetiapine. Journal of Nursing Science 2005;20(3):57‐59.
Luo 2005 {published data only}
    1. Luo Y, Zhang S‐W, Wang A‐Q. The comparative study of quetiapine and clozapine in the treatment of female schizophrene. Medical Journal of Chinese People Health 2005;17(6):269‐70.
Ma 1999 {published data only}
    1. Ma QM, Guan HY, Jiang L, Zhang YY, Yi XR, Guo JM, Sun SG, Liu KH, Gao SQ, Wu HR, Xu SW. A study of risperidone in treatment of chronic schizophrenia. Heath Psychology Journal 1999;7(3):290‐93.
McKenna 2004 {published data only}
    1. McKenna PJ. An international study of improving treatment for the most severely ill with schizophrenia. National Research Register 2004; Vol. 2.
Meehan 2000 {published data only}
    1. Meehan KM, David SR, Taylor CC, Sutton VK. Change in extrapyramidal symptoms with olanzapine in comparison with other antipsychotic agents. Schizophrenia Research 2000;41(1):192.
Mei 2001 {published data only}
    1. Mei Q, Zhu X, Shen J. A comparative study of social function in schizophrenic patients treated with risperidone or clozapine. Journal of Clinical Psychological Medicine 2001;11(2):83‐5.
Mulqueen 2000 {published data only}
    1. Mulqueen AW, Wudarsky M, Nicolson RJ, Gochman P, Hamburger S, Lenane M, Rapoport JHL. Weight gain in pediatric patients on typical and atypical antipsychotics. 155th Annual Meeting of the American Psychiatric Association; 2002 May 18‐23; Philadelphia, Pennsylvania, USA. 2002.
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Nan 2001 {published data only}
    1. Nan Z, Wang J, Ji H. A controlled study of risperidone and clozapine both influences cognitive function of patients with schizophrenia. Sichuan Mental Health 2001;14(4):198‐200.
Ni 2001 {published data only}
    1. Ni JL, Jiiang LC, Hong X, Yang H, Zheng XP. A study of clozapine and risperidone in treatment of schizophrenia. Heath Psychology Journal 2001;9(3):181‐82.
Opjordsmoen 2000 {published data only}
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Pajonk 1998 {published data only}
    1. Pajonk FG, Tiessen F, Holtzbach R, Naber D. Clozapine versus risperidone: an open comparative and prospective study on efficacy, tolerability and quality of life. Proceedings of the 21st congress of the collegium Internationale Neuro‐psychopharmacologicum; 1998 Jul 12‐16, Glasgow. 1998.
Pan 2006 {published data only}
    1. Pan SM, Zhao LJ. A study of olanzapine and clozapine in treatment of schizophrenia. Zhejiang Journal of Integrated Traditional Chinese and Western Medicine 2006;16(1):32‐3.
Pao 2004 {published data only}
    1. Pao M, Zhang SQ, Zhao Z. Influence of three antipsychotic drugs on electrocardiogram in patients with schizophrenia. Journal of Xinxiang Medical College 2004;21(5):403‐4.
Peng 2001 {published data only}
    1. Peng H, Kuang Y, Huang X. A control study of risperidone in combination with clozapine in treating refractory schizophrenia. Journal of Modern Clinical Medical Bioengineering 2001;7(2):100‐2.
Qian 2004 {published data only}
    1. Qian D, Pan B, Yang G. Cost‐effectiveness analysis of 3 kinds of therapeutic schemes for schizophrenia. Evaluation and Analysis of Drug‐use in Hospital of China 2004;4(2):110‐11.
Qin 2005 {published data only}
    1. Qin Y, Kang W, Song L. A comparative study of risperidone combining alprazolam and clozapine in the treatment of patients with schizophrenia. Heath Psychology Journal 2005;13(6):444‐5.
Rapoport 1997 {published data only}
    1. Rapoport J, Kumra S, Jacobsen LK. The spectrum of extrapyramidal symptoms in children and young adults. Proceedings of the 150th Annual Meeting of the American Psychiatric Association; 1997 May 17‐22; San Diego, California, USA. 1997.
Ren 2000 {published data only}
    1. Ren JJ, Su JL, Li BQ. A study of risperidone and clozapine in treatment of resistant schizophrenia. Baotou Medical Journal 2000;35(2):6‐7.
Ren 2004 {published data only}
    1. Ren k, Zhao X, Jiang X. Effects of risperidone and clozapine on life quality of schizophrenics. Journal of Clinical Psychosomatic Diseases 2004;10(1):3‐4.
