Haloperidol versus chlorpromazine for schizophrenia

Schizophrenia can be a long-term, chronic illness with a worldwide lifetime prevalence of about one per cent. The most common treatment of this condition is using antipsychotics. In the developed world there is a large choice of antipsychotics including some that are quite expensive, whereas in the developing world the older and cheaper drugs such as haloperidol and chlorpromazine are still used for the majority of the people. In addition, most new medications are tested for their effectiveness against haloperidol or chlorpromazine. This review looks at clinical trials comparing people with schizophrenia who have been treated with either chlorpromazine or haloperidol, in tablet form or as injection into muscle but not by long acting injection. There were 14 trials identified containing a total of 794 people. The trials varied in length from ‘several hours’ to 36 weeks but only two were six months or longer. The most recent trial was published in 1994, and the earliest 1962. As diagnosis of schizophrenia has changed over the years, some people in the early trials may have diagnoses other than schizophrenia by today’s criteria.

Overall the mental health and general functioning of people taking chlorpromazine or haloperidol improved. Compared to nowadays fewer people in both arms of the trial left the study early but those taking chlorpromazine were statistically more likely to do so. This was also the case when the oral medications were analysed on their own, but not in the case of the injected form. There was a suggestion that people may leave the study because of either adverse events or because the treatment did not work well. Haloperidol had statistically more movement side effects while chlorpromazine was statistically more likely to cause low blood pressure (hypotension). Although these trials show both haloperidol and chlorpromazine to be effective drugs for schizophrenia, a lot of data were not able to be used because some measures were not reported. Therefore the area would benefit from a new trial with a large number of people and lasting at least a year.

(Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).

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.

Read the full abstract...

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.


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.