title: Chlorpromazine versus clotiapine for schizophrenia.
abstract: BACKGROUND
  Schizophrenia is a chronic, disabling and severe mental disorder, characterised by disturbance in perception, thought, language, affect and motor behaviour. Chlorpromazine and clotiapine are among antipsychotic drugs used for the treatment of people with schizophrenia.
  
  
  OBJECTIVE
  To determine the clinical effects, safety and cost-effectiveness of chlorpromazine compared with clotiapine for adults with schizophrenia.
  
  
  METHODS
  We searched Cochrane Schizophrenia's Trials Register (last update search 16/01/2016), which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the Register.
  
  
  METHODS
  All randomised clinical trials focusing on chlorpromazine versus clotiapine for schizophrenia. We included trials meeting our selection criteria and reporting useable data.
  
  
  METHODS
  We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
  
  
  RESULTS
  We have included four studies, published between 1974 and 2003, randomising 276 people with schizophrenia to receive either chlorpromazine or clotiapine. The studies were poor at concealing allocation of treatment and blinding of outcome assessment. Our main outcomes of interest were clinically important change in global and mental state, specific change in negative symptoms, incidence of movement disorder (dyskinesia), leaving the study early for any reason, and costs. All reported data were short-term (under six months' follow-up).The trials did not report data for the important outcomes of clinically important change in global or mental state, or cost of care. Improvement in mental state was reported using the Positive and Negative Syndrome Scale (PANSS). When chlorpromazine was compared with clotiapine the average improvement scores for mental state using the PANSS total was higher in the clotiapine group (1 RCT, N = 31, MD 11.50 95% CI 9.42 to 13.58, very low-quality evidence). The average change scores on the PANSS negative sub-scale were similar between treatment groups (1 RCT, N = 21, MD -0.97 95% CI -2.76 to 0.82, very low-quality evidence). There was no clear difference in incidence of dyskinesia (1 RCT, N = 68, RR 3.00 95% CI 0.13 to 71.15, very low-quality evidence). Similar numbers of participants left the study early from each treatment group (3 RCTs, N = 158, RR 0.68 95% CI 0.24 to 1.88, very low-quality evidence).
  
  
  CONCLUSIONS
  Clinically important changes in global and mental state were not reported. Only one trial reported the average change in overall mental state; results favour clotiapine but these limited data are very difficult to trust due to methodological limitations of the study. The comparative effectiveness of chlorpromazine compared to clotiapine on change in global state remains unanswered. Results in this review suggest chlorpromazine and clotiapine cause similar adverse effects, although again, the quality of evidence for this is poor, making firm conclusions difficult.
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Mazhari
authors.affiliation: Department of Medicine, Kerman University of Medical Sciences, Jahad Blvd, Ebn Sina Avenue, Kerman, Iran, 7619813159.
authors.forename: Saeed
authors.initials: S
authors.lastname: Esmailian
authors.affiliation: Research Center for Modeling in Health, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Haft Bagh Avenue, Block C, Kerman, Iran, 7616911317.
authors.forename: Armita
authors.initials: A
authors.lastname: Shah-Esmaeili
authors.affiliation: Department of Medicine, Kerman University of Medical Sciences, Jahad Blvd, Ebn Sina Avenue, Kerman, Iran, 7619813159.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Goughari
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Bazrafshan
authors.affiliation: Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Zare
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002746:Chlorpromazine / Q000009:adverse effects / Q000627:therapeutic use*; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology; D006801:Humans; D057194:Intention to Treat Analysis; D010352:Patient Dropouts / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D002746:Chlorpromazine; C084602:clothiapine