Rettenbacher 2004 {published data only}
    1. Rettenbacher MA, Baumgartner S, Ebenbichler C, Edlinger M, Hofer a, Hummer M, Kemmler G, Lechleitner M, Fleischhacker W. Alterations of glucose metabolism under treatment with clozapine vs. amisulpride. Schizophrenia Research 2004;67(1):191.
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Scherer 2004 {published data only}
    1. Scherer H, Bedard M‐A, Stip E, Paquet F, Richer F, Beriault M, Rodriguez J‐P, Motard J‐P. Procedural learning in schizophrenia can reflect the pharmacologic properties of the antipsychotic treatments. Cognitive and Behavioral Neurology 2004;17(1):32‐40. - PubMed
Schlogelhofer 2006 {published data only}
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Schuld 2000 {published data only}
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Shao 1999 {published data only}
    1. Shao YQ. The extrapyramidal side effects of risperidone. Journal of Southeast China National Defense Medicinal Science 1999;1(1):28‐9.
Sharma 2002 {published data only}
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Sheng 2003 {published data only}
    1. Sheng Y, Liu T, Li Y. A comparison study of the blood sugar in the treatment of schizophrenic patients with risperidone, clozapine and chlorpromazine. Qilu Journal of Medical Laboratory Sciences 2003;14(1):11‐2.
Sheng 2005 {published data only}
    1. Sheng Y. Effects of clozapine and risperidone on serum interleukin‐2 and interleukin‐6 of patients with first episode schizophrenia. Qilu Journal of Medical Laboratory Sciences 2005;16(5):14‐5.
Shi 2000 {published data only}
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Shi 2001 {published data only}
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Smith 2004 {published data only}
    1. Smith R. An addition of pioglitazone or placebo to 40 patients with schizophrenia under treatment with olanzapine or clozapine. Stanley Foundation Research Programs 2004.
Speer 1997 {published data only}
    1. Speer AM, Risch SC, Hamner MB, Molloy M, Ulmer HG, Vane CL, Vincent DJ, George MS. The effect of an atypical antipsychotic (risperidone) on temporal lobe and prefrontal cortex activity in schizophrenia. Schizophrenia Research 1997;24(1, 2):173.
Su 1996 {published data only}
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Sun 2001 {published data only}
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Swanson 2006 {published data only}
    1. Swanson JW, Swartz MS, Dorn RA. Effectiveness of atypical antipsychotics for substance abuse in schizophrenia patients. Proceedings of the 159th Annual Meeting of the American Psychiatric Association; 2006 May 20‐25, Toronto, Canada. 2006.
Tandon 2004 {published data only}
    1. Octavio I, Tandon R, Stock E, Riera L, Kujawa M, Lam S, Pans M, Iwamoto T, Carson W. A naturalistic study of aripiprazole treatment in a general psychiatric setting. Proceedings of the Thematic Conference of the World Psychiatric Association on "Treatments in Psychiatry: An Update"; 2004 Nov 10‐13; Florence, Italy. 2004.
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Tang 2003 {published data only}
    1. Tang Y. A controlled study of schizophrenia treated with quetiapine and clozapine. Shanghai Archives of Psychiatry 2003;15(1):27‐9.
Tang 2005 {published data only}
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Tang 2005b {published data only}
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Tian 2005 {published data only}
    1. Tian RF. A study of risperidone and clozapine in treatment of schizophrenia in children. Journal of Clinical Psychosomatic Diseases 2005;11(3):261.
Tong 2005 {published data only}
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Trichard 1998 {published data only}
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Turrone 2002 {published data only}
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Vaughan 2000 {published data only}
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Wang 2002b {published data only}
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Wang 2003 {published data only}
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Wang 2003b {published data only}
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Wang 2003c {published data only}
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Wang 2004 {published data only}
    1. Wang X. Comparative study of effects of quetiapine and clozapine on quality of life of schizophrenics. Journal of Clinical Psychosomatic Diseases 2004;10(3):167‐8.
Wang 2004b {published data only}
    1. Wang H. Controlled study of the effect of olanzapine and clozapine on electroencephalogram of schizophrenic patients. Journal of North China Coal Medical College 2004;6(3):289‐90.
Wang 2005 {published data only}
    1. Wang Y, Sun M, Shao X. A comparative study between quetiapine and clozapine in the treatment of schizophrenia. Heath Psychology Journal 2005;13(4):271‐2.
Wang 2005b {published data only}
    1. Wang C‐H, Li Y, Ma J‐D, Wang L‐H, Pan M, Mu J‐L. Comparison of cognitive function and p300 potentials in first‐episode schizophrenia treated with risperidone and clozapine. Chinese Journal of Nervous and Mental Diseases 2005;31(4):267‐71.
