Chlorpromazine versus placebo for schizophrenia

Clive E. Adams, George A. Awad, John Rathbone, Ben Thornley, Karla Soares-Weiser

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Abstract

Background

Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia.

Objectives

To review the effects of chlorpromazine compared with placebo, for the treatment of schizophrenia.

Search methods

We searched the Cochrane Schizophrenia Group's Trials Register (15 May 2012). We also searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information.

Selection criteria

We included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care.

Data collection and analysis

We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. We analysed dichotomous data using risk ratio (RR) and estimated the 95% confidence interval (CI) around this. We excluded continuous data if more than 50% of participants were lost to follow-up. Where continuous data were included, we analysed this data using mean difference (MD) with a 95% confidence interval. We used a fixed-effect model.

Main results

We inspected over 1100 electronic records. The review currently includes 315 excluded studies and 55 included studies. The quality of the evidence is very low. We found chlorpromazine reduced the number of participants experiencing a relapse compared with placebo during six months to two years follow-up (n = 512, 3 RCTs, RR 0.65 CI 0.47 to 0.90), but data were heterogeneous. No difference was found in relapse rates in the short, medium or long term over two years, although data were also heterogeneous. We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n = 1164, 14 RCTs, RR 0.71 CI 0.58 to 0.86). Fewer people allocated to chlorpromazine left trials early (n = 1831, 27 RCTs, RR 0.64 CI 0.53 to 0.78) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n = 1627, 23 RCTs, RR 2.79 CI 2.25 to 3.45), it increases a person's chances of experiencing acute movement disorders (n = 942, 5 RCTs, RR 3.47 CI 1.50 to 8.03) and parkinsonism (n = 1468, 15 RCTs, RR 2.11 CI 1.59 to 2.80). Akathisia did not occur more often in the chlorpromazine group than placebo. Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n = 1488, 18 RCTs, RR 2.38 CI 1.74 to 3.25) and considerable weight gain (n = 165, 5 RCTs, RR 4.92 CI 2.32 to 10.43).

Authors' conclusions

The results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well-established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.

Original languageEnglish
Article number000284
Number of pages207
JournalCochrane Database of Systematic Reviews
Volume2014
Issue number1
DOIs
Publication statusPublished - 2014

Cite this

Adams, C. E., Awad, G. A., Rathbone, J., Thornley, B., & Soares-Weiser, K. (2014). Chlorpromazine versus placebo for schizophrenia. Cochrane Database of Systematic Reviews, 2014(1), [000284]. https://doi.org/10.1002/14651858.CD000284.pub3
Adams, Clive E. ; Awad, George A. ; Rathbone, John ; Thornley, Ben ; Soares-Weiser, Karla. / Chlorpromazine versus placebo for schizophrenia. In: Cochrane Database of Systematic Reviews. 2014 ; Vol. 2014, No. 1.
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abstract = "BackgroundChlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia.ObjectivesTo review the effects of chlorpromazine compared with placebo, for the treatment of schizophrenia.Search methodsWe searched the Cochrane Schizophrenia Group's Trials Register (15 May 2012). We also searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information.Selection criteriaWe included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care.Data collection and analysisWe independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. We analysed dichotomous data using risk ratio (RR) and estimated the 95{\%} confidence interval (CI) around this. We excluded continuous data if more than 50{\%} of participants were lost to follow-up. Where continuous data were included, we analysed this data using mean difference (MD) with a 95{\%} confidence interval. We used a fixed-effect model.Main resultsWe inspected over 1100 electronic records. The review currently includes 315 excluded studies and 55 included studies. The quality of the evidence is very low. We found chlorpromazine reduced the number of participants experiencing a relapse compared with placebo during six months to two years follow-up (n = 512, 3 RCTs, RR 0.65 CI 0.47 to 0.90), but data were heterogeneous. No difference was found in relapse rates in the short, medium or long term over two years, although data were also heterogeneous. We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n = 1164, 14 RCTs, RR 0.71 CI 0.58 to 0.86). Fewer people allocated to chlorpromazine left trials early (n = 1831, 27 RCTs, RR 0.64 CI 0.53 to 0.78) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n = 1627, 23 RCTs, RR 2.79 CI 2.25 to 3.45), it increases a person's chances of experiencing acute movement disorders (n = 942, 5 RCTs, RR 3.47 CI 1.50 to 8.03) and parkinsonism (n = 1468, 15 RCTs, RR 2.11 CI 1.59 to 2.80). Akathisia did not occur more often in the chlorpromazine group than placebo. Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n = 1488, 18 RCTs, RR 2.38 CI 1.74 to 3.25) and considerable weight gain (n = 165, 5 RCTs, RR 4.92 CI 2.32 to 10.43).Authors' conclusionsThe results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well-established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.",
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Adams, CE, Awad, GA, Rathbone, J, Thornley, B & Soares-Weiser, K 2014, 'Chlorpromazine versus placebo for schizophrenia' Cochrane Database of Systematic Reviews, vol. 2014, no. 1, 000284. https://doi.org/10.1002/14651858.CD000284.pub3

Chlorpromazine versus placebo for schizophrenia. / Adams, Clive E.; Awad, George A.; Rathbone, John; Thornley, Ben; Soares-Weiser, Karla.

