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Meta-Analysis
. 2008 Jan 23;2008(1):CD004278.
doi: 10.1002/14651858.CD004278.pub2.

Haloperidol versus chlorpromazine for schizophrenia

C Leucht, M Kitzmantel, L Chua, J Kane, S Leucht
Meta-Analysis

Haloperidol versus chlorpromazine for schizophrenia

C Leucht et al. Cochrane Database Syst Rev. .

Abstract

Background: Chlorpromazine and haloperidol are benchmark antipsychotic drugs. Both are said to be equally effective when used at equivalent doses, but have different side-effect profiles.

Objectives: To compare the effects of haloperidol and chlorpromazine for people with schizophrenia and schizophrenia-like psychoses.

Search strategy: We searched the Cochrane Schizophrenia Group's register (August 2006). We searched references of all included studies for further trials. We contacted pharmaceutical companies and authors of relevant trials.

Selection criteria: We included all randomised controlled trials that compared haloperidol with chlorpromazine for people with schizophrenia and/or schizophrenia-like psychoses.

Data collection and analysis: Citations and, where possible, abstracts were independently inspected by at least two reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. For dichotomous data we calculated the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis using a random-effects model. For continuous data, we calculated weighted mean differences (WMD).

Main results: We found 14 relevant studies, mostly of short duration, poorly reported and conducted in the 1970s (total n=794 participants). Nine of these compared oral formulations of both compounds, and five compared intramuscular formulations. Haloperidol was associated with significantly fewer people leaving the studies early (13 RCTs, n=476, RR 0.26 CI 0.08 to 0.82). The efficacy outcome 'no significant improvement' tended to favour haloperidol, but this difference was not statistically significant (9 RCTs, n=400, RR 0.81 CI 0.64 to 1.04). Movement disorders were more frequent in the haloperidol groups ('at least one extrapyramidal side effect': 6 RCTs, n=37, RR 2.2 CI 1.1 to 4.4, NNH 5 CI 3 to 33), while chlorpromazine was associated with more frequent hypotension (5 RCTs, n=175, RR 0.31 CI 0.11 to 0.88, NNH 7 CI 4 to 25). Similar trends were found when studies comparing intramuscular formulations and studies comparing oral formulations were analysed separately.

Authors' conclusions: Given that haloperidol and chlorpromazine are global standard antipsychotic treatments for schizophrenia, it is surprising that less than 800 people have been randomised to a comparison and that incomplete reporting still makes it difficult for anyone to draw clear conclusions on the comparative effects of these drugs. However, it seems that haloperidol causes more movement disorders than chlorpromazine, while chlorpromazine is significantly more likely to lead to hypotonia. We are surprised to have to say that we feel further, large, well designed, conducted and reported studies are required.

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Conflict of interest statement

Claudia Leucht: none known. Maria Kitzmantel: none known. Lian Chua: none known. John Kane: has received honoraria from Janssen‐Cilag (manufacturer of haloperidol). Stefan Leucht: has received honoraria from Janssen‐Cilag (manufacturer of haloperidol) and SanofiAventis (manufacturer of chlorpromazine).

