Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

Clive Elliott Adams¹ , John Rathbone¹ , Ben Thornley¹ , Mike Clarke² , Jo Borrill³ , Kristian Wahlbeck⁴ and A George Awad⁵

¹Cochrane Schizophrenia Group, Academic Department of Psychiatry and Behavioural Sciences, University of Leeds, 15 Hyde Terrace, Leeds, LS2 9LT, UK

²UK Cochrane Centre, Summertown Pavilion, Middle Way, Summertown, Oxford, OX2 7LG, UK

³Safer Custody Group, HM Prison Service, Abell House, John Islip Street, London, SW1P 4LH, UK

⁴STAKES/Vasa Central Hospital, Department of Psychiatry, FIN-65130 Vaasa, Finland

⁵University of Toronto, Humber River Regional Hospital, Keele Street Site, 2175 Keele Street, Toronto, Ontario, M6M 3Z4, Canada

author email corresponding author email

BMC Medicine 2005, 3:15doi:10.1186/1741-7015-3-15


Published:	17 October 2005

Abstract

Background

Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo.

Methods

We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated.

Results

Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth.

Conclusion

It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations.