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Meta-Analysis
. 2006 Oct 18;2006(4):CD001948.
doi: 10.1002/14651858.CD001948.pub2.

Zotepine for schizophrenia

P DeSilva  1 , M Fenton, J Rathbone
Affiliations
Meta-Analysis

Zotepine for schizophrenia

P DeSilva et al. Cochrane Database Syst Rev. .

Abstract

Background: Zotepine is a relatively new antipsychotic often used for the treatment of people with schizophrenia. It is claimed to be particularly effective for negative symptoms.

Objectives: To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.

Search strategy: For the 2006 update we searched the Cochrane Schizophrenia Group's register of trials.

Selection criteria: We included all randomised clinical trials comparing zotepine with other treatments for people with schizophrenia or other psychoses.

Data collection and analysis: We independently inspected citations and abstracts, ordered papers, re-inspected these and assessed their quality. For homogenous dichotomous data we calculated the relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity.

Main results: The review currently includes 11 studies with 966 participants. Most outcomes were short term (4-12 weeks). We found no data for outcomes such as relapse, time in hospital, satisfaction with care and day-to-day functioning. Compared with placebo, mental state ratings favoured zotepine (n=106, 1 RCT, RR No 20% decrease in BPRS 0.44 CI 0.3 to 0.7, NNT 3 CI 2 to 6) using the last observation carried forward method. For the comparison with typical drugs, limited data suggest that zotepine may be as effective as these older medications. Mental state measures of 'no clinically important improvement' favour zotepine when compared with other active drugs (n=356, 4 RCTs, RR 0.77 CI 0.7 to 0.9, NNT 7 CI 4 to 22). About one third of people in both the zotepine and control groups left the studies before trial completion. Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs. Trials have not highlighted clear differences between zotepine and other atypical drugs.

Authors' conclusions: Zotepine may be a valuable addition to the class of atypical antipsychotic drugs. However, more data from existing studies is urgently needed to increase confidence in the findings of this review. In addition to this, new data from well planned, conducted and reported long term pragmatic randomised trials are needed. Otherwise clinical use of zotepine will be based upon speculation of short explanatory trials for everyday practice.

PubMed Disclaimer

Conflict of interest statement

Mark Fenton has lead Jansen, Lilly and Zeneca sponsored workshops for clinicians.

Prasanna De‐Silva has received financial assistance to attend various scientific meetings and conferences world‐wide.

Stephen Cooper has undertaken trials of zotepine with employees of Knoll Pharmaceuticals.

The Cochrane Schizophrenia Group has received general support funding from Eli Lilly during the years 1996‐8 (see Group Module). This, along with some funds from other pharmaceutical companies, is used to support any ongoing work of the editorial base and is not linked to any particular review (annual report available on request).

