Chlorpromazine dose for people with schizophrenia

Source: Cochrane Library

Date published: 23/04/2009 10:35

Summary

by: No information given

Background
Chlorpromazine is one of the three antipsychotic drugs on the WHO Essential Drug List. It is used worldwide. The optimal dose has been the subject of evaluative research but summaries of this work are rare.

Objectives
To determine chlorpromazine dose response and dose adverse effect relationships for schizophrenia and schizophrenia-like psychoses.

Search strategy
We searched the Cochrane Schizophrenia Group Trials Register (December 2008). References of all included studies were examined for further trials.

Selection criteria
All relevant randomised controlled trials (RCTs) comparing fixed doses of chlorpromazine for people with schizophrenia and reporting clinical outcomes.

Data collection and analysis
We extracted data independently. For dichotomous data we calculated fixed-effect relative risk (RR) and their 95% confidence intervals (CI). For continuous data, we calculated weighted mean differences (WMD) based on a fixed-effect model.

Main results
We included four relevant studies (1012 participants) in this review. They are all hospital-based trials, have a duration of less than six months and are at moderate risk of bias. When low dose (≤400mg/day) was compared with medium dose (401-800 mg/day) mental state data were very few and difficult to interpret (n=22, 1 RCT, WMD 'withdrawal retardation' -2.00 CI -3.76 to -0.24). More people left for inefficacy of treatment in the low dose group (n=48, 1 RCT, RR 4.24 CI 0.24 to 74.01). In the short term, all measured extrapyramidal adverse effects tended to be lower in the low dose group (n=70, 2 RCTs, RR dystonia 0.20 CI 0.04 to 0.97). When low dose was compared with high (>800mg/day) data were taken from only one study (2gms chlorpromazine/day). Global state outcomes tended to favour the high dose group (n=416, 1 RCT, RR 'No clinically important improvement 1.12 CI 1.01 to 1.23). One case of death was reported in the high dose group (n=416, RR 0.33 CI 0.01 to 8.14) and a significantly greater number of people in the high dose group left early due to disabling adverse effects (n=416, RR 0.10 CI 0.04 to 0.27). Significantly less dystonia and unspecified extrapyramidal adverse effects were reported in the low dose group (n=416, dystonia RR 0.11 CI 0.02 to 0.45, unspecified extrapyramidal adverse effects RR 0.43 CI 0.32 to 0.59). People in both groups experienced akathisia (n=416, RR1.00 CI 0.55 to 1.83).

Authors' conclusions
The average dose of chlorpromazine given to people with schizophrenia has declined across time, but this has come about by long - and sometimes hard - experience rather than from direction from high-grade trial-based evidence. This progression towards gentler levels of dosing has taken six decades. We hope that, for modern compounds, data from relevant high-grade evaluative studies will be much more swiftly available to guide informed practice.

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Plain language summary

Chlorpromazine dose for people with schizophrenia
Schizophrenia is a serious, chronic and relapsing mental disorder. It has a worldwide lifetime prevalence of about one per cent; roughly 24 million people are suffering from this disease. Schizophrenia is characterised by both positive symptoms, such as hallucinations and delusions, and negative symptoms such as withdrawal and emotional numbness. These symptoms have a major influence on the lives of people with schizophrenia.

There are a variety of antipsychotic medications in existence, older types and newer ones. Chlorpromazine, which has been used since the mid 1950's, is a commonly prescribed drug worldwide. The World Health Organisation considers it as a part of the minimum set of medicines needed for basic health care and as one of the most effective, safe and cost-effective medicines for this purpose.

As with most medication, chlorpromazine possesses several adverse effects. As expected adverse effects tend to appear more as dose is increased. With this review we wanted to shine some light on which dose would be effective and would have an acceptable level of adverse effects.

The Review Authors' conclude that use of medium dose chlorpromazine (401-800 mg/day) is most beneficial for patients with schizophrenia. There is a worry, however, due to the small number of usable studies, that studies are overestimating the effect of certain dosages of chlorpromazine. Starting up larger trials and reporting all data found would be a desirable addition.