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Comparative Study
. 2009 Jan 21;2009(1):CD000059.
doi: 10.1002/14651858.CD000059.pub2.

Clozapine versus typical neuroleptic medication for schizophrenia

Adib Essali  1 , Nahla Al-Haj Haasan, Chunbo Li, John Rathbone
Affiliations
Comparative Study

Clozapine versus typical neuroleptic medication for schizophrenia

Adib Essali et al. Cochrane Database Syst Rev. .

Abstract

Background: Long-term drug treatment of schizophrenia with typical antipsychotics has limitations: 25 to 33% of patients have illnesses that are treatment-resistant. Clozapine is an antipsychotic drug, which is claimed to have superior efficacy and to cause fewer motor adverse effects than typical drugs for people with treatment-resistant illnesses. Clozapine carries a significant risk of serious blood disorders, which necessitates mandatory weekly blood monitoring at least during the first months of treatment.

Objectives: To evaluate the effects of clozapine compared with typical antipsychotic drugs in people with schizophrenia.

Search strategy: For the current update of this review (March 2006) we searched the Cochrane Schizophrenia Group Trials Register.

Selection criteria: All relevant randomised clinical trials (RCTs).

Data collection and analysis: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a fixed-effect model.

Main results: We have included 42 trials (3950 participants) in this review. Twenty-eight of the included studies are less than 13 weeks in duration, and, overall, trials were at significant risk of bias. We found no significant difference in the effects of clozapine and typical neuroleptic drugs for broad outcomes such as mortality, ability to work or suitability for discharge at the end of the study. Clinical improvements were seen more frequently in those taking clozapine (n=1119, 14 RCTs, RR 0.72 CI 0.7 to 0.8, NNT 6 CI 5 to 8). Also, participants given clozapine had fewer relapses than those on typical antipsychotic drugs (n=1303, RR 0.62 CI 0.5 to 0.8, NNT 21 CI 15 to 49). BPRS scores showed a greater reduction of symptoms in clozapine-treated patients, (n=1145, 16 RCTs, WMD -4.22 CI -5.4 to -3.1), although the data were heterogeneous (Chi(2) 0.0001, I(2) 66%). Short-term data from the SANS negative symptom scores favoured clozapine (n=196, 5 RCTs, WMD -5.92 CI -7.8 to -4.1). We found clozapine to be more acceptable in long-term treatment than conventional antipsychotic drugs (n=982, 16 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 15 CI 12 to 20). Blood problems occurred more frequently in participants receiving clozapine (3.2%) compared with those given typical antipsychotics (0%) (n=1031, 13 RCTs, RR 7.09 CI 2.0 to 25.6). Clozapine participants experienced more drowsiness, hypersalivation, or temperature increase, than those given conventional neuroleptics. However, clozapine patients experienced fewer motor adverse effects (n=1433, 18 RCTs, RR 0.58 CI 0.5 to 0.7, NNT 5 CI 4 to 6).The clinical effects of clozapine were more pronounced in participants resistant to typical neuroleptics in terms of clinical improvement (n=370, 4 RCTs, RR 0.71 CI 0.6 to 0.8, NNT 4 CI 3 to 6) and symptom reduction. Thirty-four per cent of treatment-resistant participants had a clinical improvement with clozapine treatment.

Authors' conclusions: Clozapine may be more effective in reducing symptoms of schizophrenia, producing clinically meaningful improvements and postponing relapse, than typical antipsychotic drugs - but data are weak and prone to bias. Participants were more satisfied with clozapine treatment than with typical neuroleptic treatment. The clinical effect of clozapine, however, is, at least in the short term, not reflected in measures of global functioning such as ability to leave the hospital and maintain an occupation. The short-term benefits of clozapine have to be weighed against the risk of adverse effects. Within the context of trials, the potentially dangerous white blood cell decline seems to be more frequent in children and adolescents and in the elderly than in young adults or people of middle-age.The existing trials have largely neglected to assess the views of participants and their families on clozapine. More community-based long-term randomised trials are needed to evaluate the efficacy of clozapine on global and social functioning as trials in special groups such as people with learning disabilities.

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Conflict of interest statement

None known.

