Chlorpromazine versus placebo for schizophrenia

Abstract

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

Objectives: To evaluate the effects of chlorpromazine for schizophrenia in comparison with placebo.

Search strategy: 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) and PsycLIT (1974-1995), by searching Cochrane Schizophrenia Group Register (June 2002). References of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were contacted.

Selection criteria: All randomised controlled trials (RCTs) comparing chlorpromazine with placebo relevant to 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: Citations and, where possible, abstracts were inspected independently by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted by BT and JR. CA and GA independently checked a 10% sample for reliability. Dichotomous data were analysed using random effects relative risk (RR) and the 95% confidence interval (CI) around this was estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics (NNH) were calculated. Continuous data were excluded if more than 50% of people were lost to follow up, but, where possible, weighted mean difference (WMD) was calculated.

Main results: Over 1000 electronic records were inspected. The review currently mentions 302 papers in its Excluded Studies table and 50 studies in its Included Studies table. Four papers are awaiting translation. Chlorpromazine reduces relapse over six months to two years (n=512, 3 RCTs, RR 0.65 CI 0.5 to 0.9, NNT 3 CI 2.5 to 4) and promotes a global improvement in a person's symptoms and functioning (n=1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10) although the placebo response is also considerable. Fewer people allocated to chlorpromazine leave trials early (n=1755, 25 RCTs, RR 0.77 CI 0.6 to 1.1) but the difference iss not statistically significant. There are many adverse effects. Chlorpromazine is clearly sedating (n=1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), it increases a person's chances of experiencing acute movement disorders (n=780, 4 RCTs, RR 3.1 CI 1.3 to 7.7, NNH 24 CI 15 to 57), parkinsonism (n=1265, 12 RCTs, RR 2.6 CI 1.2 to 5.4, NNH 10 CI 8 to 16) and, perhaps, fits (n=695, 3 RCTs, RR 2.4 CI 0.4 to 16). Amongst other things it clearly causes a lowering of blood pressure with accompanying dizziness (n=1232, 15 RCTs, RR 1.9 CI 1.4 to 27, NNH 12 CI 8 to 19) and considerable increases in weight (n=165, 5 RCTs, RR 4.4 CI 2.1 to 9, NNH 3 CI 2 to 5).

Reviewer's conclusions: This review will confirm much that clinicians and recipients of care already know, but provides quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by 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.