Bond University Research Repository Chlorpromazine versus placebo for schizophrenia Adams, Clive E.; Awad, George A.; Rathbone, John; Thornley, Ben; Soares-Weiser, Karla Published in: Cochrane Database of Systematic Reviews DOI: 10.1002/14651858.CD000284.pub3 Published: 01/01/2014 Document Version: Publisher's PDF, also known as Version of record Link to publication in Bond University research repository. Recommended citation(APA): Adams, C. E., Awad, G. A., Rathbone, J., Thornley, B., & Soares-Weiser, K. (2014). Chlorpromazine versus placebo for schizophrenia. Cochrane Database of Systematic Reviews, 2014(1), [000284]. https://doi.org/10.1002/14651858.CD000284.pub3 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. For more information, or if you believe that this document breaches copyright, please contact the Bond University research repository coordinator. Download date: 09 Oct 2020 Cochrane Database of Systematic Reviews Chlorpromazine versus placebo for schizophrenia (Review) Adams CE, Awad GA, Rathbone J, Thornley B, Soares-Weiser K Adams CE, Awad GA, Rathbone J, Thornley B, Soares-Weiser K. Chlorpromazine versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD000284. DOI: 10.1002/14651858.CD000284.pub3. www.cochranelibrary.com Chlorpromazine versus placebo for schizophrenia (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 3 BACKGROUND .................................... 6 OBJECTIVES ..................................... 6 METHODS ...................................... 6 RESULTS....................................... 12 Figure1. ..................................... 13 Figure2. ..................................... 15 Figure3. ..................................... 16 DISCUSSION ..................................... 20 AUTHORS’CONCLUSIONS . 23 ACKNOWLEDGEMENTS . 24 REFERENCES ..................................... 24 CHARACTERISTICSOFSTUDIES . 46 DATAANDANALYSES. 149 Analysis 1.1. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 1 Death. 154 Analysis 1.2. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 2 Relapse. 155 Analysis 1.3. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 3 Global state: 1a. No overall improvement (psychiatrist-rated). 156 Analysis 1.4. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 4 Global state: 1b. No overall improvement(nurse-rated). 158 Analysis 1.5. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 5 Global state: 2. Average endpoint score -shortterm(CGI,highscore=worse). 159 Analysis 1.6. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 6 Global state: 3a. Severity of illness, severely ill or worse (CGI 5+ points, psychiatrist-rated). ............... 160 Analysis 1.7. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 7 Global state: 3b. Severity of illness, severely ill or worse - medium term (CGI 5+ points, nurse-rated)................. 161 Analysis 1.8. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 8 Leaving the study early. 162 Analysis 1.9. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 9 Mental state: 1. Improved - short term (BPRS,50%change). 164 Analysis 1.10. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 10 Mental state: 2. Average endpoint scores(BPRS,highscore=worse). 165 Analysis 1.11. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 11 Behaviour: 1. Deteriorated/ disturbed/un-cooperative.. 166 Analysis 1.12. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 12 Behaviour: 2. Unchanged. 167 Analysis 1.13. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 13 Behaviour: 3. Average endpoint scores(RRS,highscore=worse). 168 Analysis 1.14. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 14 Behaviour: 4. Average endpoint score - short term (PBRS, high score=good). 169 Analysis 1.15. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 15 Behaviour: 5. Average endpoint scores - medium term (Fergus Falls Behavioural rating scale). ............... 169 Analysis 1.16. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 16 Adverse effects: 1. Movement disorders. ................................... 170 Analysis 1.17. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 17 Adverse effects: 2. Movement disorders: Average endpoint scores (Extrapyramidal Bilan, high score=worse). 173 Analysis 1.18. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 18 Adverse effects: 1. Central nervous system..................................... 174 Analysis 1.19. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 19 Adverse effects: 3. Blood, skin, liver, eyes...................................... 176 Chlorpromazine versus placebo for schizophrenia (Review) i Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 1.20. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 20 Adverse effects: 4. Other. 178 Analysis 1.21. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 21 SUBGROUP ANALYSIS: 1. MEN vs WOMEN: Behaviour: Deteriorated/disturbed/un-cooperative................. 182 Analysis 1.22. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 22 SUBGROUP ANALYSIS: 2. ACUTEvsCHRONIC. 183 Analysis 1.23. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 23 SUBGROUP ANALYSIS: 3. HIGHvsLOWDOSE. 186 Analysis 1.24. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 24 SUBGROUP ANALYSIS: 4. DIAGNOSTIC CRITERIA vs NO DIAGNOSTIC CRITERIA. 188 Analysis 1.25. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 25 SUBGROUP ANALYSIS: 5. STUDIES PRE-1990 vs STUDIES 1990-2007. 192 Analysis 1.26. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 26 SENSITIVITY ANALYSIS: 1. RANDOMISATION.. 194 Analysis 1.27. Comparison 1 CHLORPROMAZINE versus PLACEBO, Outcome 27 SENSITIVITY ANALYSIS: 2. ASSUMPTIONSFORLOSTBINARYDATA. 196 ADDITIONALTABLES. 196 APPENDICES ..................................... 197 FEEDBACK...................................... 200 WHAT’SNEW..................................... 203 HISTORY....................................... 203 CONTRIBUTIONSOFAUTHORS . 204 DECLARATIONSOFINTEREST . 204 SOURCESOFSUPPORT . 205 DIFFERENCES BETWEEN PROTOCOL AND REVIEW . .... 205 INDEXTERMS .................................... 205 Chlorpromazine versus placebo for schizophrenia (Review) ii Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Chlorpromazine versus placebo for schizophrenia Clive E Adams1, George A Awad2, John Rathbone3, Ben Thornley4, Karla Soares-Weiser5 1Cochrane Schizophrenia Group, The University of Nottingham, Nottingham, UK. 2Department of Psychiatry, University of Toronto, Toronto, Canada. 3Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia. 4Marsh Gibbon, UK. 5Cochrane Editorial Unit, Cochrane, London, UK Contact address: Clive E Adams, Cochrane Schizophrenia Group, The University of Nottingham, Institute of Mental Health, Innovation Park, Triumph Road„ Nottingham, NG7 2TU, UK. [email protected]. Editorial group: Cochrane Schizophrenia Group. Publication status and date: Edited (no change to conclusions), published in Issue 11, 2015. Citation: Adams CE, Awad GA, Rathbone J, Thornley B, Soares-Weiser K. Chlorpromazine versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD000284. DOI: 10.1002/14651858.CD000284.pub3. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. Objectives To review the effects of chlorpromazine compared with placebo, for the treatment of schizophrenia. Search 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. Selection criteria 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. Data collection and analysis 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. Main 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.