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 TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 1 Death.
1.2
1.2. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 2 Relapse.
1.3
1.3. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 3 Global impression: 1. Not clinically improved.
1.4
1.4. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 4 Global impression: 2. Not ready for discharge.
1.5
1.5. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 5 Hospitalisation: 1. Not discharged or readmitted within 1 year after discharge (long term).
1.6
1.6. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 6 Unable to work.
1.7
1.7. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 7 Participant dissatisfaction.
1.8
1.8. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 8 Leaving the study early.
1.9
1.9. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 9 Mental state: 1. Overall clinical symptoms.
1.10
1.10. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 10 Mental state 2. Negative symptoms.
1.11
1.11. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 11 Mental state 3: Positive symptoms.
1.12
1.12. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 12 Cognitive functioning: impairment ‐short term (SKT).
1.13
1.13. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 13 Cognitive functioning: Various scales.
1.14
1.14. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 14 Behaviour: 1. No change/deterioration ‐ short term (NOSIE).
1.15
1.15. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 15 Adverse effects: 1. Blood problems.
1.16
1.16. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 16 Adverse effects: 2. Drowsiness.
1.17
1.17. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 17 Adverse effects: 3. Low blood pressure /dizziness.
1.18
1.18. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 18 Adverse effects: 4. Salivation.
1.19
1.19. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 19 Adverse effects: 5a. Weight gain.
1.20
1.20. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 20 Adverse effects: 5b.Weight gain.
1.21
1.21. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 21 Adverse effects: 6. Movement disorder.
1.22
1.22. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 22 Adverse effects: 7. Fits.
1.23
1.23. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 23 Adverse effects: 8. High temperature.
1.24
1.24. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 24 Adverse effects: 9. OGTT.
1.25
1.25. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 25 Adverse effects: 10. Fasting blood sugar (high score = worse).
1.26
1.26. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 26 Adverse effects: 11. Blood suger (high score = worse).
1.27
1.27. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 27 Adverse effects: 12. Cardiovacular.
1.28
1.28. Analysis
Comparison 1 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ OVERALL, Outcome 28 Adverse effects: 13. TESS.
2.1
2.1. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 1 Death.
2.2
2.2. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 2 Relapse.
2.3
2.3. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 3 Global impression: 1. Not clinically improved.
2.4
2.4. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 4 Global impression: 2. Not ready for discharge ‐ long term.
2.5
2.5. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 5 Hospitalisation: 1. Not discharged or readmitted within 1 year after discharge (long term).
2.6
2.6. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 6 Leaving the study early.
2.7
2.7. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 7 Participant dissatisfaction ‐ long term.
2.8
2.8. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 8 Mental state: 1. Various scales.
2.9
2.9. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 9 Mental state: 2. Negative symptoms ‐ short term (low score = best).
2.10
2.10. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 10 Adverse effects 1. Blood problems.
2.11
2.11. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 11 Adverse effects 2. Drowsiness.
2.12
2.12. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 12 Adverse effects 3. Low blood pressure /dizziness.
2.13
2.13. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 13 Adverse effects 4. Salivation.
2.14
2.14. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 14 Adverse effects 5. Weight gain.
2.15
2.15. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 15 Adverse effects 6. Movement disorder.
2.16
2.16. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 16 Adverse effects 7. High temperature.
2.17
2.17. Analysis
Comparison 2 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ TREATMENT RESISTANT SCHIZOPHRENIA, Outcome 17 Adverse effects 8. Fits.
3.1
3.1. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 1 Death.
3.2
3.2. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 2 Relapse.
3.3
3.3. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 3 Global impression: 1. Not clinically improved.
3.4
3.4. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 4 Leaving the study early.
3.5
3.5. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 5 Mental state: 1. End point BPRS (low score = best).
3.6
3.6. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 6 Mental state: 2. Negative symptoms (end point SANS, low score = best).
3.7
3.7. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 7 Adverse effects: 1. Blood problems.
3.8
3.8. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 8 Adverse effects: 2. Drowsiness.
3.9
3.9. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 9 Adverse effects: 3. Too much salivation.
3.10
3.10. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 10 Adverse effects: 4. Weight gain.
3.11
3.11. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 11 Adverse effects: 5. Movement disorder.
3.12
3.12. Analysis
Comparison 3 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ CHILDREN AND ADOLESCENTS, Outcome 12 Adverse effects: 6. Fits.
4.1
4.1. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 1 Death.
4.2
4.2. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 2 Leaving the study early.
4.3
4.3. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 3 Adverse effects: 1. Blood problems.
4.4
4.4. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 4 Adverse effects: 2. Drowsiness.
4.5
4.5. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 5 Adverse effects: 3. Low blood pressure /dizziness.
4.6
4.6. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 6 Adverse effects: 4. Too much salivation.
4.7
4.7. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 7 Adverse effects: 5. Weight gain.
4.8
4.8. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 8 Adverse effects: 6. Movement disorder.
4.9
4.9. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 9 Adverse effects: 7. Fits.
4.10
4.10. Analysis
Comparison 4 CLOZAPINE versus TYPICAL ANTIPSYCHOTICS ‐ ELDERLY PEOPLE, Outcome 10 Adverse effects 8. High temperature.
5.1
5.1. Analysis
Comparison 5 SENSITIVITY ANALYSIS ‐ CHINESE TRIALS, Outcome 1 Leaving the study early.
5.2
5.2. Analysis
Comparison 5 SENSITIVITY ANALYSIS ‐ CHINESE TRIALS, Outcome 2 Mental state: 1. Overall clinical symptoms.
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Update of

