Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials
1 Cochrane Schizophrenia Group, Academic Department of Psychiatry and Behavioural Sciences, University of Leeds, 15 Hyde Terrace, Leeds, LS2 9LT, UK
2 UK Cochrane Centre, Summertown Pavilion, Middle Way, Summertown, Oxford, OX2 7LG, UK
3 Safer Custody Group, HM Prison Service, Abell House, John Islip Street, London, SW1P 4LH, UK
4 STAKES/Vasa Central Hospital, Department of Psychiatry, FIN-65130 Vaasa, Finland
5 University of Toronto, Humber River Regional Hospital, Keele Street Site, 2175 Keele Street, Toronto, Ontario, M6M 3Z4, Canada
BMC Medicine 2005, 3:15 doi:10.1186/1741-7015-3-15Published: 17 October 2005
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.
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.
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.
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.