title: Chlorpromazine versus placebo for schizophrenia.
abstract: BACKGROUND
  Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia.
  
  
  OBJECTIVE
  To review the effects of chlorpromazine compared with placebo, for the treatment of schizophrenia.
  
  
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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).
  
  
  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.
authors.affiliation: Cochrane Schizophrenia Group, The University of Nottingham, Institute of Mental Health, University of Nottingham Innovation Park, Triumph Road,, Nottingham, UK, NG7 2TU.
authors.forename: Clive E
authors.initials: CE
authors.lastname: Adams
authors.forename: George A
authors.initials: GA
authors.lastname: Awad
authors.forename: John
authors.initials: J
authors.lastname: Rathbone
authors.forename: Ben
authors.initials: B
authors.lastname: Thornley
authors.forename: Karla
authors.initials: K
authors.lastname: Soares-Weiser
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002746:Chlorpromazine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy* / Q000517:prevention & control; D055502:Secondary Prevention
chemical_list: D014150:Antipsychotic Agents; D002746:Chlorpromazine