References

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Kane 1995 (H) {published and unpublished data}
    1. Bellack AS, Schooler NR, Kane JM, Marder SR. The impact of clozapine on psychosocial competence. Schizophrenia Research 1995;15:143.
    1. Kane JM, Marder SR, Schooler NR, Wirshing WC, Umbricht D, Baker RW, Wirshing DA, Safferman A, Ganguli R, McMeniman M, Borenstein M. Clozapine and haloperidol in moderately refractory schizophrenia: A 6‐month randomized double‐blind comparison [Clozapin und haloperidol bei maessig resistenter schizophrenie]. Archives of General Psychiatry 2001;58(10):965‐72. [MEDLINE: ] - PubMed
    1. Kane JM, Schooler NR, Marder S, Wirshing W, Ames D, Umbricht D, et al. Efficacy of clozapine versus haloperidol in a long‐term clinical trial. Schizophrenia Research 1996;18:127.
    1. Marder SR. Antipsychotics in treatment‐refractory schizophrenia. Journal of Clinical Psychiatry 1998;59:259‐65.
    1. Marder SR, Kane JM, Schooler NR, Wirshing WC, Baker R, Ames D, et al. Effectiveness of clozapine in treatment resistant schizophrenia. Schizophrenia Research 1997;24:187.
Klieser 1988 (H) {published data only}
    1. Klieser E, Schönell H. Clinical pharmacological studies for the treatment of negative symptoms in schizophrenia [Klinisch‐pharmakologische studien zur behandlung schizophrener minussymptomatik]. In: Möller HJ, Pelzer E editor(s). Neuere Ansätze zur Diagnostik und Therapie schizophrener Minussymptomatik. Berlin: Springer‐Verlag, 1990, 1990.
    1. Schönell H, Klieser E. Comparison of the effects of standardized doses of haloperidol and clozapine on systematic delusions of chronic schizophrenics. Psychopharmacology 1988;96(Suppl):186.
    1. Stein D, Schönell H, Klieser E. Haloperidol for the treatment of systematised delusions of chronic schizophrenic patients [Haloperidol zur Behandlung des systematisierten Wahns chronisch schizophrener Patienten]. In: Saletu B editor(s). Biologische Psychiatrie. 2. Drei‐Länder‐Symposium für Biologische Psychiatrie. Stuttgart: Georg Thieme Verlag, 1989.
Klieser 1990 (H) {published data only}
    1. Klieser E, Lehmann E, Heinrich K. Risperidone in comparison with various treatments of schizophrenia. In: Kane JM, Möller HJ, Awouters editor(s). Medical Psychiatry. Vol. 3 Serotonin in antipsychotic treatment: mechanisms and clinical practice, New York: Marcel Dekker, 1996.
    1. Klieser E, Schönell H. Clinical pharmacological studies for the treatment of negative symptoms in schizophrenia [Klinisch‐pharmakologische studien zur behandlung schizophrener minussymptomatik]. In: Möller HJ, Pelzer E editor(s). Neuere Ansätze zur Diagnostik und Therapie schizophrener Minussymptomatik. Berlin: Springer‐Verlag, 1990.
    1. Klieser E, Strauss WH, Burtscheid W. Double‐blind comparative study of haloperidol, remoxipride and clozapine in schizophrenia. Proceedings of the 15th Congress of the Collegium Internationale Neuro‐Psychopharmacologicum; 1986 Dec 14‐17; Puerto Rico. Puerto Rico: Neuro‐Psychopharmacologicum, 1986:111.
    1. Klieser E, Strauss WH, Lemmer W. The tolerability and efficacy of the atypical neuroleptic remoxipride compared with clozapine and haloperidol in acute schizophrenia. Acta Psychiatrica Scandinavica 1994;89:S68‐73. - PubMed
Kumra 1994 (H) {published and unpublished data}
    1. Gordon CT, Frazier JA, McKenna K, Gledd J, Zametkin A, Zahn T. Childhood‐onset schizophrenia: an NIMH study in progress. Schizophrenia Bulletin 1994;20:697‐712. - PubMed
    1. Huffman GB. Efficacy of clozapine for schizophrenia in children. American Family Physician 1997;55(4):1356.
    1. Kumra S, Frazier JA, Jacobsen LK, McKenna K, Gordon CT, Lenane MC, Hamburger SD, Smith AK, Albus KE, Alaghband‐Rad J, Rapoport JL. Childhood‐onset schizophrenia. A double‐blind clozapine‐haloperidol comparison. Archives of General Psychiatry 1996;53:1090‐7. - PubMed
    1. Kumra S, Jacobsen LK, Rapoport JL. Childhood‐onset schizophrenia: a double‐blind clozapine trial. Proceedings of the American Psychiatric Association Annual Meeting; 1996 May 8; New York. New York: American Psychiatric Association, 1996.
    1. Piscitelli SC, Frazier JA, McKenna K, Albus KE, Grothe DR, Gordon CT. Plasma clozapine and haloperidol concentrations in adolescents with childhood‐onset schizophrenia: association with response. Journal of Clinical Psychiatry 1994;55:SB94‐7. - PubMed