Wang 2005c {published data only}
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Wang 2005d {published data only}
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Wang 2005e {published data only}
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Wang 2005f {published data only}
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Weickert 2003 {published data only}
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Weng 1998 {published data only}
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Wirshing 1999 {published data only}
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Wu 2002 {published data only}
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Wu 2004 {published data only}
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Wudarsky 1999 {published data only}
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Xiang 2005 {published data only}
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Xiao 2000 {published data only}
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Xie 2005 {published data only}
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Xin 2001 {published data only}
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Xu 2001 {published data only}
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Xu 2002 {published data only}
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Yagdiran 2000 {published data only}
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Yang 1998 {published data only}
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Yang 2002 {published data only}
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Yang 2004 {published data only}
    1. Yang B, Wang YD, Zhang L. Effects of clozapine, risperidone and haloperidol on plasma leptin in first‐episode schizophrenic patients. Journal of The Fourth Military Medical University 2004;25(14):1323‐25.
Yang L 2004 {published data only}
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Yang X 2004 {published data only}
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Ye 2005 {published data only}
    1. Ye S‐C, Zhang W‐Y, Zhang Y‐M. Observation of developments of the level of serum prolactin of first‐episode schizophrenia patients during the treatment. Medical Journal of Chinese People Health 2005;17(6):267‐8.
Yin 2004 {published data only}
    1. Yin HR, Fang YM, Huang RH, Yang XQ. A study of risperidone and clozapine in treatment of schizophrenia. China Medical Engineering 2004;12(3):87‐8.
Yu 2002 {published data only}
    1. Yu G, Ding G, Li X. An economic burden comparison of typical and atypical antipsychotic therapies for schizophrenia. Chinese Journal of Psychiatry 2002;35(3):177‐9.
Yuan 2002 {published data only}
    1. Yuan GZ, Huang YP, Li X. The influence of antipsychotics on the weight and glucose. Journal of Clinical Psychological Medicine 2002;12(6):369‐70.
Yuan 2005 {published data only}
    1. Yuan F‐J, Gao M‐Z, Liu X. A contrast observation of quetiapine and clozapine in affecting electroencephalogram. Journal of Practical Medical Techniques 2005;12(2B):482‐4.
Yuo 1999 {published data only}
    1. Yu GH, Huang X. A study of risperidone and clozapine in treatment of resistant patients in schizophrenia. Chinese Journal of Nervous and Mental Diseases 1999;25(6):366‐67.
Zelaschi 2000 {published data only}
    1. Zelaschi NM, Rodriguez JL, Gaitan S, Panizzo S, Sobrera A, Lopez A, Archuby F. A follow‐up study comparing clinical and endocrine effects of clozapine and risperidone. Proceedings of the 153rd Annual Meeting of the American Psychiatric Association; 2000 May 13‐18; Chicago, Illinois, USA. 2000.
Zelaschi 2006 {published data only}
    1. Zelaschi Sr NM, Rodriguez Sr JL, Gaitan S, Palacios Vallejos ME, Zieher LM. The effects of the switch of conventional neuroleptics to atypical antipsychotics: a follow‐up study of patients with chronic schizophrenia. Proceedings of the 159th Annual Meeting of the American Psychiatric Association; 2006 May 20‐25, Toronto, Canada. 2006.
Zhan 2002 {published data only}
    1. Zhan LY. Analysis of risperidone and clozapine in behavioral change in schizophrenia. Modern Rehabilitation 2002;6(19):2943.
Zhang 2002 {published data only}
    1. Zhang Q. A comparison of cognitive function in the first‐onset schizophrenia treated with risperidone and clozapine. Journal of Qiqihar Medical 2002;23(8):852‐3.
Zhang 2002b {published data only}
    1. Zhang X‐Z, Yu J‐L. Control studies of relapses between risperidone and clozapine in schizophrenia. Journal of Clinical Psychosomatic Diseases 2002;8(3):145‐47.
Zhang 2004 {published data only}
    1. Zhang HY, Lin QC, Lin JC, Guo YB. A study of olanzapine and clozapine in EEG. International Medicine & Health Guidance News 2004;10(14):113‐14.
Zhang 2005 {published data only}
    1. Zhang Y, Jiang Y, Zhao S. A comparative study of quetiapine combined with clomipramine in treatment of schizophrenia with obsessive‐compulsive symptoms. Heath Psychology Journal 2005;13(4):260‐2.
Zhang 2005b {published data only}
    1. Zhang H, Zhang M, Gu W. A comparative study of social function in schizophrenia patients treated with Seroquel (quetiapine) or clozapine. Sichuan Mental Health 2005;18(2):91‐3.
Zhang 2005c {published data only}
    1. Zhang HY, Zhan C. Cost efficiency analysis of four atypical antipsychotics in treatment of schizophrenia. Medical Journal of Chinese People Health 2005;17(12):756‐7.
