Schizophrenia Bulletin Advance Access originally published online on July 24, 2008
Schizophrenia Bulletin 2008 34(5):813-815; doi:10.1093/schbul/sbn087
© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.
Haloperidol versus chlorpromazine for treatment of schizophrenia
C. Leucht1,2,
M. Kitzmantel3,
L. Chua4,
J. Kane5 and
S. Leucht3
2 Königinstrasse 51, Munich 80539, Germany
3 Klinik für Psychiatrie und Psychotherapie der TU-München, Klinikum rechts der Isar, Ismaningerstrasse 22, 81675 München, Germany
4 Lynfield Mount Hospital, Heights Lane, Bradford BD9 6DP, UK
5 The Zucker Hillside Hospital, Psychiatry Research, Glen Oaks, NY 11004
 |
Introduction
|
|---|
Chlorpromazine and haloperidol are benchmark antipsychotic drugs
which are frequently used as standards in antipsychotic drug
trials.
1,
2 For example, in the review on second-generation antipsychotic
drugs by Davis et al.
3, haloperidol was by far the most frequently
used comparator followed by chlorpromazine. To better define
the relative efficacy and safety of both compounds is therefore
important for the methodology of randomized controlled trials
(RCTs) and for clinical practice where both agents are still
frequently used.
|
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 RCTs 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 2 reviewers, and papers ordered, reinspected,
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.
|
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
5 compared intramuscular formulations. Haloperidol was associated
with significantly fewer people leaving the studies early (13
RCTs,
n = 476, RR = 0.26, CI = 0.08–0.82). The efficacy
outcome ‘no significant improvement’ tended to favor
haloperidol, but this difference was not statistically significant
(9 RCTs,
n = 400, RR = 0.81, CI = 0.64–1.04). Movement
disorders were more frequent in the haloperidol groups (‘at
least one extrapyramidal side-effect’: 6 RCTs,
n = 37,
RR = 2.2, CI = 1.1–4.4, NNH = 5, CI = 3–33, see
figure 1), while chlorpromazine was associated with more frequent
hypotension (5 RCTs,
n = 175, RR = 0.31, CI = 0.11–0.88,
NNH = 7, CI = 4–25, see
figure 2). Similar trends were
found when studies comparing intramuscular formulations and
studies comparing oral formulations were analyzed separately.
|
Reviewer's conclusion
|
|---|
Given that haloperidol and chlorpromazine are global standard
antipsychotic treatments for schizophrenia, it is surprising
that less than 800 people have been randomized 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.
|
Implications for practice
|
|---|
Currently available data suggest that haloperidol and chlorpromazine
are similarly effective for treatment of schizophrenia. But
at least at higher doses, haloperidol seems to be associated
with more extrapyramidal side-effects (EPS) while hypotension
appears to occur more frequently when chlorpromazine is used.
Overall, haloperidol may also be more acceptable for those afflicted
by the illness.
|
Implications for research
|
|---|
High-dose haloperidol was the comparator in most RCTs on second-generation
antipsychotics.
3 This decision was in part justified because
haloperidol was the most frequent antipsychotic in many industrialized
countries. Nevertheless, this choice favored the second-generation
antipsychotics because they were compared with a very EPS-prone
standard. Future studies may take into account that less EPS-associated
conventional antipsychotics are also available, and some studies
already have.
4,
5 The fact that in many countries haloperidol
and chlorpromazine are still standard drugs administered in
the treatment of schizophrenia justifies further research to
compare the properties of these compounds.
|
Conflict of interest
|
|---|
L.C., M.K., C.L. none known. S.L. has received speaker/consultancy/advisory
board honoraria from SanofiAventis, BMS, EliLilly, Janssen/Johnson
and Johnson, Lundbeck, and Pfizer. SanofiAventis and EliLilly
supported research projects by S.L. J.M.K. has received speaker
and/or advisory board/consultancy honoraria from Abbott, AstraZeneca,
Bristol-Myers Squibb, Eli Lilly, Janssen, Johnson & Johnson
PRD, Otsuka, Pfizer, Inc., Wyeth, Lundbeck, Vanda, Astra-Zeneca,
and PGxHealth.
|
Footnotes |
|---|
1 To whom correspondence should be addressed; tel: 089-4140-4249, e-mail: claudialeucht{at}gmx.de.
|
References
|
|---|
- Adams CE, Awad G, Rathbone J. Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev (2007) (2):. doi:10.1002/14651858.CD000284.
- Joy CB, Adams CE, Laurie S. Haloperidol versus placebo for schizophrenia. Cochrane Database Syst Rev (2006) (4):. doi: 10.1002/14651858.CD003082.
- Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry (2003) 60::553–564.[Abstract/Free Full Text]
- Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med (2005) 353::1209–1223.[Abstract/Free Full Text]
- Jones PB, Barnes TRE, Davies L, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia—cost utility of the latest antipsychotic drugs in schizophrenia study (CUtLASS 1). Arch Gen Psychiatry (2006) 63::1079–1086.[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
Top
Introduction
Objectives