Lee 1994 (mainly H) {published data only}
    1. Lee MA, Jayathilake K, Meltzer HY. A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic‐responsive schizophrenia. Schizophrenia Research 1999;37:1‐11. - PubMed
    1. Lee MA, Thompson PA, Meltzer HY. Effects of clozapine on cognitive function in schizophrenia. Journal of Clinical Psychiatry 1994;55:82‐7. - PubMed
    1. Meltzer HY. Clozapine withdrawal: serotonergic or dopaminergic mechanisms?. Archives of General Psychiatry 1997;54:760‐3. - PubMed
Leon 1974 (CPZ) {published data only}
    1. Leon CA. Efficiacy of clozapine. Archives of General Psychiatry 1978;35:905. - PubMed
    1. Leon CA. Therapeutic effects of clozapine. A four‐year follow‐up study of a controlled clinical trial. Acta Psychiatrica Scandinavica 1979;59:471‐80. - PubMed
    1. Leon CA, Estrada H. The therapeutic effects of clozapine on psychotic symptoms (a double‐blind study) [Efectos terapeuticos de la Clozapina sobre los sintomas de Psicosis]. Revista Colombiana Psiquiatria 1974;3:309‐18.
Li 2003 (Lox) {published data only}
    1. Li X, Zou Z, Wang Y. Controlled study of loxapine and clozapine in the treatment of schizophrenia. International Chinese Neuropsychiatry Medicine Journal 2003;4(1):1‐2.
Lieberman 2003 (CPZ) {published data only}
    1. Lieberman JA, Phillips M, Gu H, Stroup S, Zhang P, Kong L, Ji ZKG, Hamer RM. Atypical and conventional antipsychotic drugs in treatment‐naive first‐episode schizophrenia: a 52‐week randomized trial of clozapine vs chlorpromazine. Neuropsychopharmacology 2003;28(5):995‐1003. [MEDLINE: ] - PubMed
    1. Lieberman JA, Phillips M, Kong L, Gu H, Koch G. Efficacy and safety of clozapine versus chlorpromazaine in first‐episode psychosis: results of a 52 week randomized double blind trial. Proceedings of the 39th Annual Meeting of the American College of Neuropsychopharmacology; 2000 Dec 10‐14; San Juan. San Juan: American College of Neuropsychopharmacology, 2000.
    1. Lieberman JA, Phillips M, Kong L, Gu H, Koch G. Efficacy and safety of clozapine versus chlorpromazine in first episode psychosis: results of a 52‐week randomized double‐blind trial. Schizophrenia Research 2001;49(1,2):236.
Liu 1994 (Thi) {published data only}
    1. Liu BL, Chen YY, Yang DS. Effects of thioridazine on schizophrenics and clinical utility of plasma levels. Chinese Journal of Neurology and Psychiatry 1994;27:364‐7.
Liu 2002 (CPZ) {published data only}
    1. Liu J. Clozapine in the treatment of negative symptoms of schizophrenia‐control study. Guizhou Medical Journal 2002;26(6):547‐49.
Liu 2004 (CPZ) {published data only}
    1. Liu Jun‐Biao, Wu Jing‐Hua. Chlorpromazine, clozapine, risperidone on glucose metabolism in patients with first‐episode schizophrenia, the effects of blood lipids and weight. Chinese Journal of Nervous and Mental Diseases 2004;30(4):293‐95.
Niu 2001 (CPZ) {published data only}
    1. Niu Y, Phillips M, Ji Z. A contrast study of the effect of chlorpromazine and clozapine on the cognitive function in non‐system therapeutical schizophrenic patients. Chinese Journal of Psychiatry 2001;34(4):197‐200.
Ou 1999 (CPZ) {published data only}
    1. Ou G. Comparison between chlorpromazine and clozapine in the treatment of positive symptoms in schizophrenia. Journal of Clinical Psychological Medicine 1999;9(3):155‐6.
Potter 1989 (CPZ) {published data only}
    1. Potter WZ, Ko GN, Zhang LD, Yan W. Clozapine in China: a review and preview of US/PRC collaboration. Psychopharmacology 1989;99(Suppl):87‐91. - PubMed
Rosenheck 1993 (H) {published and unpublished data}
    1. Charney DS, Rosenheck RA, Cramer J, Xu W, Jonathan T. The efficacy and cost‐effectiveness of clozapine. Proceedings of the 150th Annual Meeting of the American Psychiatric Association; 1997 May 17‐22; San Diego. San Diego: American Psychiatric Association, 1997.
    1. Cramer JA, Rosenheck R, Xu W, Thomas J, Henderson W, Charney DS. Quality of life in schizophrenia: a comparison of instruments. Schizophrenia Bulletin 2000;26(3):659‐66. [EMBASE: 2000317440; MEDLINE: ] - PubMed
    1. Rosenheck R, Chang S, Choe Y, Cramer J, Xu W, Thomas J, Henderson W, Charney D. Medication continuation and compliance: a comparison of patients treated with clozapine and haloperidol. Journal of Clinical Psychiatry 2000;61(5):382‐6. [MEDLINE: ] - PubMed
    1. Rosenheck R, Charney D. The clinical and economic impact of clozapine treatment on refractory schizophrenia. Controlled Clinical Trials 1993;14:419.