Zhang 2005d {published data only}
    1. Zhang J‐X, Zhu F‐Y, Shi X‐M, Zhang X‐M, Wei Li‐H, Ji Z‐F, Lin R‐M. Controlled study of risperidone versus clozapine in treatment of refractory schizophrenia with depressive symptoms. Journal of Clinical Psychological Medicine 2005;15(4):201‐2.
Zhang 2005e {published data only}
    1. Zhang M, Zhang H‐F, Gu W. A comparative study of quetiapine and clozapine in the treatment of schizophrenia. Shandong Archives of Psychiatry 2005;18(2):86‐8.
Zhang 2005f {published data only}
    1. Zhang R‐X, Cao Y‐F. A comparative study of EKG changed by quetiapine and clozapine in the treatment of schizophrenia. Medical Journal of Chinese People Health 2005;17(6):290‐1.
Zhang 2005g {published data only}
    1. Zhang ZP, Xie YY. 40 cases of olanzapine in treatment of schizophrenia. Shandong Medical Journal 2005;56:61.
Zhao 2005 {published data only}
    1. Zhao YH, Fang JH, Wang SH, An CG, Ma X, Li HX. A study of quetiapine and clozapine in treatment of schizophrenia. Journal of Clinical Psychological Medicine 2005;15(4):231‐2.
Zheng 2001 {published data only}
    1. Zheng H, Xu CT. A clinical study of clozapine and olanzapine in treatment of resistant schizophrenia. Journal of Qiqihar Medical 2001;22(8):865.
Zheng 2003 {published data only}
    1. Zheng YJ, Wang GH, Cheng ZL. Effects of clozapine and risperidone on the glucose metabolism in first‐episode schizophrenic patients. Chinese Journal of Psychiatry 2003;36(4):207‐10.
Zheng X 2001 {published data only}
    1. Zheng XX, Huang JH, Huang ZZ. A study of risperidone and clozapine in treatment of side effects on schizophrenia. Strait Pharmaceutical Journal 2001;13(3):79‐80.
Zhong 2003 {published data only}
    1. Zhong H, Wang H. The influence of risperidone , chlorpromazine and clozapine on ECG. Journal of Gannan Medical College 2003;23(6):644‐45.
Zhou 2003 {published data only}
    1. Zhou P, Gong F, Fan C. A control of treating chronic schizophrenia with seroquel or clozapine. Jiangxi Medical Journal 2003;6:395‐6.
Zhou 2003b {published data only}
    1. Zhou HJ, Zhu YP, Lu SL. The influence of clozapine on glucose in schizophrenia. Liaoning Journal of Practical Diabetology 2003;11(1):21‐22.
Zhou 2005 {published data only}
    1. Zhou B, Tang Y, Zhu L. Effects of risperidone vs clozapine on blood‐lipid of first‐episode schizophrenia. Journal of Clinical Psychosomatic Diseases 2005;11(4):315‐6.
Zhu 1999 {published data only}
    1. Zhu X, Mei Q. A controlled study comparing drug compliance with risperidone and clozapine in treatment of schizophrenia. Journal of Clinical Psychological Medicine 1999;9(3):151‐2.
Zhu 2002 {published data only}
    1. Zhu H, Ma C, Hou J, Yin Q, Hu H, Guo Y. Study of serum IL‐6 and a‐IFN in the pre‐and post‐treatment of 68 patients with first episode schizophrenia. Chinese Journal of Nervous and Mental Diseases 2002;28(5):324‐6.
Zhu 2003 {published data only}
    1. Zhu F, Lin R, Zhang J. Risperidone versus clozapine in treatment‐resistant schizophrenia:a randomized controlled study. Shanghai Archives of Psychiatry 2003;15(3):168‐71.
Zhu Q 2003 {published data only}
    1. Zhu QY, Zhang SW. 15 cases of risperidone in treatment of resistant schizophrenia. Herald of Medicine 2003;6(S1):13‐14.
Zoccali 2003 {published data only}
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References to studies awaiting assessment

Anand 1999 {published data only}
    1. Anand R, Alphs L, Azorin JM, Remington G, Péré J‐J, Bourdeix I. Superior efficacy of clozapine in chronic, severe schizophrenia: comparison with risperidone. Journal of Clinical Psychiatry 1999;60(Suppl 12):3‐50.
Byerly 1999 {published data only}
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Chengappa 2001 {published data only}
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Chowdhury 1999 {published data only}
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Lieberman 2001 {published data only}
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Loza 2002 {published data only}
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Magnuson 2001 {published data only}
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Oliemeulen 2000 {published data only}
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References to other published versions of this review

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