Figures

1.1
1.1. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 1 Death.
1.2
1.2. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 2 Global state: 1. Needing additional antipsychotic/sedative drugs.
1.3
1.3. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 3 Global state: 2. Not improved or worse (CGI).
1.4
1.4. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 4 Global state: 3. Average endpoint score (CGI, higher scores=poor) at 8 weeks.
1.5
1.5. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 5 Global state: 4. Hospitalisation.
1.6
1.6. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 6 Mental state: 1. No important clinical response ‐ by 4‐12 weeks (20% reduction in BPRS from baseline).
1.7
1.7. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 7 Mental state: 2a. Average total endpoint score (BPRS, higher scores=poor).
1.8
1.8. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 8 Mental state: 2b. Average total change scores by 8 weeks (PANSS, higher scores=poor, LOCF).
1.9
1.9. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 9 Mental state: 3a. Average negative symptom change scores by 8 weeks (PANSS, higher scores=poor, LOCF).
1.10
1.10. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 10 Mental state: 3b. Average negative symptom endpoint score (SANS, higher scores=poor).
1.11
1.11. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 11 Mental state: 4. Average positive symptom change scores by 8 weeks (PANSS, higher scores=poor, LOCF).
1.12
1.12. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 12 Mental state: 5. Average general psychopathology change scores by 8 weeks (PANSS, higher scores=poor, LOCF).
1.13
1.13. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 13 Mental state: 6. Average depression change score (MADRS, higher scores=poor, LOCF).
1.14
1.14. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 14 Behaviour: Specific behaviour changes.
1.15
1.15. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 15 Leaving the study early.
1.16
1.16. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 16 Adverse events: 1. Any adverse event.
1.17
1.17. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 17 Adverse events: 2. Cardiovascular problems ‐ pulse rate.
1.18
1.18. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 18 Adverse events: 3. Gastrointestinal problems ‐ constipation.
1.19
1.19. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 19 Adverse events: 4a. Metabolic problems ‐ weight gain.
1.20
1.20. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 20 Adverse events: 4b. Metabolic problems ‐ weight change.
1.21
1.21. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 21 Adverse events: 5a. Movement disorders ‐ specific problems.
1.24
1.24. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 24 Adverse events: 5d. Movement disorders ‐ change scores by 8 wks (Simpson‐Angus Scale, reduction=good, LOCF).
1.25
1.25. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 25 Adverse events: 5e. Movement disorders ‐change score by 8 wks(Tardive Dyskinesia Rating Scale, reduction=good).
1.26
1.26. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 26 Adverse events: 6. Sleep problems.
1.27
1.27. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 27 Adverse events: 7. Others.
1.28
1.28. Analysis
Comparison 1 ZOTEPINE versus PLACEBO, Outcome 28 Quality of life: Average change score by 8 weeks (SF‐36, high score=better).
2.1
2.1. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 1 Global state: 1. Not improved (CGI).
2.2
2.2. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 2 Global state: 3. Average endpoint score (CGI, high=poor).
2.3
2.3. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 3 Global state: 2. Needing additional antipsychotic/sedative drugs.
2.4
2.4. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 4 Mental state: 1. No important clinical response ‐ by 4‐12 weeks.
2.5
2.5. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 5 Mental state: 2. Average total endpoint score (BPRS, high=poor).
2.6
2.6. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 6 Mental state: 3. Average negative symptom endpoint score (SANS, high=poor).
2.7
2.7. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 7 Behaviour: Specific behaviour changes.
2.8
2.8. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 8 Leaving the study early: Any reason.
2.9
2.9. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 9 Cognition: Not improved (Syndrome Short Test).
2.10
2.10. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 10 Adverse events: 1. Any adverse event.
2.11
2.11. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 11 Adverse events: 2a. Cardiovascular problems.
2.12
2.12. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 12 Adverse events: 2b. Cardiovascular problems ‐ pulse rate.
2.13
2.13. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 13 Adverse events: 3. Gastrointestinal problems.
2.14
2.14. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 14 Adverse events: 4. Metabolic problems ‐ weight change.
2.15
2.15. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 15 Adverse events: 5a. Movement disorders ‐ specific problems.
2.18
2.18. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 18 Adverse events: 6. Sleep problems.
2.19
2.19. Analysis
Comparison 2 ZOTEPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 19 Adverse events: 7. Others.
3.1
3.1. Analysis
Comparison 3 ZOTEPINE versus ATYPICAL ANTIPSYCHOTICS, Outcome 1 Mental state: 1. Average total endpoint score (BPRS, high=poor).
3.2
3.2. Analysis
Comparison 3 ZOTEPINE versus ATYPICAL ANTIPSYCHOTICS, Outcome 2 Leaving the study early: Any reason.
3.3
3.3. Analysis
Comparison 3 ZOTEPINE versus ATYPICAL ANTIPSYCHOTICS, Outcome 3 Cognition: Not improved (Syndrome Short Test).
3.4
3.4. Analysis
Comparison 3 ZOTEPINE versus ATYPICAL ANTIPSYCHOTICS, Outcome 4 Adverse events: 1a. Movement disorders ‐ needing additional anticholinergic medication.
See this image and copyright information in PMC

Update of

References

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