    1. Rosenheck R, Charney D, Cramer J, Xu W, Thomas J. A randomized, double‐blind trial of the efficacy and cost‐effectiveness of clozapine. Schizophrenia Research 1997;24:188.
Shopsin 1978 (CPZ) {published data only}
    1. Honigfeld G, Patin J, Singer J. Clozapine antipsychotic activity in treatment‐resistant schizophrenics. Advances in Therapy 1984;1:77‐97.
    1. Klein H, Aronson M, Shopsin B. Clozapine: double‐blind controlled trial in the treatment of schizophrenia. Psychopharmacology Bulletin 1978;14:12‐5. - PubMed
    1. Shopsin B, Klein H, Aaronsom M, Collora M. Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: a controlled, double‐blind comparison. Archives of General Psychiatry 1979;36:657‐64. - PubMed
Singer 1974 (CPZ) {published data only}
    1. Singer K, Law S. Comparative double‐blind study with clozapine (Leponex) and chlorpromazine in acute schizophrenia. Journal of International Medical Research 1974;2:433‐5.
Sun 2000 (Perp) {published data only}
    1. Sun Z. Clozapine combined with perphenazine in the treatment of schizophrenia. Hebei Mental Health 2000;13(2):142‐4.
Tamminga 1994 (H) {published data only}
    1. Tamminga CA, Thaker GK, Moran M, Kakigi T, Gao XM. Clozapine in tardive dyskinesia: observations from human and animal model studies. Journal of Clinical Psychiatry 1994;55(Suppl B):102‐6. - PubMed
Volavka 2002 (H) {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 J‐PLB, 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. Proceedings of the 14th Congress of the European College of Neuropsychopharmacology; 2001 Oct 13‐17; Istanbul. Istanbul: European College of Neuropsychopharmacology, 2001, issue 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. [CINAHL 2002032396] - 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. San Francisco: American Psychiatric Association, 2003.
Wang 2001 (CPZ) {published data only}
    1. Wang C, Xiang Y, Weng Y. The drug‐compliance, dose and concentration for the maintenance treatment of clozapine in schizophrenic patients. Chinese Journal of Psychiatry 2001;34(3):138‐41.
Wang 2006a (CPZ) {published data only}
    1. Wang C, Li Y, Pan M. A clinical study of risperidone, clozapine and chlorpromazine in patients with first‐episode schizophrenia. Journal of Clinical Psychosomatic Diseases 2006;12(1):7‐9.
Wang 2006b (CPZ) {published data only}
    1. Wang C, Li Y, Li Y. Comparative study on the life quality of first‐episode schizophrenics treated with risperidone, clozapine and chlorpromazine. Journal of Clinical Psychosomatic Diseases 2006;12(2):87‐9.
Xia 2002 (CPZ) {published data only}
    1. Xia Y, Wang D. A control study of putting on weight for taking clozapine and chlorpromazine in schizophrenic patients. Health Psychology Journal 2002;10(2):137‐9.
Xu 1985 (CPZ) {published data only}
    1. Xu WR, Bao‐long Z, Qui C, Mei‐fang G. A double‐blind study of clozapine and chlorpromazine treatment in the schizophrenics. Chinese Journal of Nervous Mental Diseases 1985;11:222‐4.
Yang 1997 (CPZ) {published data only}
    1. Yang F. A control study of clozapine and chlorpromazine in the treatment of the negative symptoms of schizophrenia. Journal of Clinical Psychological Medicine 1997;7(1):6‐8.
Yang 2002 (CPZ) {published data only}
    1. Yang FD, Ji ZF. Effects of chlorpromazine and clozapine on the cognitive function in first‐episode schizophrenia patients. Chinese New Drugs Journal 2002;11(2):152‐5.
Yang 2004 a (CPZ) {published data only}
    1. Yang F, Zhang P. Blood glucose in first‐episode schizophrenia with chlorpromazine and clozapine treatment. Shanghai Archives of Psychiatry 2004;16(1):1‐3.
Zhang 1996 (CPZ) {published data only}
    1. Zhang Yan‐Jun, Xu Xi‐Yun, Tian Mao‐Sheng, Liu Ai‐Jun, Zhao Feng‐Yu, Kong Ling‐Sheng, Gong Fu‐Min, Bai Chang‐Lin, Ren Xian‐Feng. The effects of clozapine on the sedimentation rate‐control study. Shandong Archives of Psychiatry 1996;9(4):22‐4.
Zhang 2000 (Thi) {published data only}
    1. Dian‐Zhang, Yi Yan, Jiang Kun‐Huo, Zhou Min. Domestic thioridazine and clozapine treatment of schizophrenia randomized controlled study. Journal of Yichun Medical College 2000;12(4):243‐45.
Zhang 2007 (Lox) {published data only}
    1. Zhang L. Loxapine succinate women and clozapine in the treatment of schizophrenia. Medical Journal of Chinese People's Health 2007;19(17):768.