In: Cochrane Database of Systematic Reviews, Vol. 2014, No. 1, 000284, 2014.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Chlorpromazine versus placebo for schizophrenia

AU - Adams, Clive E.

AU - Awad, George A.

AU - Rathbone, John

AU - Thornley, Ben

AU - Soares-Weiser, Karla

PY - 2014

Y1 - 2014

N2 - BackgroundChlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia.ObjectivesTo review the effects of chlorpromazine compared with placebo, for the treatment of schizophrenia.Search methodsWe searched the Cochrane Schizophrenia Group's Trials Register (15 May 2012). We also searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information.Selection criteriaWe included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care.Data collection and analysisWe independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. We analysed dichotomous data using risk ratio (RR) and estimated the 95% confidence interval (CI) around this. We excluded continuous data if more than 50% of participants were lost to follow-up. Where continuous data were included, we analysed this data using mean difference (MD) with a 95% confidence interval. We used a fixed-effect model.Main resultsWe inspected over 1100 electronic records. The review currently includes 315 excluded studies and 55 included studies. The quality of the evidence is very low. We found chlorpromazine reduced the number of participants experiencing a relapse compared with placebo during six months to two years follow-up (n = 512, 3 RCTs, RR 0.65 CI 0.47 to 0.90), but data were heterogeneous. No difference was found in relapse rates in the short, medium or long term over two years, although data were also heterogeneous. We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n = 1164, 14 RCTs, RR 0.71 CI 0.58 to 0.86). Fewer people allocated to chlorpromazine left trials early (n = 1831, 27 RCTs, RR 0.64 CI 0.53 to 0.78) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n = 1627, 23 RCTs, RR 2.79 CI 2.25 to 3.45), it increases a person's chances of experiencing acute movement disorders (n = 942, 5 RCTs, RR 3.47 CI 1.50 to 8.03) and parkinsonism (n = 1468, 15 RCTs, RR 2.11 CI 1.59 to 2.80). Akathisia did not occur more often in the chlorpromazine group than placebo. Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n = 1488, 18 RCTs, RR 2.38 CI 1.74 to 3.25) and considerable weight gain (n = 165, 5 RCTs, RR 4.92 CI 2.32 to 10.43).Authors' conclusionsThe results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well-established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.

AB - BackgroundChlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia.ObjectivesTo review the effects of chlorpromazine compared with placebo, for the treatment of schizophrenia.Search methodsWe searched the Cochrane Schizophrenia Group's Trials Register (15 May 2012). We also searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information.Selection criteriaWe included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care.Data collection and analysisWe independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. We analysed dichotomous data using risk ratio (RR) and estimated the 95% confidence interval (CI) around this. We excluded continuous data if more than 50% of participants were lost to follow-up. Where continuous data were included, we analysed this data using mean difference (MD) with a 95% confidence interval. We used a fixed-effect model.Main resultsWe inspected over 1100 electronic records. The review currently includes 315 excluded studies and 55 included studies. The quality of the evidence is very low. We found chlorpromazine reduced the number of participants experiencing a relapse compared with placebo during six months to two years follow-up (n = 512, 3 RCTs, RR 0.65 CI 0.47 to 0.90), but data were heterogeneous. No difference was found in relapse rates in the short, medium or long term over two years, although data were also heterogeneous. We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n = 1164, 14 RCTs, RR 0.71 CI 0.58 to 0.86). Fewer people allocated to chlorpromazine left trials early (n = 1831, 27 RCTs, RR 0.64 CI 0.53 to 0.78) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n = 1627, 23 RCTs, RR 2.79 CI 2.25 to 3.45), it increases a person's chances of experiencing acute movement disorders (n = 942, 5 RCTs, RR 3.47 CI 1.50 to 8.03) and parkinsonism (n = 1468, 15 RCTs, RR 2.11 CI 1.59 to 2.80). Akathisia did not occur more often in the chlorpromazine group than placebo. Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n = 1488, 18 RCTs, RR 2.38 CI 1.74 to 3.25) and considerable weight gain (n = 165, 5 RCTs, RR 4.92 CI 2.32 to 10.43).Authors' conclusionsThe results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well-established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.

U2 - 10.1002/14651858.CD000284.pub3

DO - 10.1002/14651858.CD000284.pub3

M3 - Article

VL - 2014

JO - Cochrane database of systematic reviews (Online)

JF - Cochrane database of systematic reviews (Online)

SN - 1469-493X

IS - 1

M1 - 000284

ER -