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. 2000;2000(2):CD000966.
doi: 10.1002/14651858.CD000966.

Newer atypical antipsychotic medication versus clozapine for schizophrenia

Affiliations

Newer atypical antipsychotic medication versus clozapine for schizophrenia

A Tuunainen et al. Cochrane Database Syst Rev. 2000.

Abstract

Background: Clozapine is an atypical antipsychotic drug, which is claimed to have superior efficacy and to cause fewer movement disorders. However, clozapine carries a significant risk of serious blood disorders. Newer atypical antipsychotics are safer alternatives that might share the benefits of clozapine. It is thus of interest to compare the effectiveness of newer atypical antipsychotics with the effectiveness of clozapine.

Objectives: To evaluate the clinical effects of newer atypical antipsychotic drugs in comparison to clozapine for schizophrenia.

Search strategy: Publications in all languages were searched from the following databases: Biological Abstracts/BIOSIS (1980-1999), The Cochrane Schizophrenia Group's Register of Trials (1998), The Cochrane Library CENTRAL Register (Issue 4, 1999), EMBASE (1980-1998), MEDLINE (1966-1999), LILACS/CD-ROM (1998), and PsycLIT/PsycINFO (1974-1999). Trials were also sought from recent conference proceedings and reference lists of included papers. Authors of recent trials and the manufacturers of clozapine, iloperidone, olanzapine, quetiapine, remoxipride, risperidone, sertindole, ziprasidone and zotepine were contacted.

Selection criteria: All randomised controlled trials comparing clozapine with newer atypical antipsychotic drugs were included by independent assessment by two reviewers.

Data collection and analysis: Data were extracted independently by two reviewers. Relative risks (RR) and 95% confidence intervals (CI) of homogenous dichotomous data were calculated. A random effects model was used for heterogeneous dichotomous data. Where possible the number needed to treat (NNT) statistic with 95%CI were also calculated. Weighted or standardised means were calculated for continuous data. Due to the small number of included studies, sensitivity analyses or funnel plot statistics were not undertaken for this version of the review.

Main results: The current review includes eight studies (22 papers), of which three studies are 4-6 weeks in duration and only one study is of more than 12 weeks' duration. Newer atypical drugs seemed to be broadly similar to clozapine using a clinical global index or trialists' definitions of improvement, but this result was obtained from a relatively small number of studies. Due to the small number of studies and patients, wide confidence intervals were seen when their effectiveness as measured by symptom rating scales was compared. Social functioning was better in patients on newer atypical medication (risperidone) than in those on clozapine, but this finding is based on a single underpowered trial and has to be interpreted with caution. Clozapine and newer atypical drugs showed their adverse effect profile to be dissimilar: while clozapine produced more fatigue, hypersalivation, nausea, and orthostatic dizziness, new atypical drugs, with the exception of olanzapine, produced more extrapyramidal symptoms. The impact of these drugs and their effects on patients' day-to-day quality of life, service use, hospital admission, and pharmacoeconomics was not measured.

Reviewer's conclusions: The equal effectiveness and tolerability of new atypical drugs in comparison with clozapine is not yet demonstrated. Lack of statistical power to determine the comparative efficacy and effectiveness of newer atypical drugs makes it difficult to judge whether newer drugs are more effective, less effective or equivalent. Trials of sufficient power, with longer duration, measuring clinically important outcomes, are needed to assess the true comparative clinical effectiveness, tolerability and cost effectiveness of newer drugs in relation to clozapine.

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Conflict of interest statement

Arja Tuunainen has received grants from some pharmaceutical companies for travel to international meetings (including Zeneca, manufacturer of quetiapine).

Kristian Wahlbeck has received grants from several pharmaceutical companies for travel to international meetings (including Janssen‐Cilag, manufacturer of risperidone, and Pfizer, manufacturer of ziprasidone).

Simon Gilbody ‐ none known.

Figures

1.1
1.1. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 1 Death.
1.2
1.2. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 2 Global impression: 1. Clinically not improved (CGI) ‐ medium term.
1.3
1.3. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 3 Global impression: 2. Not ready for discharge ‐ short term.
1.4
1.4. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 4 Global impression: 3. CGI endpoint score (high = poor).
1.5
1.5. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 5 Global impression: 4. GAF endpoint score (high = good) ‐ short term.
1.6
1.6. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 6 Mental state: 1. Clinically not improved (< 20% change on BPRS/PANSS).
1.7
1.7. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 7 Mental state: 2. Deterioration in mental state or relapse.
1.8
1.8. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 8 Mental state: 3. Negative symptoms endpoint score (PANSS/SANS, high = poor).
1.9
1.9. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 9 Mental state: 4. Positive symptoms endpoint score (BPRS/PANSS, high = poor) ‐ short term.
1.10
1.10. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 10 Mental state: 5. Psychosis symptoms rating scale endpoint score (BPRS/PANSS, high = poor).
1.12
1.12. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 12 Acceptability of treatment: 1. Leaving the study early.
1.13
1.13. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 13 Acceptability of treatment: 2. Patient dissatisfaction.
1.14
1.14. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 14 Cognitive functioning: 1. No improvement in memory (SKT) ‐ short term.
1.15
1.15. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 15 Cognitive functioning: 2. Problem with cognitive function ‐ short term.
1.16
1.16. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 16 Cognitive functioning: 3. Intelligence endpoint score (KAI, high = good) ‐ short term.
1.18
1.18. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 18 Social functioning: 1. SFS endpoint score (high = good) ‐ short term.
1.19
1.19. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 19 Treatment satisfaction: 1. DAI‐10 endpoint score (high = good) ‐ short term.
1.20
1.20. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 20 Adverse effects: 1. Extrapyramidal symptoms.
1.21
1.21. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 21 Adverse effects: 2. Fatigue.
1.22
1.22. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 22 Adverse effects: 3. Libido decrease.
1.23
1.23. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 23 Adverse effects: 4. Nausea/vomiting.
1.24
1.24. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 24 Adverse effects: 5. Orthostatic dizziness.
1.25
1.25. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 25 Adverse effects: 6. Salivation problems.
1.26
1.26. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 26 Adverse effects: 7. Seizures.
1.27
1.27. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 27 Adverse effects: 8. Sleep problems.
1.28
1.28. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 28 Adverse effects: 9. Weight gain.
1.29
1.29. Analysis
Comparison 1 NEWER ATYPICAL ANTIPSYCHOTIC DRUGS versus CLOZAPINE, Outcome 29 Adverse effects: 10. White blood cell problems.

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