References to studies excluded from this review

Abraham 1997 {published data only}
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Adams 1991 {published data only}
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Adityanjee 1995 {published data only}
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Agelink 1998 {published data only}
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Aitchison 1997 {published data only}
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Allison 2001 {published data only}
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Altamura 1999a {published data only}
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Altamura 1999b {published data only}
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Alvarez 1997 {published data only}
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Ames 1996 {published data only}
    1. Ames D, Wirshing WC, Baker RW, Umbricht DSG, Sun AB, Carter J, Schooler NR, Kane JM, Marder SR. Predictive value of eosinophilia for neutropenia during clozapine treatment. Journal of Clinical Psychiatry 1996;57:579‐81. - PubMed
An 2003 {published data only}
    1. An BF, Liu XQ, Chen JX. A comparative study between quetiapine and clozapine in the treatment of schizophrenia and the relation with the plasman levels of IL‐2, SIL‐2R. Schuan Mental Health 2003;16(3):152‐4.
Angst 1971 {published data only}
    1. Angst J, Bente D, Berner P, Heimann H, Helmchen H, Hippius H. The clinical effect of clozapine [Das klinische Wirkungsbild von Clozapin]. Pharmakopsychiatrie Neuro‐Psychopharmakologie 1971;4:201‐11.
    1. Angst J, Jaenicke U, Padrutt A, Scharfetter C. Results of a double‐blind trial of HF 1854 (8‐chloro‐11‐(4 methyl‐1‐piperazinyl)‐5H‐dibenzo (b, e) (1.4) diazepin) compared to levomepromazine [Ergebnisse eines Doppelblindversuches von HF 1854 (8‐Chlor‐11‐(4 methyl‐1‐piperazinyl)‐5H‐dibenzo (b,e) (1,4) diazepin) im Vergleich zu Levomepromazin]. Pharmakopsychiatrie Neuro‐Psychopharmakologie 1971;4:192‐200.
Anil 2001 {published data only}
    1. Anil AE, Lee M, Jayathilake K, Meltzer HY. Clozapine's effect on primary negative symptoms and the initial level of symptom severity as a predictor of response. Proceedings of the 14th Congress of the European College of Neuropsychopharmacology; 2001 Oct 13‐17; Istanbul. Istanbul: European Neuropsychopharmacology, 2001; Vol. 3:267.
Arango 2001 {published data only}
    1. Arango c, Summerfelt A. Buchanan R. Lack of P50 changes in a randomised double‐blind study of olanzapine and haloperidol. Proceedings of the VIII International Congress on Schizophrenia Research; 2001 April 28‐May 2; British Columbia. British Columbia: Schizophrenia Research, 2001.
Atmaca 2003 {published data only}
    1. Atmaca M, Kuloglu M, Tezcan E, Ustundag B. Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics. Journal of Clinical Psychiatry 2003;64(5):598‐604. - PubMed
Bao 1988 {published and unpublished data}
    1. Bao XG. A double‐blind study on the effect of clozapine penfluridol and chlorpromazine in the treatment of schizophrenia. Chung Hua Shen Ching Ching Shen Ko Tsa Chih 1988;21:274‐6. - PubMed
Battegay 1977 {published data only}
    1. Battegay R, Coter B, Fleischhauer J, Rauchfleisch U. Results and side effects of treatment with clozapine (Leponex R). Comprehensive Psychiatry 1977;18:423‐8. - PubMed
Baymiller 2002 {published data only}
    1. Baymiller SP, Ball P, McMahon RP, Buchanan RW. Serum glucose and lipid changes during the course of clozapine treatment: the effect of concurrent beta‐adrenergic antagonist treatment. Schizophrenia Research 2002;59:49‐57. - PubMed
Beasley 2001 {published data only}
    1. Beasley CM, Dananberg, Kwong KC, Taylor CCM, Breier A. Treatment‐emergent potential impaired glucose tolerance and potential diabetes with olanzapine compared to other antipsychotic agents and placebo. Biological Psychiatry 2001;49:121S.
Bellack 2004 {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
Berardi 1998 {published data only}
    1. Berardi D, Troia M, Dell'Atti M, Bartoletti C, Cantaroni C, Ferrari G. Clozapine effectiveness in a psychiatric service in Italy. European Psychiatry 1998;13:317‐9. - PubMed
Beuzen 1998 {published data only}
    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. Glasgow: Neuro‐Psychopharmacologicum, 1998.
Bian 2003 {published data only}
    1. Bian QT, Xie GR. A comparative study of quality of life in schizophrenia treated with chlorpromazine, clozapine or risperidone. Chinese Journal of Clinical Psychology 2003;7472(2):125‐7.
Birmaher 1992 {published data only}
    1. Birmaher B, Baker R, Kapur S, Quintana H, Ganguli R. Clozapine for the treatment of adolescents with schizophrenia. Journal of the American Academy of Child and Adolescent Psychiatry 1992;31:160‐4. - PubMed