Figures

1.1
1.1. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 1 Leaving the study early.
1.2
1.2. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 2 Global state: 1. No clinically significant improvement ‐ as defined by the individual studies.
1.3
1.3. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 3 Global state: 2. Average score at endpoint (CGI, high = poor).
1.4
1.4. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 4 Mental state: Average score at endpoint (BPRS, high = poor).
1.5
1.5. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 5 Adverse events: 1. General ‐ at least one adverse event.
1.6
1.6. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 6 Adverse events: 2. Specific ‐ anticholinergic.
1.7
1.7. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 7 Adverse events: 3. Specific ‐ cardiovascular.
1.8
1.8. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 8 Adverse events: 4. Specific ‐ central nervous system.
1.9
1.9. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 9 Adverse events: 5. Specific ‐ endocrine ‐ galactorrhoea.
1.10
1.10. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 10 Adverse events: 6. Specific ‐ metabolic ‐ weight change.
1.11
1.11. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 11 Adverse events: 7a. Specific ‐ movement disorders.
1.12
1.12. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 12 Adverse events: 7b. Specific ‐ movement disorders ‐ EPS score (high=poor).
1.13
1.13. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 13 Adverse events: 8. Specific ‐ skin problems.
1.14
1.14. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 14 Adverse events: 9a. Laboratory data (binary).
1.15
1.15. Analysis
Comparison 1 HALOPERIDOL versus CHLORPROMAZINE, Outcome 15 Adverse events: 9b. Laboratory data (continuous).
2.1
2.1. Analysis
Comparison 2 SUBGROUP: HALOPERIODL INTRAMUSCULAR versus CHLORPROMAZINE INTRAMUSCULAR, Outcome 1 Leaving the study early.
2.2
2.2. Analysis
Comparison 2 SUBGROUP: HALOPERIODL INTRAMUSCULAR versus CHLORPROMAZINE INTRAMUSCULAR, Outcome 2 Global state: No clinically significant improvement ‐ as defined by the individual studies.
2.3
2.3. Analysis
Comparison 2 SUBGROUP: HALOPERIODL INTRAMUSCULAR versus CHLORPROMAZINE INTRAMUSCULAR, Outcome 3 Adverse events: 1. Specific ‐ anticholinergic.
2.4
2.4. Analysis
Comparison 2 SUBGROUP: HALOPERIODL INTRAMUSCULAR versus CHLORPROMAZINE INTRAMUSCULAR, Outcome 4 Adverse events: 2. Specific ‐ cardiovascular.
2.5
2.5. Analysis
Comparison 2 SUBGROUP: HALOPERIODL INTRAMUSCULAR versus CHLORPROMAZINE INTRAMUSCULAR, Outcome 5 Adverse events: 3. Specific ‐ central nervous system.
2.6
2.6. Analysis
Comparison 2 SUBGROUP: HALOPERIODL INTRAMUSCULAR versus CHLORPROMAZINE INTRAMUSCULAR, Outcome 6 Adverse events: 4. Specific ‐ movement disorders ‐ at least one EPS.
2.7
2.7. Analysis
Comparison 2 SUBGROUP: HALOPERIODL INTRAMUSCULAR versus CHLORPROMAZINE INTRAMUSCULAR, Outcome 7 Adverse events: 5. Laboratory data.
3.1
3.1. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 1 Leaving the study early.
3.2
3.2. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 2 Global state: 1. No clinically significant improvement ‐ as defined by the individual studies.
3.3
3.3. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 3 Global state: 2. Average score at endpoint (CGI, high = poor).
3.4
3.4. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 4 Mental state: Average score at endpoint (BPRS, high = poor).
3.5
3.5. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 5 Adverse events: 1. General ‐ at least one adverse event.
3.6
3.6. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 6 Adverse events: 2. Specific ‐ anticholinergic.
3.7
3.7. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 7 Adverse events: 3. Specific ‐ cardiovascular.
3.8
3.8. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 8 Adverse events: 4. Specific ‐ central nervous system.
3.9
3.9. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 9 Adverse events: 5. Specific ‐ endocrine ‐ galactorrhoea.
3.10
3.10. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 10 Adverse events: 6. Specific ‐ metabolic ‐ weight change.
3.11
3.11. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 11 Adverse events: 7a. Specific ‐ movement disorders.
3.12
3.12. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 12 Adverse events: 7b. Specific ‐ movement disorders ‐ EPS score (high=poor).
3.13
3.13. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 13 Adverse events: 8. Specific ‐ skin problems.
3.14
3.14. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 14 Adverse events: 9a. Laboratory data (binary).
3.15
3.15. Analysis
Comparison 3 SUBGROUP: HALOPERIDOL ORAL versus CHLORPROMAZINE ORAL, Outcome 15 Adverse events: 9b. Laboratory data (continuous).
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Update of

  • doi: 10.1002/14651858.CD004278

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