Haloperidol versus chlorpromazine for schizophrenia
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.
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.
We included all randomised controlled trials that compared haloperidol with chlorpromazine for people with schizophrenia and/or schizophrenia-like psychoses.
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).
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.
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.
- SourceAvailable from: Caroline A Bonham[Show abstract] [Hide abstract]
ABSTRACT: Second generation antipsychotic medications have become synonymous with "atypicality." To support the clinical lore of equivalent efficacy with reduced risk of extrapyramidal symptoms, clinical trials have overwhelmingly chosen a high-potency first-generation antipsychotic (e.g., haloperidol) as a comparator. Very few clinical trials have compared a second-generation antipsychotic with a low- or mid-potency first-generation antipsychotic medication. We identified eight completed, published, double-blind, randomized clinical trials that compared a second-generation antipsychotic with a low- or mid-potency first-generation antipsychotic and reviewed outcome measures for efficacy and extrapyramidal symptoms; 1,241 patients were represented in these eight trials. Although data are very limited, mid- and low-potency first-generation antipsychotics show efficacy and extrapyramidal side effects that are comparable to those of second-generation antipsychotics. Aside from clozapine, first-generation and second-generation antipsychotics represent a diverse group of medications that have heterogenous receptor profiles and side effects but comparable clinical efficacy and potential to cause extrapyramidal symptoms. Clinicians may provide better treatment for patients by considering the unique pharmacological and side-effect profile of each particular antipsychotic independent of its classification as a first- or second-generation agent.08/2008; 14(4):225-31. DOI:10.1097/01.pra.0000327312.04153.da
- [Show abstract] [Hide abstract]
ABSTRACT: Haloperidol and olanzapine are widely used antipsychotic drugs in the treatment of schizophrenia and other psychotic disorders. Despite extensive research efforts within the biopharmaceutical industry and academia, the exact molecular mechanisms of their action remain largely unknown. Since the response of patients to existing medications can be variable and often includes severe side effects, it is critical to increase our knowledge on their mechanism of action to guide clinical usage and new drug development. In this study, we have employed the label-free liquid chromatography tandem mass spectrometry (LC-MSE) to identify differentially expressed proteins in rat frontal cortex following subchronic treatment with haloperidol or olanzapine. Subcellular fractionation was performed to increased proteomic coverage and provided insight into the subcellular location involved in the mechanism of drug action. LC-MSE profiling identified 531 and 741 annotated proteins in fractions I (cytoplasmic-) and II (membrane enriched-) in two drug treatments. Fifty-nine of these proteins were altered significantly by haloperidol treatment, 74 by olanzapine and 21 were common to both treatments. Pathway analysis revealed that both drugs altered similar classes of proteins associated with cellular assembly/organization, nervous system development/function (particularly presynaptic function) and neurological disorders, which indicate a common mechanism of action. The top affected canonical signaling pathways differed between the two treatments. The haloperidol data set showed a stronger association with Huntington's disease signaling, while olanzapine treatment showed stronger effects on glycolysis/gluconeogenesis. This could either relate to a difference in clinical efficacy or side effect profile of the two compounds. The results were consistent with the findings reported previously by targeted studies, demonstrating the validity of this approach. However, we have also identified many novel proteins which have not been found previously to be associated with these drugs. Further study of these proteins could provide new insights into the etiology of the disease or the mechanism of antipsychotic medications.Journal of Proteome Research 04/2009; 8(7):3284-97. DOI:10.1021/pr800983p · 5.00 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Agitated or violent behaviour constitutes 10% of all emergency psychiatric treatment. Some guidelines do not recommend the use of chlorpromazine for rapid tranquillisation but it is still often used for this purpose. To examine the effects of oral or intramuscular chlorpromazine for psychosis induced agitation or aggression. We searched the Cochrane Schizophrenia Group Trials Register (up to July 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. Randomised control trials or double blind trials (implying randomisation) comparing chlorpromazine with another drug or placebo for people who are thought to be acutely aggressive or agitated due to psychotic illness. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effects model. One study (total n=30) met the inclusion criteria. When compared with haloperidol (Man 1973) (1 RCT, n=30) people allocated chlorpromazine were no more likely to have one additional injection than those allocated haloperidol (RR 3.00 CI 0.13 to 68.26). This remained true for 2-4 injections (RR 0.90 CI 0.52 to 1.55) and for 5 or more injections (RR 0.75 CI 0.20 to 2.79). Two people allocated chlorpromazine had sudden, serious hypotension while no one allocated haloperidol had such an effect (RR 5.00 CI 0.26 to 96.13). No extrapyramidal symptoms were observed. One person allocated chlorpromazine developed status epilepticus (RR 3.00 CI 0.13 to 68.26). Overall the quality of evidence is limited, poor and dated. Where drugs that have been better evaluated are available, it may be best to avoid use of chlorpromazine. Where chlorpromazine is used for acute aggression or where choices are limited, relevant trials are possible and urgently needed.Cochrane database of systematic reviews (Online) 04/2010; 4(4):CD007445. DOI:10.1002/14651858.CD007445.pub2 · 5.94 Impact Factor