Bitter 2004 {published data only}
    1. Bitter I, Dossenbach MRK, Brook S, Feldman PD, Metcalfe S, Gagiano CA, Furedi J, Bartko G, Janka Z, Banki CM, Kovacs G, Breier A. Olanzapine versus clozapine in treatment‐resistant or treatment‐intolerant schizophrenia. Progress in Neuro‐Psychopharmacology and Biological Psychiatry 2004;28:173‐180. - PubMed
Blum 1972 {published data only}
    1. Blum A, Mauruschat W. Temperature increases and changes in white blood therapy with neuroleptics, with particular attention to the novel Dibenzodiazepin derivative clozapine [Temperaturanstiege und Blutweissveränderungen unter der Therapie mit Neuroleptika ‐unter besonderer Berücksichtigung des neuartigen Dibenzodiazepin‐Derivates Clozapin]. Pharmakopsychiatrie Neuro‐Psychopharmakologie 1972;5:155‐69.
Boehle 1995 {published data only}
    1. Boehle C, Volz H P, Hornstein C, Preussler B, Kunze M, Rauch J, Sauer H. Neuropsychological performance of clozapine treated schizophrenics. Pharmacopsychiatry 1995;28:166.
Borovicka 1997 {published data only}
    1. Borovicka MC, Fuller MA, Konicki PE, Brescan D, Popli A, Jurjus G, Kwon K, Steele V, White J, Jaskiw GE. Treatment of Clozapine‐induced weight gain with phenylpropanolamine. Schizophrenia Research 1997;24(1, 2):185‐6.
Bourgeois 2004 {published data only}
    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
Brandt‐Christensen 1998 {published data only}
    1. Brandt‐Christensen M, Peacock L, Gerlach J. Clozapine versus typical antipsychotics in schizophrenia: EPS retrospectively (1‐20 years) and prospectively (five years). Proceedings of the 9th Congress of Association of European Psychiatrists; 1998 September 20‐24; Copenhagen. Copenhagen: Association of European Psychiatrists, 1998.
Brankovic 1998 {published data only}
    1. Brankovic S, Milovanovic S, Damjanovic A, Paunovic VR. No difference between the effects of clozapine and fluphenazine on probabilistic reasoning in paranoid schizophrenia. Proceedings of the 21st Congress of the Collegium Internationale Neuro‐psychopharmacologicum; 1998 Jul 12‐16; Glasgow. Glasgow: Neuro‐psychopharmacologicum, 1998.
    1. Ravanic DB, Djukic‐Dejanovic SM, Stojiljkovic M, Jankovic S, Paunovic VR, Bankovic D. Antipsychotic efficacy of clozapine vs fluphenazine in positive and negative schizophrenia syndrome.. Journal of Neural Transmission 1996;103:XLVI.
Brar 1997 {published data only}
    1. Brar JS, Chengappa KN, Parepally H, Sandman AR, Kreinbrook SB, Sheth SA, Ganguli R. The effects of clozapine on negative symptoms in‐patients with schizophrenia with minimal positive symptoms. Annals of Clinical Psychiatry 1997;9(4):227‐34. - PubMed
Breier 1993 {published data only}
    1. Breier A, Buchanan RW, Irish D, Carpenter WT Jr. Clozapine treatment of outpatients with schizophrenia: outcome and long‐term response pattern. Hospital and Community Psychiatry 1993;44:1145‐9. - PubMed
Broich 1998 {published data only}
    1. Broich K, Grünwald F, Kasper S, Klemm E, Biersack H‐J, Möller H‐J. D2‐dopamine receptor occupancy measured by IBZM‐SPECT in relation to extrapyramidal side effects. Pharmacopsychiatry 1998;31:159‐62. - PubMed
Buchanan 2003 {published data only}
    1. Buchanan RW, Ball MP, Weiner E, Kirkpatrick B, Gold J, Carpenter WT. Olanzapine treatment of residual positive and negative symptoms. Schizophrenia Research 2003;60(1):275. - PubMed
Buchsbaum 1996 {published data only}
    1. Buchsbaum M, Hazlett E, Haznedar M. Positron emission tomography in schizophrenics treated with sertindole and haloperidol. Proceedings of the 10th World Congress of Psychiatry; 1996 Aug 23‐28; Madrid. Madrid: World Congress of Psychiatry, 1996.
Buchsbaum 1997 {published data only}
    1. Buchsbaum M, Hazlett E, Bark N, Gupta A, Fallon J, Guich S, Haznedar M. Positron emission tomography in schizophrenics treated with atypical and typical neuroleptics. Schizophrenia Research 1997;24(1,2):163.
Buchsbaum 2004 {published data only}
    1. Buchsbaum MS, Haznedar MM, Hazlett E. Antipsychotic response prediction with fdg‐pet in schizophrenia. Proceedings of the Thematic Conference of the World Psychiatric Association on "Treatments in Psychiatry: An Update"; 2004 Nov 10‐13; Florence. Florence: World Psychiatric Association, 2004. [WO32.1]
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.
Cao 2001 {published data only}
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Cao 2003 {published data only}
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Liu 1997 {published data only}
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Liu 2003 {published data only}
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Liu 2003 a {published data only}
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Liu 2003 b {published data only}
