Chlorpromazine versus placebo for schizophrenia

Abstract

Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. To evaluate the effects of chlorpromazine for schizophrenia in comparison with placebo. We updated previous searches of the Cochrane Schizophrenia Group Register (October 1999), Biological Abstracts (1982-1995), the Cochrane Library (1999, Issue 2), EMBASE (1980-1995), MEDLINE (1966-1995), PsycLIT (1974-1995), and the Cochrane Schizophrenia Group Register (June 2002), by searching The Cochrane Schizophrenia Group Trials Register (January 2007). We searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. 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. We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. BT and JR extracted data. CEA and GA independently checked a 10% sample for reliability. We analysed dichotomous data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI) around this. Where possible we calculated the number needed to treat (NNT) or number needed to harm (NNH) statistics. 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 fixed effects weighted mean difference (WMD) with a 95% confidence interval. We inspected over 1000 electronic records. The review currently includes 302 excluded studies and 50 included studies. We found chlorpromazine reduces relapse over the short (n=74, 2 RCTs, RR 0.29 CI 0.1 to 0.8) and medium term (n=809, 4 RCTs, RR 0.49 CI 0.4 to 0.6) but data are heterogeneous. Longer term homogeneous data also favoured chlorpromazine (n=512, 3 RCTs, RR 0.57 CI 0.5 to 0.7, NNT 4 CI 3 to 5). We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n=1121, 13 RCTs, RR 'no change/not improved' 0.80 CI 0.8 to 0.9, NNT 6 CI 5 to 8). Fewer people allocated to chlorpromazine left trials early (n=1780, 26 RCTs, RR 0.65 CI 0.5 to 0.8, NNT 15 CI 11 to 24) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n=1404, 19 RCTs, RR 2.63 CI 2.1 to 3.3, NNH 5 CI 4 to 8), it increases a person's chances of experiencing acute movement disorders (n=942, 5 RCTs, RR 3.5 CI 1.5 to 8.0, NNH 32 CI 11 to 154), parkinsonism (n=1265, 12 RCTs, RR 2.01 CI 1.5 to 2.7, NNH 14 CI 9 to 28). Akathisia did not occur more often in the chlorpromazine group than placebo (n=1164, 9 RCTs, RR 0.78 CI 0.5 to 1.1). Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n=1394, 16 RCTs, RR 2.37 CI 1.7 to 3.2, NNH 11 CI 7 to 21) and considerable weight gain (n=165, 5 RCTs, RR 4.92 CI 2.3 to 10.4, NNH 2 CI 2 to 3). 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.