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Liu 2004 a {published data only}
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Liu 2004 b {published data only}
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Liu 2004 d {published data only}
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Liu 2005 {published data only}
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Liu 2005 b {published data only}
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Lu 2002 a {published data only}
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Lu 2003 {published data only}
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Lu 2004 {published data only}
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Ren 2004 a {published data only}
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Ren 2004 b {published data only}
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Shi 2000 c {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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Yang 1999 {published data only}
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Yang 2004a {published data only}
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Yao 1999 {published data only}
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Yu 2002 b {published data only}
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Yu 2004 {published data only}
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Yu 2005 a {published data only}
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Yu 2005 b {published data only}
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Yue 2004 {published data only}
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Zeng 2002 {published data only}
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Zeng 2003 {published data only}
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Zhang 1997 {published data only}
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Zhang 2000 {published data only}
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Zhang 2002 a {published data only}
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Zhang 2002 b {published data only}
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Zhang 2002 c {published data only}
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Zhang 2002 d {published data only}
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Zhang 2002 e {published data only}
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Zhang 2002 f {published data only}
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Zhang 2002 h {published data only}
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Zhang 2002 i {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):145‐7.
Zhang 2004 g {published data only}
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Zheng 2003 {published data only}
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Zhou 1997 {published data only}
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Zhou 2000 b {published data only}
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Zhou 2003 a {published data only}
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Zhou 2003 b {published data only}
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Zhu 1999 a {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 1999 b {published data only}
    1. Zhu Y, Zhang S, Zhang D. A controlled trial comparing chlorimipramine and sulpiride as adjunct to clozapine in the treatment of negative symptoms of schizophrenia. Journal of Clinical Psychological Medicine 1999;9(4):204‐5.
Zhu 2001 {published data only}
    1. Zhu F, Ji Z, Fie L. The pharmacokinetics of clozapine and it's clinical utilization. Journal of Clinical Psychological Medicine 2001;11(1):12‐5.
Zhu 2002 a {published data only}
    1. Zhu Y, Jin X. Effect of music treatment on memory decrease of patients with schizophrenia caused by clozapine. Chinese Journal of Rehabilitation Theory and Practice 2002;8(11):684‐6.
Zhu 2002 b {published data only}
    1. Zhu H, Yu G, Deng D. A study of clozapine combined with or without pipotiazine palmitate in refractory schizophrenia. Journal of Clinical Psychological Medicine 2002;12(1):15‐7.
Zhu 2002 c {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.
Zimmermann 1996 {published data only}
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Zuo 2002 {published data only}
    1. Zuo J, Xun Z, Wang M. A comparison of social ability of patients with schizophrenia treated with risperidone and those treated with clozapine. Tianjin Pharmacy 2002;20(5):54‐5.

References to studies awaiting assessment

Yang 2004 b {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.

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